Abstract
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.
Abstract
A BioPhorum member only survey to help gain further insight around how the industry is approaching scaling the production of AAV in suspension HEK- 293 cells from lab to commercial scale.
Abstract
This member only survey looks to identify the current approaches used in inactivation of AAV viral vectors, the laboratory and large-scale manufacturing, by gathering information on inactivation alternatives to 10% bleach, known risks, issues or restrictions identified and supportive literature where available.
Abstract
A BioPhorum member survey examining approaches to testing allogenic cell therapies for adventitious viral contaminants.
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A BioPhorum member survey aimed to gather initial industry benchmarking data and interest in defining an industry position on visible particulate control strategy for cell and gene therapies.
Abstract
Climate change and global warming resulting from greenhouse gas emissions are widely recognized as the biggest threats to global health. The healthcare sector is responsible for 4–5% of global emissions, more than 70% of which are driven by supply chains.
Abstract
This paper is the BioPhorum response to the recent ICH Q14 and Q2(R2) consultation. Overall, the first-draft guidelines seen by the team need to be less detailed in the main body of the documents but more specific to analytical methods. The documents must also be consistent throughout (across Q14 and Q2 and between the main body texts and examples). Further, detailed examples are needed for modalities other than small molecules (e.g., biologics, cell and gene therapies, etc.) as the small molecule examples are not relevant in some key respects. In the view of the BioPhorum team, the current documents will not drive a consistent understanding of regulatory expectations and the provision of information by industry to regulators.
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A BioPhorum member only deliverable describing the work of the Plasmids subteam
Abstract
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.
Abstract
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.
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Abstract
A BioPhorum member only benchmarking survey to understand the current challenges and strategies undertaking regarding leveraging process characterization data/use of platforms to accelerate validation.
Abstract
A BioPhorum member only survey is to gather information to benchmark what analytical controls member companies are currently using to establish methods to test identity, strength, potency and purity.
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A BioPhorum member only survey to understand viral purification and clearance practices member companies are undertaking in CGT.
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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.
Abstract
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.
Abstract
Standard methodologies for generating therapeutic cell products (with or without gene modification) continue to change as the field matures. BioPhorum has identified significant gaps in publicly available information describing industrial practices for production of cell and gene-modified cell therapies. Therefore, members of BioPhorum’s Cell and Gene Therapy Commercialization workstream have generated a series of cell and gene-modified cell therapy process maps that represent example processes, unit operations and platform technologies being used in manufacturing today. These maps are intended to be used to form a common frame of reference for scientists and engineers working within the field and support collaboration to enable process improvements benefitting future cell therapy patients by supporting acceleration of commercialization of novel modalities. They are also intended as an education tool for new members to the cell therapy field.
Abstract
Viral vector manufacturing is a relatively nascent field, with companies working in many different therapeutic areas, and employing a wide range of processes and procedures. Therefore, members of BioPhorum’s Cell & Gene Therapy Commercialization workstream has generated a set of gene therapy process maps that represent example processes, unit operations and platform technologies being used within in vivo gene therapy manufacturing. These gene therapy process maps are intended to be used as an initial introduction to the in vivo gene therapy manufacture processes and so act as an educational tool for people new to the field. They are also intended to form a general platform baseline for scientists and engineers working within the field to support collaboration enabling process improvements and accelerating commercialization of viral vector manufacturing.
Abstract
A focused short supplementary member only survey to help them resolve a few remaining questions for an article which is in the final stages of writing focusing on container closure integrity testing in CGT.
Abstract
This article looks at the role of technology in the workplace and specifically how the Senior BioPhorum Connect group is addressing issues such as the use of remote working technologies, cyber security and digitizing the cGMP space.
Abstract
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).
Abstract
This paper and supporting template identifies, shares and enhances best practices and standards, improves risk controls and increases the speed of learning. It discusses a general process designed to provide a risk assessment framework and contains a ready-to-use template. This highlights the complexity of commercial-scale manufacturing as well as considering the areas to assess, potential questions to ask while assessing them, and the other parties who may have pertinent input to the overall risk assessment. The template can form the basis for discussions between a contract manufacturer and client, or between production and development departments. The aim is to address the following questions when evaluating the CGT manufacturing process: What could go wrong? What controls are in place and are they enough? What did we learn from this?
Abstract
BioPhorum member benchmarking survey on testing strategies for AAV and LVV empty, full and partially filled capsids.
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Summary BioPhorum member only document detailing feedback and suggested recommendations on EMA draft toolbox guidance for PRIME marketing authorisation applications.
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BioPhorum members provide feedback on FDA draft guidance for industry studying multiple versions of a cellular or gene therapy product in an early-phase clinical trial.
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BioPhorum CGT Regulatory Strategy workstream members provide feedback on the FDA draft guidance on considerations for the development of CAR-T cell products .
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BioPhorum CGT Regulatory Strategy workstream provided feedback on FDA draft guidance on human gene therapy products incorporating human genome editing .
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BioPhorum CGT Regulatory Strategy workstream response to revised chapter 5.14 leading to EDQM Pharmeuropa monograph 34.3 gene therapy products for human use, chapter 5.34 and chapter 5.2.12. This content is available to BioPhorum members only.
Abstract
This member document summarizes consolidated feedback and recommendations from a collaboration of BioPhorum members on the FDA draft guidance for industry studying multiple versions of a cellular or gene therapy product in an early phase clinical trial consultation.
Abstract
A cross sub-team team of 18 members from 14 companies submitted feedback on WHO Approach towards the development of a global regulatory framework for cell and gene therapy products (document WHO/BS/2022.2424)
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BioPhorum member only summary document providing feedback and recommendations to FDA consultation Human gene therapy for neurodegenerative diseases: draft guidance for industry
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Summary of member feedback and recommendations on British Pharmacopoeia: Guidance on the application of flow cytometry for the cell and gene therapy community. A member only document.
