A. History of and Development of the Company
Introduction
We were founded in 1940 in Barcelona, Spain by Dr. José Antonio Grifols i Roig, a specialist and pioneer in blood transfusions and clinical analysis and the grandfather of our current Honorary Chairperson (non-member) of the Board. We have been making and selling plasma derivative products for more than 70 years. Over the last 25 years, we have grown from a predominantly domestic Spanish company into a global company by expanding both organically and through acquisitions throughout Europe, the United States, Latin America, Africa and Asia.
We were incorporated in Spain as a limited liability company on June 22, 1987 under the name Grupo Grifols, S.A., and we changed our name to Grifols, S.A. in 2005. We conduct business under the commercial name “Grifols.” Our registered and principal executive office is located at Avinguda de la Generalitat, 152 Parque Empresarial Can Sant Joan, 08174 Sant Cugat del Vallès, Barcelona, Spain and our telephone number is +34 93 571 0500. Additional information about the Company is available on our website at www.grifols.com.
We are a vertically integrated global producer of plasma derivatives and we believe we rank among the three largest producers in the industry in terms of total sales globally. Our activities include sourcing raw material, manufacturing various plasma derivative products and selling and distributing final products to healthcare providers. We have expanded our plasma collection network and our manufacturing capacity through a combination of organic growth and acquisitions. As of December 31, 2025 we had more than 400 operating plasma collection centers located across the United States, Germany, Austria, Czech Republic, Hungary, Canada and Egypt (through our joint venture with Egypt’s National Services Projects Organization, or “NSPO”).
We also research, develop, manufacture and market in vitro diagnostics products, including analytical instruments, reagents, software and associated products for use in clinical and blood bank laboratories and hospital products.
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Our Class A shares have been listed on the Spanish Stock Exchanges since we completed our initial public offering on May 17, 2006 and are quoted on the SIBE under the ticker symbol “GRF.” Since January 2008, we have been part of the IBEX-35 Index, which comprises the top 35 listed Spanish companies by liquidity and market capitalization. Our Class A shares are also traded in the United States in over the counter markets in the form of ADSs, evidenced by ADRs. Each ADS traded over the counter represents two of our Class A shares. Our Class B shares were issued as part of the consideration for the acquisition of Talecris Plasma Resources, Inc. (“Talecris”), a company that has since been merged into our subsidiary Biomat USA, and are listed on the Spanish Stock Exchanges and quoted on the SIBE under the ticker symbol “GRF.P.” Our Class B shares are also traded in the United States on the NASDAQ Global Select Market in the form of ADSs, evidenced by ADRs, under the symbol “GRFS.” Each ADS traded on NASDAQ represents one of our Class B shares. Our ADSs are currently traded in U.S. dollars. In November 2011, our ADSs were added to the NASDAQ Biotechnology Index.
The SEC maintains an internet site at http://www.sec.gov that contains reports, information statements and other information regarding issuers that file electronically with the SEC.
Important Milestones
The following are some of our most important historical milestones:
● On December 11, 2025, we received certification from the EMA for the entire value chain of Grifols Egypt for Plasma Derivatives (“Grifols Egypt”), our public-private partnership with the government of Egypt representing a joint investment of €280 million. This certification positions Egypt as the first country in Africa and the Middle East to operate a fully integrated plasma collection and processing system that meets the most demanding European standards of quality, safety and regulatory control. With this milestone, Egypt has achieved self-sufficiency in plasma-derived medicinal products, including immunoglobulins, albumin and coagulation factors, becoming the sixth country in the world capable of supplying itself with medicines derived from national plasma, after the United States, Germany, Austria, the Czech Republic and Hungary. See “—B. Business Overview—Raw Materials” and “—D. Property, Plant and Equipment—Plasma Fractionation Plants;”
● On November 1, 2025, we acquired a 50.1% equity stake in CPR, a Canadian private company engaged in plasma collection for the production of plasma-derived therapies, for an aggregate consideration of approximately €19 million. Following the acquisition, which strengthens our presence in Canada, CPR was renamed Grifols Canada Plasma Corporation (“Grifols Canada Plasma”). See Item 5 of this Part I, “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations—Recent Acquisitions;
● On October 16, 2025, we started manufacturing Grifols DG Gel card and reagent red blood cells (“RRBCs”) at our new plant in San Diego, California, following approvals from the FDA. Production of this key technology, used in blood type testing to ensure transfusion compatibility between donors and patients, will serve the growing demand for blood typing solutions in the U.S. The 73,541-square-foot facility, designed by Grifols Engineering, features highly automated production technologies, including a state-of-the-art quality-control laboratory, a warehouse and office space;
● On February 3, 2025, we completed the acquisition of 28 plasma collection centers in the United States from ImmunoTek GH, LLC (“ImmunoTek”). This acquisition was initiated on July 29, 2021, when we entered into an agreement with ImmunoTek, amended in 2023 and 2024, to arrange for the construction, licensing and commissioning of the 28 centers. Pursuant to this agreement, we formed the ITK JV, a joint operation company named Biotek America LLC, through which we initially held a 75% interest in each of the 28 plasma collection centers, while ImmunoTek held the remaining 25%. In 2024, we acquired 14 plasma collection centers for an aggregate amount of $266 million and, effective as of February 3, 2025, we completed the acquisition of the remaining 14 centers for an aggregate amount of approximately $281 million. See “—B. Business Overview—Raw Materials,” Item 5 of this Part I, “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations—Recent Acquisitions;”
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● On June 18, 2024, we closed the sale of a 20% equity stake in Chinese company Shanghai RAAS in exchange for approximately $1.8 billion, while retaining a stake in Shanghai RAAS of 6.58%, to the Haier group (“Haier”). We had acquired 26.58% of the voting and economic rights in Shanghai RAAS in exchange for 45% of the economic rights and 40% of the voting rights in our U.S. subsidiary, GDS, on March 30, 2020. We have maintained and extended our presence in China and used the proceeds of the sale to significantly reduce debt. See Item 5 of this Part I, “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting our Financial Condition and Results of Operations—Recent Dispositions—Shanghai RAAS;”
● On April 25, 2022, we acquired all of the existing equity interest in Grifols Biotest Holdings GmbH, formerly known as Tiancheng (Germany) Pharmaceutical Holdings AG (“Biotest Holdings”), which in turn owned 89.88% of the ordinary shares and 1.08% of the preferred equity shares of German publicly traded company Biotest, a global company that supplies plasma protein products and biotherapeutic drugs, for a total consideration of €1,090,518,254. In addition, through multiple tender offers and several over the counter transactions in 2022 and 2025, as well as the completion of a squeeze-out procedure initiated in 2022, we have since increased our shareholding stake to 100.0% of the total ordinary voting shares and 61.6% of the total non-voting preferred shares of Biotest, which in the aggregate represent 80.8% of Biotest’s share capital. See Item 5 of this Part I, “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting our Financial Condition and Results of Operations—Recent Acquisitions—Biotest Shares and Public Delisting Purchase Offer;”
● On December 1, 2021, we sold preferred shares representing 12.9% of Biomat Newco and 12.5% of Biomat USA, our U.S.-based plasma collection subsidiaries that are part of the Biomat group, also comprised of Biomat USA’s subsidiaries Grifols Bio Supplies, Inc., formerly known as Interstate Blood Bank, Inc., Talecris and Biomat USA South, Inc., the latter two of which have since been merged into Biomat USA and dissolved, respectively (collectively, the “Biomat Group”), to Parette Investment Pte. Ltd. (the “GIC Investor”), an affiliate of GIC Private Limited, which is a sovereign wealth fund established by the Government of Singapore. The purchase price received was $990 million. We used the net proceeds to (i) prepay $600 million of principal amount of the Revolving Loans under the First Lien Credit Facilities, (ii) prepay $142,360,501.31 of the principal amount of the Dollar Tranche B Term Loans under the First Lien Credit Facilities, (iii) prepay $88,003,617.48 of the Euro Tranche B Term Loans under the First Lien Credit Facilities and (iv) repurchase €97,535,000.00 of the 2019 Notes under an asset sale offer. See Item 5 of this Part I, “B. Liquidity and Capital Resources—Sources of Credit—The Biomat Transactions;”
● On October 15, 2020, we acquired 100% of the equity of Alkahest, Inc. (“Alkahest”), a California biopharmaceutical company, for a total consideration of $146 million. In 2015, we had previously acquired a significant minority stake of Alkahest and, with this transaction, we gained total control of the company;
● On October 1, 2020, we acquired a plasma fractionation facility and two purification facilities located in Montreal, Canada, as well as 11 plasma collection centers in the United States, from South Korean firm GC Pharma, for a total consideration of $457 million. Once we finish renovations and obtain all necessary licenses and regulatory approvals for the Montreal facilities, we will become the only large-scale commercial manufacturer of plasma products in Canada. In 2025, the first phase was completed with the commissioning of an albumin purification and filling plant, and we started manufacturing albumin in the Montreal facilities. Phases II and III, currently under development, include the addition of a plasma-fractionation plant and a second IVIG purification and filling facility. We expect to begin plasma fractionation and gammaglobulin manufacturing by 2027;
● In June 2018, we completed the acquisition of German based pharmaceutical company Haema GmbH (formerly known as Haema AG) for a purchase price of €220 million;
● In August 2018, we completed the acquisition of U.S. based pharmaceutical company BPC Plasma Inc. (formerly known as Biotest Pharmaceuticals Corporation), for a purchase price of $286 million;
● In December 2016, we entered into an asset purchase agreement with Hologic Inc. (“Hologic”), to acquire Hologic’s nucleic acid testing (“NAT”) Donor Screening Unit. The transaction closed in January 2017 for a purchase price of $1.9 billion;
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● In January 2014, we acquired the diagnostic business of Novartis Corporation (“Novartis”), for a purchase price of $1.7 billion;
● In June 2011, we acquired U.S. based biotherapeutics company Talecris Biotherapeutics for a purchase price of $3.7 billion; and
● In July 2003, we acquired the assets of Alpha Therapeutics Corporation, including its plasma fractionation plant in Los Angeles, California, for a purchase price of $104 million.
For further details of material changes in our operations, products and services, see Item 5 of this Part I, “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations” and Item 6 of this Part I “Directors and Senior Management.” For further details of our principal capital expenditures and divestitures, see Item 5 of this Part I, “Operating and Financial Review and Prospects—B. Liquidity and Capital Resources—Capital Expenditures, Other Intangible Assets and Rights of Use.”
B. Business Overview
General
We are one of the leading global specialty plasma therapeutics companies developing, manufacturing and distributing a broad range of biological medicines based on plasma derived proteins. Plasma derivatives are proteins found in human plasma, which once isolated and purified, have therapeutic value. These protein-based therapies extend and enhance the lives of individuals who suffer from chronic and acute, often life-threatening, conditions, including primary and secondary immunological deficiencies, Chronic Inflammatory Demyelinating Polyneuropathy (“CIDP”), A1PI deficiency and related emphysema, immune-mediated ITP, Guillain Barré syndrome, Kawasaki disease, allogeneic bone marrow transplants, hemophilia A and B, Von Willebrand Disease, traumatic or hemorrhagic shock and severe burns. In addition, we have built a diagnostic business that focuses on researching, developing, manufacturing and marketing in vitro diagnostics products for use in clinical and blood bank laboratories. We also specialize in providing infusion solutions, nutrition products and medical devices for use in hospitals and clinics.
Our products and services are used by healthcare providers in over 100 countries to diagnose and treat patients with hemophilia, immune deficiencies, infectious diseases and a range of other medical conditions, and we have a direct presence, through the operation of commercial subsidiaries, in over 30 countries.
We are a leading producer in the industry in terms of total sales globally. We believe we have a top three market position in various segments of the plasma derivatives industry, including A1PI, IG and albumin as well as in terms of plasma collection centers and fractionation capacity. Our long-term aim is to further strengthen our leadership through the development of new and differentiated plasma-derived therapeutics, and the expansion of our global plasma collection footprint via acquisitions and greenfield projects.
We organize our business into five business units: Plasma Procurement, Biopharma, Diagnostic, Bio Supplies and Others.
Plasma Procurement. The Plasma Procurement business unit includes all activities relating to plasma collection, including the evaluation and screening of plasma donors and the operation of our plasma collection centers. We report no revenue from the Plasma Procurement business unit because all plasma collected in our facilities is sold to Grifols companies in the Biopharma business unit and the revenue from these intra-group sales is offset against the intra-group expenses related to such sale upon consolidation, ensuring that only external revenue is reflected in our financial information. Due to the internal-facing nature of its operations, we describe our Plasma Procurement operations under the Biopharma unit in this annual report on Form 20-F.
Biopharma (formerly Bioscience). The Biopharma business unit includes activities relating to the manufacture of plasma derivatives for therapeutic use, including the reception, analysis, quarantine, classification, fractionation and purification of plasma and the sale and distribution of end products. The main plasma products we manufacture are IG, Factor VIII, Alpha 1 (A1PI) and albumin. We also manufacture intramuscular (hyperimmune) immunoglobulins, ATIII, Factor IX and plasma thromboplastin component (“PTC”). The Biopharma business unit accounted for €6.5 billion, or 86.2%, of our total net revenue in 2025.
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Diagnostic. The Diagnostic business unit focuses on researching, developing, manufacturing and marketing in vitro diagnostics products, including analytical instruments, reagents, software and associated products for use in clinical and blood bank laboratories, covering the entire value chain from donation to transfusion. We concentrate our Diagnostic business in transfusion medicine (immunology, immunohematology) and specialty diagnostics such as hemostasis. The Diagnostic business unit’s main customers are blood donation centers, clinical analysis laboratories and hospital immunohematology services. The Nucleic Acid Testing, or NAT, Donor Screening Unit is engaged in research, development, manufacturing and commercialization of assays and instruments based on NAT technology for transfusion and transplantation screening. NAT technology makes it possible to detect the presence of infectious agents in blood and plasma donations, contributing to greater transfusion safety. The Diagnostic business unit accounted for €640 million, or 8.5%, of our total net revenue in 2025.
Bio Supplies. Net revenue from Bio Supplies primarily consists of revenue related to biological products for non-therapeutic use and plasma sales to third parties. The Bio Supplies business unit accounted for €154 million, or 2.0%, of our total net revenue in 2025.
Other Activities and Operations. In addition to our four business units, we have other smaller operations, activities and business lines (“Others”), which revenue primarily originates from the provision of manufacturing services to third parties, third party plasma sales and research activities. Others also includes our Healthcare Solutions (formerly our Hospital Division). This business unit includes, in addition, pharmaceutical products manufactured by the Group and intended for hospital pharmacies, as well as the marketing of products that complement our own products. Others accounted for €243 million, or 3.2%, of our total net revenue in 2025.
Geographic Markets
We believe we are a leading plasma derivatives producer globally, ranking among the three largest producers in the industry in terms of total sales, along with Takeda and CSL Group. We are the world’s largest producer of A1PI, which is used for the treatment of A1PI deficiency-related emphysema.
We currently operate in over 100 countries through distributors and subsidiaries in over 30 countries. The United States is the largest sales region in the world for the plasma derivative sector. For the year ended December 31, 2025, the United States and Canada accounted for 56.5% of our total net revenue, the European Union accounted for 21.5% of our total net revenues (25.9% of which was generated in Spain) and the rest of the world accounted for 22.0% of our total net revenue.
Certain sales regions, particularly in emerging markets, have experienced continuous growth, driven by enhanced socioeconomic conditions, including a general increase in the testing of patients for immunodeficiencies, autoimmune diseases and low levels of alpha 1 protein, all conditions treatable by our products, more informed patients who are demanding better quality medical care, as well as increasing government healthcare spending on plasma derivative products. These emerging markets are expected to experience significant growth. Our presence and experience in Latin America, in countries such as Mexico, Colombia, Argentina, Chile and Brazil, where we have been marketing and selling products for over 20 years, has positioned us to benefit from this additional growth in both our Biopharma and Diagnostic business units. In the Asia-Pacific region, we have established a presence through our subsidiaries and representative offices in Malaysia, China, Thailand, Singapore, Australia, Japan, India, Hong Kong, Taiwan and Indonesia. We have also opened a Middle Eastern representative office in Dubai and Saudi Arabia.
We maintain a continuing focus on international expansion and acquisitions and will continue to selectively consider acquisitions that would generate operation synergies. For specific examples of acquisitions we have made to further enhance our operations, see “—A. History and Development of the Company—Important Milestones” above.
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The following chart reflects a summary of net revenue by each of our geographic regions for the past three years:
Year ended Year ended Year ended
December 31, % of total December 31, % of total December 31, % of total
Summary of Net Revenue by Region 2025 net revenue 2024 net revenue 2023 net revenue
(in millions of euros, except for percentages)
European Union(1)(2) 1,614 21.5 % 1,499 20.8 % 1,256 19.1 %
United States and Canada 4,253 56.5 % 4,087 56.7 % 3,899 59.1 %
Rest of the World(2) 1,657 22.0 % 1,626 22.5 % 1,437 21.8 %
Total 7,524 100.0 % 7,212 100.0 % 6,592 100.0 %
(1) Net revenue earned in the European Union includes net revenue earned in Spain.
(2) Net revenue earned in the European Union and Rest of World for 2024 has been adjusted compared to the amounts reported in our consolidated financial statements for the year ended December 31, 2024 to reflect a €42 million reclassification related to Biotest identified after their issuance. This reclassification has been incorporated in the consolidated financial statements for year ended December 31, 2025, and the presentation in this Form 20-F is consistent with the consolidated financial statements for year ended December 31, 2025.
Principal Activities
We organize our business into five business units: Plasma Procurement, Biopharma, Diagnostic, Bio Supplies and Others. The Plasma Procurement business unit generates no revenues, as all plasma collected is sold to Grifols companies in the Biopharma business unit, and does not represent a distinct source of risks and returns as its activities are fully integrated within the Biopharma value chain. As a result, our presentation of consolidated financial information excludes Plasma Procurement as an operating segment. The following chart presents our total net revenues by each of our other business units for the past three years:
Year ended Year ended Year ended
December 31, % of total December 31, % of total December 31, % of total
Summary of Net Revenue by business unit 2025 net revenue 2024 net revenue 2023 net revenue
(in millions of euros, except for percentages)
Biopharma 6,487 86.2 % 6,143 85.2 % 5,558 84.3 %
Diagnostic 640 8.5 % 645 8.9 % 670 10.2 %
Bio Supplies 154 2.0 % 216 3.0 % 160 2.4 %
Others 243 3.3 % 208 2.9 % 204 3.1 %
Total 7,524 100.0 % 7,212 100.0 % 6,592 100.0 %
The Biopharma Business Unit
The Biopharma business unit is responsible for the research and development, production and marketing of plasma derivative products. In 2025, the Biopharma business unit accounted for 86.2% of our total net revenue.
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Operational Structure
The following chart illustrates its operational structure:
From plasma donation to therapeutic application, there are four major steps in the industry value chain process: (i) plasma collection, (ii) transport and logistics, (iii) manufacturing (fractionation and purification) and (iv) marketing and distribution. We are present at all levels of the value chain, from collection centers to distribution of the final products. This vertical integration enables us to leverage our position at each stage to control the overall process, to benefit from lower prices and to introduce complementary products, such as those offered through the Bio Supplies and Diagnostics business units, to our customers.
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Plasma Procurement
Plasma is the key raw material used in the production of plasma-derived products. We have expanded our plasma collection network through a combination of organic growth by opening new plasma collection centers and acquisitions. We obtain our plasma primarily from the United States and Europe (Germany, Austria, Czech Republic, and Hungary) through more than 400 operating plasma collection centers (310 in the U.S., 97 in Europe, and 8 in the rest of the world) and, to a much lesser extent, through agreements with third parties. Over the last few years, pursuant to the implementation of our business strategy, we have acquired plasma collection centers in the United States, Canada and Europe.
In 2025, we continued to manage our plasma supply efficiently, maintaining stability in cost per liter. This performance was supported by improved operational yields at donation centers, driven by the implementation in recent years of more efficient plasmapheresis equipment based on nomogram technology, which has increased process productivity. We also continued to optimize cost per liter of plasma collected through various initiatives aimed at streamlining structural costs, optimizing donor compensation, improving the donor experience, and increasing operational efficiencies across the entire center network. See “—Raw Materials” below and Item 5 of this Part I, “A. Operating Results—Factors Affecting our Financial Condition and Results of Operations—Operational Improvement Plan.”
We believe that the majority of our plasma requirements through 2026 will be met through plasma collected at our plasma collection centers and, to a lesser extent, purchased from third-party suppliers pursuant to various plasma purchase agreements. As we source the majority of our plasma internally, we are well positioned to ensure the availability of plasma for our manufacturing needs and assure the quality of the plasma throughout our manufacturing process.
We have implemented mechanisms to ensure that plasma donors meet the guidelines set forth by applicable regulations regarding, among other things, health, age and frequency of donations. Once the plasma donation is completed, as required by applicable regulations, we test every donation for pathogens such as HIV, hepatitis A, B and C, and parvovirus B19. If we discover a unit of plasma that cannot be used in the fractionation process, we notify the donor and remove all plasma previously donated by such donor from our inventory.
