The US government is continuing to strengthen its collaborative efforts with industry and academia to de-risk and accelerate manufacturing innovation, as the learnings from the pandemic are further digested.
The pandemic experience has thrown an intense spotlight on where the barriers and the opportunities lie – and the high stakes involved – in bringing advanced technology more fully to bear in pharmaceutical manufacturing.
In turn, it has become increasingly clear that stakeholder communication and collaboration at both the domestic and international level is critical to the advancement of the knowledge sharing, platforms, standards, workforce training, and regulatory processes needed to propel innovation forward.
Among the US organizations at the forefront of these collaborative efforts are the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) and its companion institutes in the Manufacturing USA network – established in the wake of the Revitalize American Manufacturing and Innovation (RAMI) Act passed by the US Congress in late 2014.
In response to the advanced manufacturing offshoring from the US since around 2000, the act provided funding to support more collaboration between industry, government, and academia in helping the US’s strong technology R&D cross the commercial product manufacturing threshold.
Further significant boosts to the pharma manufacturing innovation efforts have come from the American Pandemic Preparedness Plan, released by the White House’s Office of Science and Technology Policy (OSTP) in September 2021, and the CHIPS and Science Act, signed by President Biden in August 2022.
The five-part IPQ story provides a wealth of insights from key leaders and policy makers on the issues at play and how government, industry, and academia are collaborating through NIIMBL and other organizations to address them in the US and internationally.
PART I: NIIMBL and Its “Going First Together” Mantra
The first part of the story provides an update on NIIMBL’s efforts to accelerate biomanufacturing innovation and develop the needed supporting standards and workforce skills. In focus is a keynote presentation by NIIMBL Director Kelvin Lee at the 2022 PDA Annual Meeting in which he explored how NIIMBL brings together government, industry, and academia to collaborate on de-risking biomanufacturing innovation on a pre-competitive basis. He reviewed the strategic program/workstream approach the institute is taking to tackle overarching issues – focusing attention on the process intensification program, in particular. Also highlighted was NIIMBL’s 200-page case study “N-mAb,” supporting the development and adoption of continuous bioprocesses for monoclonal antibodies.
PART II: US Manufacturing Innovation Leaders Weigh In
The second part moves to the opening plenary session of the 2022 NIIMBL annual meeting, during which a panel of US leaders from organizations involved in supporting biomanufacturing innovation provided their insights on the issues involved and the role that NIIMBL and their respective organizations are playing. Presenting were: ● US Senator Chris Coons ● NIST Director Laurie Locascio ● NIIMBL’s Lee ● White House OSTP Senior Advisor Matthew Hepburn ● CBER Director Peter Marks ● BIO CEO Michelle McMurry-Heath, and ● FDA Principal Deputy Commissioner Janet Woodcock. They reflected on how the pandemic had heightened the importance of the pharma manufacturing innovation dialogue and stakeholder collaboration.
PART III: The Importance of Process and Facility Innovation in Global Health
Part III of the story moves forward to the February 2023 ISPE Facilities of the Future (FOF) Conference where OSTP’s Hepburn provided more insights on the current US government efforts to work with industry on pharmaceutical manufacturing innovation and preparing for future pandemics and other outbreaks. Under discussion by Hepburn were: ● why manufacturing innovation matters and the current OSTP support approach ● the role of public-private partnerships ● pivoting ability and global vaccine delivery ● specific programs, including Manufacturing USA and BARDA Ventures, and ● the need for flexibility/scalability and international harmonization.
Also reviewed is the discussion at an FOF dinner panel of organization thought leaders on whether the global convergence of regulatory processes that took place during the pandemic could continue and the top wishes for improving the pharmaceutical industry by 2030.
A third component of this part of the story is a review of the initiative launched by ISPE in mid-February on “Enabling Global Pharma Innovation.” Included is ISPE’s description of: ● the program goals ● the problem motivating the initiative ● regulatory activities to promote pharmaceutical manufacturing innovation ● learnings from the COVID pandemic ● industry’s innovation efforts, and ● how the program is being organized.
PART IV: Charting the Advanced Therapy CMC Pathways
Following the substantial contribution made by A-mAb and A-Vax in bringing a better understanding of how to implement QbD-based principals and CMC best practices into the development of complex biologicals, NIIMBL has been strongly backing similarly informative case studies for continuous manufacturing of mAbs (“N-mAb”) and for cell and gene therapies (“A-Cell” and “A-Gene”). The latter projects, also resulting in 200-plus page documents, were carried out under the direction of the Alliance for Regenerative Medicine (ARM) with NIIMBL support. IPQ also explains the role for NIST-mAb and NIST-CHO as reference materials supporting and advancing the biotherapeutic development process.
