More difficult than it appears
Although copying an innovator's product may appear easier than developing a novel therapeutic, the difficulties of engineering
one product to match an existing product cannot be underestimated. Rudd points out that it is considerably more difficult
to produce a biosimilar product than simply inserting a DNA construct into a cell line and expecting that the innovator product
will be faithfully reproduced. For biologics, the process is intimately connected with the disposition of the final product,
but the biosimilar manufacturer does not have knowledge of the processes used by the innovator.
Xu points out, however, that manufacturers have better understanding of and more control over processes than they did 20 years
ago. Implementation of process analytical technology and use of quality-by-design principles in setting up the process will
greatly facilitate production of a consistent product. For any biosimilar, he recommends engaging the analytical team early
in the process so that the developer can determine how process changes will affect critical quality attributes. In some instances,
there may be correlations between process parameters and protein structural attributes, allowing the protein attributes to
be fine-tuned.
EMA is well ahead of the US in biosimilars development, having approved its first biosimilar in 2006, and with 14 biosimilar
products now on the market. EMA has already released guidance documents that are specific for different product types, including
epoetins, filgastrims, and a draft guidance for monoclonal antibodies (8–10). Such product-specific specifications will doubtless
be released by FDA in time, and will help better define what a fingerprint looks like.
References
1. FDA, Draft Guidance, Scientific Considerations in Demonstrating Bioimilarity to a Reference Product (Rockville, MD, February 2012).
2. FDA, Draft Guidance, Quality Considerations in Demonstrating Bioimilarity to a Reference Product (Rockville, MD, February 2012).
3. FDA, Guidance for Industry on Biosimilars: Q & As Regarding Implementation of the BPCI Act of 2009 (Rockville, MD, February 2012).
4. FDA, Generic Enoxaparin Questions and Answers,
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm220037.htm, accessed May 2012.
5. ICH, Q6B Specifications: Test Procedures and Acceptance Criteria for. Biotechnological/Biological Products (1999).
6. P. Hossler, SF Khattak, and ZJ Li, Glycobiol.
19 (9), 936–949 (2009).
7. D. Fernandes, BioPharm Intl. 24 (1) (2011).
8. EMA, Guidance on Similar Medicinal Products Containing Recombinant Erythropoietins (Sept. 2010).
9 . EMA, Guidance on Biosimilar Medicinal Products Containing Recombinant Granulocyte-Colony Stimulating Factor (June 2006).
10. EMA, Draft Guideline, Similar Biological Medicinal Products Containing Monoclonal Antibodies (Sept. 2010).
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