BioRationality: How the FDA Can Bypass Congress to Change Biosimilar Guidance

In a position paper submitted to the FDA Commissioner at his request, I have detailed the changes that are needed in the Biologics Price Competition and Innovation Act (BPCIA) to enable faster entry of affordable biosimilars.

I believe the most creative proposal, based on legal analysis is how the FDA need not entertain any legislative changes or modifications to BPCIA to change all policies related to biosimilars. The Secretary of HHS is granted this authority, but it has been legally challenged in the past by stakeholders who oppose the expansion of biosimilars. In my comparative global analysis, I am teaching the FDA Commissioner how to create guidelines that will not be subject to legal challenges. Here are the changes I am proposing:

• Make clinical efficacy studies nonmandatory, leaving the onus of proving that they are not necessary on the filer. However, where it is obvious, prevent developers from conducting such studies to avoid human abuse.
• Remove the need for clinical pharmacology studies, pharmacokinetic, and pharmacodynamic if intravenous (IV) administration of the product is not required or where non-IV administration with instant absorption is possible.
• Analytical similarity testing is divided into 2 parts: the first is molecular similarity, which does not require multiple lots of reference products; the second is matching the release specification rather than conducting a side-by-side analytical similarity assessment. This will also allow the use of legacy limits that do not require comparison.
• Allow the US Pharmacopeia to create product release specifications (PRS) instead of a monograph and provide validated test methods, thereby eliminating the need to secure multiple lots of the reference product.
• Products with identical formulation, whether current or prior (due to intellectual property issues), should be required.
• No unmatched degradation product is allowed; it must be removed by chromatography—no scientific justification allowed.
• Post-translation attributes must match in identity and quantity within a 10% tolerance.
• No immunogenicity testing required.
• The prescribing information will be the same as the reference product information, modified as needed, without any changes to the formulation.
• All biosimilars should be interchangeable unless the prescribers suggest otherwise.
• Biosimilars will be allowed a Drug Master File to allow developers to secure drug substance just like it is done for the active pharmaceutical ingredient. However, the drug product qualification must be met with a complete dossier.
• The FDA is expected to take an active role in addressing double-patenting, following the recent withdrawal by the US Patent and Trademark Office.
• Injection of biosimilars will require point-of-use filtration to reduce the risk of aggregates causing immunogenicity.
• No consultation with stakeholders to avoid conflict of interest; only scientific opinions will be sought, and that too, not from organizations with an agenda.
• No consultation with associations of biosimilar developers, as these are based on non-scientific views. In my opinion, drug distribution and other issues, such as pharmacy benefit managers, are not related to the FDA agenda.
• 351(k) applications will be treated as fast-track, with a token applied for faster approval; the maximum limit of approval from the filing date is no more than 6 months.

All these changes can be brought by introducing guidelines, regardless of the details or requirements listed in the BPCIA. The correct language of these guidelines is also provided in the detailed paper I have submitted to the US FDA Commissioner. I anticipate meeting him soon.