Pre Conference Workshop Day
9:00 – 12:00 pmWorkshop A
Building an Analytical Development Strategy to Best Support Process Development
Synopsis
Effectively defining virus quality is the heart of successful gene therapy product development. Process analytical technology (PAT) is essential to providing information on critical quality attributes (CQAs) throughout the manufacturing process and QC release testing. Realtime process feedback is essential for increased process monitoring and control to ensure manufacturing success, but often critical process feedback is delayed due to lengthy testing times. Consequently a harmonised and efficient approach to-process analytics is hugely advantageous.
This workshop will set out to address:
• Defining standard operating procedures and analytical standards in quality control
• Analytical standards for the characterisation and stability of raw materials: setting up analytical standard stability programmes and characterising off-the-shelf-material to track stability
• Addressing challenges in scaling up the upstream/ downstream process development
• Enhancing bridging assay transfer from analytical development to quality control
• Strengthening the link between quality and process development teams: enhancing communication, knowledge transfer, and manufacturing/PD in GMP investigations
• Ensuring product compliancy and quality in analytical assays, and discussing methods of handling complex functional assays in the QC team
1:00 – 4:00 pmWorkshop C
Biological Standardisation for Bioassays – Developing Appropriate Reference Materials & Consensus Standards
Synopsis
Reference standards are a critical component of process control strategies for therapeutic proteins. Although some international or national standard materials are available for gene therapy products, most manufacturers are developing their own product-specific internal reference standards for product development and commercialisation. For this unique class of products templated approaches to reference standards should be feasible for accelerating development. This workshop will set out to address:
• Gene Therapy standardisation and best practices for establishing, characterising, and qualifying in-house primary reference material and working reference materials
• Outlining the need for consensus standards to be defined
• Discussing which reference materials are necessary to develop and safe and efficacious product
• Discussing appropriate analytical standards and critical reagent identifications and qualifications
• Translating your reference standards from early phase to late phase assays
• Understanding how to adapt your reference standard when you have made process changes: and developing new reference standards representative of the new manufacturing standard
9:00 – 12:00 pmWorkshop B
Preparing for Late-Stage Extended Characterisation
Synopsis
Extended characterisation is a pivitol piece of the analytical toolbox needed to take a product through late phase development into approval. Yet with only a handfull of approvals on the market thus little to base experience from and regulatory guidelines trying to catch up with the understanding of a hugely complex product, there is still much to be understood regarding extedned characterisation. It is essential to implement simple, fast AAV quantification methods for accurately providing extended characterisation.
This workshop will set out to address:
• What variables are typically examined within extended characterisation and how is this different from a typical biologic product?
• What are regulators deeming to be “important” to look at for extended characterisation
• What assays should be selected to best support extended characterisation
• What does a phase appropriate characterisation strategy look like?
• Moving into really late stage (BLA submission) what do extended characterisation packages look like?
1:00 – 4:00 pmWorkshop D
Acing Potency Assay Development
Synopsis
Given the complex nature of gene therapy products being able to adequately demonstrate that the drug product has the ability to make had a desired effect on a given result is a difficult task. Thus, potency assay development remains one of the fields greatest analytical challenges. In vivo models used during proof-of-concept and efficacy studies provide an early readout of potency by measuring a desired physiological response in animals. For product approval, in vitro assays must be developed providing a quantifiable readout that can be validated. Although in vitro potency assays have been used in small molecule and monoclonal antibody drug development for more than a decade, applications in cell and gene therapy (CGT) product development are more recent. CGT products present specific challenges for developing in vitro potency assays due to complex or unclear mechanisms of action, complicated manufacturing processes & variable critical quality attributes (CQAs).
This workshop will set out to address:
• Should expression and functional activity both be considered within a single assay?
• Will the assay be used for characterising both the drug substance and drug product?
• What considerations for the capsid, gene, enzyme, or protein of interest need to be made?
• How to assess general cell culture considerations such as availability, growth, and morphology?
• How to assess product-specific characteristics such as compatibility with the capsid, promoter, and any interacting enzymes or proteins?
• What is best practice for characterisation of the cell line to facilitate expression and functional assays?
• What is the importance of fine-tuning of cell culture conditions such as the cell density, plating format, and time for transduction?
• What detection method is used to quantify the output from the functional assay (extraction, linearity, specificity, accuracy, and precision for the analyte of interest)?
• What does long term programme management look like for potency as the life cycle of your product evolves