Covered in this part of the story are recent webinars NIIMBL has run addressing its initiatives on big data, process intensification, viral vector manufacturing and analytics, and biomanufacturing readiness levels.
PART V: CBER’s Marks On Taking CGT Development to the Next Level
As the guest speaker at a “Maryland BioNetworking Summit” cosponsored by NIST and the University of Maryland held in February 2023, CBER’s Marks began by reviewing the current state of cell and gene therapy R&D and product approvals. He then discussed some of the barriers to further CGT development and how they can be overcome – focusing on the role that increased global regulatory collaboration needs to play in particular. He concluded his talk by highlighting some of CBER’s current CGT innovation support initiatives. During the Q&A that followed, Marks addressed: ● approving and paying for rare disease therapies ● nonviral vectors ● Phase 0 trials in gene therapy ● standardizing lab processes ● long-term follow-up for gene therapies, and ● price control.
A LOOK BACK AT IPQ’S CONTRIBUTION TO THE INNOVATION DIALOGUE
2022
● Europe’s Focus on CMC Innovation and Agile Regulation
● Innovation Issues Explored at CASSS CMC Forum in Europe
● MHRA’s “New Era in Regulation”
● EMA Perspective on its Toolbox Guidance and OPEN Initiative
● Industry View on Efficiency Tools and CMC Flexibility Learnings from COVID
● Panel Discussion on Effective Tools for the Future
mRNA-LNP Vaccines Spur Global Dialogue on Nanomaterial Standards and Regulatory Approaches
● Pfizer/BioNTech Lipid Challenges with mRNA-LNP COVID Vaccine
● FDA’s Novel Excipient Review Pilot Program and Nanomaterials Guidance
● USP’s Draft Guideline and Other Efforts on mRNA Vaccine Quality
● The EDQM Nanomedicines Dialogue and WHO on Regulating mRNA Vaccine Quality
● Potency Assays for mRNA-LNP Vaccines
NASEM-Led Study for FDA is Helping Drive Industry/Regulator Agenda on Innovation Needs
● The NASEM Study and FDA Reflections
● Existing Mechanisms to Enable Innovation
● Challenges and Opportunities
● The Path Forward
● The Evolving Landscape of Pharmaceutical Operations
● Government-Industry Collaboration in This and Future Pandemics
● Reducing the Cost of Vaccine Manufacturing for Broader LMIC Access
Progress in Addressing Impurity Challenges in Focus at USP’s 2022 Peptide/Oligo Workshop
● US and European Regulator Perspective on the CMC Challenges of Oligonucleotides
● USP Standards Development Efforts for Peptides and Oligos
● Peptide and Oligo Analytical, Manufacturing and Raw Material Considerations
● The Advancing Knowledge-aided Assessment Component of KASA
● Bringing Biologics into the KASA System
● The Progress of FDA’s PQ/CMC Initiative
● The Goals of Accumulus Synergy in CMC Data IT and Regulatory Communication
● The Drivers for Revising ICH M4Q and Evolving the CMC Regulatory Process
● Update on EMA GMP-related Activities
● MHRA Innovation Pathway and Proposal for Point-of-Care Regulatory Framework
● Insights from Europe and ICMRA Regarding Onsite Inspection Alternatives
2021
● Update on USP’s Evolving Role and Current Initiatives In the Biologics Arena
● European Pharmacopoeia and FDA Join USP in Focusing on Particulate Control
● Implementing the Pfizer/BioNTech mRNA Vaccine Development Plan
● New Digitalized Facility as Springboard for Moderna’s mRNA Vaccine
● Oxford University/AZ Partnership for Global Adenovirus Vaccine Access
● J&J’s Experience in Handling the Supply Chain Challenges
● Novavax’s Approach to Assuring Comparability for its Protein-based Vaccine
● Inter-Company Panels at DIA and ISPE Meetings on Vaccine Experience
● Biotech Regulator Vantage Point on Raw Material Control
● The Added Challenges of Materials Management for CGTs
● Biomanufacturer Use and Control of Polysorbates
● Recent CMC/Regulatory Challenges of Oligonucleotide Drugs
