Regulators Share Pandemic’s CMC Impact at CASSS Japan Forum; Guidance Output Continues Apace in Q1 2021

At the opening session of the December 2020 CASSS CMC Strategy Forum Japan, regulators from the US, Europe, and Japan explored the impact of the COVID-19 pandemic on their biotherapeutic and vaccine CMC regulatory processes.

This multi-part story provides the insights shared at the forum on the challenges, opportunities, and learnings as these agencies have sought to support the accelerated product development and review called for by the pandemic, while assuring that CMC/quality standards are met and keeping up with their non-COVID-related workload.

Also included are updates on the guidances and other quality-related initiatives that have been forthcoming during the first quarter (Q1) of 2021.

Part I:  EMA Perspective

Leading off the session with a discussion of EMA’s regulation of biologic product CMC during the pandemic was EMA Quality Office Principal Quality Specialist Ragini Shivji. She began by addressing how communications have been impacted, including regulator transparency and company/authority interactions. Shivji then discussed regulatory flexibilities and how they have come into play in authorizing both new and existing products. In the last part of her presentation, she focused on the CMC challenges that have presented themselves and how they are being addressed.

Among EMA offerings in Q1 2021 have been a guidance on adapting vaccines to address variants and the launching of an international scientific evaluation process for vaccines and therapeutics, “Project OPEN.”

Part II: FDA CBER Perspective

The second part of the story provides an FDA Center for Biologics Evaluation and Research (CBER) perspective on the regulatory challenges encountered during the pandemic in accelerating CMC development and review for vaccines, while ensuring their quality. At the Japan forum, CBER Office of Vaccines Division of Viral Products Deputy Director Robin Levis began by discussing the issues in moving from normal to accelerated vaccine development. She then explained the lessons that were learned from Ebola vaccine development, and how these and other advances in the vaccine knowledge base and regulation have been applied in the COVID-19 vaccine context.

A follow-up presentation on the vaccine CMC issues at the UGA/FDA International GMP Conference in March 2021 included a review by Levis of the update that CBER released in February of its October 2020 vaccine EUA guidance, which includes an appendix on CBER’s recommendations regarding the evaluation of vaccines to prevent COVID-19 caused by variants.

Part III: FDA CDER Perspective

The third part explores the experience of CDER’s Office of Pharmaceutical Quality (OPQ) in interacting with industry on CMC issues during the pandemic. CDER OPQ Office of Biotechnology Products (OBP) Supervisory Biologist Marjorie Shapiro began her presentation by explaining the information and resources that have been made available on FDA’s website related to COVID-19. She then turned her attention to CDER’s approach to pre-INDs and INDs. In the latter part of her presentation, she focused on the regulatory flexibilities that have come into play regarding neutralizing antibodies and repurposed drugs, the COVID-specific guidance documents developed for drugs and biologics, and the Operation Warp Speed initiative.

A number of COVID-related guidances have emerged from the CDER pipeline during Q1 2021 addressing issues such as potency and virus variation considerations for mAbs and other therapeutic proteins. A broader perspective on how CDER’s OPQ has handled the challenges of the pandemic and advanced its mission was provided in its 2020 annual report released in February.

Part IV: Panel Discussion Among US, Europe, and Japan Regulators

The final part of the story reviews the discussions that took place in the latter part of the first-day session of the CASSS forum, in which Shivji, Levis and Shapiro, along with representatives from the Japanese industry and regulatory agency PMDA, had a chance to explore further the pressing CMC regulatory issues.

The panelists addressed questions focused on: ● the pandemic’s impact on agency/sponsor interactions, workload, and resources ● the regulatory expectations for establishing in-house reference standards under expedited timelines ● the carry-over of pandemic regulatory flexibilities ● preapproval inspection challenges and virtual inspection learnings ● setting process parameters and specs with limited manufacturing experience ● the challenges and opportunities of new modalities ● the challenges and availability of emergency use-type programs ● the rolling review of CMC data for accelerated programs, and ● lessons learned from the pandemic.

[CLICK HERE for the complete story. Nonsubscribers can get information on individual IPQ subscriptions and organization-wide licenses by contacting Jonathan Trethowan (]