Apples and Oranges?

Biosimilars: The Sophistication of Generics

Biologics—therapeutics derived from living cells—remain complex to produce…and reproduce.  Due to the molecular and structural complexity of large (relatively speaking) biologic proteins, a generic biologic equivalent can only be made “similar,” not identical, to the original, hence the industry term “biosimilar”—this is unlike small-molecule drugs, whose chemical structures can be completely characterized.

With all of the technology at our disposal, why is this the case? Alas, while companies striving to manufacture a biosimilar have access to the commercial biologic drug they wish to replicate, they do not have access to the same biologic cell line used by the innovator or direct knowledge of the manufacturing process nuances involved in bringing the biologic drug to market in the first place. This lack of “inside” information and inherent biologic complexity accounts to a large extent for the tremendous time and effort currently associated with manufacturing a biosimilar.

But let’s make no mistake, biosimilars are coming, as evidenced by companies like technology giant Samsung with little or no experience in pharma/biologic development. Samsung is currently devoting the equivalent of 25% of the Korean GDP toward a commitment to healthcare—including. and in particular, biosimilars. Wow!

Layer on that,the innovators’ competitive response to biosimilars looming on the horizon. In the case of biologics, the competitive race is on within the halls of large and small pharma alike to discover new ways to advance their therapeutic platforms while driving down the costs of production, sales, and distribution.

And the reason all of this is important to pharma, clinicians, patients, and the healthcare system as a whole? Safety, efficacy, and outcomes—key factors that payers and HCPs consider when selecting and reimbursing for a drug. Despite biosimilars having the same “biologic” protein structure as the innovator, small differences resulting from the heterogeneity of biological processes and environmental conditions used (ie, formulation, light, temperature, moisture, packaging materials, container closure systems, and delivery device materials) affect safety, purity and potency—important and key differences that can negatively impact product performance. Additionally, process-related impurities may increase the likelihood and/or severity of an adverse immune response to a protein product.

Contrast this competitive biosimilar hurdle to market entry with that of the public health objectives promoted by the Hatch-Waxman Act, which “waxed” the new drug application pathway for generics over three decades ago, eliminating the need for preclinical and clinical studies for “bioequivalent” drugs, resulting in a tsunami of generics, as the process was straightforward (and state, federal and private payers looked to reduce drug costs). With the immense and increased pressure to reduce the cost of healthcare, how long before the FDA will be able to approve biosimilars (apples) as a cost-saving alternative to reference biologics with the same relative ease associated with licensing a generic (oranges)?

With several biosimilar drugs already licensed in Europe, there are several companies working feverously to submit biosimilar applications under the Health Care Reform Act in the US—navigating an abbreviated approval for which the strength of evidence required for biosimilar registration approval is currently unclear. While it may be a bit longer before a biosimilar is approved in the US, it is particularly crucial, given some of the high-profile large- and small-molecule drug shortages of late, that an agency have an integrated team of scientists, marketers, and reimbursement experts…with a deep and thorough understanding of biologics and the complexities of these potentially life-extending drugs.

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