Drug Product Considerations for Biosimilars
Biosimilars are increasingly important for the expansion of access to life-saving biologics and to reduce the cost of prescription medicine. The design of the drug product for a biosimilar is of utmost importance, as it directly relates to patient efficacy, safety and product quality, even as it defines the similarity of the product to the reference innovator product. There are various components of a drug product: the formulation, the container closure system and/or device, and the drug product manufacturing process that must be considered during any biologic parenteral drug product development. The biosimilar drug product development strategy has to take additional multiple factors into consideration including matching the reference product presentation, intellectual property and the current state of the art in science and technology. This chapter reviews these factors in detail using case-studies from currently approved biosimilars.
KeywordsProduct Composition Formulation Dosage form Device Manufacturing process Container closure
- Agalloco J. Open letter in reponse to MHRA blog on Vapour Hydrogen Peroxide fragility. 2018. https://www.linkedin.com/pulse/open-letter-response-mhra-blog-vapour-hydrogen-jim-agalloco/. Accessed June 2018.
- Carpenter JF, Randolph TW, Jiskoot W, Crommelin DJ, Middaugh CR, Winter G, Fan YX, Kirshner S, Verthelyi D, Kozlowski S, Clouse KA, Swann PG, Rosenberg A, Cherney B. Overlooking subvisible particles in therapeutic protein products: gaps that may compromise product quality. J Pharm Sci. 2009;98(4):1201–5.PubMedPubMedCentralGoogle Scholar
- Celltrion. CT-P13 (infliximab biosimilar). Briefing Document for the Arthritis Advisory Committee. 2016. https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/arthritisadvisorycommittee/ucm484860.pdf. Accessed June 2018.
- Dimitrova MN, Bee JS, Lu L, Fernandez JF. Development of prefilled syringe combination products for biologics. In: Warne NW, Mahler H-C, editors. Challenges in protein product development. AAPS/Springer; 2018. p. 203–24.Google Scholar
- European Agency for Safety and Health at Work. Directive 2010/32/EU - Prevention from sharp injuries in the hospital and healthcare sector. 2010. https://osha.europa.eu/en/legislation/directives/council-directive-2010-32-eu-prevention-from-sharp-injuries-in-the-hospital-and-healthcare-sector. Accessed June 2018.
- Hopkins A. VHP (vapour hydrogen peroxide) fragility. 2018. https://mhrainspectorate.blog.gov.uk/2018/04/20/vhp-vapour-hydrogen-peroxide-fragility/. Accessed June 2018.
- Jahn M. Leachables and extractables: from regulatory expectations to laboratory assessment. In: Warne NW, Mahler HC, editors. Challenges in protein product development. AAPS/Springer; 2018. p. 337–51.Google Scholar
- Kolhe P, Goswami S. Bulk protein solution: freeze-thaw process, storage and shipping considerations. In: Warne NW, Mahler HC, editors. Challenges in protein product development. AAPS/Springer; 2018. p. 313–36.Google Scholar
- Lambert P. Dispensing biopharmaceuticals with piston and peristaltic pumps. PharmTech; 2008.Google Scholar
- Metcalfe JW. Microbiological quality of drug products after penetration of the container system for dose preparation prior to patient administration. Am Pharm Rev. 2009;12(1, Jan/Feb):84–9.Google Scholar
- Rubic-Schneider T, Kuwana M, Christen B, Assenmacher M, Hainzl O, Zimmermann F, Fischer R, Koppenburg V, Chibout SD, Wright TM, Seidl A, Kammuller M. T-cell assays confirm immunogenicity of tungsten-induced erythropoietin aggregates associated with pure red cell aplasia. Blood Adv. 2017;1(6):367–79.PubMedPubMedCentralGoogle Scholar
- Sandoz. FDA Oncologic Drugs Advisory Committee Meeting. Zarxio (filgrastim). Advisory Committee Briefing Materials. 2015. https://wayback.archive-it.org/7993/20170405222933/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM428782.pdf. Accessed June 2018.