We describe our Plasma Procurement operations under the Biopharma unit in this annual report on Form 20-F because plasma collection is a fundamental part of our vertically integrated value chain. Rather than portraying plasma procurement as a standalone business, we integrate it into the Biopharma business unit’s description to reflect its primary role in securing raw materials for our plasma-derived therapies. This approach aligns with the industry practice of linking upstream supply chain activities to the core biopharmaceutical operations that generate end-products for commercialization. We believe that by consolidating the description of plasma procurement within Biopharma, we provide a clearer picture of how plasma sourcing directly supports revenue generation, cost efficiency and strategic decision-making, while also ensuring consistency in segment reporting and financial disclosures.
Transport and Logistics
Once plasma has been collected, it is frozen at the collection center and sent to fractionation centers. One essential aspect of this process is the implementation of safety procedures to guarantee the quality and safety of the donated plasma. To ensure preservation of the proteins found in plasma, plasma must be kept at or below a temperature of -20 degrees Celsius (-4 degrees Fahrenheit). In accordance with European and United States requirements, we store our plasma at a temperature of -30 degrees Celsius (-22 degrees Fahrenheit). During transportation, plasma is kept at a temperature at or below -20 degrees Celsius. Our frozen plasma is transported by two major transport companies, each supported by a network of logistic companies.
In the year ended December 31, 2025, we continued to see positive results from the initiatives related to our Operational Improvement Plan to optimize our supply chain and distribution logistics. These initiatives included maximizing available space in transport containers, increasing the amount of plasma transported per container by 7.0%, therefore reducing total transport figures. Other measures included optimizing the frequency of plasma collection routes in European workplaces, promoting full truckloads between plasma collection points, warehouses and the Barcelona manufacturing complex and using larger U.S. pallets to optimize storage and transport.
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Fractionation and Purification
Once plasma has been obtained, it may be used for plasma transfusions. It may also be frozen (as fresh frozen plasma) and manufactured into plasma derivatives through the fractionation process. The fractionation process consists of the separation of specific proteins through temperature and pH changes, as well as the use of filtration and centrifugation techniques. Fractionation occurs in tanks at near freezing temperatures to maintain the integrity of the proteins. All known plasma derivative products can be fractionated from the same batch of plasma. As a result, the development of a new or higher yield plasma derivative product would likely generate incremental sales without increasing the requirement for additional plasma.
We currently operate two Biopharma manufacturing facilities in the United States (Clayton, North Carolina, and Los Angeles, California), one in Spain (Parets del Vallès), one in Ireland (Dublin), one in Canada (Montreal) and one in Germany (Dreieich). Our plasma derivative products are manufactured at our Clayton, Los Angeles and Parets facilities. Our Clayton facility is one of the world’s largest integrated protein manufacturing sites, including fractionation, purification and aseptic filling and finishing of plasma-derived proteins. In 2025, we began construction of a new plasma-fractionation plant in Lliçà de Vall (Barcelona, Spain) with the goal of doubling our fractionation capacity in Europe. See “—D. Property, Plant and Equipment.”
Currently, the Clayton, Los Angeles, Dreieich and Parets facilities are equipped and licensed to produce certain plasma derivative products for the United States, European and other markets. For example, we produce our Flebogamma DIF, Gamunex and Yimmugo IVIG products for all of our markets at the Clayton, Los Angeles and Parets facilities.
Through an agreement with Grifols Canada Plasma (formerly named Canadian Plasma Resources Corporation) we have the right to obtain plasma donated at collection centers owned by Grifols Canada Plasma. In November 2025, we acquired 50.1% of Grifols Canada Plasma. See Item 5 of this Part I, “A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations—Recent Acquisitions—Canadian Plasma Resources Corporation.”
On July 29, 2022, we executed a 15-year renewable collaboration agreement with Canadian Blood Services (“CBS”), a non-profit organization in Canada that operates on a national basis within the Canadian healthcare system. CBS provides services to patients on behalf of all provincial and territorial governments of Canada except Quebec, safeguarding Canada’s national system to provide lifesaving therapies related to blood, plasma, stem cells, organs and tissues. By means of this agreement, we committed to supply an amount of IG to CBS equivalent to 25% (2.4 million grams) of the Canadian patient consumption needs (excluding Quebec). In addition to plasma collected at Grifols Canada Plasma’s centers, we fulfill this agreement with other plasma collected from a Canada-based plasma collection center network owned and managed by us, manufacturing our products in our facility in Montreal, Quebec (described below).
As part of the arrangements with CBS, we have access to a network of 17 plasma collection centers in Canada, 8 of which are wholly owned by us. For each liter of Canadian plasma we use to supply IG, we will also supply to CBS all remaining manufactured paste for the processing of other plasma-derived products.
In October 2020, we purchased from GC Pharma a plasma fractionation facility and two purification facilities located in Montreal, Canada (as well as 11 plasma collection centers located in the United States). Once we finish renovations and obtain all necessary licenses and regulatory approvals for these facilities, we will become the only large-scale commercial manufacturer of plasma products in Canada. In 2025, the first phase was completed with the commissioning of an albumin purification and filling plant, and we started manufacturing albumin in the Montreal facilities. Phases II and III, currently under development, include the addition of a plasma-fractionation plant and a second IVIG purification and filling facility. We expect to begin plasma fractionation and gammaglobulin manufacturing by 2027.
We also continually optimize utilization of our fractionation capacity by obtaining FDA and EMA licenses, and completing further requirements, that allow us to purify at any of our other facilities intermediate products that are produced at one of our facilities. We have obtained the following FDA licenses, among others:
● to sell Fesilty, fibrinogen concentrate indicated for the treatment of acute bleeding episodes in pediatric and adult patients with congenital fibrinogen deficiency;
● to manufacture RhoD-C hyperimmune immunoglobulin using the caprylate purification/chromatography process;
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● to introduce a new presentation of Gamunex-C in a flexible sterile bag (Flexibag);
● to expand the approved labeling of Thrombate III to include pediatric patients with hereditary antithrombin deficiency;
● to use at our Clayton facility the Fraction II+III made at both our Los Angeles and Parets facilities to make Gamunex;
● to use at our Los Angeles facility the Fraction II+III made at both our Los Angeles and Clayton facilities to make Gamunex;
● to use Fraction V obtained at our Los Angeles facility to produce albumin at our Parets facility;
● to use Fraction V obtained at both our Clayton and Parets facilities to produce Albutein in our Los Angeles facility;
● to use Fraction IV-1 obtained at our Los Angeles facility to produce Prolastina, an A1PI we market in Spain, at our Clayton facility;
● to use Fraction IV-1 obtained at our Los Angeles facility to produce Prolastin-C lyophilized at our Clayton facility;
● to use Fraction IV-1 obtained at our Clayton facility to produce Prolastin-C liquid at our Parets facility;
● to use the same method currently in place in our Parets facility to produce Fanhdi in our Los Angeles facility;
● to produce nano-filtered Gamunex and the 40 gram vial presentation; and
● to use Cryoprecipitate obtained at our Clayton facility to produce Alphanate at our Clayton facility, which is later sent to our Los Angeles facility to be filled.
We are continuing our efforts to obtain additional FDA licenses of this nature. The flexibility provided through such licenses allows us to increase production efficiency and to better address changes in demand between the United States, the European Union and other world markets.
For more information on our manufacturing facilities, see “—D. Property, Plant and Equipment” below.
Safety
We have never experienced a mandatory recall of any batch of our finished biological products due to a safety risk. In alignment with our commitment to safety and quality, we have in the past voluntarily withdrawn some product lots as a precautionary measure due to a higher rate of allergic/hypersensitivity type reactions that we found to be isolated to a small subset of plasma donors. These withdrawals were conducted with the knowledge of the governmental authorities of the applicable jurisdictions. Our philosophy is that the health of the plasma donor and the patient are the paramount considerations. None of the withdrawn products involved reports of any significant impact on patients. We strongly believe that our safety philosophy is consistent with the business objective of generating profit. We also believe that we have a strong reputation for safety in our markets, thus making our products particularly attractive to customers. We further believe that our vertically integrated business model allows us to help assure the safety and quality of our plasma derivative products through the implementation of our safety standards.
The plasma collection, fractionation and purification process is long, complex and highly regulated. We have adopted and maintain rigorous safety standards that we believe exceed those required by health authorities in Europe and the United States. The Grifols Group is periodically inspected and certified for Good Manufacturing Practices (“GMP”) competent health authorities, such as European authorities, the FDA, and other relevant government authorities of other countries where our products are marketed. In 2025, we performed over 490 quality control supplier audits to ensure compliance with GMP.
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We maintain standards that we believe are consistent with other industry participants with regard to plasma safety and are periodically certified by the Plasma Protein Therapeutics Association (“PPTA”), under the International Quality Plasma Program (“IQPP”), for plasma donation centers, and under the Quality Standards of Excellence, Assurance and Leadership Program (“QSEAL”), for fractionation plants. For example, source plasma inventory is held for not less than 60 days after donation, to allow for retrieval and destruction of plasma units if the donor is disqualified during this period (after seroconversion or due to high-risk behavior or international travel). We have also introduced innovative methods such as the Plasma Bottle Sampling system, which automatically prepares, codes and labels test samples at the time of plasma donation, and the PediGri On Line system, designed to provide full traceability of human plasma raw material throughout the plasma supply chain. See “—Distribution Process” below. We conduct routine health screenings and medical evaluations before each donation, ensuring plasma donor health remains a priority.
Our manufacturing plants have been designed to comply with the current GMP standards and applicable regulations for clean areas, and are designed to minimize clean areas as well as human intervention, with the objective of lowering the risk of contamination. The facilities are subject to a cleaning and sanitizing plan and to a corrective and preventive maintenance program. Periodically, we voluntarily shut down all of our manufacturing facilities to perform maintenance work, expansion projects and other capital investments. Our manufacturing facilities have never been subject to mandatory shut down because of regulatory noncompliance while under our operation. We believe that our voluntary shutdown procedure lowers the risk of any mandatory shutdown.
We have processes in place to ensure that all of our plasma derived products are manufactured strictly following validated and approved procedures, and in accordance with the corresponding marketing authorization. Also, each manufacturing process includes at least one validated specific virus inactivation or removal step as a precautionary measure to avoid improbable virus contamination.
Since our products are proteins that cannot be terminally sterilized, they therefore are sterilized by filtration before being aseptically filled in their final container. We have patented the Grifols Sterile Filling (“GSF”) system which minimizes the risk of microbial or particulate contamination during the aseptic filling process. During this process, sterilized containers are filled with the product under Grade A laminar air flow. The partially closed containers (vial with stopper and protector) are sterilized prior to filling. The container closure unit remains partially closed until the moment of filling, after which it is immediately sealed thus reducing the risk of contamination by reducing the product and container exposure to the controlled environment. The filling process is recorded, which enables us to identify the cause of, and rectify more easily, any related problem. These records are maintained according to our data retention policy.
Once aseptically filled, each unit of product is laser-marked with the objective of individually identifying each container and preventing and detecting counterfeits. This allows us to protect the integrity of our manufacturing process.
After plasma derivatives are manufactured, every unit of each lot is visually inspected in order to detect the presence of foreign particles or other imperfections in the container closure system. Each lot is also tested during production and at the end of the manufacturing process according to the licensed specifications, marketing authorization and corresponding Pharmacopoeia monographs. All processes are overseen by the quality systems in place at Grifols with the objective of ensuring that products are marketed with the appropriate quality, purity, potency and safety.
Finally, once the product is marketed, our pharmacovigilance system allows us to control all potential adverse reactions resulting from the administration of our products, and our surveillance system tracks adverse incidents due to the use of medical devices and in vitro diagnostic, thus ensuring the safety of our products around the world.
We continually invest in the improvement of our manufacturing facilities and plasma fractionation process, as well as in other related systems, in order to ensure the quality and safety of our products.
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Distribution Process
With each batch of plasma derivatives, we deliver electronic information regarding the origin, characteristics and controls of each of the units of plasma that we use in the preparation of the batch to our customers. This feature, called the PediGri On Line system, allows healthcare users of our products and regulatory authorities to have immediate and easy access to this information, tangible proof of the full traceability of our products. We have had this system in place since 1996, and we believe we are the only fractionator that provides this feature to customers.
We have our own sales and distribution networks covering substantially all of our markets, staffed with highly trained personnel. A majority of our sales in 2025 were made through our own distribution network, which is experienced in the proper handling of our products. We believe that this network provides for greater safety because it allows us to track our products and react quickly in the case of a potential product recall. In countries where we do not have our own distribution network, we use carefully selected distributors who are required to follow all of our safety standards.
For further information, see “—Marketing and Distribution” below.
Biopharma Products and Services
Collected plasma, whether source or recovered, is fractionated into different component proteins. We fractionate and purify a broad range of plasma derivative products that improve patient care. Our Biopharma business unit also sells a non-plasma derivative medicinal product, Tavlesse (fostamatinib), in Europe.
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The chart below presents our principal products by brand name and their respective therapeutic indications:
Product Description Main Therapeutic Indications
Gamunex/Gamunex-C. Immune Globulin Injection (Human), 10% Caprylate/Chomatography Purified. Flebogamma 5% and 10% DIF. Immune Globulin Intravenous (Human). Globally, IVIG is used for the treatment of: primary and secondary immunological deficiencies and autoimmune conditions including immune-mediated ITP; Measles pre/post exposure prophylaxis in patients to whom active immunization is contraindicated or not advised; Guillain Barré syndrome; Kawasaki disease; chronic inflammatory demyelinating polyneuropathy (“CIDP”); and multifocal motor neuropathy (“MMN”). Severe acute myasthenia exacerbations is an approved indication for Gamunex-C in Europe.
Xembify. Immune Globulin Subcutaneous (Human) - klhw 20% solution. In the United States, it is used to treat Primary Humoral Immunodeficiency (“PI”). In Europe and Australia, Xembify is also indicated to treat hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (“CLL”) in whom prophylactic antibiotics have failed or are contra-indicated, hypogammaglobulinaemia and recurrent bacterial infections in multiple myeloma (“MM”) patients, and hypogammaglobulinaemia in patients pre- and post- allogeneic haematopoietic stem cell transplantation (“HSCT”).
HyperRAB Rabies Immune Globulin (Human). Anti-rabies immunoglobulin indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies who have not been previously vaccinated with a rabies vaccine and have a confirmed adequate rabies antibody titer.
Prolastin/Prolastin-C/ Prolastin-C Liquid/Prolasplan/ Prolastina/Pulmolast/Lynspad. Alpha 1-Proteinase Inhibitor (Human). Used to treat adults with clinical evidence of emphysema due to severe hereditary alpha-1 antitrypsin deficiency (“A1PI deficiency”).
Fanhdi and Alphanate. Antihemophilic Factor/von Willebrand Factor Complex (Human). Used for the prevention, management and control of bleeding in Factor VIII deficiency (hemophilia A) and indication for Von Willebrand Disease.
Koate-DVI. Antihemophilic Factor (Human). Used for the prevention and control of bleeding in Factor VIII deficiency (hemophilia A).
Albutein/ Albutein FlexBag / Human Albumin Grifols/Plasbumin. Albumin (Human) 5%, 20% and 25%. Used to re-establish and maintain circulation volume in the treatment of hypovolemia (i.e., traumatic or hemorrhagic shock, septic shock and severe burns) and to treat complications related to Cirrhosis.
Vistaseal/VeraSeal. Human fibrinogen/human thrombin. Used as a supplemental treatment in adults where standard surgical techniques are insufficient for improvement of haemostasis, and as suture support in vascular surgery.
Tavlesse. Fostamatinib Disodium Hexahydrate Film Coated Tablets. Used for the treatment of chronic immune thrombocytopenia (“ITP”) in adult patients who are refractory to other treatments.
Intravenous immunoglobulin (IVIG)
Gamunex-C IVIG, a ready-to-use liquid IVIG product, is one of the leading products in the IVIG segment. We believe Gamunex-C IVIG is one of the premium products in its category since its launch due to a comprehensive set of differentiated product characteristics. We are one of the market leaders in the production and marketing of immunoglobulin, with 26.0% market share in volume in the United States for the twelve-month period ended September 30, 2025, according to PPTA.
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Subcutaneous Immunoglobulin (“SCIG”)
Xembify, our 20% SCIG, was first launched in the United States in 2019, with the indication for treatment of primary immunodeficiencies. In 2024, the FDA approved a label expansion that allows patients who are IG treatment-naïve (meaning, who have never received a certain drug or therapy for a specific condition) to start SCIG therapy with Xembify without having to first go through IVIG therapy, making Xembify the first 20% SCIG product in the United States with such indication. This FDA approval also included new biweekly dosing (as opposed to the prior weekly dosage) enhancing flexibility and convenience for patients. Xembify is also approved for use in both primary and secondary immunodeficiencies in Canada and several countries in the European Union. We launched Xembify in eleven additional countries between 2023 and 2025 (Spain and Australia in 2023, followed by Norway, Sweden, France, Czech Republic, Slovakia, Iceland, Finland, the United Kingdom in 2024 and Italy in 2025).
In 2025, we continued the Phase III clinical trial program evaluating the safety, efficacy and pharmacokinetics of Xembify in the prevention of infections in patients with chronic lymphocytic leukemia (CLC), multiple myeloma (MM) and Hodgkin lymphoma (HL) with secondary immunodeficiency (SID).
Human Rabies Immunoglobulin (“HRIG”)
We believe HyperRAB is the world’s leading HRIG indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies who have not been previously vaccinated with rabies vaccine. HyperRAB, a 300 IU/ml formulation of which is available in the United States, is the only HRIG provided as a higher-potency formulation, potentially requiring fewer injections in administration of each dose. We had an estimated 87.0% market share in sales of anti-rabies immunoglobulins in the United States as of December 2025.
Alpha-1-Antitrypsin Augmentation Therapy (AAT)
We believe that we are the global market leader in the sales of AAT products. On December 31, 2025, our AAT products had 76 licenses in 29 countries worldwide, 56 of which are located in North America and Europe. Based on our estimations we had more than a 69.0% global sales market share for AAT as of December 2024. Our main brand for AAT products is Prolastin, a chronic augmentation and maintenance therapy to treat emphysema related to severe hereditary A1PI deficiency. We sell the freeze-dried powder formulation of Prolastin primarily in North and South America and Europe. Between 2024 and 2025, we launched new 4- and 5-gram vial sizes for this formulation of Prolastin in a number of countries in Europe, including Germany, Denmark, France, Austria, Spain, Portugal and Italy. In addition, our ready-to-use liquid formulation of AAT (Prolastin-C Liquid) is FDA-approved and sold in the United States. We are currently conducting a worldwide clinical trial (SPARTA) to meet post-approval regulatory commitments and obtain regulatory approval for Prolastin-C Liquid in Europe. In 2024, we sponsored over 150,000 genetic tests to rapidly accelerate patient diagnosis.
Hemophilia A
Between Koate-DVI, Fanhdi and Alphanate, all products to control bleeding in hemophilia A patients, we had an estimated 13.8% market share based on volume globally in the pdFVIII hemophilia A market in 2024 (excluding Von Willebrand Disease use).
Albumin
We have several albumin-based products, primarily under our Albutein brand. We sell our albumin-based products globally, with an estimated 17.6 % market share in sales volume in 2025. Our albumin products meet U.S., European and Chinese requirements, making them attractive to biotechnology companies and genetic labs, as well as hospitals and physicians. In 2021 and 2022, we launched and began to market in the United States Albutein 25% and 5% FlexBag, a flexible container designed to add convenience, ease of use, and durability. In 2025, sales of Albutein 25% and 5% FlexBag in the United States represented 19.0% of the total Albutein brand sales (as compared to 15.0% in 2024).
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Chronic Immune Thrombocytopenia (ITP)
Tavlesse, the first oral therapy commercialized by Grifols Biopharma, is a novel SYK-inhibitor in-licensed from Rigel Pharmaceuticals for commercialization in Europe and additional markets in the Middle East and North Africa. Tavlesse is indicated to treat chronic immune thrombocytopenia in adult patients who are refractory to other treatments. In 2024, we launched Tavlesse in Slovakia and the United Arab Emirates and also sell the product in Czech Republic, Norway, Denmark, The Netherlands, Germany, Spain, Italy, France Poland, Finland, Ireland and the United Kingdom. In 2025, we expanded our Tavlesse sales into Saudi Arabia.
Other Products
We produce antithrombin products such as Anbinex and Thrombate III, which are used in the prevention and treatment of thromboembolic complications in patients with antithrombin deficiency; and AlphaNine, Profilnine and Factor IX Grifols, which are used in the prevention and control of bleeding in patients with hemophilia B.
We commercialize intramuscular (hyperimmune) immunoglobulins, which are used for the prevention and treatment of tetanus, prevention and treatment of hepatitis B, and Rh factor complications during birth. Niuliva and Igantibe are used after liver transplants to prevent hepatitis B reinfection of the graft.