● Comparability Challenges in Crossing Over to Generics
● Comparing Peptide and Oligonucleotide CMC Issues
● Starting Material Specifications for Oligonucleotides
A Confluence of Forces Is Now Spurring Combination Product Regulatory Reform in Europe
● EU Pharma Strategy Roadmap, Comments from Industry, and Related Agency Strategies
● Culture/Structure/Process Change and Global Alignment
● HPRA CEO Lorraine Nolan on HPRA and EMA Strategy
● EMA’s Zaïde Frias and NB/Industry Perspectives on EU Regulatory Transformation
● Industry Quality Leaders on the Global PAC Regulatory Problem and Solutions
● Evolving the Quality Regulatory Paradigm at the Global Level
● ICH Q9 Revision Lead O’Donnell on the Evolution of QRM
● FDA’s Rick Friedman on Advancing Aseptic Processing through QRM
● Industry/Academia Thought Leaders on the Evolving QRM/KM Relationship
● EMA Perspective
● FDA CBER Perspective
● FDA CDER Perspective
● Panel Discussion Among US, Europe, and Japan Regulators
● NIIMBL’s Engagement with Academia on Workforce Development Needs
● ISPE Workforce of the Future Traction at UMBC and UC Davis
● Keck Institute’s Behrens on Biopharma Talent Needs and KGI/Industry Partnering
● Xavier’s Phillips on Sharable Quality and Regulatory Science Curriculum
● CASSS Panel on Opening Up Biopharma Career Pathways
● European and Global Workforce Development Collaborations
Pandemic Intensifies USP’s Focus on Supply Chain Vulnerabilities and Vaccine Development
2020
Pandemic Spurs Deepening of Pharmacopoeia/Regulator/Industry Communication Channels
● EDQM Pandemic Actions Continue Apace in Fall 2020
● Pharmacopeia, Regulator and Industry Expert Panel Explores Pandemic and Nitrosamine Communications
● Second Panel Focuses on Pandemic Organizational Impacts and Key Learnings
● EDQM and Ph. Eur. Evolution Addressed by Leaders Keitel and Vielle
COVID-19 Vaccine Urgency Throws Spotlight on Next-Gen Sequencing as Key Facilitator
● Adventitious Agent Testing in Focus at CASSS CMC Forum Europe
● Sanofi Pasteur and Ghent University Experience with NGS
● A Decade of Regulator/Industry Collaboration on NGS
● Stakeholder Engagement Begins on ICH Q5A Revision
● Effort to Reduce Animal Testing for Vaccines Includes Global Health Fund Support for NGS
Attention Heightens on Creating an Independent Regulatory Pathway for Introducing Novel Excipients
● FDA’S Novel Excipient Program Proposal and Stakeholder Comments
● IPEC/IQ Thought Leaders on the Novel Excipient Drivers
● Subcutaneous Biotherapeutics, Pediatrics, and Delayed Release
● USP Initiatives Supporting Novel Excipient Development
● Assessing and Managing Excipient Risks
2019
CBER Reviewers Are Working with Sponsors in Exploring CMC Flexibility for Cell and Gene Therapies
Regulators and Industry Are Probing More Deeply into the Complexities of Preservative Usage
KASA and PQ/CMC Initiatives Gain Momentum in FDA’s Effort to Strengthen Quality Review Process
IPEC Continues to Encourage China to Align with Global Science-Based Excipient Standards
MHRA Inspectors are Advocating Data Mapping as a Key First Step on the Data Integrity Pilgrimage
Data Integrity Guidance Revisions by FDA and PIC/S Deepen Industry’s DI Resource Pool
FDA’s Focus Has Sharpened on Water Systems in the Wake of Nonsterile Product Microbial Contamination
UK MHRA’s “No Deal” Brexit Preparations Include Role for “Responsible Person – Import”
2018
IPEC Digesting Implications of China’s Ending of Separate Excipient Approval Process
Novel Excipients, DMFs, and Atypical Actives Among Pressing Issues on IPEC-Americas’ Front Burner
Role of Established Conditions Drawing Attention in Global Dialogue on ICH Q12’S Potential
Pharma is Exploring How to Maximize ICH Q12 Value in Practice; Q12 EWG Encourages Feedback
Expanding Field of Advanced Therapies Puts Pressure on FDA’s Review Staff to Keep Pace
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