FDA Releases Draft Biosimilars Guidance

The Food and Drug Administration has issued three guidance documents in draft on biosimilar therapeutics — functional equivalents of biologic therapies — that the agency says will soon be open for public comment. Guidance documents offer insights into the current thinking of FDA on key scientific and regulatory topics, and are not binding on the agency or public.

Biological products are therapies made from human or animal materials, rather than chemical processes used for most pharmaceuticals. Biologics, as they are called, include vaccines, blood and blood components, gene therapies, tissues, and proteins. Biosimilars are therapies very much like the original biologics, but may have small differences in clinically unimportant components, with little or no difference in safety or effectiveness.

The Patient Protection and Affordable Care (health reform) Act of 2010 has a provision in section 351(k) creating a shorter approval process for biologics that are shown to be highly similar or interchangeable with biologics already approved by FDA. Those FDA-approved biologics are called reference products.

The three documents are:

– Scientific Considerations in Demonstrating Biosimilarity to a Reference Product

In this document, FDA says it plans to apply its normal approach taking in the totality of the evidence provided by a sponsor to support a demonstration of biosimilarity. The draft recommends that sponsors use a stepwise approach in their development of biosimilar products that compares the proposed and reference products on factors such as structure, function, animal toxicity, interactions between the therapeutics and body, clinical immunogenicity, and clinical safety and effectiveness. FDA says it will consider as well the complexity of therapeutic protein products, the use of data derived from studies comparing a proposed product with a non-U.S.-licensed product, and safety monitoring after approvals.

– Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product

The draft provides guidance on analytical studies for assessing the similarity of the proposed biosimilar protein product and a reference product. The guidance specifically discusses therapeutic proteins, but FDA says the general scientific principles may help in the development of other proteins, such as those used in vivo protein diagnostics. The analytical studies required for biosimilars applications include chemical, manufacturing, and controls (CMC) analyses relevant to biosimilarity, as well as animal and human clinical studies.

– Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009

The Biologics Price Competition and Innovation Act of 2009 was folded into the 2010 health reform law, and includes not only the shortened approval process for biosimilars, but also exclusivity periods for the original biologics and procedures for resolving patent disputes. The Q&A document covers procedural matters — e.g., how to request meetings with the FDA — as well as addressing differences between the reference and proposed products, and requests for exclusivity.

FDA says it plans to issue a Federal Register notice soon seeking public comment on the guidance documents.

Read more: FDA Issues Regulatory Science Modernization Plan

Photo: ZaldyImg/Flickr

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