We also manufacture Vistaseal/Veraseal, a biological fibrin sealant composed of fibrinogen and human thrombin used in surgical operations to expedite the healing process. This product is commercialized in the United States and Canada, in some European countries (i.e. Germany, United Kingdom, Switzerland, Estonia, Latvia, Lithuania, Austria, Ireland, Netherlands, France and Italy) as well as in South Korea, Taiwan, Singapore, Puerto Rico, Israel and Australia by Johnson & Johnson MedTech (a Johnson & Johnson company). In 2024, VistaSeal received approval to treat surgical bleeding in pediatric patients with its fibrin sealant solution in the United States, Canada and Australia.
To sell medicinal products, we must first register the products with the relevant authorities of the jurisdictions where the products are to be marketed and sold. To comply with the regulatory requirements in a given jurisdiction, we have a core team in Spain and the United States that prepares, files and coordinates the registration process with the technical personnel at the subsidiary assigned to that jurisdiction. As of December 31, 2025, we had 1,117 Biopharma product licenses registered in 90 countries throughout Europe, the United States, Latin America, Asia and the rest of the world. As of December 31, 2025, our most significant government-issued licenses for Biopharma products are:
● Gamunex/Gamunex-C/Flebogamma DIF. We have 227 licenses for the marketing and sale of one or more IVIG products;
● Xembify. We have 53 licenses for the marketing and sale of this product;
● Prolastin/Prolastin-C/ Prolastin-C Liquid/Prolasplan/Prolastina/Pulmolast/Lynspand. Alpha 1-Proteinase Inhibitor (Human). We have 76 licenses for the marketing and sale of one or more of these A1PI products;
● Fanhdi/Alphanate/Koate- DVI Factor VIII. We have 214 licenses for the marketing and sale of one or more of these Factor VIII products;
● Albutein/Human Albumin Grifols/Plasbumin. We have 281 licenses for the marketing and sale of one or more of these albumin products in their various concentrations;
● VistaSeal/VeraSeal. We have 35 licenses for the marketing and sale of this product; and
● Tavlesse. We have EMA authorization for Tavlesse in the European Union and national authorization in the United Kingdom. Tavlesse is currently sold in Czech Republic, Norway, Denmark, The Netherlands, Germany, Spain, Italy, France, the United Kingdom, the United Arab Emirates, Slovakia, Finland, Poland, Sweden and Iceland.
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In addition to the sale of products described above, we also support and collaborate with countries to increase their plasma self-sufficiency. The company leads this objective through the Grifols Self-Sufficiency Program. In parallel, its global industrial plasma fractionation programs contribute to reducing healthcare costs, promoting better and greater access to plasma treatments, and contributing to more sustainable healthcare systems. In Spain, we operate under a centralized plasma fractionation contract with the Spanish Ministry of Health. Under this framework, recovered and source plasma collected by Spanish transfusion centers are fractionated and further manufactured into plasma-derivatives products under our brand name for hospital use. We receive service fees from the applicable transfusion entities for the fractionation and manufacturing services provided under this arrangement. We also maintain similar arrangements with other public-sector counterparties, including in Italy (Emilia Romagna Region), and support self-sufficiency initiatives in Canada and Egypt through strategic collaboration agreements, including with Canadian Blood Services (CBS) and with the Egyptian government.
Furthermore, the product launches and regulatory approvals obtained during the year will continue strengthening the Biopharma portfolio and its competitive positioning. In the U.S, Yimmugo was launched following FDA approval. This next-generation intravenous immunoglobulin, developed and manufactured at Biotest’s facility in Germany and marketed in Europe since 2022, expands the Group’s immunoglobulin offering to meet growing market demand. Distribution in the U.S. is carried out through Kedrion Inc., and it is expected to contribute positively to the Group’s future growth.
Additionally, after obtaining the corresponding regulatory approvals, we began marketing Prufibry in Europe in 2025. This fibrinogen concentrate is indicated for the treatment of congenital (CFD) and acquired (AFD) fibrinogen deficiency. The launch began in Germany and was followed by Austria, with a progressive introduction planned across additional EU countries. We also obtained FDA approval for Fesilty, our fibrinogen concentrate indicated for the treatment of acute bleeding episodes in pediatric and adult patients with congenital fibrinogen deficiency. Commercialization in the United States is expected in the first half of 2026, enabling us to strengthen our position in high-value specialized therapies.
The Diagnostic Business Unit
The Diagnostic business unit, which accounted for €640 million, or 8.5% of total net revenue in 2025, focuses on researching, developing, manufacturing and marketing in vitro diagnostics products, including analytical instruments, reagents, software and associated products for use in diagnostic clinical and blood bank laboratories.
On December 31, 2025, more than 97.0% of our in vitro diagnostics products, including, but not limited to, Gel cards, Reagent Red Blood Cells and Molecular Diagnostics assays, had received In Vitro Diagnostic Regulation (“IVDR”) certification. IVDR is the regulatory basis for placing on the market, making available and putting into service in vitro diagnostic medical devices in the European market. We are currently implementing all remaining requirements to obtain IVDR certification in a timely manner for all of our in vitro diagnostics products. Additionally, we have several approvals in other markets, including FDA approvals in the United States for the majority of our portfolio.
The main areas of specialization of this business unit are transfusion medicine and specialty diagnostics.
In transfusion medicine, we have a significant market share in NAT blood donor screening solutions. In addition, we have increased our sales in the Blood Typing segment with automated immunohematology systems and reagents to hospital transfusion services and blood centers in several key global markets. We also continue to grow our portfolio of specialty diagnostic products in selected areas, including autoimmunity and infectious diseases. Our principal diagnostic products are:
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Product Description Main Applications
Transfusion Medicine:
Procleix Panther systems/Procleix Panther with Automation Ready Technology (ART). Automated NAT blood screening systems, assays and software. Used to detect infectious viruses and parasites in donated blood and plasma including: HIV (Types 1 & 2); Hepatitis A, Hepatitis B, Hepatitis C and Hepatitis E; parvovirus B19; Plasmodium, Babesia and Arbovirus like, Chikungunya, West Nile Virus, Dengue, Zika.
Wadiana/Erytra /Erytra Eflexis analyzers. Automated immunohematology analyzers that use gel agglutination technology to enable automatic processing of DG Gel system, including DG Gel cards, reagent red blood cells, antisera and associated software. Manual and semiautomated equipment are also part of the DG Gel system. Used for routine pre-transfusion compatibility testing, including blood typing, unexpected antibody screening and identification, extended phenotype and cross-match tests, among others.
BLOODchip ID/ IDCoreXT/ IDHPAXT/ IDRHDXT / IDCORECONTROL / BIDSXT. A multiplex blood group genotyping family of products based on Luminex technology, including kits for the main allelic variants of red blood cells, human platelet antigens, a positive control for ID COREXT, and an accompanying software. Used to help determine blood groups in individuals who may not be able to be typed with traditional blood grouping methods due to recent transfusions, autoantibodies, or other limitations.
Antigens. Critical component of certain infectious disease tests. Used in the manufacture of clinical diagnostic and blood donor screening immunoassays.
Specialty Diagnostics:
Promonitor. Highly specific immunoassays for quantification of serum drug levels and anti-drug antibodies of various biological drugs. Used to measure quantity of drug and antibodies for a number of biological drugs, commonly used in the treatment of various inflammatory diseases.
AlphaIDTM. Genetic test for patients for alpha-1 deficiency. This is a free cheek swab to screen for alpha-1, the most common genetic form of Chronic Obstructive Pulmonary Disease (“COPD”).
We manufacture most of our gel cards and red blood cells and assemble our immunohematology analyzers at our Parets facility in Spain. We also manufacture gel cards in Australia and red blood cells in Switzerland. We manufacture antigens at our Emeryville facility in the United States, while oligos and other critical components of the transcription-mediated amplified NAT kits for blood and plasma infectious diseases screening are manufactured at our San Diego facility in the United States. We also started manufacturing gel cards and RRBCs in our San Diego facilities in 2025.
In several countries, we distribute BLOODchip blood group genotyping tests manufactured by our subsidiary Progenika Biopharma, S.A. (“Progenika”). This product line includes ID CORE XT, which determines 37 antigens of red blood cell groups, ID RHD XT, a molecular diagnostic kit that detects the most relevant RhD variations, HPA-1 and ID HPAXT kit to determine 12 Human Platelet Antigen (“HPA”) systems. BIDSXT is the software tool that allows the analysis, interpretation and database management to transmit the results to the Laboratory information system (“LIS”).
The production, marketing and sale of many of our Diagnostic business unit products are subject to the prior registration of such products with the relevant authorities of the applicable jurisdictions. As of December 31, 2025, we had 4,117 diagnostic product licenses registered in over 50 countries in Europe, the United States, Canada, Latin America, Asia-Pacific, Middle East and Africa. In addition to the products noted above, we offer our customers solutions developed in collaboration with, or manufactured by, third-parties that we believe complement our product lines.
Our Diagnostic business unit includes a complete line of products and systems to ensure compatibility between donors and patients for safe transfusion aimed at detecting the pathogenic agents of transfusion-related infectious diseases such as HIV (Types 1 & 2), Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis E, parvovirus B19, Plasmodium, Babesia and Arboviruses such as Chikungunya, West Nile Virus, Dengue and Zika.
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Recent Efforts in Transfusion Medicine
As part of our strategy of geographic expansion, we continue to consider requests to include NAT screening for blood and plasma donations in countries as they develop their health systems. From 2020 to 2025, we entered several new countries, such as Guatemala, Paraguay, Czech Republic and Sweden. In recent years we have focused on obtaining FDA and other regulatory approvals to expand our portfolio. The following table summarizes such recent efforts:
Product Description and Main Applications Licensing Update
Procleix Quality Controls, intended for use as an external assayed quality control material to monitor the performance of several assays performed on the Procleix Panther system. FDA 510(k) clearance in 2022.
Procleix Plasmodium Assay, for use on the Procleix Panther System, in Brazil. Approval in Brazil in 2023.
Through our U.S. subsidiaries Biomat USA and Grifols Bio Supplies, Inc (formerly named Interstate Blood Bank Inc.), we have entered into an agreement with Creative Testing Solutions (“CTS”), a nonprofit blood donor testing laboratory organization in the United States. Pursuant to this agreement, which was amended in 2025, CTS agreed to operate until 2045 (renewable for up to another ten years) our three testing laboratories located in Memphis, Tennessee and San Marcos and Austin, Texas, to perform donor screening for blood and plasma collections.
Grifols Laboratory Solutions will continue to provide specialty testing as well as diagnostic solutions for clinical issues related to Molecular and Serological Immunohematology. The facility in Austin, Texas, provides testing, consultation and integrated solutions to optimize patient care for specialists in Hematology, Oncology, Perinatology, Obstetrics, Pharmacy, Transplantation and Transfusion Medicine.
We operate a product line of high-quality antigens — including HIV and HCV antigens — that are critical components of immunoassay diagnostics and blood screening applications. Our joint business arrangement with Ortho (QuidelOrtho), initiated over 40 years ago, was originally focused on the development and production of HIV and HCV antigens by us and the profit-sharing of related assay sales by Ortho. As this market has matured over time, we agreed to terminate the arrangement effective January 1, 2026, pursuant to a Settlement and Termination Agreement executed on April 11, 2026. We agreed on a settlement amount of $65.0 million to be paid by QuidelOrtho to us as a final and comprehensive settlement of all matters arising from the termination, payable in three installments: $25.0 million in Q2 2026, $25.0 million in Q1 2027, and $15.0 million in Q1 2028. In connection with the termination, we entered into a new multi-year Exclusive Supply Agreement with Ortho under which we continue to manufacture and supply antigens to Ortho, as well as to third parties including Abbott Laboratories, Siemens and OraSure Technologies.
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The table below summarizes our recent efforts to obtain more licenses and increase the market of our immunohematology products:
Immunohematology Product Description and Main Applications Licensing Update
Blood Typing Manager, designed to aid in the interfacing and managing of data among immunohematology instruments, blood establishment computer software and laboratory information systems as part of the DG Gel System. CE mark in 2022; FDA 510(k) clearance in 2022; Approval in Brazil 2023.
Weak D Control, to ensure accurate validation of weak D results, supporting blood banks and donor centers in maintaining the highest standards of quality and compliance. By confirming agglutination, it verifies that RhD typing procedures are functioning correctly, reinforcing routine quality control processes. It is a dual-use weak positive control with a confirmed weak expression of the RhD antigen to be used in parallel with D typing tests either using DG Gel System or tube technique. CE Mark in 2025.
Grifols sCD38, designed to counteract daratumumb-mediated pan-reactivity without significantly diluting the patients’ plasma and enables subsequent screening and identification of irregular antibodies in DG Gel system and tube techniques, and crossmatch in DG Gel system. Daratumumab is a CD38-directed monoclonal antibody for treating multiple myeloma. However, during treatment the drug binds to the CD38 protein on red blood cells and can alter the results of critical blood pre-transfusion tests. This can delay lifesaving transfusions for these patients. CE mark in 2022. Approvals in Brazil, Vietnam and Singapore in 2025.
DG Gel 8 Direct Coombs card, used for the evaluation of the direct antiglobulin test of two different human blood samples. This product is designed to differentiate red blood cells sensitized in vivo by IgG type immunoglobulins or the complement C3d fractions. The card is intended to be used with the DG Gel System. FDA approval in 2022.
The DG Gel DC Scan Plus, intended to be used in gel technique for the evaluation of the direct antiglobulin test. This test permits the differentiation of red blood cells sensitized in vivo by IgG, IgA and IgM type immunoglobulins and/or with the complement C3b, C3d and C4b fractions in human blood samples. The DG Gel DC Scan Plus card is intended for the investigation of clinical situations where the presence of hemolysis has been established, or is suspected, to distinguish immune from nonimmune hemolytic anemia. The card can be used manually or with automated instruments of the DG Gel System. CE mark in 2022; Approval in Brazil 2023; Approval in Australia 2023. Approval in Mexico 2025.
Sero-Cyte Pool Dia 0.8%, designed for routine testing for the screening of irregular antibodies, including the antigen Dia, in donors. This reagent complements the existing reagent red blood cells and allows us to reinforce our presence in markets, such as Brazil, where the identification of the antigen Dia is required by local regulations. CE mark in 2022; Approval in Brazil 2023.
DG Reader NET, a single card processing platform operating with the same consumables and reagents as our fully automated systems. This product is designed to be used on our DG Gel systems. CE mark in 2016; FDA 510(k) clearance in 2018; Approval in China 2023.
Procleix Plasmodium Assay, an assay to detect ribonucleic acid (“RNA”) from Plasmodium species (P. falciparum, P. knowlesi, P. malariae, P. ovale, and P. vivax) in whole blood specimens that cause Malaria disease. The assay is designed to be used for routine screening by blood banks on the Procleix Panther system, where we estimate that we are currently the market leader and continue our efforts to offer innovative solutions to blood banks. CE Mark in 2022.
DG Gel Neutral, is a gel card used for the detection of antibodies to red blood cell antigens and as a control microtube, supporting saline and enzymatic immunohematology techniques within the DG Gel System. DG GEL Rh Pheno is a gel card designed for the determination of Rh blood group antigens (C, E, c, and e) on red blood cells, enabling efficient and reliable Rh phenotyping using gel technology. Registered in China in 2025.
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Immunohematology Product Description and Main Applications Licensing Update
DG Gel Card, original 8-well gel cards based on column agglutination technology, used for blood group typing and investigation of unexpected antibodies, and compatible with manual, semi-automated, and fully automated DG Gel systems. Red-cell reagents (DG Gel system), standardized reagent red blood cells used with DG Gel cards to support blood typing, antibody screening, and antibody identification in column agglutination testing. Obtained FDA license to manufacture at San Diego facility in 2025.
Data-Cyte Plus P 0.8%, our first papain-treated red-cell panel. Obtained FDA license to manufacture in the U.S. in 2025.
In addition, in 2025, we entered into a strategic agreement with Inpeco, a global leader in laboratory automation solutions, pursuant to which we have the exclusive right to sell certain of Inpeco’s TLA automation technologies to transfusion medicine labs, aiming to modernize workflows and boost efficiency. The agreement also enables us to expand our diagnostic offering with scalable automation capabilities adaptable to laboratories of different sizes and evolving technological needs;
Specialty Diagnostics
We retain the first FDA-approved biological molecular test that uses the DNA of the patient for the diagnostic. This genetic test to detect alpha-1 antitrypsin deficiency (the “A1AT Genotyping Test”) can be conducted on DNA extracted from blood as well as a drop of blood collected on paper (a “Dry Blood Spot”) or human saliva samples collected as buccal swabs. This test was developed by Progenika. In 2022, A1AT Genotyping Test was also CE-marked. Although highly complex, the test has been designed so any molecular biology laboratory can process it with minimal human intervention.
AlphaID, our cheek swab that greatly simplifies the sample collection process, allows physicians and healthcare providers to obtain a sufficient oral sample for alpha-1 screening avoiding the need to order lab results. The test has been available in the U.S. since 2019. Our subsidiary Progenika has developed a free service named “AlphaID At Home Genetic Health Risk Service,” offering, directly to homes, a diagnostic solution to potential patients of alpha-1 antitrypsin deficiency. Since its FDA approval in 2022, this complex multidisciplinary project has brought together six international companies led by Progenika. Since its May 2023 launch, almost 100,000 AlphaID At Home kits have been requested and more than 35,000 people have taken the test.
Through our subsidiary Progenika, we manufacture a genetic diagnosis test for Familial Hypercholesterolemia (“FH”) using next generation sequencing technology (“NGS”). The Diagnostic business unit continues its efforts to broaden the Promonitor line, used to monitor biologic drugs as sales continue in Chile, select European Union countries, Australia and in the U.S. The Promonitor product line includes an ELISA (enzyme-linked immunoabsorbent assay) device line also developed by Progenika to monitor patients being treated with biological medicines for rheumatoid arthritis and other chronic inflammatory diseases. Progenika also co-developed with DIESSE Diagnostica Senese the Chorus Promonitor, an adaptation of the Promonitor ELISA kits to DIESSE’s Chorus Analyzer.
Pursuant to an exclusive agreement with AESKU Diagnostics GmbH & Co. (“AESKU”), we distribute autoimmunity diagnostic products in Chile, Mexico, Portugal and Spain.
The Bio Supplies Business Unit
The Bio Supplies Business Unit provides human biological materials for the biotechnology industry intended for research, clinical trials and manufacturing of pharmaceutical and diagnostic products. Most materials and products come from our collection centers with vertical integration manufacturing processes (in-house production). The Bio Supplies business unit accounted for €154 million, or 2.0% of our total net revenue in 2025.
Products in our Bio Supplies business unit cover a broad spectrum of applications where the need for human-based biological material cannot be replaced by other types of products, such as:
● Cell Therapy: providing human-based cell culture supplements, plasma proteins, and leukocyte apheresis (white blood cell concentrate obtained through apheresis and used in the development of new cell therapies).
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● Pharma Manufacturing: human-based plasma proteins to be used as excipients (i.e. inactive substances that serve as vehicles or mediums for a drug or other active substances in the manufacturing of therapeutic drugs). Human plasma and intermediates used to manufacture plasma derived medicines.
● Diagnostic Manufacturing: human blood cells, proteins, plasma and serum for the manufacturing of quality controls and calibrators used in in vitro diagnostics tests.
● Life Science Research: Human blood derived products and biospecimens used in life science basic research or by in vitro diagnostic companies to develop and validate their analytical assays.
Our Bio Supplies business unit also sold plasma to third parties in 2024 and 2025.
Other Activities and Operations (“Others”)
“Others” represents operations and activities, including the provision of manufacturing services to third parties and third-party plasma sales, and pharmaceutical products manufactured by the Grifols Group intended for hospital pharmacies.
Since 2022, the activities of our former “Hospital Division” were significantly reduced, which caused us to reallocate such activities and related products into a smaller business line named healthcare solutions (“Healthcare Solutions”), which is also accounted as Others. Others accounted for €243 million, or 3.2%, of our total net revenue in 2025.
The Healthcare Solutions business line provides services and manufactures products used by hospitals, blood banks, plasma collection centers and other healthcare systems. These products include parenteral solutions, robotics and software, as well as third parties’ products that we market to supplement the products that we manufacture. The Healthcare Solutions business accounted for €138 million, or 1.8%, of our total net revenue in 2025.
Research and Development
Research and development is a significant aspect of our business. Our principal research and development objectives are (i) to discover and develop new products, (ii) to research new applications for existing products and (iii) the improvement of our manufacturing processes to improve yields, safety and efficiency. In the years ended December 31, 2025, 2024 and 2023, our research and development spending was €426 million, €384 million and €395 million, respectively. In the last five years, we invested a total of €1.9 billion in research and development and innovation.
On December 31, 2025, we had an amount of approximately €1.7 billion as development costs in progress (compared to €1.7 billion at December 31, 2024). This includes (1) an amount of €267 million in ongoing research and development projects for products for neurodegenerative disorders, neuromuscular diseases, and ophthalmological diseases acquired from Alkahest; and (2) an amount of €895 million in ongoing research and development projects in plasma therapies acquired from Biotest (Fibrinogen and Trimodulin). See Note 7 to our audited consolidated financial statements included in this annual report.
In addition, as of December 31, 2025, we had 1,379 scientists and support staff dedicated to research and development.
