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COVID Vaccine Industry Project Leaders Are Sharing Insights on How the Daunting CMC Challenges Were Addressed

Nov 18th, 2021

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INTRODUCTION

The leaders of industry’s major COVID vaccine efforts have been sharing insights at recent conferences on: ● how their companies managed to address the daunting development, manufacturing, and supply chain challenges involved in delivering a vaccine in unprecedented speed during a pandemic, and ● the lessons that can be garnered from that experience in moving forward.

Critical to achieving the goal, the companies agree, have been the major sacrifices made by their staffs internally, the external manufacturing and supply collaborations that had to be forged, and the close engagement with regulators on addressing the CMC issues and clearing the regulatory pathways.

IPQ’s six-part story is based on the revelations that have been forthcoming in presentations and panel discussions at the conferences about how the companies managed, over the next year and half, to implement the ambitious plans they made as the pandemic was just emerging in the first quarter of 2020. In focus in the story are how the complex challenges were addressed in the Pfizer/BioNTech, Moderna, AstraZeneca/Oxford, Johnson & Johnson, and Novavax projects, in particular.

PART I: Implementing the Pfizer/BioNTech mRNA Vaccine Development and Manufacturing Plan

In March 2020, Pfizer and BioNTech agreed to collaborate on a plan to combine BioNTech’s strong mRNA knowledge base with Pfizer’s extensive global manufacturing and distribution capabilities and deliver a hundred million doses of a safe and effective vaccine for the SARS-CoV-2 virus by the end of the year. Part I provides a wealth of insights from key players from BioNTech and Pfizer involved in implementing the “audacious” plan on how the two companies actually brought it to fruition. Included is an update on related Q3 2021 regulatory/distribution developments.

PART II: New Digitalized Facility as Springboard for Moderna’s Well-Characterized mRNA Vaccine

Explored in this part is how a newly completed state-of-the-art digitalized and modularized facility provided a springboard for the rapid development and scale-up of Moderna’s mRNA COVID vaccine as the pandemic was taking hold. Also reviewed are insights from Moderna leaders on: ● developing patient-centric CMC specifications for its “well-characterized” vaccine ● vaccine production and access in low- and middle-income regions such as Africa, and ● how the company designed a plan to rapidly cross the high hurdles to commercial production and then build employee/supplier teams to implement it. A recent update on Moderna’s mRNA program developments is also provided.

PART III: Oxford University/AZ Partnership for Global COVID Adenovirus Vaccine Access

Like the BioNTech/Pfizer partnership, that between Oxford University and AstraZeneca provides valuable insights on effectively and efficiently combining the strengths of a small, innovative R&D operation with large-scale biomanufacturing and distribution knowledge and capabilities. Reviewed are how the cultural and operational differences were bridged by Oxford and AZ to take advantage of the respective capabilities so that the global access goals for their COVID adenovirus vaccine could be met in the dramatically foreshortened timeframes necessitated by the pandemic.

PART IV: J&J’s Experience in Handling the Supply Chain Challenges

A key focus in the review of J&J/Janssen’s successful adenovirus vaccine project are the learnings it has garnered in addressing the challenges of bringing a dozen production sites into play that were not previously part of the J&J network under the duress of the pandemic. Explored are how communication and team/relationship building efforts were ramped up by J&J and the innovative and collaborative ways of working that were established. J&J’s contribution to the dialogue at a pivotal conference on manufacturing and access in Africa in which Oxford and Moderna participated is also highlighted.

PART V: Novavax’s Approach to Assuring Comparability for its Protein-Based COVID Vaccine

The fifth part of the story throws a spotlight on how Novavax approached characterizing its complex-protein nanoparticle COVID vaccine and demonstrating comparability for multiple manufacturing sites under accelerated timelines. Included is a review of the announcement in early November 2021 that the Novavax vaccine, which is being manufactured by partner Serum Institute of India, had received emergency use authorization from Indonesia – the first EUA for the vaccine.

PART VI: Inter-Company Panels at DIA and ISPE Meetings on Vaccine Experience and Learnings

The last part provides a review of two highly engaging panel discussions that brought project leaders from these companies together to compare notes on the challenges they faced and their experience and learnings in addressing them. The panel discussions took place at the DIA annual meeting in late June 2021 and at the ISPE biotechnology conference in late September. Joining the DIA meeting panel was CBER Director Peter Marks. The ISPE panel was composed of the presenters at the vaccine session referenced in Parts I-IV and a Sartorius’ expert, who provided a supplier vantage point on the issues under discussion.

 

NIH’S Graham Highlights Foundation for Precision and Speed in Vaccine Development

Among the venues that the story draws from was the opening session at the January 2021 CASSS WCBP conference, which focused on “developing a vaccine manufacturing process and control strategy during the SARS-CoV-2 pandemic.”

