CMC Europe 2022

The EFPIA Biomanufacturing Working Group is a cross-company industry team working to aid the development of biological products for patients. Through areas of special interests, the group supports and develops cutting edge science and technology strategies. In the first half the session the Working Group will show showcase some of the current concept papers under development.

In the second half of the session, presentations on the conversion of IV to SubQ Application will explore this key topic for the biomanufacturing community, with consideration of the challenges and opportunities it presents such as CMC device & formulation and bioavailability considerations, immunogenicity, modelling, and patient centric approaches to bridging, followed by a panel discussion.

Session Speakers - Concept Paper 2022 Updates:
Industry Perspective on Polysorbate Degradation and Control Strategies for Biopharmaceutical Products
Klaus Wüchner, Janssen Pharmaceutical R&D, Switzerland

Establishing a Platform Master Files Approach for Human Medicinal Products in the EU/EEA
Mihai Bilanin, GSK, Belgium

Session Speakers - Conversion of IV to SubQ Application Scientific Session:
Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities
Beate Bittner, Roche Diagnostics GmbH, Germany

Immunogenicity (or Not) of Biologics in the Subcutaneous Space  
Sathy Balu-Iyer, University of Buffalo, United States 

Modelling of Subcutaneous Injection & Bioavailability to Bridge IV/SubQ    
Joel Gresham and Max Dixon, Crux, United Kingdom

SubQ Bioavailability Considerations
Manuel Sanchez-Felix, Novartis Institutes for BioMedical Research, United States

CMC Aspects When Switching from IV to SubQ Formulations 
Christian Mayer, AGES MEA, Austria

Kathy Lee, Genentech, a Member of the Roche Group, United States and Tara Sanderson, UCB Pharma Ltd., United Kingdom

Digitalisation is already transforming industries and its application in the world of regulatory assessment is on the horizon. Multiple recent efforts have focused on digitalisation and its potential to increase efficiency in submission and review, for both industry and agencies. Initiatives such as Accumulus, data standardization, and the revision of M4Q are all intended to facilitate global harmonization, thereby enhancing submission efficiency, regulatory assessment, and enabling pharmaceutical supply to patients worldwide. This session will focus on several key efforts in this space and will explore the specific activities ongoing in each, as well as reflections from Industry and Regulatory Agencies perspectives.  

Session Speakers:
EMA Perspectives on ICH M4Q(R2) and Digital Regulatory Assessments
Klara Tiitso, EMA-European Medicines Agency, Netherlands

FDA Perspective on Opportunities for Modernization of Regulatory Submissions
Ingrid Markovic, CBER, FDA, United States

M4Q ICH Current Status and Vision from Industry
Sarah Pope Miksinski, AstraZeneca, United States

The Power of Data Exchange CMC Interoperability and a Cloud-based Ecosystem
Michael Abernathy, Amgen Inc., United States

To meet the demands of increasingly complex medicinal products, technologies like mass spectrometry are needed – also in a QC lab. However, for methods like MAM by LC-MS and HCP by MS little experience on how to handle mass spectrometry in a QC lab is currently available. Emerging new technologies (currently used during characterisation of new therapeutic drug modalities) as release testing methods are discussed in this session.

Session Speakers:
Regulatory Considerations for the Application of Multi-attribute Method by Mass Spectrometry for QC Release and Stability Testing of Biopharmaceuticals 
Annick Gervais, representing EFPIA, Belgium

A Status Report from the MAM Implementation Phase 
Alexander Buettner, Roche Diagnostics GmbH, Germany

A Roadmap to Get Host Cell Protein Analysis by Mass Spectrometry in a GMP Environment
Cyrille Chéry, UCB Pharma SA, Belgium

Novel HCP Analysis and Characterisation Tools Provide Freedom of Operation for Efficient Process Development
Brian Kåre Kristensen, Novo Nordisk A/SA, Denmark

Over recent years, an increasing number of medicines have been developed for orphan indications and for treatment of unmet clinical need. The abbreviated development times associated with such clinical programmes has required sponsors to expedite CMC activities. Furthermore, the development of precision medicines has driven pharmaceutical development into more complex manufacturing of sophisticated drug products and dosage forms. This paradigm shift in pharmaceutical development has encouraged companies to challenge traditional approaches to product and process development. One area, which has until now been under explored is the use of models in CMC submissions.
Various modelling approaches can have different objectives, including increasing predictability, improving processes understanding, or expediting CMC development. This is particularly relevant for data driven models governing stability, control strategy, process validation, and product and process design. Examples of such approaches include stability models to predict shelf life, chemometric models for quality control of finished product, and adaptive process models used to adjust a manufacturing process in real time.
Nonetheless, while it is recognised that such models may have wide applicability in many areas of CMC, there are perceived regulatory barriers to their adoption. The intent of this session is to share industry experiences on how new modelling approaches can be applied, to get regulators’ views on the development of new guidance on models, and to discuss potential regulatory barriers to the successful implantation of such models in CMC submissions.