We have several decades of successful innovation history. For example, we developed a unique fractionation design that reduces the risk of contamination and maintenance costs and increases the amount of product extracted per liter of plasma. We also developed the first centrifugation unit for the automated cleaning of blood cells. In addition, we were one of the first plasma fractionators to conduct double viral inactivation processes for Factor VIII and have designed and implemented a new process for the sterile filling of vials that reduces exposure to potential contaminants as compared to other existing processes. Further, we have developed a nanofiltration method of viral inactivation for our IG, alpha-1 PI, and ATIII products.
Our key therapeutic areas of study focus on immunology, hepatology and intensive care, pulmonology, hematology, neurology and infectious diseases. Our next innovations into these therapeutic areas will go beyond plasma-derived proteins, as our significant investments to increase R&D capabilities are allowing us to develop a new class of recombinant antibodies and small-molecules candidates.
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Biopharma Initiatives
We have a number of research and development projects in our Biopharma business unit underway, 12 of which are in the clinical development phase. The following table reflects the total number of research and development projects in our Biopharma business unit by development phase as of the end of the last three years.
As of December 31,
Development Phase 2025 2024 2023
Discovery 17 19 24
Pre-clinical 11 32 23
Clinical 12 15 22
Post Commercialization Studies 5 6 14
Rest of projects 42 10 16
Total Biopharma Research and Development Projects 87 82 99
The table below presents the most important of our research and development projects:
Product Candidate Therapeutic Area Product Type Potential Use Development Phase
Xembify Immunology Plasma-derived Secondary Immunodeficiency in Chronic Lymphotic Leukemia, Multiple Myeloma and Non-Hodgkin Lymphoma Phase III (clinical trial program currently underway)
Alpha-1 Proteinase Inhibitor Pulmonology Plasma-derived Emphysema due to congenital deficiency Phase I/II (clinical trial program in subcutaneous administration currently underway). Phase I/II completed in 2025, with Phase III planned to start in 2026).Phase IV US/ Phase III EU (clinical trial program in intravenous administration currently underway)
Immunoglobulin Ophthalmology Plasma-derived Dry Eye Disease Phase II (clinical trial program currently underway)
Fibrinogen Hematology Plasma-derived Congenital deficiency & severe hypofibrinogen / acquired deficiency Regulatory Approval received in 2025 for EU countries (Congenital & Acquired Deficiency) and U.S. (Congenital Deficiency)Phase III U.S. Acquired Deficiency (clinical trial program to start in 2026)
Trimodulin Infectious diseases Plasma-derived Severe community acquired pneumonia (“sCAP”) Phase III (clinical trial program currently underway)
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Xembify – Secondary immunodeficiency in CLL. The primary objective of this clinical trial (NCT05645107) is to obtain an indication for Xembify in secondary immunodeficiency as result of chronic lymphocytic leukemia (“CLL”), multiple myeloma (MM) and Non-Hodgkin Lymphoma (“NHL”). CLL is the most common leukemia in older adults in Western countries, with an average age at diagnosis of 72. The disease is characterized by an accumulation of monoclonal, mature, CD5+ B cells in the peripheral blood, bone marrow, and secondary lymphoid organs. Patients with CLL are subject to an increased risk of infections and recurrent or severe infections are a major cause of morbidity and mortality in patients with CLL, causing between 30% and 50% of deaths in this population. MM is the second most common hemato malignancy, with an estimated incidence of 7.1 and 4.5 to 6.0 cases per 100,000 people per year in the United States and Europe, respectively. In general, MM is frequently diagnosed in patients from 65 to 74 years of age. MM is a clonal disorder characterized by the accumulation of malignant mature plasma cells in the bone marrow (and sometimes also with extramedullary involvement) and the production of an abnormal monoclonal paraprotein, named the M protein. NHL represents a heterogeneous group of malignancies of different biology and prognosis. NHL includes many subtypes, each with distinct epidemiologies; etiologies; morphologic, immunophenotypic, genetic, and clinical features; and responses to therapy. These tumors originated from lymphoid tissues, mainly of lymph nodes. Current evidence suggests that hypogammaglobulinemia resulting of the secondary antibody deficiency in B-cell lymphoproliferative diseases such as CLL, MM and NHL predispose the patient to develop serious infections due to the patient’s underlying disease or their cancer. The Phase III clinical trial is aiming to enroll more than 380 patients in sites across the United States and in European countries to support an FDA submission in the United States.
Alpha-1 Proteinase Inhibitor – Emphysema due to congenital deficiency. SPARTA (Study of Prolastin-C Randomized Therapy with Alpha-1 augmentation; NCT01983241), our Phase IV (U.S.) / Phase III (E.U.) clinical trial designed to determine if alpha-1- antitrypsin deficiency (AATD) (alpha-1) patients with emphysema have a slower progression of lung tissue loss when treated weekly with two separate dose regimens of intravenous (IV) Grifols Prolastin-C Alpha-1. Alpha-1- antitrypsin deficiency (AATD) is an underdiagnosed genetic disorder that can result in chronic obstructive pulmonary disease (COPD), a group of respiratory diseases that includes emphysema, which can occur when a patient has low levels of AAT, a protective protein that safeguards the lungs. The currently approved dosage is 60 mg/kg in weekly IV infusions. SPARTA, the largest randomized, double-blind, placebo-controlled study on AAT augmentation therapy to-date, is designed to evaluate the potential of Prolastin-C to significantly reduce emphysema progression in alpha-1 patients by raising AAT protein levels through weekly administration of two active dose levels versus placebo. The clinical trial is taking place across 16 countries and more than 50 sites. It will evaluate the efficacy and safety of two separate dose regimens of Prolastin-C (60 and 120 mg/kg/week) versus placebo for 156 weeks (i.e., three years), measuring the rate of pulmonary-tissue loss through whole lung computed tomography (CT) densitometry as the primary measure of clinical efficacy.
We have also conducted a Phase II/III study (NCT04722887) evaluating Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% (Alpha-1 15%), a subcutaneous (SC) AAT treatment being compared to Liquid Alpha1-Proteinase Inhibitor (Human) IV. This first in-human SC approach to treating alpha1-antitrypsin deficiency, if proven successful in clinical trials, could give patients the convenience and flexibility to administer their medication from home. We completed the Phase I/II study in 2025 and plan to start the Phase III study in 2026.
Immunoglobulin. In 2023, we entered into a global collaboration and licensing agreement with Selagine, a pioneering developer of eye disease treatments, to explore the potential of an immunoglobulin eye drop to treat dry eye disease (DED), a pathology that affects more than 100 million people worldwide in 2023. In a pilot Phase I/II clinical trial, subjects treated with eye drops based on Grifols Flebogamma DIF twice daily for eight weeks, secured a significant reduction in the signs and symptoms of DED, and with no difference in tolerability or adverse events. Several different sources of inflammation, including proteins (cytokines or chemokines), cells (neutrophils, T-cells and dendritic cells) and pathogenic antibodies, are present on the ocular surface in DED and contribute to its signs and symptoms which may benefit from application of immunoglobulin. We completed an FDA pre-IND meeting in respect of this immunoglobulin in September 2023. In 2024, we successfully completed the preclinical development phase. In 2025, we completed IND submission and initiated enrollment for the phase II clinical trial for the use of Flebogamma DIF 5% in the treatment of DED.
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Fibrinogen. The AdFirst study is a prospective, active-controlled, multicenter Phase III study investigating the efficacy and safety of the fibrinogen concentrate BT524 in patients with acquired fibrinogen deficiency (“AFD”), which typically occurs during surgical procedures when there is insufficient fibrinogen to arrest bleeding. Patients who have high blood loss during planned spinal and abdominal surgery are randomized 1:1 to treatment with BT524 or FFP/Cryoprecipitate. To evaluate efficacy, further blood loss is compared between the two treatment options. The study concluded in September 2023. The AdFirst Study met its primary endpoint in February 2024, demonstrating that the fibrinogen concentrate BT524 is as effective in treating AFD as the current standard of care for this condition. The concentrate reduces intraoperative blood loss in patients with AFD undergoing planned major spinal or abdominal surgery.
In 2025, we received approval in Germany for congenital fibrinogen deficiency (CFD) and Acquired Fibrinogen Deficiency (AFD), and approval in the United States of a Biologics License Application (BLA) for BT524 for the treatment of CFD. Following discussions with the FDA, we decided to strengthen the clinical evidence for AFD with U.S. patients before seeking approval for this indication in the United States. We launched the Fibrinogen product in Germany in late 2025 and expect to start selling it in the United States in 2026. We hold significant patents on the fibrinogen production process.
Trimodulin. Study 996: This multinational Phase III clinical trial plans to enroll approximately 590 adult hospitalized patients with severe sCAP (Community Acquired Pneumonia) requiring invasive mechanical ventilation. The ESCAPE trial will be conducted worldwide and patients are treated either with trimodulin or with a placebo as add-on therapy to standard of care.
The clinical concept of this prospective, double-blind, placebo-controlled, Phase III trial was developed based on promising results from the previous Phase II clinical trial (“CIGMA”) with 160 sCAP patients requiring invasive mechanical ventilation. In the CIGMA trial, a subgroup of patients with signs of severe inflammation showed an encouraging reduction in mortality rate through rapid normalization of inflammation when treated with Trimodulin. The trial is currently being conducted in up to 20 countries, including the United States, and recruitment of patients is ongoing.
Other Biopharma research and development projects undertaken during the last three years included:
2025:
● new presentation of Gamnuex-C in a flexible sterile bag;
● continued process optimization for increased IgG yields across manufacturing facilities;
● commissioning of new manufacturing facilities and ongoing manufacturing optimization;
2024:
● new container closure systems for Gamunex and Xembify;
● process optimization for increased IgG yields across manufacturing facilities;
● commissioning of new manufacturing facilities and ongoing manufacturing optimization;
● development of an improved process to provide greater product safety and yield for manufacture of Rho-D; and
● development for a modified process to manufacture Plasmanate.
2023:
● process optimization for increased IgG yields across manufacturing facilities;
● development of an improved process to provide greater product safety and yield for manufacture of Rho-D;
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● development for a modified process to manufacture Plasmanate; and
● transfer of albumin process to our subsidiary Grifols Canada Plasma, Inc. (formerly known as Prometic Plasma Resources, Inc.);
All clinical trials involve risks and uncertainties. Preclinical and clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failure of one or more of our clinical trials can occur at any stage of testing. We may experience numerous unforeseen events during or as a result of preclinical testing and the clinical trial process that could delay or prevent our ability to receive regulatory approval or commercialize our product candidates. For a discussion of these unforeseen events, see Item 3 of this Part I, “Key Information—D. Risk Factors—Risks Relating to the Company and Our Business—We may not be able to commercialize products in development.” Upon the completion of each of the development stages we evaluate the results achieved as compared to the objectives pursued. Each of the key projects listed above has met our expectations with respect to results at the various development stages and we expect to move forward with the development process for each.
We believe that our current liquidity is sufficient to fund the ongoing costs of our key projects listed above through their completion as well as our other research and development initiatives.
Diagnostic Initiatives
Research and development in the Diagnostic business unit supports various business areas, including transfusion medicine, clinical diagnostics, and the recombinant protein business. The Diagnostic business unit focuses on the development of in vitro diagnostic reagents/assays, instrumentation, and software for donor screening, which includes pathogens detection to assure safety and blood typing tests to determine donor/recipient blood compatibility. Here, research and development focus on opportunities to develop new assays for emerging pathogens, increase multiplex test capabilities (simultaneous detection of several analytes in a single reaction), as well as improved automation solutions in order to increase efficiency and throughput for customers. The Diagnostic business unit also develops products for clinical diagnostics, including a next generation immunoassay platform in the area of neurology and oncology, as well as a next-generation molecular testing platform covering infectious diseases.
The research and development team employs a diverse technology portfolio, including transcription mediated amplification (“TMA”), polymerase chain reaction (“PCR”), next generation sequencing (“NGS”) for molecular assays, immunologic based methods using red blood cells (“RBC”), and agglutination. We are also leveraging ultrasensitive single molecule counting detection technology to develop new immunoassays, as well as a fast-PCR technology to develop next generation molecular assays. We continue research and development for new recombinant proteins, antibodies and enzymes as critical raw materials to support internal and external diagnostics customers in various fields such as infectious diseases, neurodegenerative diseases and immunohematology. Our Diagnostics Research & Development team continues to evaluate new technologies and research tools, including artificial intelligence (AI), to assess their potential for improving our competitive advantage and for integration into our development portfolio.
In 2023, the Diagnostics business unit continued to release innovative products for our immunohematology product line, including new software versions across the platform portfolio to increase efficiency and productivity for our customers. We launched our BTM middleware in the United States, while also achieving regulatory approval in China for Eflexis, our flagship blood typing platform, in order to expand our geographic footprint. We also launched DC Scan Plus, a new DG Gel test under IVDR regulation that extends specificity beyond routine analytes and improves patient care by increasing sensitivity and specificity, thereby improving clinical patient management and outcomes in the field of donor screening. We also released new versions of our pooler software, as well as software to facilitate increased automation and ease of use for testing labs. Additionally, we launched in the United States the first-ever free direct-to-consumer program (consisting of an innovative and sophisticated genotyping test and service) to screen for the genetic risk of alpha1-antitrypsin deficiency (Alpha-1).
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In 2024, the Diagnostics business unit continued to develop and introduce new high multiplex donor screening solutions to the market to drive efficiency improvements and address developing trends in transfusion-transmitted diseases. The team obtained CE mark approval for the Procleix ArboPlex Assay, which tests for four arboviruses: chikungunya virus RNA, dengue virus RNA, West Nile virus RNA and Zika virus RNA. The team also completed the U.S. clinical trials for the Ultrioplex W assay, which detects HIV-1, HIV-2, hepatitis C virus (“HCV”), hepatitis B virus (“HBV”), and West Nile virus (“WNV). Additionally, we completed U.S. clinical trials for the Procleix Plasmodium assay and developed a research use only (“RUO”) assay to screen for severe fever with thrombocytopenia syndrome virus (“SFTSV”) in an effort to address oncoming emerging pathogens. We are also developing new software to support new assay products on the Procleix donor screening platform, as well as to enable efficiency improvements to middleware solutions and increased productivity for our donor screening customers. In the field of blood typing, the Diagnostics business unit advanced development of a next generation blood typing platform, initiated development of an automated antisera program with extended phenotyping for the United States, and launched multiple innovative software releases across the instrument portfolio, including an automated titration method on Eflexis — all with the goal to increase efficiency and productivity for our customers. Additionally, the 2024 commercial success in Europe of our innovative blood typing interference solution for anti-CD38 antibody-treated patients has driven the pursuit of future expansion of this solution to the U.S. market.
In 2025, the Diagnostics business unit continued to develop and introduce new high multiplex donor screening solutions to the market to drive efficiency improvements and address developing trends in transfusion-transmitted diseases.
The new Ultrioplex W assay, which detects HIV-1, HIV-2, hepatitis C virus (“HCV”), hepatitis B virus (“HBV”), and West Nile virus (“WNV), was under review by the FDA in 2025, with some additional studies requested and started at the end of 2025. We also submitted to the FDA in 2025 the Procleix Plasmodium assay as well as 510(k) submissions for multiple Procleix controls. R&D also provided a research use only (“RUO”) assay that we developed to the Japanese Red Cross to screen for severe fever with thrombocytopenia syndrome virus (“SFTSV”) in an effort to address oncoming emerging pathogens. Our R&D team initiated development of a next generation pooler, strengthened our in-house software capabilities, and secured secondary sources for critical consumables for business continuity. We also released multiple software enhancements to address cybersecurity and increase efficiency and productivity for our molecular donor screening customers.
In the field of blood typing, the Diagnostics business unit advanced development of a next-generation blood typing platform, continued development of an automated antisera program with extended phenotyping for the United States, and expanded DG Gel products into China. We also launched multiple innovative software releases across the instrument portfolio, including an enhanced automated titration method on Eflexis and new middleware — all with the goal of increasing efficiency and productivity for our customers. Additionally, the increasing commercial success in Europe of our innovative blood typing interference solution for anti-CD38 antibody-treated patients has driven the pursuit of future expansion of this solution to the U.S. market and additional countries in 2025.
Moreover, the Diagnostics business unit in 2025 continued to partner with Inpeco to develop a total lab automation solution for blood/plasma testing labs.
In 2024, the Diagnostics business unit filed over 16 new patents, spanning composition of matter, methods and devices, further growing our intellectual property portfolio and competitive position in the areas of molecular testing, infectious disease, blood typing, clinical diagnostics. In 2025, the Diagnostics business unit filed over 12 new patent applications and two new design applications, spanning composition of matter, methods and devices, further growing our intellectual property portfolio and competitive position in the areas of molecular testing, infectious disease, blood typing, clinical diagnostics.
In 2025, the Diagnostics business unit focused on developing blood typing platforms to ensure compatibility between donors and recipients. These gel-based assays identify major blood groups like ABO and Rh, as well as detect less common blood groups that are still highly relevant to human pathologies, such as sickle cell anemia and cancer. We also began developing new tests for personalized medicine, focused on prognosis, response prediction and monitoring of biologic drugs, as well as molecular diagnostic and prognostic tests in oncology, autoimmunity, cardiovascular medicine and the central nervous system.
In 2025, more than 37 million blood donations were analyzed using Grifols’ NAT technology and more than 68 million blood typing cards with gel technology were supplied.
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Other Initiatives
Through our subsidiary Araclon Biotech, S.L. (“Araclon”), we are dedicated to finding solutions that promote new diagnostic and therapeutic approaches to Alzheimer’s disease, to be applied in the early stages of the disease. Araclon is working on the validation of an early diagnostic test and the development of a vaccine (ABvac40) to combat Alzheimer’s disease in the asymptomatic stage. The vaccine has passed the animal experimentation stage and Phase I and Phase II clinical trials have been completed.
The Phase II trial of ABvac40, initiated in 2018 and ended in 2023, showed positive outcomes. ABvac40 had a good safety profile, stimulated a robust immune response against Aβ40 peptide, and demonstrated potential cognitive benefits in early-stage AD patients, meeting primary endpoints. Though the trial was not designed to assess efficacy on neuropsychological scales, we observed promising results in secondary endpoints between the ABvac40-treated group and the placebo group. Post-hoc analyses in 2024 indicated greater benefits for patients with amyloid deposits, with fewer cases of significant decline on the Mini-Mental State Examination (“MMSE”) scale, especially among top responders. We noted lower incidence of new cerebral microhemorrhages in ABvac40-treated patients compared to placebo. In 2025, we presented final results from the phase II clinical trial of ABvac40, an active vaccine against the Aβ40 peptide for the treatment of early-stage AD, which showed a favorable safety profile and a robust and durable immune response against Aβ40, meeting the primary objectives of the clinical study. We continue to evaluate the data and share our findings at various conferences, while also engaging with companies in the Alzheimer’s disease field to explore licensing-out opportunities.
Our subsidiary Alkahest focuses on identifying proteins that change with age and also with the onset of diseases that have a biological impact. To date, Alkahest has identified over 10,000 separate proteins using advanced molecular analysis techniques at the cellular level. In 2024, Alkahest pivoted to advancing Chronos, a target proteomic platform that aims to detect diseases before they manifest phenotypically. Chronos’ initial focus is Parkinson’s Disease, with plans to move to other disease areas. In January 2025, Alkahest initiated the Chronos research program to analyze longitudinal plasma samples for early biomarkers associated with Parkinson’s disease. Chronos remains a research-stage initiative, and no diagnostic products or therapeutic candidates have been approved or submitted for regulatory approval to date.
Our subsidiary GigaGen Inc (“GigaGen”) is developing a novel class of therapeutics, recombinant polyclonal antibodies, to address unmet needs in infectious disease. In 2025, the phase I clinical trial evaluating the safety and tolerability of GIGA-2339, GigaGen’s first recombinant polyclonal candidate for the treatment of hepatitis B virus (HBV) infection, continued recruitment. GIGA-2339 includes more than 1,000 recombinant human antibodies targeting HBV to mimic the body’s natural immune response, with the potential to eliminate the virus and activate the immune system. There is presently no cure for HBV, which affects more than 296 million people globally and causes over 800,000 deaths every year. Additionally, in 2025, GigaGen’s phase I clinical trial evaluating GIGA-564 for the treatment of advanced solid tumors successfully completed the phase I-a dose-escalation trial and is currently enrolling patients in the phase I-b multiple-dose cohorts.
In 2025, we developed a strategic partnership with the Biomedical Advanced Research and Development Authority (“BARDA”), part of the U.S. Department of Health and Human Services, to evaluate the nonclinical efficacy of ocular surface immunoglobulin (“OSIG”) eye drops for the treatment of sulfur mustard-induced ocular injury. This proof-of-concept study aims to assess the anti-inflammatory and immunomodulatory potential of OSIG in neutralizing the long-term effects of exposure to sulfur mustard — a chemical warfare agent known to cause debilitating corneal damage. The investigational OSIG therapeutic is being repurposed from an ongoing development program targeting dry eye disease (“DED”), for which a Phase II clinical trial began in 2025. This initiative represents a significant step in expanding the applications of our IG platform into ophthalmology and biodefense. In addition, in 2024, GigaGen was awarded a $135 million contract by BARDA to develop a recombinant polyclonal antibody therapy for botulin neurotoxins and a second biothreat of interest to BARDA that will be determined at a later date.
