FDA-EMA workshop discusses quality challenges for PRIME, breakthrough therapies
Last November, officials from the EMA and FDA met with industry representatives in London to discuss the various quality challenges that arise when the development of investigational products is accelerated.
The EMA’s launch of its priority medicines (PRIME) scheme and the FDA’s breakthrough therapy designation have enabled companies to speed certain treatments to market, although there have been difficulties in identifying possible scientific and regulatory approaches to facilitate the type of robust quality data packages necessary to ensure that patient safety and product quality and efficacy are not compromised, according to a report released Wednesday on the workshop.
In addition to the focus on early access approaches, the workshop discussed process validation, control strategies, good manufacturing practice (GMP) compliance, comparability, stability and regulatory tools.
Ramesh Sood, senior scientific advisor at the FDA’s Office of New Drugs, discussed the agency’s breakthrough program, noting the challenges faced by applicants collecting the necessary manufacturing data and providing an adequate manufacturing control strategy.
“It becomes important for the Agency reviewers to do a risk-benefit assessment regarding [the] risk of less manufacturing information versus patient benefit,” the workshop report says of Sood’s presentation. “This requires innovative risk-mitigation strategies to ensure product quality and reduce the quality-related product risk to an acceptable level.”
Veronika Jekerle of the EMA’s quality office also discussed the scientific challenges for PRIME candidates, which include abbreviated timelines that add constraints to setting up commercial manufacturing sites.
“An analysis examining scientific issues most commonly identified by PRIME applicants (as indicated by SA [scientific advice] requests) revealed the following areas as the most critical: starting materials, comparability, process validation, analytical control strategy, specifications and stability,” the report says.
Stuart Finnie, director of regulatory CMC at AstraZeneca, also presented on a small molecule product that earned the FDA’s breakthrough designation but ran into process validation problems that meant supplies of the drug would come four months after approval.
AstraZeneca approached the FDA and discussed decoupling the validation of drug substance and drug product, and discussed plans to use drug substance manufactured in the clinical facility to supply drug product validation.
“Three key elements lead to the success of this proposal,” the report says of the AstraZeneca work. “Firstly, the applicant provided the Agency with significant evidence of similarity in terms of quality, manufacturing process and quality system between the clinical campaigns and the proposed commercial campaign. Secondly, during the site inspection there was open and close engagement between the inspectors, reviewers, subject matter experts and quality departments ensuring that questions raised were answered swiftly leading to a balanced and aligned view on risk assessment. Finally, and most importantly, it was clear that throughout the interactions all parties were focused on ensuring supply to the patient.”
Other industry presentations involved representatives from Pfizer, Amgen, Celgene, MSD (known as Merck in the US), Biogen and several vaccine manufacturers, among others.
As far as future joint EMA-FDA actions, the report points to the use of models for stability and shelf life determinations, innovative process validation approaches and allowing launches from clinical manufacturing sites.
“In addition, the organizing committee proposes to develop a ‘Toolbox- guidance’ for PRIME products, which shall summarise the identified scientific elements/regulatory tools that are already available in the EU to address some of the challenges faced during the development of products under PRIME and generation of robust quality packages for MAA [marketing authorization application] review,” the report says.
Acting FDA Commissioner Ned Sharpless added in a statement: “We will continue to work with our EMA colleagues and industry to discuss ways to address quality challenges associated with expedited development programs to help ensure patients receive safe, effective drugs.”
RAPS: First published in Regulatory Focus™ by the Regulatory Affairs Professionals Society, the largest global organization of and for those involved with the regulation of healthcare products. Click here for more information.