Providing the opening keynote address at the conference and the context for the discussions at the session, was NIH National Institute for Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC) Deputy Director Barney Graham.

Drawing from the strong role he and his VRC colleagues have played in advancing vaccine R&D and related public-private partnerships, Graham explained how the research, technologies and partnerships that have been gelling in recent years made possible the precision and speed of the vaccine development effort that followed COVID-19’s emergence in 2020. He also highlighted the potential that these advances are providing to take a more proactive approach to mitigating future virus threats.

Graham spoke about structure-based design and some of the new approaches to mRNA and protein engineering and delivery, including self-assembling nanoparticles. These approaches, he stressed, can not only be more precise and predicable but also more rapid than traditional methods. “And combining precision and speed is what we need in order to address emerging infectious diseases that we have faced over this last decade,” including the current COVID pandemic. [See IPQ February 2, 2021 for Graham’s full remarks. IPQ has made the story openly available. Here is a link to access a handful of other stories IPQ has made openly available to help in addressing the pandemic.

 

Global Discussions Intensify on Applying Pandemic Learnings

At the session that followed Graham’s presentation, Moderna’s Julia O’Neill and Novavax’s Mark Schenerman reviewed the CMC challenges that were faced in developing a COVID vaccine and the strategies their companies deployed for addressing them. [O’Neill’s and Schenerman’s presentations are included in full in parts II and V, respectively.]

Also participating at the session was GSK Technical R&D Advisor Cristiana Campa, who addressed how the pandemic experience was “fostering unprecedented cross-industry collaboration to identify and address common issues and ensure coordinated dialogue with regulators.”

Prominently engaged in this effort have been Vaccines Europe (VE) and the International Federation of Pharmaceutical Manufacturers (IFPMA). They created a “CMC/GDMP COVID task force” to assess the experience companies and regulators had garnered in accelerating CMC development and how the learnings could strengthen industry and regulatory practices and collaborations at the global level. Companies actively involved in this effort, Campa noted, included Pfizer, AZ, Janssen, and Novavax, as well as GSK, Sanofi Pasteur, Curevac, Seqirus and MSD.

Active in the dialogue in cooperation with the VE/IFPMA initiative, Campa explained, were the COVAX development and manufacturing workstream, led by the Coalition for Epidemic Preparedness Innovations (CEPI) and the associated Regulatory Advisory Group (RAG).

Co-chaired by WHO along with CEPI, and with global regulator input, RAG was focused on identifying and addressing where the primary vaccine CMC challenges and improvement opportunities lay. Topics that had been identified for attention as 2021 began included comparability, process validation, testing and batch release, stability, and post-approval changes – areas very much in focus in the assessments by the companies provided in this story.

 

April Africa and July ICMRA Meetings Further Global Dialogue in 2021

Making a powerful contribution to the global dialogue on the pandemic experience and learnings regarding the manufacturing and access issues from the low-and-middle-income country (LMIC) perspective was a conference sponsored by the Africa Centers for Disease Control (CDC) and the African Union in April 2021. Parts II, III, and IV of this story include insights provided at the conference by leaders from Moderna, Oxford, and J&J, respectively.

Political, health policy, regulatory and industry leaders from across Africa and around the world came together virtually at the meeting to wrestle with the problems around the continent’s access to quality medicines – and to COVID vaccines in particular – and expanding its manufacturing capabilities. The prominence of the participants and the intensity of the discussions reflected a year of global health crisis and the realization that overcoming the crisis has to include addressing the access problems in Africa – which currently makes only about 1% of the vaccines it uses. The challenges that were aired during the two days are significant, but the mandate and the will for action were palpable, and concrete next steps were laid out.

In July 2021, the International Coalition of Medicines Regulatory Authorities (ICMRA) in cooperation with industry held another pivotal workshop to further the international effort to accelerate the availability of COVID-19 vaccines and therapeutics.

The overall aims of the workshop were to: ● “enhance regulators’ understanding” of the specific challenges faced by manufacturers in increasing manufacturing capacity ● “improve industry’s awareness of current regulatory approaches” in use to enable the rapid increase of manufacturing capacity, and ● “identify opportunities for further collaboration, alignment, and/or harmonization.”

[Editor’s Note: IPQ will be providing extended coverage of the intensified international dialogue that has been taking place on how to use the wealth of experience that has been garnered during the pandemic on advancing CMC practices and regulatory processes to better accommodate accelerated development and global access. The coverage will include more in-depth coverage of the Africa and ICMRA meetings as well as important discussions that have taken place at other major association venues during 2021.]