In 2025, we also initiated an R&D collaboration with FcR Therapeutics, a Dutch company, to discover and develop new therapeutics targeting 2 Fc receptors for the treatment of autoimmune diseases.
Seasonality
Our businesses are not significantly affected by seasonal trends.
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Raw Materials
Plasma is the key raw material we use to make our products and therapies. We obtain our plasma primarily from our network of plasma collection centers located in the United States and Europe (Germany, Austria, Czech Republic, and Hungary), and, to a much lesser extent, from third party suppliers. See “—Principal Activities—The Biopharma Business Unit—Plasma Procurement.” We are dependent on healthy individuals to donate human plasma to develop and manufacture our products. As such, our cost to acquire plasma may vary depending on the ability of donors to visit our plasma collection centers and the compensation we pay for the plasma donations. See Item 3 of this Part I, “D. Risk Factors— Risks Relating to the Company and Our Business—A significant disruption in our supply of plasma, including as a result of macroeconomic conditions, pandemics or changes in immigration policies and enforcement could have a material adverse effect on our business and our growth plans.”
In 2025, we continued to manage our plasma supply efficiently, maintaining stability in cost per liter. This performance was supported by improved operational yields at donation centers, driven by the implementation in recent years of more efficient plasmapheresis equipment based on nomogram technology, which has increased process productivity. We also continued to optimize cost per liter of plasma collected through various initiatives aimed at streamlining structural costs, optimizing donor compensation, improving the donor experience, and increasing operational efficiencies across the entire center network.
Our plasma supply increased significantly in 2025 in comparison to the volumes collected in 2024, validating the effectiveness of the strategic measures implemented during 2023 and 2024 to enhance plasma collection and manufacturing efficiencies, strengthen financial management, and execute our Operational Improvement Plan (as defined in Item 5 of Part I, “A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations—Operational Improvement Plan”). In 2025, our plasma collection increased significantly in comparison to 2024 as a result of our acquisition of plasma donation centers from ImmunoTek in February 2025, plus the optimization of our existing plasma centers. We also saw an increase in unique donors to over one million people. In addition, we implemented new nomogram technology in 80% of our U.S. plasma centers.
We closely monitor, continuously review and revise the supply sourcing strategy for our products to identify in a timely manner any risks in our supply chain. Where necessary, we strategically manage our inventory levels of either key materials or finished products to address potential risks relating to operational and quality issues, production capacity and single sourcing among others. We also continue to monitor the efficiency of our plasma collection platform and have concentrated all our plasma testing into laboratories in Austin and San Marcos, Texas, Memphis, Tennessee, Boca Raton, Florida, Leipzig and Dreieich, Germany, Parets del Vallés, Spain, and Cairo, Egypt (through our joint business with NSPO).
Our long-term aim is to further strengthen our leadership through the development of new and differentiated plasma-derived therapeutics, and the expansion of our global plasma collection footprint via acquisitions and greenfield projects, as described below:
● On December 11, 2025, we received certification from the EMA for the entire value chain of Grifols Egypt for Plasma Derivatives (“Grifols Egypt”), our public-private partnership with the government of Egypt representing a joint investment of €280 million. This certification positions Egypt as the first country in Africa and the Middle East to operate a fully integrated plasma collection and processing system that meets the most demanding European standards of quality, safety and regulatory control. With this milestone, Egypt has achieved self-sufficiency in plasma-derived medicinal products, including immunoglobulins, albumin and coagulation factors, becoming the sixth country in the world capable of supplying itself with medicines derived from national plasma, after the United States, Germany, Austria, the Czech Republic and Hungary. See “—B. Business Overview—Raw Materials” and “—D. Property, Plant and Equipment—Plasma Fractionation Plants;”
● On November 1, 2025, we acquired a 50.1% equity stake in CPR, a Canadian private company engaged in plasma collection for the production of plasma-derived therapies, for an aggregate consideration of approximately €19 million. Following the acquisition, which strengthens our presence in Canada, CPR was renamed Grifols Canada Plasma Corporation (“Grifols Canada Plasma”). See Item 5 of this Part I, “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations—Recent Acquisitions;
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● In February 2025, we completed the acquisition of 28 plasma collection centers in the United States from ImmunoTek. This acquisition was initiated on July 29, 2021, when we entered into an agreement with ImmunoTek, amended in 2023 and 2024, to arrange for the construction, licensing and commissioning of the 28 centers. Pursuant to this agreement, we formed ITK JV, a joint operation company through which we initially held a 75% interest in each of the 28 plasma collection centers, while ImmunoTek held the remaining 25%. In 2024, we acquired 14 plasma collection centers for an aggregate amount of $266 million and, effective as of February 3, 2025, we completed the acquisition of the remaining 14 centers for an aggregate amount of approximately $281 million. See Item 5 of this Part I “Operating and Financial Review and Prospects—A. Operating Results—Subsequent Events” and “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations—Recent Acquisitions—Acquisition of Plasma Collection Centers from ImmunoTek.”
● On April 25, 2022, we acquired all of the existing equity interest in Biotest Holdings from Tiancheng International Investment Limited (“TIIL”) and accepted an assignment of certain shareholder loans granted by TIIL to Biotest Holdings. Biotest Holdings in turn owned a majority stake in Biotest, a global company that supplies plasma protein products and biotherapeutic drugs, which has given us access to 28 additional plasma collection centers. See Item 5 of this Part I, “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations—Recent Acquisitions—Biotest Shares and Public Delisting Purchase Offer.”
● On March 31, 2021, we acquired seven U.S.-based plasma donation centers from Kedplasma, LLC for a total purchase price of $55 million.
● On February 28, 2021, we acquired 25 U.S.-based plasma centers from BPL Plasma Inc. for $385 million by means of an asset sale agreement. See Item 5 of this Part I, “Operating and Financial Review and Prospects—A. Operating Results—Factors Affecting Our Financial Condition and Results of Operations—Acquisitions.”
● In October 2020, we purchased 11 collection centers in the United States, as well as a plasma fractionation facility and two purification facilities in Montreal, Canada, from GC Pharma for a total consideration of $457 million on a debt free basis.
● In April 2019, we acquired 26 plasma collection centers and ten blood donation centers in the United States as part of our acquisition of 100% of the equity stake of the Interstate Blood Bank Group (Interstate Blood Bank, Inc., Bio-Blood Components, Inc. and Plasma Biological Services, LLC), which has since been merged into our subsidiary Grifols Bio Supplies, Inc.
● On December 28, 2018, our subsidiary GWWO, BPC Plasma Inc. (formerly known as Biotest Pharmaceuticals Corporation), Haema GmbH (formerly known as Haema AG) and Grifols, S.A. entered into a plasma supply agreement (the “Plasma Supply Agreement”), whereby GWWO agreed to acquire all of the plasma collected from approximately 60 plasma collection centers owned by BPC Plasma Inc. and Haema GmbH. Grifols, S.A. guarantees all GWWO obligations under the Plasma Supply Agreement, which, on January 1, 2019, was extended for a 30-year period. See Item 7 of this Part I, “Major Shareholders and Related Party Transactions—B. Related Party Transactions—Transactions involving Haema GmbH, BPC Plasma Inc. (formerly known as Biotest Pharmaceuticals Corporation) and Scranton Enterprises B.V. and their respective subsidiaries—Plasma Supply Agreement and Advance Payments from GWWO to Scranton Plasma B.V.”
The principal raw materials for our intravenous therapy products are plastic and glass bottles, which we purchase from various European suppliers.
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Marketing and Distribution
We currently sell Biopharma, Diagnostic and Healthcare Solutions products to hospitals, specialty pharmacies, clinics, GPOs, governments and other distributors in over 100 countries.
For Biopharma and Healthcare Solutions in the United States, the sales model is complex, with many intermediaries, requiring us to execute multi-faceted arrangements for the distribution of our products. Sales of finished goods are distributed through various channels such as distributors, wholesalers, specialty pharmacies, home health care companies, clinics, hospitals, government entities and directly to physician offices. Payers and purchasers also control access to products, requiring separate negotiations with payers and GPOs. GPOs are entities that act as purchasing intermediaries for their members, which are primarily hospitals. GPOs negotiate the price and volume of supplies, equipment and pharmaceutical products, including plasma derivatives, used by their members.
We market our products to healthcare providers and other decision-makers, such as those in hospitals and pharmacies, through focused sales presentations. Although price and volume are negotiated through contractual agreements with intermediaries, demand for our products is generated through promotional efforts by Grifols’ sales representatives. In the case of GPOs, the actual sales are made to the authorized distributor(s) of each GPO at the contract price, and the distributor then sells the products to the members of that GPO. We promote our products directly to the GPO’s members. For safety and post-sale service reasons, the distributor is required to provide us with the specifics of the ultimate delivery to the client.
For Diagnostics, the sales model consists of direct sales of Grifols solutions by a dedicated sales force primarily focusing on Integrated Delivery Networks (IDNs) and the GPOs that represent them. For IDNs belonging to a GPO, pricing is negotiated with the GPO.
We market and promote our solution to healthcare professionals and other decision makers within hospitals and contracts are entered into directly with hospitals, following requests for proposals, typically for a period of three to seven years.
For Biopharma, the sales, marketing and distribution process is different in Europe, where the bulk of sales are generally made directly to hospitals. We have developed long-standing relationships with major hospitals in most of our European markets, and we believe that hospitals are loyal customers that recognize the high quality and safety of our products, our reliability as a supplier and the strong product expertise and service provided by our sales representatives. Due to the nature of our customer base and the prevalence of repeat sales in the industry, we market our products through focused sales presentations rather than by advertising campaigns.
Sales to Eastern Europe, the Middle East and some Asian countries are made mostly by third parties outside of our sales network. Our sales in Latin America are made mainly by our sales network in Chile, Brazil and Mexico, as well as by third-party distributors elsewhere.
For Diagnostics in Europe, the Middle East and Africa, sales and marketing is done through affiliates and distributors. The majority of the customer base for our Diagnostics division products is public and follows local public procurement laws tender processes. In Asia, Latin America and the Pacific, we sell through a mix between direct sales and sales through distributors.
In China, sales and marketing are made by channel partners and sub-distributors with indirect support from the our affiliate in China.
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Sales Representatives
For Biopharma, we require our sales representatives to be able to highlight the technical differences between our products and those of our competitors. This skill requires a high degree of training, as the salesperson must be able to interact and discuss product differences with doctors, pharmacists and other medical staff in an appropriate manner. Sales representatives call on office-based healthcare providers and hospital-based healthcare providers, departmental heads, purchasing agents, senior hospital directors, lab directors and pharmacy managers. We compensate our sales representatives by means of a fixed salary and a bonus component based on sales achievements. We divide our sales efforts along the lines of our main product categories. Our sales personnel are primarily located in Europe and the United States, but we also have sales personnel in Latin America and Asia-Pacific.
In our Biopharma business unit, we utilize mixed sales units comprised of both marketing and sales personnel. In some countries, we have product line-specific sales units for immunology & neurology, pulmonary, intensive care and coagulation factors.
For Diagnostics, we require our sales representatives to be able to highlight the value of our solutions compared to our competitors. This ability requires a high degree of technical and sales training, as well as soft skills to aptly describe our products. The salesperson must be able to interact and discuss the value of our solutions to all levels of stakeholders. The interactions with customers are a mix of in-person and virtual meetings.
Advertising
We participate in medical conferences, conventions and fairs and occasionally publish advertisements in medical journals and trade magazines. This promotional activity is also supported by online activities.
Distribution
We believe that having our own distribution network staffed with highly trained personnel is a critical element of a successful sales and marketing effort. Through this network, we are able to provide high-quality pre- and post-sales service, which we believe enhances brand recognition and customer loyalty. Our distribution network is experienced in the proper handling of our products and allows us to know where our products are located, enabling us to act quickly in the event of a suspected problem or product recall.
Our distribution network personnel are located in Europe, Latin America, the United States and Asia-Pacific and handle the distribution of our biological medicine, diagnostic and other medical products as well as goods manufactured by other premier healthcare companies that complement our own products.
During 2025, we distributed the majority of our products through our own distribution network. In some cases, particularly in the field of Diagnostics, we distribute products through marketing partners and third-party distributors. We have a direct presence in more than 30 countries and we carefully select distributors in the countries where we do not have a direct presence. We have a responsive, effective logistics organization that is able to punctually meet the needs of hospital centers and other customers throughout the world.
Our sales, marketing and distribution network included 1,613 employees as of December 31, 2025, which included 1,419 sales and distribution personnel and 194 marketing employees.
Each of our commercial subsidiaries is responsible for the requirements of its respective local market. It is our goal for each commercial subsidiary to be recognizable as one of our companies by its quality of service, ethical standards and knowledge of customer needs. Strong local knowledge enables us to build and maintain long-term relationships with customers to earn their trust and confidence.
We continually require technical services to perform the installation and maintenance of the systems sold in our medical equipment and software offerings. The Diagnostics business unit and the Healthcare Solutions division each have their own structure of support staff appropriately trained to provide such services, which is an important part of the competitive success of these solutions.
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In the Diagnostics business unit, we rely on distributors to sell and support our products. We have 163 distributors in Europe, the Middle East, Africa, Latin America, China and Asia Pacific. In order to provide responsive, region-specific services and maintain long-standing relationships, local presence and proximity to the customers are valuable assets to our Diagnostic business. Our Diagnostics business unit engages in direct sales and marketing and offers post-sale support in 16 countries. As of December 31, 2025 our Diagnostics business unit had 1,600 employees.
Safety in the blood transfusion process is the highest priority for us. We are constantly innovating new solutions to improve safety, efficiency, and standardizations to promote the fast availability of safe blood to patients globally.
Patents, Trademarks and Licenses
Patents and Trademarks
Through our patent ownership, co-ownership and licensing, we seek to obtain and maintain intellectual property protection for our primary products.
As of December 31, 2025, we owned 2,528 patents and patent applications in various countries throughout the world, of which 543 are in the final application process. In some countries, these patents grant a 20-year protection period. Of these patents, 1,276 are set to expire in the next ten years. The patent for the production process of thrombin expired in January 2024, and the patent for the Coagulometer Q expired in November 2025.
As of December 31, 2025, we also owned 2,929 trademarks and trademark applications in various countries throughout the world, of which 102 are in the final application process. In addition, we co-own certain patents and patent applications with third parties, including patent rights co-owned with Novartis following the Novartis Acquisition.
We maintain a department with personnel in Spain and Germany to handle the patent and trademark approval and maintenance process and to monitor possible infringements.
Patents for Plasma Derivative Products
As of December 31, 2025, we owned 1,978 patents and patent applications related to plasma derivatives, including 896 in Europe, 277 in the United States and Canada, and 805 in the rest of the world. The most important of these patents relate to:
● a concentrated subcutaneous alpha-1 antitrypsin;
● the use of low volume plasma exchange for the treatment of Alzheimer’s disease;
● transferrin for neurodegenerative applications;
● transferrin for the treatment of Hipoxia inducible factor related conditions;
● plasmin in wound healing;
● plasmin in organ transplantation;
● a concentrated subcutaneous Immunoglobulin G injection;
● concentrated Immunoglobulin M preparations for the treatment of bacterial infections;
● hyperimmune immunoglobulin for treatment of Covid-19;
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● anti-thrombin to treat blunt trauma;
● anti-thrombin to treat stroke;
● Mip1a as marker of effectiveness of albumin treatment in Alzheimer disease;
● the use of plasma exchange for removal of exosomes causing neurodegenerative disease;
● the use of plasma exchange for removal of exosomes causing cancer;
● 3D-printable multi-component bone compositions based on fibrinogen, thrombin, and hydrogels; and
● print head device to print a 3D composition.
Patents for Diagnostic Products and Healthcare Solutions
As of December 31, 2025, we owned 550 patents and patent applications related to our Diagnostic products and Healthcare Solutions business line, including 312 in Europe, 91 in the United States and Canada and 147 in the rest of the world. The most important of these patents relate to the:
● BlisPack, a blister handling machine;
● Erytra Eflexis, a mid-sized instrument to perform pre-transfusion compatibility tests using DG Gel technology;
● innovative containers for human plasma proteins;
● novel HIV antigens for blood screening;
● soluble recombinant form of CD38 receptor;
● soluble recombinant form of CD47 receptor;
● recombinant antigens for detection of COVID-19;
● multiplex technology for molecular detection; and
● single tube sequencing amplification system.
Licenses from Third Parties
We license certain intellectual property rights from third parties, including Singulex, Novilux and Hologic. Singulex granted us an exclusive worldwide license under certain intellectual property rights to develop, manufacture and commercialize certain products and services for blood donor and plasma screening. Novilux granted us a non-exclusive worldwide license under certain intellectual property rights to develop, manufacture and commercialize certain products for the in vitro clinical diagnostic field. Pursuant to an intellectual property license with Hologic, we obtained a fully paid-up license to certain of Hologic’s intellectual property for use in the NAT Donor Screening Unit.
In addition to licenses, we acquire intellectual property rights from third parties, such as Anapa Biotech A/S, to support the development of new products that will enable us to expand our business in the field of molecular testing.
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Licenses from Government Authorities
Government authorities in the United States, at the federal, state and local level, and in other countries throughout the European Union, Latin America, Asia and elsewhere, through licenses, approvals, reviews, inspections and other requirements, extensively regulate the research, development, testing, approval, manufacturing, labeling, post-approval monitoring and reporting, packaging, promotion, storage, advertising, distribution, marketing and export and import of healthcare products such as those that we collect, manufacture, sell or are currently developing.
For example, in order to sell our plasma derivative products we must hold appropriate product licenses from applicable governmental authorities. We have 1,117 Biopharma product licenses registered in 90 countries, which include the licenses we hold from the FDA for the sale in the United States of IG, A1PI, albumin, Factor VIII, Factor IX, ATIII and PTC. The production, marketing and sale of many of our Diagnostic business unit products are subject to the prior registration of such products with the relevant authorities of the applicable jurisdictions. We have 4,117 diagnostic product licenses registered in 50 countries in Europe, the United States, Canada, Latin America, Oceania and Asia.
Governmental oversight extends to the various facilities involved in our operations. For example, our Parets and Murcia facilities are subject to applicable regulations and standards of the European health authorities. With respect to oversight by the FDA, our Instituto Grifols Biopharma plant at our Parets facility has been registered with the FDA since 1995, and our other manufacturing facilities maintain FDA registration, and all are subject to FDA standards. We lease most of our plasma collection centers as well as our main laboratory facility located in Austin, Texas, and maintain licenses with the appropriate regulatory authorities, including the FDA, for all of these locations.
For more information on government licenses and regulation, see “—Principal Activities” above and “—E. Regulatory Matters” below.
Regulatory
For detailed information regarding the regulations applicable to our business, see “—E. Regulatory Matters” below.
Insurance Coverage
General and Product Liability
We have a program of insurance policies designed to protect us and our subsidiaries (including the United States subsidiaries) from product liability claims. Effective as of May 1, 2025, we have product liability insurance coverage for up to $230 million per claim and in annual aggregate for Diagnostic and Bio Supplies business units for products manufactured in all of their facilities and for third-party product sales. That limit is $395 million per claim and in the annual aggregate for Biopharma business unit. This policy expires on April 30, 2026, and we expect to renew it for another year prior to such expiration date.
Our liability program also protects from certain environmental liabilities arising in those countries in which Grifols’ subsidiary companies have operations. This risk is covered up to a maximum of $230 million per claim and in annual aggregate.
We maintain a separate liability insurance policy for donor centers. The policy covers their professional liability for plasmapheresis activities and expires on April 30, 2026. The maximum amount of coverage for liability claims under the policy is $15 million per claim and in the annual aggregate. In addition, our general liability insurance provides excess coverage.
Property Damage and Business Interruption
Our property damage and business interruption insurance program covers us and our subsidiaries (including the United States subsidiaries). This insurance program, which expires on April 30, 2026, covers damages suffered by plants and buildings, equipment and machinery. Under the current terms, the insurer will cover damages to our facilities produced by fire, smoke, lightning and explosions, among others, for up to $2 billion per occurrence (although some sub-limits for other coverages may apply). It also covers property damage produced by flooding, for up to $110 million per claim and in the annual aggregate. This policy also covers loss of profit up to a certain amount.
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We also have a transit and inventory insurance program, which covers damages to raw materials, supplies, semi-finished products and finished products for up to $25 million per claim for transit and $700 million for inventory in annual aggregate. This insurance program expires on April 30, 2026, and we expect to renew the policy for another year prior to its expiration date.
Cyber
Our cyber insurance covers financial losses up to $95 million resulting from data breaches and ransomware attacks. This insurance program expires on April 30, 2026, and we expect to renew the policy for another year prior to its expiration date.
Self-insurance
We are self-insuring part of the risks described above through the purchase of a portion of the relevant insurance policies by Squadron Reinsurance DAC, one of our wholly owned subsidiaries. We also self-insure a portion of the main insurance global programs such as general liability, property and business interruption, professional liability for donor centers, transit, inventory and cyber.