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A BioPhorum member only summary document detailing consolidated feedback and suggested recommendations from the High-Level Analytics team on MHRA / British Pharmacopoeia: Guidance on the application of vector copy number for the cell and gene therapy community​.
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A member only survey to benchmark industry experience with replication competent AAV testing. The outcome of the survey will help stimulate further discussion of the topic within the workstream.
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BioPhorum member only survey exploring how member companies are using leukopaks and the key challenges facing the industry.
Abstract
This conversation with the authors highlights the important challenges within the RNA field that are being addressed by the RNA workstream within BioPhorum Cell & Gene Therapy . The paper introduces this critical area and shows its unique challenges.
Abstract
Cell and gene therapies (CGTs) are medicines with enormous potential to create personalized therapeutics for patients with diseases that were once untreatable. However with these opportunities come challenges. One is how IT and CGT teams understand each other’s needs and challenges – only once this knowledge gap is bridged will CGTs be produced and administered commercially. This paper uses analogies to help specialists from CGT and IT to discuss and understand the key issues in commercializing CGTs and important aspects of IT systems and infrastructure. The analogies also reveal those differences in a relatable way that stimulates creativity and joint problem solving, which are critical in this fledgling but fast-growing industry.
Abstract
There are many differences in manufacturing cell and gene therapies (CGTs) compared to established small molecule and biologics platforms and this profoundly affects the IT systems requirements. Some products are personalized so the process includes personal screening and sequencing data, with traceability and data privacy throughout. Starter cell variability adds complexity to a manufacturing process that must have a rapid turnaround, very dynamic scheduling and rapid deviation management. Outcomes must be tracked for the long term to improve patient outcomes as well as to support novel reimbursement models.Industrialization of CGTs therefore needs the support of advanced systems for manufacturing execution, orchestration, traceability, scheduling, patient data and outcome tracking. Some processes will be encapsulated in closed systems, and there may be analytical requirements for continuous process verification and dynamic adjustment. Operators distributed across the globe will be supported remotely by augmented and virtual reality technologies. This paper helps executives and IT professionals to understand the IT needed to support CGT manufacture, and stimulates collaboration across the industry to meet these challenges.
Abstract
This paper discusses the issues around trace elements and gives a suggested approach for developing a method for analyzing trace elements in cell culture media and hydrolysates. The approach is based on a ground breaking BioPhorum collaboration that shared blinded data and compared analytical methods between biopharmaceutical and media manufacturers.
Abstract
A BioPhorum member only survey identifying member input on container closure integrity testing and reserve sample testing in CGT.
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A BioPhorum member only survey to gather opinion on potency and Infectivity testing in cell and gene therapy.
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A BioPhorum member only survey on stability testing in cell and gene therapy.
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A BioPhorum member survey looking at sterility and bioburden testing during batch manufacture/release testing of gene therapy products within BioPhorum C> member companies. The results are available to members of BioPhorum C>.
Abstract
Historically, the biopharmaceutical industry has relied on traditional pharmaceutical manufacturing practices to make and release products. This publication examines the future of biopharmaceutical manufacturing by presenting the vision of fully implemented in-line monitoring (ILM) and real-time release. This aspirational vision includes full ILM, predictive analytics and advanced process controls (APC) enabling release of product in real time, with concomitant predictive and preventative alerts and resolution of process, equipment and other production issues.
Abstract
This commentary highlights the published work from the BioPhorum Validation workstream indicating the unique challenges and possible solutions when attempting to validate cell and gene therapy products.
Abstract
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.Â
Abstract
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.
Abstract
A survey to understand what the industry current understanding of the FDA approach to fresh versus cryopreserved apheresis as a starting material for autologous/allogenic cell therapy programs.
Abstract
BioPhorum response to British Pharmacopoeia ATMP working party draft Part 1 guidance; ‘Characterisation of the Particle Population in AAV Products’.
Abstract
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.Â
Abstract
This BioPhorum member only questionnaire presents a tool for sponsors to ascertain the suitability of the contract organization services and for the contract organizations to understand the scope, requirements, and timelines of the RNA transfer project.Â
Abstract
Member only document highlighting the scope and initial desired focus of the RNA workstream within BioPhorum C>.
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BioPhorum member only benchmarking exercise seeking member experience on expectations for mycoplasma testing of cell therapies.
Abstract
A BioPhorum member only benchmarking survey to understand industry approaches to evaluating containment of single-use closed system failures resulting in spill, splash or aerosol release.
Abstract
The purpose of this BioPhorum member only survey is to understand current industry best practices, understand member experience and if any of the workstream members has had regulatory success leverage prior knowledge.
Abstract
This article and template summarize the main steps in a suggested EHS risk assessment process and can form the basis for discussions between a contract manufacturer and client or between production and development departments.
Abstract
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.
Abstract
Two BioPhorum member only blinded surveys to gather data on the use of transfection reagents.
Abstract
This BioPhorum member only publication is intended to provide a guide of unique RNA product aspects that should be discussed during the NPI kick off meeting for an RNA product to enhance the probability of success of a product transfer between sponsor and contract organizations.
Abstract
A BioPhorum member only survey to understand how companies are performing viral clearance studies prior to Phase I/II and if members are including these studies within IND submissions for AAV products.
Abstract
A BioPhorum member only survey, the goal of which is to understand what the current industry standard is for visual inspection of final drug product bag for Phase I/II autologous/allogeneic cell therapy programs.