Session Speakers:
Regulatory Considerations for Modelling as a Tool for Process Understanding and Control
Matthew Popkin, GSK plc., United Kingdom

Enhanced Process Characterization through Monte-Carlo Simulations: From a Local to a Global Understanding of the Process 
Hervé Broly, Merck Serono, Switzerland 

Using Stability Prior-knowledge from 'Like-molecules' to Determine Shelf-life
Andrew Lennard, Amgen Limited, United Kingdom

Some Reflections on the Use of Models in Module 3
Nick Lee, HPRA-Health Products Regulatory Authority, Ireland

Accelerated CMC and regulatory efficiency tools can be used to support the approval of medicines in early access programmes, such as emergency medicines and medicinal products for unmet medical need. In such cases, where certain CMC data may be limited at the time of submission, a suite of tools is needed to take CMC off the critical path and facilitate timely approval of critical medicines.
In particular, this session will specifically cover the following:
1. Setting of specifications in marketing applications, which may be wider than the release data of the limited number of batches used in clinical trials, by using additional sources of information beyond clinical experience.
2. Submission of complex and innovative raw materials, which has always presented challenges for approval and lifecycle management as these are often proprietary to third party manufacturers and CMC information is not easily available for regulatory submissions.
3. The most beneficial tools for accelerating CMC will be discussed in the context of the lessons learned from recent approvals of Covid-19 vaccines and medicinal products for unmet medical need from an Industry and Regulators perspective.
The purpose of this session is to share the experiences from Industry and Regulators on how such efficiency tools can be leveraged to facilitate acceleration of CMC development.  

Session Speakers:
How to Leverage Pharmaceutical Development and Manufacturing Data for Marketing Authorisations – EMA’s Perspective
Veronika Jekerle, EMA-European Medicines Agency, Netherlands

Setting Acceptance Criteria for Release Specification Based on Limited Batch Data 
David Kirke, BioMarin U.K. Ltd, United Kingdom

Industry Proposal for the Use of QbD and ICH Q12 Principles to Enable Second Sourcing of Raw Materials
Kavita Aiyer, Seagen Inc., United States

CMC Lessons Learned from COVID
Mark Pellett, AstraZeneca, United Kingdom

There are lots of exciting developments and innovations for biopharma products and processes that have the potential to transform healthcare treatment and delivery. Regulators, industry and academia are increasingly working together to help ensure that new products can reach patients more efficiently, via collaborative activities that have been catalyzed by the COVID-19 pandemic.

In some cases, novel technologies or manufacturing flexibilities are challenging the current regulatory paradigm. To address this, in the last year, EMA has announced the intention to form a Quality Innovation Group and held a survey on novel products and processes, MHRA launched a ‘Point-of-care manufacture’ consultation, and FDA has been engaging at conferences on FRAME – their Framework for Regulatory Advanced Manufacturing Evaluation.

At the same time, the MHRA Innovation Office, EMA Innovation Task Force and FDA Emerging Technology Program have been encouraging more early engagement and dealing with higher numbers of queries on more complex products and processes.

In this session, we will explore innovative approaches in manufacturing including decentralized, flexible, mobile, adaptive, 3D printing and end-to-end continuous manufacturing approaches. In addition, we will discuss the regulatory framework needed to support novel manufacturing and hear about the different initiatives under development by the regulatory agencies to support MAs to be submitted in the next 5-10 year period.

Session Speakers:
Support to Innovation by EMA - Facilitating Translation of Technology into Medicinal Products
Robert Bream, EMA - European Medicines Agency, Netherlands

Agile Manufacturing: Transfer and Scale-up of Biologics Aseptic Manufacturing Processes through Control Site Concept
Karoline Bechtold-Peters, Novartis Pharma AG, Switzerland

Continuous Manufacturing in Biologics Adoption and Regulatory Engagement
Ana-Silvia Nita, MSD, Switzerland

Platform Protocol Templates: An Innovative Upcoming Tool for Comparability Assessment and Process Validation
Olga Rovira, CEPI-Coalition for Epidemic Preparedness Innovations, Belgium