We self-insure $50 million per claim per year of our global liability program (except that amount is $85 million per claim and in the annual aggregate for the Biopharma business unit), for property damage and business interruption up to a maximum annual aggregate of $10 million, for transit and inventory losses up to a maximum annual aggregate of $5 million, for professional liability in the donor centers up to a maximum annual aggregate of $5 million, and for losses related to cyber-security risks up to a maximum annual aggregate of $5 million. These amounts are in excess of the deductibles for each of the policies that make up our insurance programs.
Climate Change
Aligned with the United Nations’ plan to achieve the sustainable development goals defined in its 2030 agenda, we have set commitments to help preserve the environment. Since 2020, our corporate environmental program included the reduction of emissions and decarbonization milestones for our business. By 2030, we are committed to reducing our greenhouse gas emissions, increasing our energy efficiency per unit of production and ensuring that 100% of the electricity consumed in our facilities originates from renewable sources.
Since 2024, our short-term emission reduction targets have been approved by the Science Based Targets initiative (SBTi), which verified that our Scope 1, 2 and 3 commitments align with the ambition of limiting global warming to 1.5°C. As part of our broader climate strategy and goal of achieving climate neutrality by 2050, in 2025 we implemented a transition plan towards Net Zero. This plan provides a structured pathway to advance decarbonization and ensure the long-term resilience of our business model in a low-emissions economy. It builds on the targets validated by the SBTi and establishes a clear framework for reducing emissions across the value chain.
In the short term, we have committed to:
1. Reducing absolute Scope 1 and 2 greenhouse gas (“GHG”) emissions by 42% by 2030, using 2022 as the baseline.
2. Reducing absolute Scope 3 emissions by 25% by 2030, covering purchased goods and services, capital goods, fuel- and energy-related activities, and upstream transport and distribution.
We have also set an internal long-term objective—distinct from but aligned with our SBTi-validated targets—to reduce Scope 1, 2 and 3 emissions by 90% by 2050 compared with 2022, thereby reaching Net Zero by 2050. This roadmap positions us to advance coherently with international decarbonization frameworks and global climate neutrality commitments.
Our action plan to achieve such SBTs includes (i) minimizing air travel among our different industrial and operational locations by increased use of technology such as video calls; (ii) increasing the levels of remote work by our employees with policies providing for flexible hour; (iii) optimizing logistics in our plasma transportation network, including by shipping intermediate products from our facilities in the United States to Ireland by ship, rather than air transport; (iv) minimizing the impact of employee travel and commutes with measures such as providing subsidized shared transportation service to employees in our facilities; and (v) increasingly rely on renewable energy by purchasing energy generated from renewable sources through PPAs.
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In 2025, we consumed 272 million kWh of renewable electricity, 56.0% of our total consumption, through actions such as power purchasing agreements (“PPAs”), the use of two photovoltaic plants (in Barcelona and Murcia) and refrigeration plants with refrigerant gases with a global warming potential equal to zero. With the aim of replacing the most polluting technologies, we regularly analyze the technological options available on the market, with a special focus on technologies that increase the climate resilience of our facilities.
Our GHG emissions inventory covers all scopes (1, 2, and 3) and categories, following the GHG Protocol and encompassing all company activities:
● Scope 1 emissions are direct emissions generated by our business activity itself, including by combustion sources. In 2025, our Scope 1 emissions were 121,884 tCO2e, representing a decrease of 1.1% compared to 123,224 tCO2e in 2024;
● Scope 2 emissions are indirect emissions from the generation of purchased energy, primarily electricity consumed by our business. Using the market-based approach, in 2025 our Scope 2 emissions were 83,893 tCO2e, representing a decrease of 15.2% compared to 98,968 tCO2e in 2024 (which such figure accounts for Biotest’s Scope 2 emissions of 25,092 tCO2e). Using the location-based approach, Scope 2 emissions were 132,698 tCO2e in 2025, representing an increase of 37.1% compared to 96,774 tCO2e in 2024 (which such figure accounts for Biotest’s Scope 2 emissions of 12,431 tCO2e) due to higher electricity consumption and changes in national grid emission factors.
● Scope 3 emissions are all other indirect emissions that occur in the value chain of our business both upstream and downstream. Scope 3 includes emissions by suppliers throughout the life cycle of our products or services, business trips, employee travel and commutes, among others. In 2025, our Scope 3 emissions remain virtually unchanged compared with 2024, totaling 1,152,449 tCO2e. Category 1 goods and services continue to account for 48% of Scope 3 emissions, followed by Grifols contracted transportation.
Since 2019, we have regularly updated our climate risk map as part of our integrated approach to managing climate-related risks and opportunities. This framework helps the company determine whether a potential impact constitutes a material risk or opportunity. In 2025, within the framework of the company’s resilience assessment, we updated our climate risk and opportunity analysis based on recommendations from the international scientific community and the general criteria established by key reporting frameworks such as the CSRD. The analysis included a stressed pessimistic scenario (SSP5-8.5) from the Intergovernmental Panel on Climate Change to assess physical climate risks; a stressed optimistic scenario (“NZS”) from the International Energy Agency to evaluate transition risks; and a strategic analysis aligned with recommendations of the Task Force on Climate-related Financial Disclosures, based on a 2°C global warming scenario (SSP2-RCP-4.5). Additionally, we are developing a Decarbonization Plan that is expected to be published in 2026.
We also estimated the potential financial impacts of each material risk and opportunity in respect of climate change. For this process, we evaluated 27 potential climate-related risks and opportunities across the company’s entire value chain, including suppliers (upstream), our own operations and infrastructure, and the distribution and use of our products (downstream). Following this analysis, we identified 12 material risks and opportunities: 2 physical risks, 6 transition risks and 4 opportunities.
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C. Organizational Structure
Grifols, S.A. is the parent company of the Grifols Group, which was comprised on December 31, 2025, of 90 companies, associates and other subsidiaries. Subsidiaries in which Grifols, S.A. directly or indirectly owned the majority of equity or voting rights have been fully consolidated, as have been companies that Grifols, S.A. controls. In addition, there were three companies that were accounted for using the equity method, because Grifols, S.A. owned between 20% and 50% of its share capital and had no power to govern its financial or operating policies.
See Notes 1 and 2(b) to our audited consolidated financial statements included in this annual report on Form 20-F for details of our consolidated and non-consolidated companies.
D. Property, Plant and Equipment
Our headquarters is in Barcelona, Spain. As of December 31, 2025, we owned or leased facilities in eight countries, with our main factory locations established in Spain, Germany and the United States. We currently own or lease manufacturing facilities in 16 sites in 7 different locations, four of which have plasma fractionation capabilities. We are currently constructing two plants in Montreal and Egypt that, when complete, will also have plasma fractionation capabilities. The table below shows the geographic location and business purpose of our principal properties as of December 31, 2025.
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Location Facility Own/Lease (2) Business Purpose
Parets del Vallès, Spain Industrial Facility One Parets 66% owned; 34% of the property is leased from a third party Plasma fractionation Manufacture of plasma derivatives & business unit support activities
Industrial Facility Two Parets 80% owned; 20% of the property is leased from a third party Manufacture of Diagnostic and Healthcare Solutions products
Industrial Facility Three Parets 70% owned; 30% of the property is leased from a third party Plasma storage & other operating activities
Los Angeles, California, U.S. – Valley Industrial Facility, U.S. 92% owned; 8% of the property is leased from a third party Plasma fractionation Plasma purification Manufacture of plasma derivatives
Los Angeles, California, U.S. – City of Industry City of Industry, U.S. 100% leased Plasma storage
Clayton, North Carolina, U.S. Clayton Facility 100% owned Plasma fractionation Plasma purification Manufacture of plasma derivatives
Durham, North Carolina, U.S. Research Triangle Park 22% owned, 78% of the property is leased from a third party Research and Development Labs and Offices
Emeryville, California, U.S. Emeryville Facility 100% owned Manufacture of Diagnostic products
San Carlos, California, U.S. Alkahest site 100% leased Research and Development Labs and Offices
South San Francisco, California, U.S. GigaGen site 100% leased Research and Development Labs and Offices
Murcia, Spain Industrial Facility Murcia 100% owned Manufacture of Healthcare Solutions products
Fribourg, Switzerland Industrial Facility Switzerland 100% leased Manufacture of Diagnostic products
Melbourne, Australia Industrial Facility Australia 100% owned Manufacture of Diagnostic products
Vista, California, U.S. Grifols Bio Supplies, INC 100% leased Manufacture of Biological products
San Marcos, Texas, U.S. Plasma Testing Lab 100% owned Plasma testing
San Diego, California, U.S. San Diego Facility 75% owned; another 25% of the property is leased from a third party Manufacture of components of the TMA amplified NAT kits
Dublin, Ireland Global Operations Center 100% leased(1) Operating activities related to the Biopharma business unit
Sant Cugat del Vallès, Barcelona, Spain Headquarters 100% leased Headquarters
Derio, Bizkaia, Spain Progenika Biopharma 90% owned, 10% leased Manufacture of Diagnostic products & Research and Development
Zaragoza, Spain Araclon Biotech 100% leased Research and Development Labs and Offices
Boca Raton, Florida, U.S. Grifols Bio Supplies, Inc 100% leased Specialty testing
Arrasate, Guipuzcoa, Spain Kiro Grifols 100% leased Manufacture of Hospital equipment and Offices
Memphis, Tennessee, US Grifols Bio Supplies, Inc 57% owned, 43% leased Plasma Lab
Leipzig, Germany Haema 100% owned Headquarters, Lab & Warehouse
Montreal, Canada Industrial Facility Montreal 100% owned Plasma fractionation Plasma purification
Dreieich, Germany Cairo, Egypt Industrial Facility Dreieich Industrial facility Cairo 86% owned, 14% leased Joint venture with NSPO (49% owned by Grifols, 51% NSPO) Plasma fractionation Plasma Testing Laboratory Plasma Storage
(1) We hold a 999 year leasehold interest in the property.
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(2) Lease percentage based on property size.
Plasma Fractionation Plants
Our plasma derivative products are manufactured at our Parets, Los Angeles, Clayton and Dreieich facilities. All of our fractionation facilities have FDA and EMA certification. As of December 31, 2025, our facilities had an aggregate fractionation capacity sufficient to cover our current production needs.
The Parets facility has a unique design that separates the maintenance area from the clean areas required for the fractionation and purification procedures. This design, which we developed in-house, minimizes the risk of contamination and reduces maintenance costs. In addition to licenses from the European Union and other required specific authorities for the production of various plasma derivative products, the Parets facility is also licensed by the FDA. In addition to the plasma fractionation facilities, the Parets site also has protein purification, fill and finish, packaging, storage, research and development and energy co-generation facilities for the Biopharma business unit and manufacturing for the Diagnostic business unit and Healthcare Solutions business line. The Parets facility holds GMP’s, ISO 13485 and ISO 14001 for the Biopharma, Diagnostic and Healthcare Solutions plants and ISO 9001 certifications for its diagnostic manufacturing facilities.
In 2025, we began construction of a new plasma-fractionation plant in Lliçà de Vall (Barcelona, Spain), with a total planned investment of €160 million. We expect that this facility will enable us to double our fractionation capacity in Europe. The project will be integrated into the existing industrial complex in Parets, consolidating a biotechnology hub of approximately 25 hectares. The campus will include fractionation capacity, logistics, analytical laboratories, storage facilities, and a new space dedicated to Grifols Engineering. From an operational and environmental standpoint, the new plant has been designed as a highly digitalized and sustainable campus, with 100% of its electricity consumption covered by renewable sources, advanced monitoring systems, intelligent resource-management technologies, and energy-efficiency and circular-economy principles.
The Los Angeles facility contains purification and aseptic filling areas for coagulation factors, IG and albumin. The facility is licensed by the FDA and Grifols is working to certify the Los Angeles facility with ISO 14001 certification, similar to the rest of our manufacturing plants.
The Clayton facility in North Carolina is one of the world’s largest fully integrated facilities for plasma-derived therapies, including plasma receiving, fractionation, purification, filling/freeze drying and packaging capabilities, as well as freezer storage, testing laboratories and a cGMP pilot plant for clinical supply manufacture. This facility holds the ISO 14001 certification, which recognizes excellence and continuous improvement in environmental performance. The scope of the certification includes research, development, production and quality control of pharmaceutical specialties derived from human plasma.
In October 2020, we acquired our plasma fractionation facility (together with two purification facilities) in Montreal from GC Pharma. Once we finish renovations and obtain all necessary licenses and regulatory approvals for the Montreal facilities, we will become the only large-scale commercial manufacturer of plasma products in Canada. In 2025, the first phase was completed with the commissioning of an albumin purification and filling plant, and we started manufacturing albumin in the Montreal facilities. Phases II and III, currently under development, include the addition of a plasma-fractionation plant and a second IVIG purification and filling facility. We expect to begin plasma fractionation and gammaglobulin manufacturing by 2027.
We have an albumin purification, dosing and sterile filling plant in Dublin, Ireland. This plant allows a significant increase to our capacity for filling albumin in flexible packaging. Aligned with our measures to combat the effects of climate change, the Dublin plant has the latest eco-efficiency technologies to save energy and water.
In April 2022, we acquired the Dreieich facility as a result of the Biotest acquisition. The facility has plasma fractionation capabilities, as well as bulk production plants for albumin, new fibrinogen and IgM concentrate product lines and next-generation polyvalent immunoglobulins.
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Grifols Egypt, our joint venture with the NSPO, is currently building a new manufacturing site in Cairo that will feature fractionation and purification plants, logistics facilities and a plasma analysis lab to be fully automated. This project is designed to create a complete plasma value chain in Egypt, encompassing plasma donor recruitment, collection centers, laboratory testing, fractionation, purification, and final product manufacturing. Through this joint venture, Egypt achieved self-sufficiency in immunoglobulins, albumin, and coagulation factors in 2025, becoming the sixth country in the world to reach this level of autonomy in plasma-derived medicines. In addition, Grifols Egypt also currently owns 16 plasma-donation centers in Egypt (13 of which are already operating), with plans to expand to 20 in 2026.
Global Operations Center
Our facility in Dublin, Ireland, serves as a global operations center for our Biopharma business unit. This facility occupies 22,846 square meters and operates as the global supply chain management center for the Grifols Group. Our global operations center houses our Biopharma’s global logistics and distribution activities; warehousing of plasma, intermediate paste and finished product, labelling and secondary packaging of products; as well as regulatory and quality assurance activities relating to the supply of plasma and plasma derivatives. Finally, our Dublin facility also centralizes our treasury function and acts as our point of access to the capital markets.
E. Regulatory Matters
Government Regulation
Government authorities in the United States and in other countries extensively regulate, among other things, the research, development, testing, approval, manufacturing, labeling, post-approval monitoring and reporting, packaging, promotion, storage, advertising, distribution, marketing and export and import of healthcare products such as those we collect, manufacture, sell or are currently developing. The process of obtaining regulatory approvals and complying with all applicable laws and regulations requires the expenditure of substantial time and financial resources. The following is a summary of the overall regulatory landscape for our business.
United States Government Regulation
In the United States, the FDA regulates drugs, biologics, plasma collection and medical devices under the FDCA and, as applicable, the PHS Act, and their implementing regulations. Failure to comply with the applicable FDA requirements at any time during the product-development process, approval process or after approval may result in administrative or judicial sanctions. These sanctions could include, as applicable, the FDA’s imposition of a clinical hold on trials for drugs, devices or biologics, refusal to file or approve pending applications, withdrawal of an approval, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties or criminal prosecution or any combination of these sanctions. Any agency or judicial enforcement action could have a material adverse effect on us.
The BLA (Biologics License Application) Approval Process
Drugs that are also biological products, such as our plasma derivative products IG, A1PI, Factor VIII and albumin, and also certain in vitro diagnostic products associated with testing blood and blood components, must also satisfy the requirements of the PHS Act (Public Health Service Act) and its implementing regulations. In order for a biological drug product, or for these in vitro diagnostic tests, to be legally marketed in the United States, the product must have a BLA (Biologics License Applications) approved by the FDA. Obtaining BLA approval from the FDA is a robust process involving, among other things, completion of preclinical laboratory tests, controlled human clinical trials conducted in compliance with Good Clinical Practice (GCP) requirements, submission of manufacturing and chemistry data, and multiple statistical and physical review processes by the FDA. During all phases of clinical development, regulatory authorities require extensive monitoring and auditing of all clinical activities, clinical data and clinical trial investigators, including reports regarding adverse events and safety issues.
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Given the robust process, certain of our clinical trials may not be completed successfully within any specified period, if at all. Furthermore, we or the FDA may suspend or terminate clinical trials at any time on various grounds, for example, that the subjects or patients may be exposed to an unacceptable health risk, have experienced a serious and unexpected adverse event, or that continued use in an investigational setting may be unethical. Similarly, an IRB may suspend or terminate approval of research if the research is not being conducted in accordance with GMP or if the research has been associated with unexpected serious harm to patients.
Overall, the testing and approval processes require substantial time and effort and there can be no assurance that the FDA will accept the BLA for filing and, even if filed, that any approval will be granted on a timely basis, if at all. In most cases, the BLA must be accompanied by a substantial user fee.
In the United States, our main market, there is an abbreviated regulatory approval pathway for biological products found to be “biosimilar” to or “interchangeable” with a biological “reference product” previously licensed under a BLA. This abbreviated approval pathway is intended to permit a biosimilar product to come to market more quickly and less expensively by relying to some extent on the data generated by the reference product’s sponsor, and the FDA’s previous review and approval of the reference product. The law provides that no biosimilar application may be accepted for FDA review until four years after the date the reference product was first licensed by the FDA, and that the FDA may not make approval of an application effective until 12 years after the reference product was first licensed. The law also includes an extensive process for the innovator biologic and biosimilar manufacturer to litigate patent infringement, validity, and enforceability, which could increase costs of protecting our reference products. Once approved, biosimilars likely would compete with, and in some circumstances may be deemed under applicable laws to be “interchangeable with,” the previously approved reference product. The extent to which a biosimilar product, once approved, will be substituted for any of our products, in a way that is similar to traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing. In connection with the FDA’s authority to ensure the development of safe and effective biosimilars, in September 2022, the FDA Biosimilar User Fee Amendments of 2022 were signed into law. The FDA Biosimilar User Fee Amendments of 2022 reauthorize for an additional five years (through 2027) the Biosimilar User Fee Act of 2012, which allows the FDA to assess and collect fees for biosimilars. In October 2025, the FDA issued draft guidance that proposes to eliminate the need for sponsors of biosimilar products to conduct comparative human clinical efficacy studies.
The testing and approval processes to obtain a BLA require substantial time, effort and financial resources, and each process may take several years to complete. Data obtained from clinical activities is not always conclusive and may be susceptible to varying interpretations, which could delay, limit or prevent regulatory approval. The FDA may not grant approval on a timely basis, or at all. We may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing our products. The FDA may limit the indications for use or place other conditions on any approvals that could restrict the commercial application of the products. In addition, competition from lower-priced biosimilars following loss of exclusivity may materially reduce sales.
Post-approval Requirements
After regulatory approval of a product is obtained, we are required to comply with a number of post-approval requirements. For example, as a condition of approval of a BLA, the FDA may require post-marketing testing and surveillance to monitor the product’s safety or efficacy. In addition, holders of an approved BLA are required to keep extensive records, to report certain adverse reactions and production problems to the FDA, to provide updated safety and efficacy information and to comply with requirements concerning advertising and promotional labeling for their products. Also, quality control and manufacturing procedures must continue to conform to cGMP regulations and practices, as well as the manufacturing conditions of approval set forth in the BLA. The FDA periodically inspects manufacturing facilities to assess compliance with cGMP, which imposes certain procedural, substantive and recordkeeping requirements. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.
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Future FDA inspections may identify compliance issues at our facilities or at the facilities of our third-party suppliers that may disrupt production or distribution, or require substantial resources to correct and prevent recurrence of any deficiencies, and could result in fines or penalties by regulatory authorities. In addition, discovery of problems with a product or the failure to comply with applicable requirements may result in restrictions on a product, manufacturer or holder of an approved BLA, including withdrawal or recall of the product from the market or other voluntary, FDA-initiated or judicial action that could delay or prohibit further marketing. Newly discovered or developed safety or efficacy data may require changes to a product’s approved labeling, including the addition of new warnings and contraindications.
The ACA established and provided significant funding for a Patient-Centered Outcomes Research Institute to coordinate and fund comparative effectiveness research. While the stated intent of comparative effectiveness research is to develop information to guide providers to the most effective therapies, outcomes of comparative effectiveness research could influence the reimbursement or coverage for therapies that are determined to be less cost effective than others.
