Regulatory Spotlight for Biotech: On the Horizon for CBER

Morgan Lewis - As Prescribed

Morgan Lewis - As Prescribed

FDA’s Center for Biologics Evaluation and Research (CBER), the locus of regulating cell and gene therapies among other expanding areas of biotech, is poised for change on a number of important fronts—leadership, significant growth, and plans to address challenging scientific and regulatory issues. With a well-earned reputation of stability, and slow, plodding progress, moments with so many elements in flux at FDA don’t come around often, so it is worth keeping an eye on how these begin to unfold to have a sense of where CBER—central to many of the exciting developments in industry—is headed.


Earlier this year, CBER underwent a reorganization that, most notably, established the Office of Therapeutic Products (OTP) as a “Super-Office” within the center. With the aims of increasing review capacity, expertise, consistency, and discipline alignment, the new OTP is largely replacing the office formerly known as the Office of Tissues and Advanced Therapies (OTAT).

Highlighting the importance of manufacturing for these products, the new OTP contains three dedicated divisions focused on manufacturing (one specific to gene therapies, another specific to cell therapies, and a third covering other products, including recombinant products and plasma protein products), coupled with individual divisions covering clinical, pharm/tox, and regulatory management.

Growth & Leadership

Of course, the blueprints for a regulatory structure only tell us so much. Critically, CBER and OTP in particular are poised for significant growth, as one of the largest areas of growth targeted under the current Prescription Drug User Fee Act reauthorization (PDUFA VII), which will be entering its second year on October 1. While CBER reports significant incoming hires to date, it is also working against formidable turnover headwinds, slowing progress on this front. As described further below, CBER has a very long and ambitious to-do list, and its success depends on obtaining and maintaining talented staff.

Continued leadership vacancies may be contributing to recruitment challenges, although CBER has just made an important step forward on this front. Though other leadership vacancies remain, the center very recently announced that Dr. Nicole Verdon has taken the mantle of OTP’s Super-Office director. Formerly the director (and deputy director) of CBER’s Office of Blood Research and Review, Verdun joined the agency in 2012 holding a number of positions in the Center for Drug Evaluation and Research’s Office of New Drugs (OND).

Verdun, replacing long-time head of OTAT, Wilson Bryan, is an experienced FDA leader and a seasoned regulator who has worked in dynamic areas of growth while at the agency—all critical elements for a successful leader for OTP at this juncture.

How and when Verdon chooses to round out her leadership team will be important, not in the least because Verdon is herself currently filling in for three other leadership positions in OTP’s clinical office, in addition to her role as Super-Office director, among other permanent leadership vacancies.

Evolving Review Program

While the reorganization and growth of CBER may work to address the expected (and continued) increase in investigational new drug (IND) applications and biologics license applications (BLAs) headed to CBER, significant resources will also be required to address commitments under PDUFA VII and growth in CBER’s Regenerative Medicine Advanced Therapy program, as well as make progress toward the many ambitious goals CBER has recently set. Among these are the following on the review-program front:

  • INTERACT Meetings: Initial Targeted Engagement for Regulatory Advice on CBER/CDER Products (INTERACT) meetings, which are intended to be very early product development meetings seeking to facilitate novel or challenging issues that might otherwise delay entry into the clinic, are called for in PDUFA VII. (FDA just issued a revision to its formal meetings guidance, in part, to address these new meetings.)
  • Reducing Clinical Holds: Dr. Peter Marks, CBER’s long-time center director, has stated that one of his hopes for CBER’s growth is the eventual reduction of clinical holds issued by the center, which may be achieved by dedicating sufficient resources to identifying and addressing with IND sponsors potential hold issues earlier and more aggressively in the review cycle.
  • Increased In-Person Meetings/Reduced WROs: CBER has also stated a goal of returning to a phase of increased in-person meetings and decreasing its reliance on written responses only (WROs) in response to meeting requests, coming both as the center emerges from the demands of the pandemic, but also as it works to address a workload crunch that has been building in CBER.
  • “Warp Speed” for Rare Disease: Finally, Dr. Marks discussed ideas for an Operation-Warp-Speed-like program for rare disease. Though details are so far scant, a Federal Register notice this fall may provide more details for what has been described to be a more responsive and nimble program for the advancement of rare disease development programs.

Though each of these would be welcome additions to the meeting and review program arsenal, as it works to grow in capacity and strength, it may be a challenge for CBER to keep up with the demand and meaningfully spur the progress in the development programs these are meant to address, not in the least because CBER may be working to implement these in parallel.

Policy and Regulatory Advances

On the regulatory front, Dr. Marks has spoken about plans to develop a program to publish more “real-time,” shorter guidances, drawing at least some inspiration from the “bulleted guidance” practices that CDER/OND implemented a few years ago. If the CDER experience holds true, this may ultimately represent efficiency gains for the center, guidance development and publication time may be shortened, and greater numbers of guidance documents may be published, in particular in specific areas of drug development.

However, on the policy and scientific fronts, Dr. Marks has also noted a number of potentially challenging areas where significant advancement is needed. Among other things, these include the following:

  • What constitutes a new product?: At what point do changes to a product, including its manufacturing methods, alter the product such that CBER will consider it a new product, requiring a new and independent regulatory submission? While this issue is not new, advances in the cell and gene therapy space especially have brought renewed focus and attention to this question.
  • Platforms and Data Leveraging: Along with new statutory provisions relating to “platform technologies” enacted in connection with the PREVENT Pandemics Act at the end of 2022, clarifying how and when data and methods from one product can be leveraged across multiple development programs (again, especially in the cell and gene therapy spaces) have been stated goals from Dr. Marks.
  • Increased Use of Accelerated Approval: Based on comments from Dr. Marks, we may expect to see increased use of FDA’s accelerated approval pathway by CBER, especially for rare disease, at a time when FDA as a whole implements the statutory changes to the pathway introduced at the end of 2022 in the Food and Drug Omnibus Reform Act of 2022 (FDORA).
  • Artificial Intelligence/Machine Learning (AI/ML): Dr. Marks has repeatedly noted the need for progress in the arena of biologics manufacturing in general when it comes to regulation and product development. He has noted gene therapy as a particular area of need in this arena and has noted the promise that AI/ML technologies may bring to bear here. While FDA has taken a few initial steps in advancing its thinking of applying these technologies to drug development, real progress will require close collaboration between FDA and industry, including FDA devoting efforts to advancing policy in this space that realistically allows for the incorporation of these technologies.

It is worth noting that none of these scientific or policy questions are straightforward, and while Dr. Marks is right that progress is needed on these fronts to adequately support the development of new and needed technologies, these thorny issues add to CBER’s already long list of promised deliverables. Dr. Verdun and others in CBER leadership will have the significant task of bringing these advancements to a reality, which includes ensuring that these goals are met at the review level of individual applications.

In an era with anticipated evolution of scientific and regulatory approaches, coupled with significant growth in CBER’s staff and leadership, heightened coordination with CBER and clear communication with FDA will be significant factors for success moving forward.

[View source.]

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

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