FDA Centers Seek Regulatory Harmonization to Ease Industry Burden

Pictured: FDA Headquarters, iStock, Grandbrothers

In response to growing calls from the biopharma industry, two FDA regulatory centers are increasingly working in sync to make it easier for sponsors to comply with regulatory requirements, thereby providing time and cost savings for the industry and improving patient access to medical products.

The efforts at the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) to increase collaboration and harmonization have been ongoing for decades, Lucy Vereshchagina, senior vice president of science and regulatory advocacy at the Pharmaceutical Research and Manufacturers of America (PhRMA), told BioSpace. But the two centers intensified their efforts following discussions with industry and stakeholders as part of the reauthorizations of the Prescription Drug User Fee Act (PDUFA), particularly the latest PDUFA VII, added Vereshchagina, who served as a lead negotiator on the legislation.

Most recently, CBER and CDER released the latest version of their Data Standards Joint Action Plan in May. It contains a comprehensive list of the centers’ joint initiatives related to data standards. Notable efforts include the pharmaceutical quality/chemistry, manufacturing and controls standardization, and the March 2023 final guidance on the implementation and use of the Identification of Medicinal Products standards.

CDER Director Patrizia Cavazzoni told BioSpace that harmonizing the program across the centers makes sense since they both use many of the same data standards. CBER and CDER “strive for consistency in all aspects of our regulations and policies across regulatory review programs,” she said.

The new action plan, first released in January, is a reformatted version of a CDER document that has existed since 2013 when CDER first embarked on a data standardization plan. It is a product of the joint CBER-CDER Data Standards Strategy, the broader initiative announced by the centers in October 2022. The program’s stated goals are to support consensus-based data standards development, maintain and promote a well-defined data standards governance function, promote the electronic submission of regulatory data using established standards and optimize the regulatory review process to fully leverage data conformed to standards.

Vereshchagina said that having consistent data standards and policies across the agency is particularly important due to the increasing volume of data submitted to FDA. “It helps with more efficient data capture, collection, submission and analysis, [which is] particularly critical when working with real-world data,” she said.

One area where the FDA is starting to deal with a data deluge is in cell and gene therapy. “Those data volumes are tremendous,” Vereshchagina said.

Greg Meyer, vice president of regulatory affairs at Premier Consulting, agreed that harmonization is particularly useful for cell and gene therapies, and even more so for rare disease indications, because these applications have very small clinical trial data sets that go into the approval decision.

Similarly, regulatory harmonization should be particularly helpful for small- to mid-size manufacturers as it allows for more efficient allocation of resources, Vereshchagina said.

Over the years, more and more industry stakeholders have called on the FDA to ensure cross-center consistency. As a result, CBER and CDER have collaborated on an increasing number of guidance documents.

“These intra-agency collaborations are a critical necessity in our efforts to facilitate and support research, development and regulation of medical products for patients in need,” Cavazzoni said.

The onus, then, is on companies to read them, Meyer noted. “When you go in front of the agency and present your plan, if you get back a response . . . that makes it clear that you haven’t read the guidance for your specific type of product. You’ve wasted a lot of time, and it was 100% your fault.”

In addition to the uptick in guidance documents, the FDA has launched a handful of other initiatives that, like the new CBER-CDER Data Standards Strategy, aim to streamline and make consistent its regulatory processes.

The Electronic Common Technical Document (eCTD) format, for example, was made mandatory in 2017 for all sponsors seeking approval from CDER or CBER. This is the standard format for submitting applications, amendments, supplements and reports to these centers. eCTD guidance for industry was finalized in February 2020.

Vereshchagina said the use of this format is especially important because many companies run global drug development programs. “We want to make sure that data generated across geographic regions and countries meet the same standards and can be submitted to the FDA or other regulatory agencies.”

Another example is the FDA’s Sentinel Initiative, a national electronic system to monitor the post-market safety of FDA-regulated medical products. Sentinel serves as a repository for safety data from various sources, including outside the context of clinical trials. It began undergoing a five-year transformation in 2019 that will culminate this year.

Once again, this initiative will be particularly important for cell and gene therapies, Meyer said. That is because FDA receives most of the safety information after the cell or gene therapy product is approved, he explained.

All of these initiatives allow for data sharing, maintaining compliance and ensuring that there is a rational, statistically based backing to the approval processes, Meyer said. This is particularly important in rare diseases, which have a small patient population to collect data from, he added.

The goal will never be to achieve complete harmonization across centers, given the inherent nature of the different products under CDER’s and CBER’s purview, Cavazzoni said. “The scientific considerations in specific diseases or medical conditions are unique and may require case-by-case considerations for the particular development program at issue,” she noted.

But overall, Meyer and Vereshchagina agreed, there has been a much-welcomed shift toward greater harmonization across the agency, and in particular between CDER and CBER.

“The best way to describe the shift . . . is that the consistency across review divisions and across centers is now really built into how the agency approaches their efforts and initiatives,” Vereshchagina said. “That’s built in from the beginning, and it’s not an afterthought.”

Ana Mulero is a freelance writer based in Puerto Rico. She can be reached at anacmulero@outlook.com and @anitamulero on Twitter.