Orphan Drug Designation
The FDA may grant orphan drug designation to drugs intended to treat a “rare disease or condition” that affects fewer than 200,000 individuals in the United States, or that affects more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such a disease or condition will be recovered from sales in the United States for that drug. Orphan drug designation must be requested before submitting an application for marketing approval. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. Orphan drug designation can provide opportunities for grant funding towards clinical trial costs, tax advantages and FDA user fee exemptions. In addition, if a product that has an orphan drug designation subsequently receives the first FDA approval for the indication for which it has such designation, the product is entitled to orphan drug exclusivity, which means the FDA may not approve any other application to market the same drug for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or a meaningfully different mode of administration. Competitors may receive approval of different drugs or biologics for the indications for which the orphan product has exclusivity. However, if a company with orphan drug exclusivity is not able to supply the market, the FDA could allow another company with the same drug a license to market for said indication. The FDA granted Gamunex IVIG orphan drug status, which provided marketing exclusivity for the CIDP indication in the United States through September 2015. Gamunex IVIG was the first IVIG product approved for CIDP in the United States.
Fast Track Designation
The FDA currently offers certain programs, including fast track designation, breakthrough therapy designation, accelerated approval, and priority review which are designed to facilitate the development and review of new drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs for the conditions. For example, fast track designation applies to a combination of the product and the specific indication for which it is being studied. The sponsor of a product designated for fast track designation may engage in close early communication with the FDA, including through timely meetings and feedback on clinical trials. Products that receive fast track designation also may receive FDA priority review or accelerated approval. Sponsors may also be able to submit completed portions of an application before the entire application is completed; however, the review clock will not officially begin until the entire completed NDA or BLA is submitted to and filed by the FDA. The FDA may notify a sponsor that its program is no longer classified as a fast track development program if the fast track designation is no longer supported by emerging data, the designated drug development program is no longer being pursued, or another product that meets the unmet medical need for the same indication is approved first.
Plasma Collection
The FDA requires a licensing and certification process for each plasma collection center prior to opening and conducts periodic inspections of facilities and processes. Many states also regulate plasma collection, imposing similar obligations and additional inspections and audits. Collection centers are subject to periodic inspections by regulatory authorities, which if noncompliance is alleged, may result in fines, citations, the temporary closing of the centers, loss or suspension of licenses or recall of finished products.
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Diagnostic Devices
Certain of our products are regulated as medical devices, which are typically subject to clearance for commercialization in the United States, often referred to as an FDA “510(k) clearance,” based on a pre-market notification to the FDA demonstrating the device to be marketed is safe and effective by proving substantial equivalence to a legally marketed device (predicate device). The manufacturers of medical devices must register their establishments with the FDA, and the production of the devices must accord with applicable current good manufacturing practices and quality system regulations. Some states also regulate the manufacture or distribution of certain medical devices, imposing additional licensing, inspection and audit requirements. With respect to the manufacture and sale of immunoassay antigens and antibodies to screen human donated blood and blood products, these products are manufactured and sold under a BLA issued by the FDA, and are subject to the heightened regulatory oversight associated with biological products.
Drug Supply Chain Security Act
The Federal Drug Quality and Security Act of 2013 regulates pharmaceutical supply chain requirements and pre-empts certain state laws. Title II of this act, known as the Drug Supply Chain Security Act (“DSCSA”) establishes a national electronic, interoperable system to identify and trace certain prescription drugs as they are distributed in the United States, including certain of our products. The DSCSA’s track and trace requirements (applicable to manufacturers, wholesalers, repackagers and dispensers (e.g., pharmacies) of prescription drugs) replaced the former FDA drug pedigree requirements and pre-empt state requirements that are inconsistent with, more stringent than, or in addition to, the DSCSA requirements. The DSCSA also establishes certain requirements for the licensing and operation of prescription drug wholesalers and third party logistics providers (“3PLs”), and includes the creation of national wholesaler and 3PL licenses in cases where states do not license such entities to be established in FDA regulations yet to be finalized. The DSCSA generally requires that wholesalers and 3PLs distribute drugs in accordance with certain standards regarding the recordkeeping, storage and handling of prescription drugs. Under the DSCSA, states are pre-empted from imposing any licensing requirements that are inconsistent with, less stringent than, directly related to, or covered by U.S. federal standards, however, the FDA has clarified that current state licensing requirements may remain in effect until the FDA national licensing regulations are finalized and take effect.
Anti-fraud and Abuse Regulation
Since we supply products and services that are reimbursed by U.S. federal healthcare programs such as Medicare and Medicaid, our activities are also subject to regulation by CMS (U.S. Centers for Medicare & Medicaid Services) and enforcement by the OIG (U.S. Office of the Inspector General). The federal Anti-Kickback Statute prohibits providers and others from directly or indirectly soliciting, receiving, offering or paying any remuneration with the intent of generating referrals or orders for services or items covered by a government health care program. Many states have similar laws. Courts have interpreted this law very broadly, including by holding that a violation has occurred if even one purpose of the remuneration is to generate referrals, even if there are other lawful purposes. There are statutory and regulatory exceptions, or safe harbors, that outline arrangements that are deemed lawful. However, the fact that an arrangement does not fall within a safe harbor does not necessarily render the conduct illegal under the Anti-Kickback Statute. In sum, even legitimate business arrangements between the companies and referral sources could lead to scrutiny by government enforcement agencies and require extensive company resources to respond to government investigations. Also, certain business practices, such as payment of consulting fees to healthcare providers, sponsorship of educational or research grants, charitable donations, interactions with healthcare providers that prescribe products for uses not approved by the FDA and financial support for continuing medical education programs, must be conducted within narrowly prescribed and controlled limits to avoid potential liability for wrongfully influencing healthcare providers to prescribe or purchase particular products or as a reward for past prescribing.
The FCA (Federal False Claims Act) is violated by any entity that knowingly presents or causes to be presented a false claim for payment to the U.S. federal government, or that knowingly makes or causes to be made a false record material to such a false claim, or knowingly conceals or avoids an obligation to pay to the government, including by knowingly retaining an overpayment. Payments in violation of the Anti-Kickback Statute can also form the basis for FCA liability.
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The FCA has been subject to heightened enforcement activity as a result of whistleblowers (called “relators”) who file complaints in the name of the United States (and if applicable, particular states), and who may receive up to 30% of total government recoveries. FCA violators may be liable for treble damages, mandatory penalties, loss of licensing and exclusion from federal and state healthcare programs. Such penalties could have a material adverse effect on our business. Also, these measures may be interpreted or applied by a prosecutorial, regulatory or judicial authority in a manner that could require us to make changes in our operations or incur substantial defense and settlement expenses. Even unsuccessful challenges by regulatory authorities or relators could result in reputational harm and the incurring of substantial costs. Most states have adopted similar state false claims laws, which could lead to significant additional penalties.
We also are subject to certain United States and foreign laws and regulations concerning the conduct of our foreign operations, including the U.S. Foreign Corrupt Practices Act, the U.K. Bribery Act, German anti-corruption laws and other anti-bribery laws and laws pertaining to the accuracy of our internal books and records, which have been the focus of increasing enforcement activity globally in recent years.
The “PPS Act” (Physician Payments Sunshine Act) imposes reporting and disclosure requirements for biologic, drug and device manufacturers with regard to payments or other transfers of value made to physicians, physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, certified nurse-midwives, teaching hospitals, manufacturers and for GPOs (group purchasing organizations), with regard to practitioner and teaching hospital ownership interests in the reporting entity. CMS publishes information from these reports on a publicly available website, including amounts transferred and practitioner and teaching hospital identities. The PPS Act preempts similar state reporting laws, although we or our subsidiaries may also be required to report under certain state transparency laws that address circumstances not covered by the PPS Act, and some of these state laws, as well as the federal law, can be ambiguous. We are also subject to foreign regulations requiring transparency of certain interactions between suppliers and their customers.
Other Health Care Regulation
In the United States, pricing concerns have led to heightened scrutiny and ongoing governmental efforts to increase transparency around healthcare and pharmaceutical drugs costs. For example, on November 12, 2020, CMS issued final rules imposing price transparency requirements on hospitals and group health plans, which went into effect in three stages from 2022 to 2024. As of January 1, 2024, hospitals and group health plans must disclose in-network provider negotiated rates (which include rates with device suppliers and manufacturers), historical out-of-network allowed amounts for all covered items and services, including all prescription drugs and drug pricing information. States have also enacted a variety of transparency rules and regulations. The publication of our negotiated rates could affect our ability to independently negotiate sales contracts and rate agreements.
Another notable Medicare healthcare reform initiative, the Medicare Access and CHIP Reauthorization Act of 2015 (“MACRA”), established a new quality payment program, which modifies certain Medicare Part B payments to “eligible clinicians,” including physicians, dentists and other practitioners. Under MACRA, certain eligible clinicians are required to participate in Medicare through the Merit-Based Incentive Payment System (“MIPS”) or the Advanced Alternative Payment Models (“APMs”), through which Medicare Part B reimbursement is adjusted up or down based on reported data related to quality, promoting interoperability, cost, and improvement activities. MIPS-eligible clinicians must report annual performance data by March 31 of the following year. Payment adjustments based on submitted data are applied to Medicare Part B claims during the performance year following data submission. MACRA provides substantial financial incentives for physicians to participate in risk contracts, while increasing physician information technology and reporting obligations. MACRA continues to evolve and its implications depend on future regulatory activity and physician activity in the marketplace. New payment and delivery system reform programs, including those modeled after such federal program, are also increasingly being rolled out at the state level through Medicaid administrators, as well as through the private sector, which may further alter the marketplace and impact our business.
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Recently, a number of states in the United States have also proposed or passed legislation that seeks to directly or indirectly regulate pharmaceutical drug pricing, such as by requiring drug manufacturers to publicly report pricing information or to place a maximum price cap on pharmaceutical products purchased by state agencies. For example, in June 2024, New York implemented a prescription drug price transparency law that requires prescription drug manufacturers to provide advance notice and explanation for certain drug price increases that exceed a specified threshold. California, Colorado, Minnesota, Oregon, Washington and New Jersey have created prescription drug affordability boards, and a number of other states have enacted or are considering similar legislation. Laws of this type may cause us to experience additional pricing pressures on our affected products. For more details on these pressures, see “—Pharmaceutical Pricing and Reimbursement” below.
Antitrust and Consumer Protection
The U.S. federal government, most U.S. states and many foreign countries have antitrust laws that prohibit certain types of conduct deemed to be anti-competitive, as well as consumer protection laws that seek to protect consumers from improper business practices. At the U.S. federal level, the FTC oversees enforcement of these types of laws, and states have similar government agencies. Violations of antitrust or consumer protection laws may result in various sanctions, including criminal and civil penalties. Private plaintiffs may also bring civil lawsuits against us in the United States for alleged antitrust law violations, including claims for treble damages.
European Community Government Regulation
In addition to regulations in the United States, we are subject to a variety of regulations in other jurisdictions governing clinical trials and commercial sales and distribution of our products. Whether or not we obtain FDA approval for a product, we must obtain approval of a product by the comparable regulatory authorities of countries outside the United States before we can commence marketing that product in those countries. The approval process varies from country to country, and the time may be longer or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country. Also, in addition to approval of final products, plasma collection centers for manufacture into products to be distributed in the European Union must also be approved by the competent European health authority.
Medicines can be authorized in the European Union by using either the centralized authorization procedure or national authorization procedures. The EMA is responsible for the centralized authorization procedure.
Centralized Authorization Procedure
The EMA is responsible for the centralized procedure, or Community authorization procedure, for human medicines. This procedure results in Community marketing authorization, the single marketing authorization that is valid across the European Union, as well as in the European Economic Area/European Free Trade Association states Iceland, Liechtenstein and Norway.
The Community authorization procedure is compulsory for:
● medicines derived from biotechnology processes, such as genetic engineering;
● advanced-therapy medicines, such as gene-therapy, somatic cell-therapy or tissue-engineered medicines;
● medicinal products for human use containing a new active substance that did not receive Community marketing authorization when the Community authorization procedure was first implemented, for which the therapeutic indication is the treatment of human immunodeficiency virus (“HIV”) or acquired immune deficiency syndrome (“AIDS”), cancer, neurodegenerative disorders, diabetes, autoimmune diseases and other immune dysfunctions or viral diseases; and
● officially designated orphan medicines (medicines for rare diseases).
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The Community authorization procedure is optional for products:
● containing new active substances for indications other than those stated above;
● representing significant therapeutic, scientific or technical innovations; or
● for which the granting of a Community marketing authorization would be in the interests of European Union public health.
Our blood derivative products are not subject to compulsory Community authorization, but it is an option for our new products. Flebogamma DIF 50 mg/ml and 100 mg/ml, VeraSeal solutions for sealant and Tavlesse (fostamatinib) were approved through the Community authorization procedure.
Applications through the Community authorization procedure are submitted directly to the EMA. Evaluation by the EMA’s relevant scientific committee takes up to 210 days, at the end of which the committee adopts an opinion on whether the medicine should be marketed. This opinion is then transmitted to the European Commission, which has the ultimate authority for granting marketing authorizations in the European Union.
Once a Community marketing authorization has been granted, the holder of that authorization can begin to make the medicine available to patients and healthcare professionals in all European Union countries.
National Authorization Procedures
Each European Union member state has its own procedures for the authorization, within its own territory, of medicines that fall outside the scope of the Community authorization procedure. There are two possible routes available to companies for the authorization of such medicines in several countries simultaneously.
● Decentralized procedure. Using the decentralized procedure, companies may apply for simultaneous authorization in more than one European Union country of medicines that have not yet been authorized in any European Union country and that do not fall within the mandatory scope of the centralized procedure.
● Mutual-recognition procedure. In the mutual-recognition procedure, a medicine is first authorized in one European Union member state, in accordance with the national procedures of that country. Following such authorization, further marketing authorizations can be sought from other European Union member states in a procedure whereby the countries concerned agree to recognize the validity of the original, national marketing authorization.
Our products Niuliva 250 I.U./ml and Xembify 200 mg/ml were approved through the decentralized procedure. Our products Prolastina 1000 mg/ml, and Gamunex 10% and some of the Human Albumin Grifols / Albutein licenses were approved through the mutual-recognition procedure. All our other products were approved pursuant to individual national procedures. We expect to use the mutual-recognition procedure if we want to extend our product licenses to other European countries in the future.
In some cases, disputes arising in these procedures can be referred to the EMA for arbitration as part of a “referral procedure.”
Orphan Drug Designation
Applications for designation of orphan medicines are reviewed by the EMA through the Committee for Orphan Medicinal Products. The criteria for orphan designation are:
● the medicinal product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting no more than five in 10,000 persons in the European Union at the time of submission of the designation application (prevalence criterion);
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● the medicinal product is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition, and without incentives it is unlikely that the revenue after marketing of the medicinal product would cover the investment in its development; and
● either no satisfactory method of diagnosis, prevention or treatment of the condition concerned is authorized, or, if such method exists, the medicinal product will be of significant benefit to those affected by the condition.
Companies with an orphan designation for a medicinal product benefit from incentives such as:
● protocol assistance (scientific advice for orphan medicines during the product-development phase);
● direct access to centralized marketing authorization and 10-year marketing exclusivity;
● financial incentives (fee reductions or exemptions); and
● national incentives detailed in an inventory made available by the European Commission.
Orphan medicinal products are eligible for the following level of fee reductions:
● full (100%) reduction for small- and medium-sized enterprises, or SMEs, for protocol assistance and follow-up, full reduction for non-SME sponsors for pediatric-related assistance and 75% reduction for non-SME sponsors for non-pediatric assistance;
● to determine which companies are eligible for SME incentives, the EMA applies the definition of micro-, small- and medium-sized enterprises provided in the Commission of the European Communities’ Commission Recommendation 2003/361/EC. To qualify for assistance, companies must be established in the European Economic Area, employ less than 250 employees and have an annual turnover of not more than €50 million or an annual balance sheet total of not more than €43 million;
● full reduction for pre-authorization inspections for all sponsors and 90% reduction for post-authorization inspections for small- and medium-sized enterprises;
● full reduction for SMEs for new applications for Community marketing authorization and 10% reduction for non-SME sponsors; and
● full reduction for post-authorization activities including annual fees only to small and medium sized enterprises in the first year after granting a marketing authorization.
We have EMA Orphan Drug Designations for the following products:
● alpha-1 proteinase inhibitor (for inhalation use) for the treatment of cystic fibrosis; and
● alpha-1 proteinase inhibitor (for inhalation use) for the treatment of congenital alpha-1 antitrypsin deficiency.
Because each of these products is already authorized for a non-orphan indication in the EU, in order to obtain marketing authorization for any of the above-mentioned orphan indications, we would be required to apply for a separate marketing authorization through the Community authorization procedure for such indication, using a different proprietary name. It is not possible to extend the existing marketing authorization to cover the new orphan indication. Orphan and “non-orphan” indications cannot be covered by the same marketing authorization.
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United Kingdom Regulatory Process
The United Kingdom (“U.K.”) withdrew from the E.U. on January 31, 2020, and is no longer an E.U. Member State. A transition period, during which E.U. pharmaceutical law continued to be applicable to the U.K., ended on December 31, 2020.
As of January 1, 2021, the protocol in Ireland/Northern Ireland was applicable and had an impact on marketing authorizations for medicinal products in the U.K. with respect to Northern Ireland. However, as of January 1, 2025, a new agreement between the E.U. and the U.K. called the “Windsor Framework” amended the Protocol of Northern Ireland and set out the long-term arrangements for the supply of medicines into Northern Ireland. The Windsor Framework ensures that medicines can be approved and licensed on a U.K.-wide basis by the Medicines and Healthcare products Regulatory Agency (“MHRA”) and medicines can be supplied in the same packs across the U.K. It also provides for the disapplication of European Union Falsified Medicines Directive (“FMD”) requirements for medicines marketed and supplied in Northern Ireland.
There are several routes to obtain a marketing authorization in the U.K. The options available are determined by the intended market and the type of application. To obtain a marketing authorization, you need to use one of the following procedures:
National Routes:
● National Procedure. Applies to U.K. national marketing authorization applications for both innovative and established medicines, but the requirements, procedures and timetables differ. The innovative medicines timetable allows for a positive decision within 150 clock-on days if all issues are resolved following one round of questions. The established medicines timetable allows for a final decision within 210 days, with the possibility of an earlier decision if only minor issues are raised;
● Rolling review. Permits the submission of your application in module(s), to obtain a marketing authorization in the United Kingdom. This is a new route for marketing authorization applications, where an applicant for a new active substance in the U.K. or for a similar biological medicinal product (a biosimilar) submits modules of the eCTD dossier incrementally for pre-assessment by the MHRA, rather than as part of a consolidated full dossier submission.
This rolling review is intended to streamline the development of novel medicines by offering periodic enhanced regulatory interaction and advice to reduce the risk of failure at the final phase and may be integrated with the Target Development Profile (“TDP”) to provide a clearer pathway for development of innovative medicines.
Marketing authorization applications for any new active substance based on a “full dossier,” including biosimilar products, are eligible for the rolling review;
● International recognition procedure (a 60-day to 110-day procedure). As of January 1, 2024, the EC Decision Reliance Procedure and the Mutual Recognition/Decentralized Reliance Procedure have been replaced by the new International Recognition procedure (“IRP”). This route applies to new marketing authorization applications, variations, line extensions and renewals and is open to applicants that have already received an authorization for the same product from one of MHRA’s specified Reference Regulators (“RRs”). A positive opinion from the Committee for Medicinal Products for Human Use or a Mutual Recognition/Decentralized positive end of procedure outcome is an RR authorization for the purposes of IRP. Apart from the EMA and the E.U. Member State Competent Authorities, there are other possible RRs (such as Australia, Canada and the United States). IRP will allow the MHRA to take into account the expertise and decision-making of trusted regulatory partners for the benefit of U.K. patients. The MHRA will conduct a targeted assessment of IRP applications but retain the authority to reject applications if the evidence provided is considered insufficiently robust.
● Unfettered Access (UAP) from Northern Ireland (a 70-day procedure). Applicants may seek recognition in the UK of a marketing authorization approved in Northern Ireland under certain qualifying conditions. Following implementation of the Windsor Framework, if granted, a marketing authorization (MA) made through UAP will result in a UK-wide MA and the Northern Ireland MA will be revoked.
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This route is available for marketing authorizations approved in Northern Ireland via European procedures (MR or DC procedures only).
Applications should include the dossier as approved for marketing in Northern Ireland, accompanied by all iterations of the relevant RMS assessment reports.
International routes (collaborative procedures):
● Access consortium. The Access consortium is a medium-sized coalition of regulatory authorities that work together to promote greater regulatory collaboration and alignment of regulatory requirements for companies intending to market a medicine in the U.K., Australia, Canada, Singapore and/or Switzerland. The MHRA joined the consortium in 2020 and commenced work-sharing applications in January 2021; and
● Project Orbis. Project Orbis is a program coordinated by the FDA involving the regulatory authorities of Australia (TGA), Canada (Health Canada), the United Kingdom (MHRA), Singapore (HSA), Brazil (ANVISA), Israel (IMoH) and Switzerland (Swissmedic) to review and approve promising cancer treatments.
Further information can be found in the U.K.’s website for license applications (www.gov.uk).
