Regulating Biologics

Published on: 
BioPharm International, BioPharm International-07-01-2018, Volume 31, Issue 7
Pages: 20

BioPharm International asked an FDA spokesperson how the agency plans on handling these issues in the future.

API sourcing and generic-drug competition are popular topics for industry and regulators, both in regard to ensuring patient safety and patient access to medications. Drug developers and manufacturers are increasingly sourcing materials from international suppliers; securing the safety of the supply chain for these materials is of utmost importance to regulators.

Making sure patients have access to affordable medications is also a concern for regulators. FDA has made an effort to promote the development of generic, more affordable versions of branded drugs (1).

The complex nature of biologics, however, adds additional concerns in both the quality of ingredients and the development of biosimilars. BioPharm International asked an FDA spokesperson how the agency plans on handling these issues in the future.

BioPharm: How are regulators addressing the additional quality control concerns that come with the complex nature of biologics, particularly the sourcing of biologic APIs and other materials manufactured internationally?

FDA: Current good manufacturing practice (CGMP) regulations are flexible and allow appropriate consideration of complex products. In addition to the flexibility in regulations, FDA has issued guidance to provide transparency and clarity with respect to complex issues concerning biologics.

FDA has accumulated decades of experience with complex biologics. With that said, there is always the potential to learn about new aspects of biologics quality. The agency anticipates scientific advancement will occur, and FDA will address any concern in the best way possible. This may include developing additional regulatory guidance as the need arises.

The agency anticipates that methods of greater resolution and sensitivity will be developed. This may raise questions regarding how to assess the clinical relevance of the information gained using high resolution and high sensitivity methods.


In terms of quality control, the duties of the quality control unit do not change based on the product. And, in the near future, we do not see challenges related to quality controls, so much as challenges related to the entry of new manufacturers into the biologics space, as well as their need to understand and address manufacturing issues.

With respect to the regulators’ perspective on internationally sourced API and manufacturing, all components are subject to the same level of oversight in qualifying suppliers and interrogating incoming materials. Regulators continue to emphasize quality agreements regardless of the location of the supplier.

Biosimilars Development

BioPharm: Will the increased development of biosimilars come with more complex regulatory concerns?

FDA: FDA will continue to build on its experience implementing the Biologics Price Competition and Innovation (BPCI) Act to identify areas where the agency can provide additional regulatory clarity to facilitate the increased availability of biosimilar and interchangeable products. To date, FDA has issued several guidance documents that provide recommendations to stakeholders about scientific and regulatory issues related to the development and approval of biosimilar and interchangeable products, such as the draft guidance Considerations in Demonstrating Interchangeability With a Reference Product Guidance for Industry and final guidances: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product, and Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product. In addition, FDA engages with sponsors during the early stages of product development, through FDA’s Biosimilar Product Development Program, to provide specific advice on the development of biosimilar and interchangeable products.


1.  FDA, Statement from FDA Commissioner Scott Gottlieb, MD, on New Policies to Reduce the Ability of Brand Drug Makers to Use REMS Programs as a Way to Block Timely Generic Drug Entry, helping promote competition and access, May 31, 2018.

Article Details

BioPharm International
Vol. 31, No. 7
Page: 20