BioProcess Blog |

By Sheila Magil  (smagilbptccom)  

The biopharmaceutical industry has been waiting for guidance from the FDA on the approval process for biosimilars since the EMA published its Guideline on Biosimilar Biological Medicinal Products in 2005. Through the enactment of the Biologics Price Competition and Innovation Act of 2009, Congress directed the FDA to develop a process for approval of biosimilars. However, the Agency still has yet to publish a guideline for biosimilar approval.

Kozlowski S, et al offer a hint as to what the published pathway may look like in a recent article titled, “Developing the Nation’s Biosimilars Program,” published in the August 4th issue of the New England Journal of Medicine. Alluding to the EMA experience with approval of biosimilars, the article suggests that a “one size fits all” approach is not likely and that the FDA is unlikely to sign off on a biosimilars route that eliminates the requirement for animal and possibly human studies. It is also doubtful that the Agency will answer questions about the need for these studies without first reviewing the characterization and in vitro data for the proposed biosimilar. What the FDA appears to propose is a stronger Agency-sponsor interaction to identify any necessary animal or human testing and that the decisions will be risk-based and built on the understanding of the underlying mechanism of action. The greater the body of knowledge, the more readily the risk can be evaluated from characterization data alone.

In the end the expectation is that a biosimilar submission will have to include more than simple analytical characterization comparisons. It remains to be seen whether the effort required to gain approval for a biosimilar is reduced sufficiently to support this approach or whether it is more rational to develop a “biobetter” and have 12 years of market exclusivity.

by James Blackwell  (jblackwellbptccom)   and Howard Levine  (hlevinebptccom)  

On March 16, 2011, the FDA and EMA announced a pilot program for parallel assessment of Quality by Design programs in new drug marketing applications. This is a very positive step forward towards regulatory harmonization and provides additional impetus for companies to adopt QbD as a standard practice for drug development. This pilot program is clear recognition that QbD guidelines are being interpreted differently by FDA and EMA member states despite the fact that these guidelines were developed and adopted through the collaborative efforts of these regulatory authorities.

Initially, the pilot program will only include chemical entities and will extend to biologics in a step-wise approach after some experience has been gained with simpler molecules. We commend the “walk before you can run” approach due to the complexities of biologics, however, we also encourage FDA and EMA to incorporate biologics into the program as soon as tenable. Since the program is scheduled to end by March 31, 2014, we hope that the regulatory authorities are ready to address biologics in time to get meaningful feedback before the pilot program ends. We’re pleased to see that one of the key components of the pilot program is the commitment to propose new topics for discussion and guidance development through ICH or regionally, as appropriate, and to make joint presentations of key findings public through conferences and/or publications.

Part of the ongoing challenge to fully implementing QbD for biologics has been the disconnect in expectations of reviewers and field investigators and the lack of clarity on the amount and type of data required to support a QbD filing. As we have pointed out before, the lack of clear guidance on exactly what type of data and how much will constitute an acceptable level to support a QbD filing has hampered full adoption of QbD. During his presentation at the recent IBC Process and Product Validation, Patrick Swan, Deputy Director, Division of Monoclonal Antibodies, Office of Biotechnology Products, CDER, FDA, noted that this question of data requirements for QbD submissions is still an open one.

Nevertheless, the pilot program’s goal of increasing awareness of the concepts of QbD is commendable. We applaud this pilot program and the continued effort to harmonize the regulatory environment, especially with respect to QbD, even though we would have liked to see more proactive language in the announcement acknowledging that more can be done to harmonize reviewers and investigators on both sides of the pond. By hopefully lowering the risks and increasing the benefits of adopting QbD, the pilot program should benefit industry and patients by helping to accelerate product approval in both markets.

By Patti Seymour  (pseymourbptccom)   and Howard Levine  (hlevinebptccom)  

While recent efforts to repeal the Patient Protection and Affordable Care and Biologics Price Competition and Innovation acts were unsuccessful, there remains a long road before biosimilars are a reality in the US. During a recent public hearing, FDA sought input on such controversial issues as exclusivity period, non-US reference product use, and proprietary drug names for biosimilars. Since then, the debate over exclusivity has intensified with a bipartisan Senate group urging FDA commissioner Margaret Hamburg to allow FDA to begin reviewing biosimilar applications four years after the reference product’s approval rather than waiting for the end of the 12 year exclusivity period. Waiting until the end of the 12 year period before initiating biosimilar product review would effectively extend exclusivity well beyond 12 years. President Obama’s 2012 budget proposes to shorten exclusivity to 7 years (potentially saving $2.3 billion over 10 years), but Commissioner Hamburg said in an interview that the agency is not focusing on this proposal because it would require Congress to change existing law.

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By Alex Kanarek  (akanarekbptccom)   and Howard Levine  (hlevinebptccom)  

Since the issue of its cGMP Initiative in 2002, FDA has concentrated on applying risk-evaluation techniques to the various procedures involved in new drug approval. Following this trend, the agency recently issued a completely revised Compliance Guidance Manual on Pre-Approval Inspections for use by field staff.

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By Howard Levine  (hlevinebptccom)   and Patti Seymour  (pseymourbptccom)  

Recent moves by Congress to repeal the healthcare reform act of 2010 (Patient Protection and Affordable Care Act [PPACA]) threaten to wipe out a pathway for the introduction of biosimilars in the US (Biologics Price Competition and Innovation Act [BPCIA]).

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