Immunogenicity and Adverse Reactions to Biosimilar Erythropoietin Products in Thailand: The Significance of Science and Quality Driven Process for Approval
The immunogenicity of recombinant human erythropoietin (r-HuEpo) by subcutaneous exposure has been well described. This adverse immunological effect causes anti-r-HuEpo-associated pure red cell aplasia (PRCA). There have been increasing cases of anti-r-HuEpo-associated PRCA after subcutaneous exposure in Thailand. The casual mechanism of this disease may relate to HLA immunogenic, protein aggregation, stability during storage and handling of drug products, formulation and drug product quality.
The r-HuEpos have been licensed for treatment of renal anemia in Thailand include innovator products and more than 20 biosimilar products. Lack of a scientific product characterization and quality driven process to approve such biosimilars may lead to different immunogenicity and safety profiles. The Prospective Immunogenicity Surveillance Registry of r-HuEpo with Subcutaneous Exposure in Thailand estimated the incidence of anti-r-HuEpo associated PRCA among subjects who had subcutaneous exposure to any r-HuEpo product currently available in Thailand, addressed the risk of anti-r-HuEpo-associated PRCA, and the association of product qualities towards adverse immunogenicity.
The experiences of biosimilar r-HuEpo in Thailand and anti-rHuEpo associated PRCA in Thailand illustrated the need to evaluate biosimilar product on a case-by case basis. Considering patients ‘safety as the first priority, the approval process for biosimilar drug licensing should be designed to assess quality, characterization and impurity profile and comprehensive evaluation of the non-clinical and clinical aspects. Pharmacovigilance could be the final step to narrow the gap between quality and safety and can be assessed in totality with cost-effectiveness and patient benefit that such drug offer.
KeywordsImmunogenicity of recombinant human erythropoietin (r-HuEpo) Renal anemia Pure red cell aplasia (PRCA)
- Dorey E. How the biologics landscape is evolving. Clin Pharm. 2014;6(9):1–6.Google Scholar
- Erslev AJ. Pure red cell aplasia. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, editors. Williams hematology. New York: McGraw-Hill; 1995. p. 448.Google Scholar
- FDA Briefing Document. Onchologic Drugs Advisory Committee Meeting, May 25, 2017, BLA 125545 “Epoetin Hospira”, a proposed biosimilar to Epogen/Procrit 9epoetin alfa). Applicant: Hospira Inc., Pfizer Company.Google Scholar
- Fijal B, Ricci D, Vercammen E, Palmer PA, Fotiou F, Fife D, Lindholm A, Broderick E, Francke S, Wu X, Colaianne J, Cohen N. Case-control study of the association between select HLA genes and anti-erythropoietin antibody-positive pure red-cell aplasia. Pharmacogenomics. 2008;9(2):157–67.CrossRefGoogle Scholar
- Fujimori K, Lee H, Phillips J, Nashed-Samuel Y. Development of an inductively coupled plasma mass spectrometry method for quantification of extracted tungsten from glass prefilled syringes used as a primary packaging for pharmaceutical and therapeutic protein products. PDA J Pharm Sci Technol. 2013;67(6):670–9.CrossRefGoogle Scholar
- Macdougall IC, Casadevall N, Locatelli F, Combe C, London GM, Di Paolo S, Kribben A, Fliser D, Messner H, McNeil J, Stevens P, Santoro A, De Francisco ALM, Percheson P, Potamianou A, Foucher A, Fife D, Mérit V, Vercammen E, PRIMS Study Group. Incidence of erythropoietin antibody-mediated pure red cell aplasia: the prospective immunogenicity surveillance registry (PRIMS). Nephrol Dial Transplant. 2015;30(3):451–60.CrossRefGoogle Scholar
- Praditpornsilpa K, Buranasot S, Bhokaisuwan N, Avihingsanon Y, Pisitkul T, Kansanabuch T, Eiam-Ong S, Chusil S, Intarakumtornchai T, Tungsanga K. Recovery from anti-recombinant-human-erythropoietin associated pure red cell aplasia in end-stage renal disease patients after renal transplantation. Nephrol Dial Transplant. 2005;20(3):626–30.CrossRefGoogle Scholar
- Praditpornsilpa K, Kupatawintu P, Mongkonsritagoon W, Supasyndh O, Jootar S, Intarakumthornchai T, Pongskul C, Prasithsirikul W, Achavanuntakul B, Ruangkarnchanasetr P, Laohavinij S, Eiam-Ong S. The association of anti-r-HuEpo-associated pure red cell aplasia with HLA-DRB1∗09-DQB1∗0309. Nephrol Dial Transplant. 2009;24:1545–9.CrossRefGoogle Scholar
- Praditpornsilpa K, Tiranathanagul K, Kupatawintu P, Jootar S, Intragumtornchai T, Tungsanga K, Teerapornlertratt T, Lumlertkul D, Townamchai N, Susantitaphong P, Katavetin P, Kanjanabuch T, Avihingsanon Y, Eiam-Ong S. Biosimilar recombinant human erythropoietin induces the production of neutralizing antibodies. Kidney Int. 2011;80(1):88–92.CrossRefGoogle Scholar