- Scott Morton F, Stern AD, Stern S. The impact of entry of biosimilars: evidence from Europe; Harvard Business School Working Paper. No. 16-141: June 2016. Revised April 2018. https://www.hbs.edu/faculty/Pages/item.aspx?num=51309. Accessed June 2018
- Singh SK. Storage considerations as part of the formulation development program for biologics. Am Pharm Rev. 2007;10(2, Mar/Apr):26–33.Google Scholar
- Singh SK. Sucrose and trehalose in therapeutic protein formulations. In: Warne NW, Mahler HC, editors. Challenges in protein product development. AAPS/Springer; 2018. p. 63–95.Google Scholar
- Singh SK, Mahler H-C. Current trends in control and monitoring of subvisible particulate matter in biotherapeutics. BioPharma Asia. 2018;7(1, Jan/Feb):30–7.Google Scholar
- Singh SK, Nema S. Freezing and thawing of protein solutions. In: Jameel F, Hershenson S, editors. Formulation and process development strategies for manufacturing biopharmaceuticals. Hoboken: Wiley; 2010. p. 625–75.Google Scholar
- Singh SK, Afonina N, Awwad M, Bechtold-Peters K, Blue JT, Chou D, Cromwell M, Krause HJ, Mahler HC, Meyer BK, Narhi L, Nesta DP, Spitznagel T. An industry perspective on the monitoring of subvisible particles as a quality attribute for protein therapeutics. J Pharm Sci. 2010;99(8):3302–21.PubMedGoogle Scholar
- Thakrar K, Bodalia P, Grosso A. Assessing the efficacy and safety of omnitrope. Br J Clin Pharm. 2010;2:298–301.Google Scholar
- U.S. Department of Labor. Occupational exposure to bloodborne pathogens: Needlestick and other sharps injuries. Final rule. OSHA Federal Register Final Rules 2011;66:5317--5325. https://www.osha.gov/SLTC/bloodbornepathogens/recognition.html. Accessed June 2018.
- U.S. FDA. FDA Briefing Document. Oncologic Drugs Advisory Committee Meeting. BLA 125553. EP2006, a proposed biosimilar to Neupogen (filgrastim). Sandoz Inc.; 2015a. http://patentdocs.typepad.com/files/briefing-document.pdf. Accessed June 2018.
- U.S. FDA. Scientific Considerations in Demonstrating Biosimilarity to Reference Product. Guidance for Industry. 2015b. https://www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Accessed June 2018.
- U.S. FDA. CDER. Application Number 125533Orig1s000. Other Review(s). Zarxio (filgrastim-sndz). 2015c. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/125553Orig1s000OtherR.pdf. Accessed June 2018.
- U.S. FDA. BLA 761024. Approval Letter Amjevita (adalimumab-otto). 2016a. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/761024Orig1s000ltr.pdf. Accessed June 2018.
- U.S. FDA. BLA 125544. Approval Letter Inflectra (infliximab-dyyb). 2016b. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/125544Orig1s000ltr.pdf. Accessed June 2018.
- U.S. FDA. BLA 761042. Approval Letter Erelzi (etanercept-szzs). 2016c. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/761042Orig1s000ltr.pdf. Accessed June 2018.
- U.S. FDA. CDER Application Number 761024Orig1s000. Chemistry Reviews ABP501 (adalimumab-otto). 2016d. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761024Orig1s000ChemR.pdf. Accessed June 2018.
- U.S. FDA. CDER Application Number 125544Orig1s000. Chemistry Reviews CT-P13 (infliximab-dyyb). 2016e. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/125544Orig1s000ChemR.pdf. Accessed June 2018.
- U.S. FDA. CDER. Application Number 761042Orig1s000. Other Reviews. Erelzi (etanercept-szzs). 2016f. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761042Orig1s000OtherR.pdf. Accessed June 2018.
- U.S. FDA. CDER. Application Number 761024Orig1s000. Other Reviews. ABP501 (adalimumab-otto). 2016g. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761024Orig1s000OtherR.pdf. Accessed June 2018.
- U.S. FDA. Considerations in demonstrating interchangeability with a reference product. Guidance for Industry. Draft Guidance. 2017a. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537135.pdf. Accessed June 2018.
- U.S. FDA. Guidance for Industry and FDA Staff: Current Good Manufacturing Practice Requirements for Combination Products. 2017b. https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm429304.pdf. Accessed June 2018.
- U.S. FDA. FDA briefing document. Oncologic Drugs Advisory Committee Meeting. BLA 761074. MYL-1401O, a proposed biosimilar to Herceptin (trastuzumab). Mylan Pharmaceuticals. 2017c. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM566369.pdf. Accessed June 2018.
- U.S. FDA. FDA Briefing Document. Oncologics Drug Avisory Commitee Meeting. BLA 125545. “Epoein Hospira”, a proposed biosimilar to Epogen/Procrit (epoetin alfa). Hospira Inc.; 2017d. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM559967.pdf. Accessed June 2018.
- U.S. FDA. BLA 760158. Approval Letter Cyltezo (adalimumab-adbm). 2017e. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761058Orig1s000ltr.pdf. Accessed June 2018.
- U.S. FDA. BLA 761054. Approval Letter Renflixis (infliximab-abda). 2017f. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761054Orig1s000ltr.pdf. Accessed June 2018.
- U.S. FDA. BLA 761072. Approval Letter Ixifi (infliximab-qbtx). 2017g. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761072Orig1s000ltr.pdf. Accessed June 2018.
- U.S. FDA. Search orphan drug designations and approvals. 2018a. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/. Accessed June 2018.
- U.S. FDA. FDA withdraws draft guidance for industry: Statistical approaches to evaluate analytical similarity. 2018b. https://www.fda.gov/Drugs/DrugSafety/ucm611398.htm. Accessed July 2018.