Why Precise Manufacturing of Biological Medicines Matters

How biological medicines are manufactured directly affects their efficacy and safety as medications.

Biological medicines are typically derived from living organisms.1-3 They're made by genetically engineering living cells (also called the cell line)—and a high level of precision is required in the commercial manufacturing process to produce a consistent biological product each time.3-5 The protein produced by the cells will be influenced by individual cell characteristics, the growing environment and the nutrients provided during the manufacturing process.6 The entire process can take from several weeks to months to complete.7

Once the cell line is established, the manufacturing process may be divided into 3 phases: cell culture, recovery, and purification, fill, and finish.7

A Typical Biotechnology Manufacturing Process Frozen cell from unique cell line is thawed for beginning of cell growth process. Cell is placed in seed bioreactors to multiply. As the number of cells increases, they are transferred to larger seed bioreactors as needed. Grown cells are transferred from a seed bioreactor to a production bioreactor. Cells are harvested from the final production bioreactor through filtration or a centrifuge for cell separation. Depending on the cell type used, this process can involve homogenizers and centrifuges. Proteins produced by cells are then transferred to a collection tank for removal of any remaining impurities. Primary purification begins. Viral inactivation/microbial control. Chromatography. Ultrafiltration/difiltration process. Purified bulk filtration. Formulation, sterile filtration, fill, and finish. All therapeutic proteins must be extensively purified to remove impurities and contaminants, including versions of the product that are undesirable. Storage and transport. Administration (injection/IV)
Read a list of biologics questions answered by Dr. John Petricciani, M.D., an expert in biologic medicines.

Expert Opinion

with Dr. Petricciani

“A manufacturer's biological medicine is a unique creation and an identical copy cannot be made by other manufacturers.”

Review the Q&A on issues concerning biological medicines
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References
  1. Lee JF, Litten JB, Grampp G. Comparability and biosimilarity: considerations for the healthcare provider. Curr Med Res Opin. 2012;28(6):1053-1058.
  2. Schellekens H. Biosimilar therapeutics—what do we need to consider? NDT Plus. 2009;2(suppl 1):i27-i36.
  3. Zhang J. Mammalian cell culture for biopharmaceutical production. In: Baltz RH, Davies JE, Demain AL, eds. Manual of Industrial Microbiology and Biotechnology, Third Edition. Washington, DC: American Society of Microbiology; 2010:157-178.
  4. Sekhon BS, Saluja V. Biosimilars: an overview. Biosimilars. 2011;1(1):1-11.
  5. Wurm FM. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol. 2004;22(11):1393-1398.
  6. Palomares LA, Estrada-Mondaca S, Ramirez OT. Production of recombinant proteins: challenges and solutions. In: Balbas P, Lorence A, eds. Methods in Molecular Biology, Vol. 267: Recombinant Gene Expression: Reviews and Protocols, Second Edition. Totowa, NJ: Humana Press Inc.; 2004:15-51.
  7. Hora M. Manufacturing fundamentals for biopharmaceuticals. In: Jameel F, Hershenson S, eds. Formulation and Process Development Strategies for Manufacturing Biopharmaceuticals. Hoboken, NJ: John Wiley & Sons, Inc.; 2010:589-604.
  8. Walsh G. The drug manufacturing process. Biopharmaceuticals: Biochemistry and Biotechnology, Second Edition. Hoboken, NJ: John Wiley & Sons; 2003:93-187.
  9. Schmidt F-R. From gene to product: the advantage of integrative biotechnology. In: Gad SC, ed. Handbook of Pharmaceutical Biotechnology. Hoboken, NJ: John Wiley & Sons; 2007:1-52.
  10. Liu HF, Ma J, Winter C, Bayer R. Recovery and purification process development for monoclonal antibody production. mAbs. 2010;2(5):480-499.