January Flurry: Our Regulatory experts share their perspective on a busy month at the FDA

Despite the recent US government shutdown, the FDA has been busy this month. PAREXEL’s experts chimed in on key updates from the Agency and their impact on the industry.

Commentary on Commissioner Gottlieb’s statement regarding growth in Cell and Gene therapy IND’s, by Mo Heidaran, PhD., Vice President Technical, PAREXEL Consulting

In a recent statement, FDA Commissioner Gottlieb acknowledged tremendous growth in number of INDs submitted in cell and gene therapy, pointing to 200 new INDs per year and 800 active INDs in this space.

To address this and keeping pace with the number of INDs submitted to the agency, Dr. Gottlieb announced hiring as many as 50 new clinical reviewers, without mentioning any plan for expansion of staff that conduct non-clinical and/or CMC reviews at FDA.

CMC readiness remains one of the major challenges in the expedited development of cell and gene therapy products. While Dr. Gottlieb’s plan is a significant step forward, it is only part of the solution. In view of these extraordinary demands facing the field it behooves the agency to plan for the expansion of not only clinical reviewers but also consider increasing the capacities and capabilities for CMC and non-clinical reviewers.

Not doing so most likely will create a very disruptive imbalance in the review management process creating unintended consequences that could impact safety and robust commercial processing of the products being evaluated in clinical trials. PAREXEL is committed to filling this gap by providing a comprehensive and fully integrated service to our clients streamlining product development lifecycle by avoiding the major pitfalls in early and late stage product development.

FDA Publishes Draft Guidance-Rare Diseases: Common Issues in Drug Development, by Brad Gillespie, Principal Consultant, PAREXEL Consulting

FDA issued a draft guidance document intended to assist sponsors in the development of orphan drugs. This document is largely focused on strategies to facilitate the conduct of more efficient and ultimately more successful development programs for drugs intended to treat or prevent rare diseases.

While the need to fully document the safety and efficacy is the same for orphans as for all drugs, FDA is open-minded in its approach due to the challenges inherent to the development these compounds. In this important document, several approaches are described that are intended to facilitate and expedite the development of orphan drugs.

A full analysis of the guidance is available here. In summary, publication of this guidance provides assurance that FDA is serious about supporting the development of drugs to counter rare diseases. Some of the suggested approaches are novel and may require unique expertise.

Lastly, a central theme of this document is the benefit of maintaining early and frequent communication with the Agency. PAREXEL is acutely aware of the challenges associated with orphan drugs. While the foundation of PAREXEL is broad and deep internal expertise in all phases of orphan drug development, it has also gained extensive Regulatory and Clinical development experience, guiding a variety of orphan drug clients through successful development and regulatory interactions.

FDA Publishes Draft Guidance - Labeling for Human Prescription Drug and Biological Products Approved Under the Accelerated Approval Regulatory Pathway January 2019, by Mamata Gokhale, Principal Consultant, PAREXEL Consulting

The accelerated approval is one of several approaches used by the FDA to expedite the development of drugs for serious or life-threatening diseases and conditions upon determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on an intermediate endpoint that can be measured earlier than irreversible morbidity or mortality.

This draft guidance focuses on how accelerated approval is represented in the Indications and Usage section of product labeling (USPI) and offers recommendations to sponsors on language that best conveys different circumstances specific to accelerated approval. 

PAREXEL has internal expertise (industry and ex-FDA) in accelerated drug development and corresponding labeling for drugs and biologics, and we highlighted some specific recommendations of interest for companies seeking accelerated approval:

• Indication and Usage statement for drugs approved under the accelerated approval framework must acknowledge that the drug was approved based upon accelerated approval and that continued approval for the drug (or indication) may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials.
  
  
• Effect on surrogate endpoint or intermediate clinical endpoint such as response rate that supported the accelerated approval needs to be described in the Indication and Usage statement and should be cross referenced to the Clinical Studies section of the label.
  
  
• A similar presentation should also be used under the Indications and Usage heading in Highlights without a cross-reference to the Clinical Studies.
  
  
• Continuation of accelerated approval is subject to the requirement that confirmatory trials verify the drug’s clinical benefit. Therefore the Indication and Usage statement also needs to state that continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 

How should labeling be revised after successful verification and description of clinical benefit in post-marketing studies? Read more in our PAREXEL Consulting Blog here.

FDA Accelerates Initiatives to Modernize and Strengthen 510(k) Program, by Sugato De, Vice President – Technical, PAREXEL Consulting

Since its inception over forty-two years ago, FDA’s 510(k) clearance pathway has served as a core pillar of medical device marketing authorizations in the United States. 

Under this pathway, manufacturers of Class II medical devices and in vitro diagnostics have been able to pursue a streamlined path to clearance based on a demonstration of substantial equivalence to a legally marketed predicate device. 

Beginning in earnest with the issuance of FDA’s Medical Device Safety Action Plan in early 2018, FDA has put renewed focus on advancing multiple initiatives to enhance the safety of medical devices and keep pace with the increased complexity of rapidly evolving technologies. 

Last week, FDA issued an announcement of two key developments that signal progress toward its previously reported goal to modernize the 510(k) program. 

First, FDA posted its final guidance entitled “Safety and Performance Based Pathway,” which updates a draft guidance from April 12, 2018.  The guidance introduces a new option for manufacturers to obtain 510(k) clearance by referencing objective performance criteria recognized by FDA to facilitate demonstrations of substantial equivalence. 

Second, FDA is soliciting public comment on steps the Agency can take to further enhance the safety of 510(k) devices.  To learn more about each of these updates, please visit our PAREXEL Consulting blog here.

Evolving standards of care and the proliferation of innovative technologies demand a regulatory environment where new medical devices are held to a higher bar.  Patients deserve access to medical devices that conform to modern safety and performance standards, and regulators should not be expected to operate within a framework that enables the clearance of new medical devices based on comparison to outdated predicates that represent the lowest common denominator of that device type.

FDA’s sentiment and initiative in this area is laudable, and it is a positive sign that the Agency is seeking further input to refine its approach.  PAREXEL Consulting’s experts support companies in developing regulatory strategies, clinical development plans, premarket submissions and compliance programs for medical devices and are actively tracking updates and providing input to FDA’s 510(k) modernization initiative.

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