IPQ’S COVID-19 PANDEMIC COVERAGE

The following is a listing of the recent IPQ stories most directly related to the COVID-19 pandemic. They include a wealth of input from industry, government agency and pharmacopeial leaders on the development, manufacturing and control, and supply chain challenges that the pandemic placed before them, the efforts and adaptations made to address the challenges, and what learnings can be taken forward from the experience gained. IPQ’s early 2018 story at the bottom of the listing on preparing for an anticipated surge in natural, political and disease-induced crises – written in the wake of Hurricane Maria but well before the COVID pandemic had begun – is included due to the high relevance of what it conveys on preparing for and responding to operation and supply chain disruptions.

IPQ has made a handful of the stories in the listing below openly available beyond the normal subscription base to help in the pandemic response efforts. These are indicated and links provided for non-subscriber access.

There are a lot of other stories in the IPQ archives of high relevance in the pandemic context, which explore the efforts that have been intensifying globally to create a more effective, flexible, coherent, innovation-friendly, and collaborative approach to CMC practice and regulation.

Pandemic Urgencies Highlight Constraints in Manufacturing Change Regulatory Paradigm and Where Adjustments Are Needed — May 11, 2021

Part I: Industry Quality Leaders on the Global PAC Regulatory Problem and Solutions
Part II: Evolving the Quality Regulatory Paradigm at the Global Level

Regulators Share Pandemic’s CMC Impact at CASSS Japan Forum; Guidance Output Continues Apace in Q1 2021April 1, 2021

Part I: EMA Perspective
Part II: FDA CBER Perspective
Part III: FDA CDER Perspective
Part IV: Panel Discussion Among US, Europe, and Japan Regulators

Recent Technology and Partnership Advances Made Possible Precision and Speed of Vaccine Response to Pandemic, NIAID’s Graham Stresses at CASSS WCBP Conference
— February 2, 2021
[Non-subscribers can click here for access.]

Pandemic Intensifies USP’s Focus on Supply Chain Vulnerabilities and Vaccine Development — January 28, 2021

Pandemic Spurs Deepening of Pharmacopoeia/Regulator/Industry Communication Channels — December 23, 2020

Part I: EDQM Pandemic Actions Continue Apace in Fall 2020
Part II: Pharmacopeia/Regulator/Industry Panel Explores Pandemic Communications
Part III: Second Panel Focuses on Pandemic Organizational Impacts and Key Learnings
Part IV: EDQM and Ph. Eur. Evolution Addressed by Leaders Keitel and Vielle

COVID Vaccine Global Distribution Challenges Explored by Bio Supply Management Alliance (BSMA) Panel of European Experts — December 3, 2020

Pandemic Stresses Increase FDA Attention on Risk Management Plans for Drug Shortage Prevention and Mitigation — November 15, 2020

USP’s Global Efforts to Strengthen Standards and Accelerate Innovation for Biologics Include ICH Engagement — November 9, 2020

CBER Director Marks Traverses the Complex COVID-19 Vaccine/Therapy Regulatory Landscape at FDLI’s Annual Conference — October 13, 2020 [Non-subscribers can click here for access.]

Design-Based Development Paradigm for Cell/Gene Therapies Will Significantly Reduce Costs, Timelines and Regulatory Concerns, AGT CEO Galvin Maintains — August 27, 2020

USP Convention Meets Virtually in May 2020 to Review Upcoming Priorities, with Both 200-Year Legacy and Current Pandemic in Focus — July 16, 2020

COVID-19 Vaccine Urgency Throws Spotlight on Next-Gen Sequencing as Key Facilitator 
— May 31, 2020
[Non-subscribers can click here for access.]

PART I: Adventitious Agent Testing in Focus at CASSS CMC Forum Europe
PART II: Sanofi Pasteur and Ghent University Experience with NGS
PART III: A Decade of Regulator/Industry Collaboration on NGS
PART IV: Stakeholder Engagement Begins on ICH Q5A Revision
PART V: Effort to Reduce Animal Testing for Vaccines Includes Global Health Fund Support for NGS

NIIMBL Progress Includes Partnership with Biophorum on Buffer Mixing and Global Health Fund with Gates Foundation — May 15, 2020 [Non-subscribers can click here for access.]

Existing Accelerated CMC, Advanced Manufacturing, and Inspection Initiatives are Supporting Regulators in Pandemic Response, FDA’s Cruse Explains in Recent Field Office Updates — April 7, 2020

Emergency Preparations Draw Heightened Industry and Regulator Attention as Natural and Man-Made Disasters Proliferate — December 27, 2018 [Non-subscribers can click here for access.]

PART I: Biogen and Baxter among Pharma Companies Investing More in Disaster Preparation
PART II: FDA Rises to the Emergency Response Challenge
PART III: Natural, Societal, and Political Drivers Are Putting Supply Chains at Risk
PART IV: Expert Panel Discusses Impact of Hurricane Maria

[The story continues for subscribers on p. 2.  Nonsubscribers can get information on subscribing by contacting Jonathan Trethowan ([email protected]).]

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