How similar is your Biosimilar?
by Jon S. Kauffman, Ph.D., director, Biopharmaceutical Services
The Food and Drug Administration (FDA) defines a generic drug as “a drug product which is comparable to a reference (brand) listed drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use.” The Hatch-Waxman Act of 1984 paved the way for facilitating an abbreviated process in the United States for approval of generic versions of small molecule drugs. Today almost three-quarters of all small molecule drugs sold are generic.
However, an increasing number of drugs on the market are considered biologics or biopharmaceutical products, which are made from living organisms. Biopharmaceutical products include monoclonal antibodies (mAbs), therapeutic proteins, vaccines, antibody drug conjugates (ADCs) and nucleic acids. To address this class of products that falls outside the Hatch- Waxman Act, the Patient Protection and Affordable Care Act (PPAC Act), signed into law by President Obama on March 23, 2010, creates an abbreviated approval pathway for biological products that are demonstrated to be “highly similar” (biosimilar) to an FDA-approved biological product. The FDA followed up on February 9, 2012, by issuing three draft guidance documents on biosimilar product development to assist industry. This is quite relevant since in the 6 year period between now and 2017, patents of some of the top-selling biologics, including Enbrel, Rituxan/MabThera, Herceptin, Neulasta and Lantus face patent expiration.
The European Union (EU) led the way with establishing a legal framework for approving biosimilars in 2003 and guidelines for an abbreviated registration process soon followed. The European Medicines Agency (EMA) has approved 14 biosimilars to date beginning with Omnitrope in 2006. Therefore, the FDA is able to look back at both the successes and lessons learned from the European approach – and central to this approach is the concept of comparability. This approach was first used when sponsors needed to convince FDA that changes in a manufacturing resulted in a “comparable” product. The EMA then adapted this approach to biosimilars where the new product (biosimilar) is shown to be comparable to an approved (reference) product from a different sponsor.
A major component of comparability studies performed during process development is full analytical characterization of the product and process impurities. Eurofins Lancaster Laboratories has the experience and wide range of tools, including mass spectrometry (MS), size-exclusion chromatography (SEC), capillary electrophoresis (CE), circular dichroism (CD), etc. to help sponsors and contract manufacturers with this task.