Canadian Regulatory Process
Authorization to Market. In 2024, Health Canada implemented several regulatory modernization initiatives to streamline product approvals and enhance responsiveness to public health needs. Notably, in November 2024, Health Canada introduced the Agile Licensing Framework, amending the Food and Drug Regulations (“FDR”) and Medical Devices Regulations (“MDR”). These amendments expand Health Canada’s authority to impose terms and conditions on market authorizations and formalize the use of rolling reviews to facilitate earlier access to promising therapies. Therapeutic products can be marketed in Canada after they have been subject to a review to assess their safety, efficacy and quality. A New Drug Submission must be submitted to Health Canada for review, and a Notice of Compliance (“NOC”), and/or a Drug Identification Number (“DIN”), must be received by the sponsor prior to marketing a product in Canada. Responsibility for review of pharmaceutical drug products resides with Health Canada’s Therapeutic Products Directorate (“TPD”), while responsibility for review of biological products is under the Biologics, Radiopharmaceuticals and Genetic Therapies Directorate (“BGTD”). An active DIN is required for any product being marketed in Canada. Our IG, A1PI, albumin and hyperimmune products are subject to these review and authorization processes.
Changes to Market Authorization. There are four classes of changes to existing market authorizations in Canada. Level 1 changes are considered “significantly different” and have the potential to impact safety, efficacy, quality or effectiveness of the product. These require the filing of a Supplemental New Drug Submission, and a NOC must be issued by Health Canada prior to implementation of the change. Level 2 changes are not considered “significant,” but a “Notifiable Change” submission must be filed to Health Canada for review, and approval is provided via a “No Objection” letter to the sponsor. Level 3 changes have minimal potential to impact safety, quality or effectiveness and can be made without prior approval of Health Canada; a summary of these changes is reported to Health Canada with the sponsor’s Annual Drug Notification. Level 4 changes are implemented without any notification to Health Canada, based on no expectation of risk.
Shortage Management. In December 2024, Health Canada proposed amendments to the FDR and MDR to strengthen its authority to manage drug and medical device shortages. If adopted, these amendments will require market authorization holders to report shortages, discontinuations, and unexpected surges in demand, enabling Health Canada to respond more proactively to supply risks.
Clinical Trials. A Clinical Trial Application (“CTA”), must be submitted to Health Canada prior to conducting any study protocol that proposes the use of a new product, or the use of an existing product, where the indication, target population, route of administration or dosing differs from the current market authorization. The CTA should include summaries of preclinical and clinical studies conducted and (if applicable) chemistry, manufacturing and control data, and is submitted to either TPD (for drug products) or BGTD (for biological products) for review. The TPD or BGTD are responsible for assessing protection and safety of the participants as well as quality of the product; they will issue a “No Objection” letter to sponsors for studies deemed acceptable. Research ethics board approval for each trial is also required prior to conduct of the study.
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Establishment Licensing. All establishments in Canada that are involved in the fabrication, packaging/labeling, testing, import, distribution or warehousing of drug products must have a current establishment license (once an establishment license is issued, an annual report must be submitted by April 1 of each year to maintain the effectiveness of that license). As an importer/distributor, part of the licensing requirements include demonstration that any foreign (non-Canadian) facilities involved in fabrication, packaging/labeling or testing of products imported/distributed under the license comply with cGMP.
Post-Approval Requirements. In December 2024, Health Canada amended the regulatory framework governing product recalls, introducing mandatory reporting obligations to enhance oversight and response capabilities. The Health Products and Food Branch Inspectorate continues to inspect licensed establishments for cGMP compliance. Adverse drug reactions must be reported in accordance with Health Canada’s pharmacovigilance requirements to the Marketed Health Products Directorate.
Regulatory Coordination. As of May 1, 2024, the CADTH transitioned into Canada’s Drug Agency (“CDA”). The CDA now plays a broader role in coordinating national drug policy, providing evidence-based evaluations of health technologies and therapeutics, and advising public payers on funding decisions.
Regulatory Process for Markets outside the United States, Europe, United Kingdom and Canada
The majority of regulatory authorities in countries outside the United States, Canada and Europe require that a product first be approved by the FDA or European authority prior to granting the market authorization in their country. There are a limited number of countries (Bahamas, Bermuda, Guam, Oman and Qatar) that do not require further local product registration for products and they may be distributed based on the existing FDA approval.
In addition to requiring the submission of a license application containing documentation supporting the safety, efficacy and quality of the product, many countries require the submission of FDA Export Certificates for our products to provide assurance that such products can be legally marketed in the United States. The Certificate of Pharmaceutical Product (“CPP”), and/or the Certificate to Foreign Government (“CFG”), are issued by the FDA at the request of the manufacturer seeking licensing in the country outside the United States. The CPP conforms to the format established by the World Health Organization (“WHO”), and is intended for use by the importing country when considering whether to license the product in question for sale in that country. The CFG serves to document that the product can be legally marketed in the United States and the manufacturer is in compliance with GMP. A limited number of regulatory authorities in countries outside United States, Canada and Europe conduct onsite inspections to verify GMP compliance. Failure to maintain and document GMP compliance could result in withdrawal of marketing authorization. In addition changes to manufacturing or testing procedures for the product require approval of the change in the United States prior to the submission of the variation to the registration in the international market. These changes may require approval in each market in order to maintain product distribution. Furthermore, any changes in the distributors supporting our export business could result in a loss of sales.
Pharmaceutical Pricing and Reimbursement
In the United States and other countries, sales of our products depend, in material respects, on the availability of reimbursement from third-party payors. Third-party payors include government health programs, managed care providers, private health insurers and other organizations. These third-party payors are increasingly challenging the prices and examining the cost-effectiveness of medical products and services. In addition, significant uncertainty exists as to the reimbursement status of healthcare products newly approved by regulatory authorities. For example, third-party payors may deny reimbursement if they do not consider the products to be cost-effective as compared to available alternative products. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.
United States Pharmaceutical Pricing and Reimbursement
In the United States, our products are reimbursed or purchased under several government programs, including Medicaid, Medicare (Parts B and D) and hospitals may purchase at discounted prices under the 340B Program. Medicaid is a joint state and federal government health plan that provides covered outpatient prescription drugs for low income individuals. Medicare is a federally run program that provides healthcare to persons aged 65 and over, as well as certain persons of any age with certain disabilities. The 340B Program is a U.S. federal government drug pricing program under the PHS Act. The availability of federal funds to pay for our products under the Medicaid and Medicare Part B programs requires that we extend discounts under the 340B Program.
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Medicaid, the 340B Program and the Department of Veterans Affairs.
Medicaid includes a variety of reimbursement programs that differ state by state and imposes reimbursement requirements applicable to both fee-for-service and managed care arrangements. These requirements are applicable to certain of our products. Under Medicaid, drug manufacturers pay rebates to the states based on utilization data provided by the states and pricing information provided by manufacturers, such as AMP (average manufacturer price) and the lowest price available from the manufacturer during the rebate period to any entity in the United States in any pricing structure in the same quarter for which the AMP is computed (“Best Price”). The states share the rebates with the U.S. federal government. The rebate amount for most brand name drugs is the greater of 23.1% of the AMP per unit or the difference between the AMP and Best Price per unit as adjusted by the U.S. Consumer Price Index for All Urban Consumers (“CPI-U”), subject to certain exceptions. For example, the rebate amount for certain clotting factors such as Factor VIII and Factor IX is the greater of 17.1% of the AMP per unit or the difference between the AMP and the Best Price per unit as adjusted by the CPI-U, and the rebate amount for non-innovator multiple source (generic) drugs is equal to a minimum of 13.0% of AMP.
The availability of federal funds to pay for our products under Medicaid requires that we extend discounts under the 340B Program. The 340B Program extends prescription drug discounts to certain entities, including a variety of community health clinics and certain other entities that receive governmental health care grants, as well as hospitals that serve a disproportionate share of low income individuals, certain cancer centers, children’s hospitals, critical access hospitals and rural referral centers. The 340B Program prescribes a pricing methodology based on a PHS Act ceiling price that generally cannot be greater than the AMP less the unit rebate amount established under the Medicaid drug rebate program. We have entered into a PPA with the government whereby we participate in the 340B Program by charging eligible entities no more than the PHS Act ceiling price for drugs intended for outpatient use. The HRSA (Health Resources & Services Administration) of the HHS, the federal agency overseeing the 340B Program, continually issues evolving requirements with respect to the 340B Program, which creates uncertainty. For example, in February 2026, HRSA officially withdrew its 340B Rebate Model Pilot Program and subsequently issued a request for information seeking comments on launching a new 340B Program rebate model.
Also as a condition for Medicaid reimbursement, we make our products available for purchase by authorized government users of the Federal Supply Schedule (“FSS”) pursuant to such users’ FSS contracts with the Department of Veterans Affairs. These transactions involve establishing a FSS price in negotiation with the Department of Veterans Affairs. Companies are also required to offer discounted drug pricing to four federal agencies — the Department of Veterans Affairs, the Department of Defense, the Coast Guard and the PHS (including the Indian Health Service) — for federal funding to be made available for reimbursement of products under the Medicaid program. Sales to those four federal agencies must utilize a ceiling price methodology that generally requires drug prices to be at least 24.0% below the non-federal AMP for the prior fiscal year.
Medicare and the 340B Program.
The primary Medicare programs that may affect reimbursement for the Grifols Group are Medicare Part B, which covers physician services and outpatient care, and Medicare Part D, which provides a voluntary outpatient prescription drug benefit.
Medicare Part B reimburses providers for certain covered drugs and biologicals furnished in the outpatient setting, such as physician offices and hospital outpatient settings, generally at a rate of average sales price (“ASP”) + 6%. Starting January 1, 2018 a CMS rule reduced Medicare Part B reimbursement for 340B hospital outpatient drugs to a rate of ASP - 22.5%. Such reduction was ruled unlawful by the U.S. Supreme Court on June 15, 2022, causing CMS to reinstate the general ASP + 6% rate retroactively to January 1, 2018. Following this ruling, CMS issued a new rule on November 8, 2023 determining that affected hospitals will receive a one-time lump-sum amount plus a budget-neutrality offset going forward, which together equal the approximate payment they would have received if the 2018-2022 340B Program payment policy had never existed. The 340B Program remains subject to legal challenges involving litigation that may result in program changes, which creates uncertainty. We believe that we meet the requirements of the 340B Program and are continuing to review and monitor these and other developments affecting the 340B Program. In addition, under the Bipartisan Budget Act of 2013 and subsequent measures, Medicare is subject to a 2% reduction in federal spending, or “sequestration,” including drugs reimbursed under Medicare, for federal fiscal years 2013 through 2032. The full ramifications of this sequestration for Medicare reimbursement remain uncertain, as further Congressional action may reduce, eliminate or otherwise change this payment reduction.
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Medicare Part D coverage is administered through private insurers that contract with CMS. To obtain payments under this program, which covers certain of our products, we are required to negotiate prices with private insurers operating pursuant to federal program guidance, and these prices may be lower than we might otherwise obtain. In addition, the Medicare Part D Program had included a coverage gap feature, where once beneficiaries had expended certain amounts for drugs payable under Medicare Part D, Medicare Part D benefits were decreased for a period until certain levels of out-of-pocket spending were incurred by such beneficiaries. Pursuant to this coverage gap, drug manufacturers were required to provide a 70% discount (the “Coverage Gap Discount”) for certain drugs falling within a beneficiary’s coverage gap. However, as of January 1, 2025, under the federal Inflation Reduction Act of 2022, CMS eliminated the coverage gap design and Coverage Gap Discount, and implemented a “Manufacturer Discount Program” under which, after beneficiaries meet their Medicare Part D deductible, drug manufacturers generally must provide discounts of 10% on applicable drugs during an initial coverage phase and 20% during a catastrophic coverage phase. Because this new design is expected to decrease Medicare beneficiaries’ out-of-pocket costs, manufacturers’ share of those costs may increase. Consequently, our net revenue, beginning in 2025, may be adversely affected.
Additionally, the Inflation Reduction Act of 2022 provides Medicare, for the first time, with the ability to negotiate drug prices directly with drug manufacturers to determine the price Medicare will pay for certain drugs covered under Medicare Part D (effective as of 2026) and Medicare Part B (effective as of 2028). Certain drugs are excluded from the negotiation process, such as drugs with an orphan designation as their only FDA-approved indication and certain plasma-derived drugs. To the extent our drugs fall within any of the aforementioned excluded categories, Medicare would not have the ability to negotiate our prices for those drugs. Manufacturers that fail to comply with program requirements may be subject to civil monetary penalties and excise taxes.
Also under the Inflation Reduction Act of 2022, if a manufacturer increases the prices generally for brand name prescription drugs and biologicals covered under Medicare Part B or certain drugs and biologicals covered under Medicare Part D, in each case at a higher rate than the applicable inflation rate for such products, then such manufacturer will be required to pay rebates to Medicare. If our products are used by Medicare beneficiaries, we will be required to pay rebates to Medicare or potentially face fines representing the difference between the actual and the inflated prices. And, beginning in 2025, this law modifies a manufacturer’s liability relating to Medicare’s spending above a beneficiary’s out-of-pocket cap. In a December 13, 2023 guidance document, CMS generally outlined its calculation methodologies and processes, including certain adjustments (such as in the event of drug shortages, with, for example, certain greater reductions provided for plasma-derived products). CMS issued final rulemaking for the Medicare Prescription Drug Inflation Rebate Program on November 1, 2024, including to codify these programs. Beginning in 2025, CMS issued the first round of invoices to drug manufacturers for these rebates, including for years 2022, 2023 and 2024. Manufacturers’ failure to timely pay a rebate amount due may result in the imposition of civil monetary penalties. We are continuing to review and monitor these new Inflation Reduction Act programs under Medicare, which create uncertainty and may adversely affect our business.
Other Relevant Regulations.
The ACA imposes an annual fee on certain manufacturers and importers of branded prescription drugs and biologics in general if the entity has aggregated branded prescription drug and biologic sales of over $5 million to specified United States government health programs such as the Department of Veteran Affairs, or pursuant to coverage under such specified government health programs, such as Medicare Part B, Medicare Part D and Medicaid. The fee to each covered entity generally is calculated as an allocated portion of an aggregate amount of branded sales attributed to all covered entities, which aggregate amount is subject to change. Since 2019, the aggregate annual fee amount has been $2.8 billion. In addition, the Prescription Drug User Fee Act (“PDUFA”) sets forth user fees that pharmaceutical and biological companies pay to the FDA for certain applications for approvals of drugs and biologicals, licensing of certain biological products, and certain prescription drug program fees assessed annually for eligible products. The fees under PDUFA cover a substantial portion of the FDA’s operating budget, and the measure also addresses aspects of the regulatory approval process, such as timing and procedures. The PDUFA is subject to reauthorization by Congress every five years and, in September 2022, the FDA User Fee Reauthorization Act of 2022 was signed into law, reauthorizing the PDUFA for fiscal years 2023 through 2027.
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Federal, state and local governments in the United States have enacted and continue to consider additional legislation to limit the growth of healthcare costs, including the costs of prescription drugs. In May 2025, the United States government issued an executive order directing the HHS to facilitate direct-to-consumer purchasing programs for prescription drug manufacturers that sell their products to American patients at the most-favored-nation price and to communicate most-favored-nation price targets to manufacturers and propose a rulemaking plan to impose most-favored-nation pricing if “significant progress” is not made towards achieving such pricing. For example, in May 2025, the United States government issued an executive order aiming to implement “most-favored-nation” pricing tying U.S. prescription drug prices with prices in selected comparably developed nations. In July 2025, several pharmaceutical companies received letters from the United States government seeking commitments to advance such “most-favored-nation” drug pricing goals. In addition, CMS’s proposed Global Benchmark for Efficient Drug Pricing (GLOBE) and Guarding U.S. Medicare Against Rising Drug Costs (GUARD) models would assess a rebate for certain drugs payable under Medicare Part B and Part D.
An increasing number of states in the United States have also proposed or passed legislation that seeks to directly or indirectly regulate pharmaceutical drug pricing, such as by requiring drug manufacturers to publicly report pricing information or to place a maximum price ceiling on pharmaceutical products purchased by state agencies. For example, in June 2024, New York implemented a prescription drug price transparency law that requires prescription drug manufacturers to provide advance notice and explanation for certain drug price increases that exceed a specified threshold. Laws of this type may cause us to experience additional pricing pressures on our affected products, and could adversely affect our business.
Furthermore, the marketability of any products for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement. Existing and future legislation could limit payments for our existing products or for drug candidates that we are developing, including possibly permitting the federal government to negotiate prices directly with manufacturers. This increasing emphasis on managed care in the United States has increased and will continue to increase the pressure on pharmaceutical pricing. For a discussion of certain risks related to reimbursement and pricing, see Item 3 of this Part I, “Key Information—D. Risk Factors—Risks Relating to the Healthcare Industry—United States Healthcare Reform may adversely affect our business.”
European Union Pharmaceutical Pricing and Reimbursement
Our operations in the E.U. are subject to strong regulations affecting the pricing of and market access to our products. Ministries of Health (MoH) across E.U. Member States oversee the price of pharmaceutical products through cost containment measures applied to national healthcare systems. As such, over the last decades, governments in the E.U. Member States have been introducing severe Health Economics and Outcomes Research (“HEOR”) criteria, a multidisciplinary field that studies the economic, clinical and societal impact of healthcare interventions, to limit increases in costs, particularly with respect to innovative prescription drugs.
HEOR criteria are implemented by Health Technology Assessment (HTA) organizations on a national basis, a process that evaluates the effects and impacts of health technologies and interventions to inform policy and decision-making in healthcare, and include cost-effectiveness analysis, budget impact models and additional clinical benefits versus existing marketed (or in development) drugs used as benchmarks for comparison, with the objective to appraise the value proposition and determine the price and reimbursement levels. E.U. Member States also seek to limit healthcare expenditure by passing legislation and health policies to impose mandatory rebates for pharmaceutical products and financial claw-backs to the pharmaceutical industry, as well as International Reference Pricing (“IRP”), a cost-control mechanism where a country benchmarks its drug prices to those in other countries either applying the lowest or average calculation among a basket of selected countries. We expect that E.U. Member States will continue to pursue actions to reduce healthcare expenditures in the upcoming years.
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Pricing and Reimbursement in Other Countries
Many countries around the world have been taking steps to control healthcare costs, particularly as they relate to prescription drugs. For example, in Asia, pharmaceutical pricing and reimbursement regulations vary significantly across countries, reflecting diverse healthcare infrastructures and economic conditions. In China, the government has implemented several reforms to control drug prices and improve access. The National Healthcare Security Administration (“NHSA”) oversees the centralized procurement of drugs, which has led to significant price reductions for many medications. In India, the National Pharmaceutical Pricing Authority (“NPPA”) regulates drug prices to ensure medicines remain affordable. The NPPA enforces the “Drug Price Control Orders,” which set ceiling prices for essential medicines based on factors like production costs and market competition.
Australia’s Medical Services Advisory Committee (“MSAC”) also uses a HTA framework to assess applications for public funding, including: (i) a PICO (population, intervention, comparator, outcome) to describe the population, intervention, comparator and outcome for the health service or technology; (ii) an assessment report (developed by the applicant or an HTA group) to review the clinical evidence and conduct HEOR evaluations of the service or technology; (iii) an independent critique (commentary) of applicant-developed assessment reports; and (iv) consultation input from stakeholders. Recently, patient groups have also been invited to provide feedback in the frame of a more patient-centric approach.
Japan’s healthcare fees are administered on a fee-for-service (“FFS”) basis, in which the provider calculates reimbursements based on the number of points allocated for each item and is then reimbursed for the service or product based upon the number of points. The Japanese payment system (diagnosis procedure combination, or “DPC”) is similar to the diagnosis related groups (“DRG”) prospective payment system (“PPS”) found in the U.S. and in some European countries. Although DPC has not resulted in lower costs due to its unique mix of PPS with FFS, there is strong opposition against further integration of PPS.
In Latin America, countries employ diverse strategies to regulate pharmaceutical pricing and reimbursement, often combining direct price controls with reference pricing systems. In Brazil, the Chamber for Regulation of the Medicines Market (“CMED”) sets maximum prices for medications considering factors such as production costs and economic evaluations. In Argentina, the government also implements direct price controls, negotiating prices with pharmaceutical companies to maintain affordability. These are examples of countries utilizing reference pricing systems, benchmarking drug prices against those in other nations to ensure competitiveness and prevent excessive pricing, a practice that is used in many jurisdictions globally.
In Canada, pharmaceutical pricing and reimbursement are governed by a combination of federal oversight and provincial/territorial collaboration. The Patented Medicine Prices Review Board (“PMPRB”) is a federal agency responsible for ensuring that prices of patented medicines are not excessive. It establishes maximum allowable prices by reviewing factors such as the prices of similar drugs in Canada (Internal Reference Pricing rule) and internationally (International Reference Pricing). The pan-Canadian Pharmaceutical Alliance (“pCPA”) negotiates drug prices on behalf of public drug plans across provinces and territories, aiming to achieve consistent and lower drug costs. Furthermore, the Canadian Agency for Drugs and Technologies in Health (“CADTH”), now renamed Health Technology Review, conducts health technology assessments, including clinical and economic evaluations, to inform reimbursement decisions for most public drug plans in Anglophone Canada, whereas in Francophone Canada the responsible body for HTA of pharmaceutical products is Institut National d’Excellence en Santé et en Services Socieux (“INESSS”).
Item 4.A.UNRESOLVED STAFF COMMENTS
None.