This paper shares industry feedback after the publication of two BioPhorum papers that complement ongoing efforts in the wider CGT field. It supplements these publications by delving into identity testing and cross-contamination for plasmid master cell banks and plasmid DNA, and other plasmid DNA release tests (including DNA homogeneity, residual DNA and host RNA, and sterility or bioburden).
POI - Cell and Gene Therapy
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Closure analysis of a mock autologous cell therapy process
Dec 2021 | Cell & Gene Therapy, Commercialization, Deliverables Report, POI - Cell and Gene Therapy, Publication
In its current state, cell therapy manufacturing comprises several open and manual operations which increase the risk of contamination. Members of BioPhorum’s Cell & Gene Therapy Commercialization workstream have generated a ‘mock’ process detailing the manufacture of a generic autologous CAR-T product operated through a series of process steps combining some open and some closed system elements. The mock process has undergone an end-to-end closure analysis to identify those operations that pose the highest contamination risks, and to provide suggested mitigation solutions to minimize such risks. Suggestions include options that are currently available, as well as potential future ‘desired state’ options. This paper details the full process and summarizes potential risks and possible mitigations. The primary aim of this paper is to demonstrate systematic application of a closure analysis method on an ex vivo gene therapy (also known as gene-modified cell therapy) process so that organizations can apply similar analyses to their own processes. The secondary aim is to propose process closure solutions that companies could implement in their own operations.
The challenges of using RNA as a therapeutic or a gene editing tool
Dec 2021 | Cell & Gene Therapy, Deliverables Report, POI - Cell and Gene Therapy, Publication, RNA as a Therapeutics and a Gene-Editing Tool
While previously only found in academic, pre-clinical and early clinical stages, RNA technologies, including mRNA therapeutics, have emerged as a promising drug modality due to their essential biological role in protein expression and their potential versatility in manufacturing. RNA is in the global spotlight and is being
prioritized due to the COVID-19 pandemic. However, to maintain the current momentum as industry and agencies return to a ‘normal’ cycle of development for a wider range of drugs and therapies, experts in this field need to come together to identify and address challenges unique to the RNA modality. BioPhorum has started this by bringing together industry leaders to identify RNA-focused manufacturing challenges, and is working toward solutions to common challenges and improving current processes. The purpose of this article is to introduce this critical area and to show the unique RNA challenges, not only limited to mRNA therapeutics already identified by the cross-industry team, but also to include how these challenges could potentially negatively impact companies and the RNA industry. It sets out what the team is hoping to achieve via this collaboration, both in terms of outputs and benefits to the industry.
Challenges for potency assay development for in vivo and ex vivo gene therapies and the matrix approach
Sep 2021 | Cell & Gene Therapy, High Level Analytics, POI - Cell and Gene Therapy, Publication, Regulatory Strategy
This paper highlights some of the challenges to develop potency assays for gene therapies and promotes a potential solution. It seeks to establish Industry alignment on the benefits of a matrix approach and provides high level guidance on how to adopt this strategy towards potency assay development and validation with examples for in vivo and ex vivo GT processes.
Risk assessment of cells used in early development
Sep 2021 | Cell & Gene Therapy, EHS, POI - Cell and Gene Therapy, Publication, Raw materials
This paper is the first in a series considering real-world scenarios where the EHS companion risk assessment template has been completed. This assessment focuses on cell expansion operations working with the cell line only in R&D labs to develop procedures and controls; it does not include production operations, such as transfection or viral infections.
Cell and gene therapy validation challenges
Aug 2021 | Cell & Gene Therapy, Commercialization, Deliverable, POI - Cell and Gene Therapy, Publication
This paper highlights the numerous challenges in validating cell and gene therapy (CGT), drug substance (DS) and drug product (DP) manufacturing processes and analytical methods. It showcases some of the challenges associated with validation of viral vector-mediated gene therapy and gene-modified cellular therapy manufacturing processes and analytical methods validation and offers potential solutions for these. It aims to make readers more aware of the complexity and challenges associated with validating CGT products and the industry-wide consensus in addressing some of these to help drive regulatory acceptance.
A discussion to help establish release specifications for master cell banks of parental host cells
Jul 2021 | Cell & Gene Therapy, Deliverable, EHS, POI - Cell and Gene Therapy, Publication
The purpose of this article is to identify, share, and enhance a framework for master cell bank (MCB) testing and release. It is intended to increase the speed of learning and ultimately influence and/or aid regulatory agencies in developing guidance or policies around GT development and manufacturing.
CGT considerations when assigning responsibilities during a product transfer between a sponsor and a contract development manufacturing organization
Apr 2021 | Cell & Gene Therapy, Deliverable, POI - Cell and Gene Therapy, Publication, Validation
With over 1000 CGT developers worldwide, the FDA expects to approve 10-20 CGT products per year annually from the year 2025. Based on this information, there is an industry emphasis on streamlining the technology transfer process for new products into CDMOs. There are many considerations that are unique to CGT and if discussed early in the NPI process, could help reduce the risk of unplanned disruptions and align expectations in the early stages. This paper presents a common understanding and proposed ownership of these unique aspects, developed via a consensus of CGT sponsor (client) and CDMO participants in the Validation workstream of BioPhorum Cell and Gene Therapy. These recommendations could serve well as pre-established expectations or as an agenda for an NPI–kickoff meeting upon the initiation of a CGT sponsor CDMO relationship.They could also be used to support master supply agreement and quality agreement discussions.
Raw materials: Cell and gene therapy critical starting material: a discussion to help establish release specifications for plasmids and the bacterial master cell banks used to produce them
Nov 2020 | Cell & Gene Therapy, Deliverable, POI - Cell and Gene Therapy, Publication, Raw materials, Raw Materials Sourcing
BioPhorum Cell and Gene Therapy is asking for your help – and is giving you the opportunity to have a say in a scientific community discussion that will influence its suggested testing practices for plasmid release specifications. The team is proposing a platform framework for testing plasmid master cell banks and plasmid DNA.
Raw Materials: Perspectives on raw and starting materials risk assessment for cell and gene therapy (CGT) processes
Oct 2020 | Cell & Gene Therapy, POI - Cell and Gene Therapy, Publication, Raw materials, Raw Materials Sourcing
The risk assessment of raw materials in the biopharmaceutical industry has been the subject of much study and review. The cell and gene therapy (CGT) field has the potential to revolutionize the healthcare industry. It utilizes novel manufacturing processes and has distinctive requirements for raw or starting materials. This paper outlines some of the unique challenges for raw materials as addressed by CGT manufacturers when working with the suppliers of materials. Case studies are presented to provide practical examples of the application of a risk matrix approach to the CGT industry and to highlight some challenges of managing raw materials for CGT manufacturing.