A new guidance document released this week by the US Food and Drug Administration (FDA) aims to clarify the interaction of the 2012 Biologics Price Competition and Innovation Act (BPCI) and the 1983 Orphan Drug Act with respect to monoclonal antibody products.
FDA's orphan drug regulations are intended to create market-based incentives for manufacturers of products for populations with rare diseases. Per the Orphan Drug Act, a rare disease is defined as any disease affecting fewer than 200,000 individuals in the US in any given year.
The act allows FDA to give the products approved to treat the orphan conditions special marketing protections (7 years of market exclusivity), tax credits to offset some of the costs of development, faster regulatory reviews and additional assistance from FDA reviewers during the development and review process.
Meanwhile, the BPCI was passed in 2012 under the Patient Protection and Affordable Care Act (PPACA), better known as "Obamacare," and is intended to establish a pathway for the approval of "biosimilar" products which are similar to, but not the same as, already-approved biological products. The "biosimilars pathway" being established by FDA should allow for companies to bring near-copies of biologics to market more quickly and cheaply, thereby increasing competition and lowering the price of equivalent therapies for consumers.
In return for this expedited market access for biosimilars, biological products are granted 12 years of market-based exclusivity during which time FDA cannot approve a biosimilar application based on the same drug and therapeutic claims.
What does one (the Orphan Drug Act) have to do with the other (the BPCI)?
It all comes down to the structure of antibody molecules, FDA said in its guidance document, Interpreting Sameness of Monoclonal Antibody Products Under the Orphan Drug Regulations.
Under the BPCI, molecules would be "the same" if they contained "the same principal molecular structural features (but not necessarily all of the same structural features) and is intended for the same use as a previously approved drug." (21 CFR 316.3(b)(13)(ii))
In addition, the two molecules would only be considered "the same" if the only differences "were due to post-translational events or infidelity of translation or transcription or were minor differences in amino acid sequence."
The problem: FDA's existing definitions never touch on how to define "sameness" for antibody products.
The agency's new guidance does just that.
FDA goes on to define what "the same" means in terms of molecular structure of naked monoclonal antibody products, antibody conjugates, fusion protein products, and biospecific antibodies. Companies will need to compare their respective products' framework regions, constant regions and antibody fragments, depending on which types of proteins are involved.
The takeaway: If a company's product is "the same" as one approved earlier and given orphan drug designation, that company will have to wait until its 7 years of market-based exclusivity run out before it's eligible to file a biosimilar application (known as a 351(k)).
Interpreting Sameness of Monoclonal Antibody Products Under the Orphan Drug Regulations (FR)