CMC Strategy Forum Europe Welcome

May 11, 2020 1:00pm ‐ May 11, 2020 2:25pm

Identification: M101

Keynote Presentation - Medical Products Agency and the Biotech Arena in Sweden

May 11, 2020 1:35pm ‐ May 11, 2020 2:05pm

Identification: M101d

EFPIA Biomanufacturing Satellite Session: Concept Paper 2020 Updates

May 11, 2020 2:30pm ‐ May 11, 2020 3:25pm

Identification: M102

The EFPIA MQEG Biomanufacturing sub-team has published a number of position papers and is currently progressing industry consensus activities on other key topics. Updates will be given on the progress of recent position papers relating to certain key topics such as drug device combination products, antibody drug conjugates and polysorbates. A subsequent session comprising of presentations followed by a panel discussion will be dedicated to AAV: Current Status, Manufacturing Challenges and Opportunities. The number of clinical studies in which adeno-associated viral (AAV) vectors are used for in vivo gene transfer is steadily increasing. Excellent safety profile and high transduction efficiency for numerous target tissues speak for AAV vectors in in vivo gene therapy in diseases such as coagulation disorders, hereditary blindness and neurodegenerative diseases. Gene therapies are predicted to have a similar increase kinetics as has been the case for monoclonal antibodies since the beginning of the 1980s. However, there are still a number of hurdles to be overcome in the field of manufacturing and control before a similar market penetration as for monoclonal antibodies can be envisaged. Especially the complexity of manufacturing and analytics restrict a broad application of the technology. The current main problem for gene therapy with AAV is the low yields and small manufacturing scales. Depending on the selected manufacturing technology (suspension/adherent cell culture, flatware/fixed bed, etc.), the manufacturing units may have to be significantly multiplied for larger numbers of patients, which can only be limited by significantly intensifying the process. This is also currently being pursued for the production of monoclonal antibodies. This satellite symposium will use case studies of successful AAV-based therapies to familiarize participants with the basic therapeutic mechanisms but also shed light on manufacturing-related challenges and opportunities in particular whilst also giving an overview of the regulatory challenges of AAV therapeutics.

Multi-company Survey on the Use and Characterization of Polysorbates in Biotech Products – First Results

May 11, 2020 2:50pm ‐ May 11, 2020 3:00pm

Identification: M102c

Polysorbates (PS) are the most common surfactants in biopharmaceutical products and used to stabilize proteins against various (interfacial) stresses during the product life-cycle. Commercially available PS are complex mixtures with a large structural heterogeneity and variable composition. Additionally, PS may degrade in the therapeutic protein formulation by oxidation or hydrolysis (chemical or enzymatically driven) forming multiple degradants which even may precipitate out and form subvisible and visible particles. This complexity poses challenges during different stages of product development. Within the European Federation of Pharmaceutical Industries and Associations (EFPIA) a group of 23 experts from 16 pharmaceutical companies started to exchange scientific and technical information on the use and characterization of polysorbate in biopharmaceutical products. They worked out a survey with 137 questions to benchmark the handling, analysis, degradation, control strategies, and regulatory aspects of polysorbate. Preliminary results of this survey will be presented.

CMC Regulatory Considerations for ADCs

May 11, 2020 3:00pm ‐ May 11, 2020 3:10pm

Identification: M102d

Antibody drug conjugates unite the specificity and long circulation time of an antibody with the toxicity of a chemical cytostatic drug using smart linkers to reduce systemic toxicity and increase therapeutic index. This combination of a large biological molecule and a small synthetic molecule creates an inherent increase in complexity. Multiple production processes are required to produce the naked antibody, the drug and the linker, followed by conjugation of aforementioned entities to form the final antibody drug conjugate. The connected processes further increase the number of points of control, resulting in necessity of additional specifications and an increased load of analytical characterization. By combining scientific understanding of the production processes with risk-based approaches, quality should be demonstrated at those points where control is required and redundant comparability studies, specifications or product characterization avoided. Over the product development lifecycle, this will allow process qualification to focus on those areas affected by a change and prevent redundant studies. The structure of a module 3 global technical dossier for an ADC needs to reflect each of the production processes and the combined overall approach to quality. Historically, regulatory authorities have provided varied expectations on its structure. An overview is provided of essential information to be included showing that multiple approaches work as long as adequate cross-referencing is included. This talk outlines the content of a white paper soon to be published by a workstream under the Biomanufacturing Working Group by EFPIA.

Discussion - Questions and Answers

May 11, 2020 3:10pm ‐ May 11, 2020 3:25pm

Identification: M102e

EFPIA Biomanufacturing Satellite Session: AAV: Current Status, Manufacturing Challenges and Opportunities

May 11, 2020 3:30pm ‐ May 11, 2020 5:00pm

Identification: M103

Intensifying the Viral Vector Manufacturing Process: Challenges and Progress

May 11, 2020 3:30pm ‐ May 11, 2020 3:45pm

Identification: M103a

With several recent FDA approvals and a strong drug pipeline, gene therapy is coming of age. With this comes the requirement to ensure that there are robust manufacturing processes in place in order to scale with demand and to make these therapies readily accessible to those who need them. However, current manufacturing processes for gene therapies have often been developed with limited scalability in mind and large shifts in technology have to take place to enable industrialization. This also has to be done while keeping costs in mind. Here, we will present the challenges and solutions to scale up process steps required to develop manufacture iCELLis bioreactor process for scalable production, purification and analytics of AAV viral vector. After implementation of a large-scale of the entire process, we offer the client scalability and speed to the market

Regulator’s Perspective on AAV

May 11, 2020 4:00pm ‐ May 11, 2020 4:15pm

Identification: M103c

Scientific literature shows that, recombinant AAV vectors derived from human- versus insect cell manufacturing platforms exhibit significant different potency. The causes for these differences seem currently not entirely clear. It is reasonable to conclude that we do not yet know certain important quality attributes of the rAAV products. This lack of knowledge is especially critical in case of manufacturing changes and scale-up activities during development of the manufacturing process because comparability of the resulting rAAV material has to be ensured. Thus, with respect to a future Marketing Authorization Application it is important to apply a state-of-the-art characterization panel in order to have the best possible picture of the manufactured rAAV material.

Panel Discussion – Questions and Answers

May 11, 2020 4:30pm ‐ May 11, 2020 5:00pm

Identification: M103e