Individualized gene therapy: FDA considering device-like manufacturing approval process

CBER Director Peter Marks said the agency could streamline development by allowing sponsors to depend on an already-approved manufacturing platform.

Derrick Gingery

March 9, 2020

4 Min Read
Individualized gene therapy: FDA considering device-like manufacturing approval process
Image: iStock/marekuliasz

CBER Director Peter Marks said the agency could streamline development by allowing sponsors to depend on an already-approved manufacturing platform and reviewing any modifications that are proposed.

Individualized gene therapy approvals at the US Food and Drug Administration (FDA) could speed up using a 510(k)-like process under consideration.

Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), said the FDA needs a workable pathway not requiring new authority from Congress to deal with the growing sector.


Image: iStock/marekuliasz

During a panel discussion at the agency’s 24 February Rare Disease Day meeting, Marks said CBER is looking to “leverage” existing authority and information and is considering allowing manufacturing applications that are based on an existing process to use that prior approval.

“If a product has been made using one manufacturing technique and only a small modification has been made to that product so that it can address a different disease or a different subset of a given disease, can we allow the manufacturer to leverage the application of the original product as they have this modified product?” he asked. “Those types of things are things we’re having a vigorous dialogue about.”

Marks’ description sounds similar to the approach of 510(k) device approval process. That pathway allows sponsors a faster review by basing their application on an already-approved device. They then must show the modifications made do not increase safety risks compared to the prior device and still meet FDA efficacy standards.

Marks seemed to be interested in embracing a platform approach to gene therapy products, where base manufacturing processes can be reproduced and slightly modified for each new product.

Center for Drug Evaluation and Research (CDER) director Janet Woodcock added during the meeting that several small-molecule individualized therapies also have arrived at the agency and more are expected.

Woodcock said CDER also is wrestling with regulatory as well as commercialization issues.

“We are on top of this I think is the best way to say it,” she said.

Woodcock has predicted that drug approvals may become more “device-like” to deal with the potential for small product adjustments based on genotype. Woodcock admitted that clinical trials could not be realistically completed for each new genotype, but said registry data could help facilitate the approval.

Ongoing efforts to develop a technology platform for manufacturing individualized gene therapies will be discussed during a 3 March FDA workshop titled Facilitating End-to-End Development of Individualized Therapies. Stakeholders also will discuss clinical and safety concerns and other issues limiting product development, as well as potential solutions the FDA could implement.

Idea may become guidance

Officials hope the new idea will be described in upcoming guidance, Marks said, adding that the agency must find ways to increase access to what could become life-saving treatments for rare and other diseases.

Marks also said that sponsors and regulators should think globally and not create development programs to satisfy individual countries when the product would only treat a handful of patients in each.

“We don’t want to repeat mistakes that have been made in the past,” he said. “Unless we can find ways toward commercial viability or toward some sustainable method that these products can be provided, we’re not going to be doing the job that we need to for patients in need.”

FDA officials have been hastening to implement policies for so-called “bespoke therapies” or “N of 1” products. The difficulty is creating policies to deal with therapies that are not created with commercial potential in mind and often are initiated by academics without formal training or knowledge of new molecular entity development requirements. Questions such as how patients will continue to receive the therapy if it works are particularly challenging.

So many policies created, so many more to write

Some gene therapy policies already are in place, but Marks and others have said that many more are needed in order to handle the industry’s growth.

CBER issued several guidance documents in January related to gene therapy development in hemophilia, retinal disorders and rare diseases, as well as long-term patient follow-up.

The guidance on gene therapy development in rare diseases did not remove the requirement for placebo controls in clinical trials, but did remove language related to biomarker validation.

Guidance is also available describing agency thinking on chemistry, manufacturing and controls, safety and other issues.

In addition, the FDA is encouraging gene therapy manufacturers to adopt advanced manufacturing techniques to improve quality for scale-up and licensure. Former Commissioner Scott Gottlieb advocated for manufacturing “cassettes” with enough product for a small number of patients in a clinical trial. If the product shows promise in the trial, the sponsor could produce more cassettes.

Agency officials also view gene therapy as a potential way of drawing more drug manufacturing back to the US. FY 2019 and FY 2020 budget requests included funding increases to create frameworks for evaluating new technologies for producing vaccines and gene therapies.

This article was first published on 28 February 2020 in The Pink Sheet.

Award-winning journalist Derrick Gingery has been reporting on regulatory issues for “The Pink Sheet” and “The Pink Sheet” Daily since 2010. He can be reached at [email protected] or @dgingery

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