Former CDER OSI Associate Director for Risk Science to Speak at CPhI North America 2017

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Pharmaceutical Technology spoke with CPhI North America presenter Jonathan Helfgott to discuss navigating GDUFA and helpful tips for submitting successful ANDAs.

Pharmaceutical Technology spoke with Jonathan Helfgott, coordinator and adjunct professor for the Johns Hopkins University Graduate Program in Regulatory Science and former associate director, Office of Scientific Investigations, Center for Drug Evaluation and Research (CDER), about challenges pharmaceutical companies face when submitting abbreviated new drug applications (ANDAs). Helfgott will be speaking on this and other related topics during his presentation “Navigating GDUFA–Reduce Cost and Accelerate Delivery” at the CPhI North America Conference from May 16–18, 2017 in Philadelphia, PA.

ANDA submission challenges

PharmTech: What are some typical challenges facing pharma companies submitting an ANDA? Do you have any suggestions for addressing these challenges?

Helfgott: Typical challenges facing pharma companies include ensuring that ANDA submissions use the electronic common technical document (eCTD) format and consist of high-quality data.

As of May 5, 2017, the eCTD format is required for all ANDA applications. All electronic submissions must use the version of eCTD supported by FDA, comply with the required specifications, and be appropriately validated before submissions. Selection of an appropriate eCTD software vendor can be helpful to ensure a successful eCTD submission that complies with FDA’s requirements.

Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research, has defined the term ‘high quality data’ as the absence of errors that matter-errors that matter are typically errors that can have an impact on the interpretation of study results. Incorrect, missing, or inaccurate data can result in a refuse-to-receive or a complete response letter.

Pharma companies can address these challenges by hiring people that have experience with and understand the intricacies of the regulatory submission and filing (e.g., eCTD) process to verify proper formatting and application completeness. Perhaps even more importantly, companies should build quality into their processes to avoid these types of challenges all together.

PharmTech: In October 2016, FDA released a guidance on prior approval supplements. How does this guidance work to further clarify the ANDA submission process?

Helfgott: This particular FDA final guidance is focused on clarifying the requirements of prior approval supplements (PASs) and amendments to PASs for ANDAs. The guidance describes how the Generic Drug User Fee Amendments (GDUFA) performance metric goals apply to a PAS subject to the refuse-to-receive standards, a PAS that may or may not require an FDA site inspection, an amendment to a PAS, and other PAS-related matters. The guidance further clarifies sections in the Federal Food Drug and Cosmetic Act that define the following categories of changes to an approved indication-major, moderate, or minor, while noting that the criteria for submitting information as a PAS, as a changes-being-effected (CBE), or in an annual report were not changed by GDUFA.


PharmTech: How has GDUFA impacted the ANDA review process at FDA? Please comment on efficiency.

Helfgott: FDA provided an FY 2016 Performance Report to Congress on GDUFA’s impact on the ANDA review process. Highlights from this report include the GDUFA performance goals, workload, management priorities, review times, inspections, drug safety, and research priorities. As of October 2016, FDA had issued a first action on approximately 93% of the GDUFA backlog applications since program launch, meeting the GDUFA backlog commitment 15 months ahead of the goal. Prior to the passage of GDUFA, domestic facilities were routinely inspected about once every two years while their foreign counterparts were inspected about once every seven to 13 years. This regulatory disparity, combined with limited resources and the associated cost of inspecting foreign facilities, produced an increasing gap in the level of oversight that was needed to ensure the safety of the human generic drug supply. FDA now applies a risk-adjusted inspection focusing on sites that have not been previously inspected, utilizing site inspection outcomes conducted by foreign regulatory bodies, and making inspection classification results publicly available.

Bioequivalence studies

PharmTech: What advice would you give a company conducting a bioequivalence study?

Helfgott: Companies need to thoroughly understand FDA’s draft guidance on Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an Abbreviated New Drug Application as well as any product-specific guidances that describe the agency’s current thinking and expectations on how to develop generic drug products therapeutically equivalent to specific reference-listed drugs.

Companies need to do their homework and make sure that they pick a reputable bioequivalence firm that has a good FDA inspection track record. There could be premiums associated with using higher end bioequivalence services, but I believe the cost of non-compliance will always be greater than not spending the time and effort to do it the right way up front. It’s also important that companies select the right methods, which are validated and well accepted; the reference standards used also need to be pure and clean. Common pitfalls to avoid include poor chain of custody, sloppy documentation, and weak processes.

A pre-ANDA meeting is a great opportunity for firms to discuss complex and critical issues and for FDA to provide guidance on how to design a bioequivalence study.

What to expect at CPhI North America

PharmTech: What will participants learn during your CPhI North America session?

Helfgott: Participants in the CPhI North America session will learn:

  • Tips for a successful ANDA submission

  • FDA’s focus during an ANDA review

  • The role of GDUFA and its’ impact on ANDA reviews

  • When a bioequivalence study is required to support an ANDA

  • How to conduct high-quality bioequivalence studies and prepare for an FDA inspection

  • Effective use of technologies to support bioequivalence studies.