The RAPS website recently experienced issues that we continue to monitor.  Certain areas of the site including news may be limited.  We apologize for any inconvenience.

Regulatory Focus™ > News Articles > FDA Publishes New Guidance on Common Biosimilarity Questions

FDA Publishes New Guidance on Common Biosimilarity Questions

Posted 12 May 2015 | By Alexander Gaffney, RAC

FDA Publishes New Guidance on Common Biosimilarity Questions

A newly revised guidance document published by the US Food and Drug Administration (FDA) provides additional insight into how the agency plans to regulate biosimilar products.

The latest guidance, Biosimilars -- Additional Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act, is closely related to another guidance document released on 30 April 2015 by FDA.

Both guidance documents are intended to act as question-and-answer-style documents answering some of the most common questions about the development and regulation of biosimilar products, including biosimilarity and interchangeability, the submission of biologics license applications (BLA) and biologics exclusivity.

The Basics

For example, FDA's latest guidance contains information regarding the amount and number of samples to be held in reserve after clinical testing. Samples should be retained for five years, FDA said. Such samples are used to allow regulators to confirm "the validity and reliability of the results of the study and facilitate investigation of further follow-up questions that arise after the studies are completed," FDA said.

Another section defines what FDA considers to be "publicly-available information" to support a finding that a reference product is safe, pure and potent. At minimum, such information should include information found in the "action package for a BLA," FDA writes in the guidance. "FDA intends to post on the Agency’s Web site publicly available information regarding FDA’s previous determination that certain biological products are safe, pure, and potent in order to facilitate biosimilar development programs and submission of 351(k) applications," FDA said.

Another hot topic addressed in the guidance is interchangeability.

"Can an applicant obtain a determination of interchangeability between its proposed product and the reference product in an original 351(k) application?" asks the hypothetical biopharmaceutical company in FDA's guidance.

"Yes," FDA answers, but that's still easier said than done.

"At this time, it would be difficult as a scientific matter for a prospective biosimilar applicant to establish interchangeability in an original 351(k) application given the statutory standard for interchangeability and the sequential nature of that assessment," regulators wrote. "FDA is continuing to consider the type of information sufficient to enable FDA to determine that a biological product is interchangeable with the reference product.

New Additions

The revised guidance also contains several new sections on biosimilarity. For example, FDA includes an extensive section on fulfilling obligations under the Pediatric Research Equity Act (PREA), a law intended to require companies to conduct pediatric testing as a condition of approval.

In short, if a reference product lacks adequate pediatric information, the biosimilar product will need to either request a deferral from PREA or submit a pediatric study plan. Otherwise, PREA obligations will generally be met by the extrapolation of data from the reference product to the biosimilar.

Another new and notable addition regards the way in which applicants can demonstrate that their biosimilar product "has the same 'dosage form' as the reference product"—a key requirement for proving biosimilarity under federal law. FDA said it plans to take a strict interpretation of the similarity requirements. For example, an injectable solution would be found to be different than a lyophilized powder intended for injection, even if it is otherwise biosimilar in effect.

Other new sections cover, respectively, INDs for non-US-licensed products intended for importation (not required), the type of marketing application needed for antibody-drug conjugates (a BLA), and whether applicants can apply for marketing exclusivity using a form 351(k) (yes, they can).


Biosimilars -- Additional Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act (FR)

Regulatory Focus newsletters

All the biggest regulatory news and happenings.