BioReliance® Cell and Gene Therapy Testing Services

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Gene therapy and gene-modified cell therapy developers provide life-saving treatments to many patients. A critical part of the development process are the biosafety tests and characterization of the cell and viral products. These vital steps help you to mitigate safety concerns and gain a better understanding of your product and process well in advance of patient administration.

A lot has changed since we first started partnering with cell and gene therapy clients 30 years ago, and we continue to evolve and transform as a testing partner with our clients. Our BioReliance® gene therapy services provide the confidence to get products to market quickly and safely. We provide you with best-in-class biosafety testing of clinical and commercial products, giving you:


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Viral Vector Characterization Services – Innovative Solutions

Clients benefit from our innovative development programs and comprehensive solutions for viral vector therapies. We offer the widest range of assays to fully characterize and analyze the identity, potency, safety and stability of your vector. Due to the unique nature of gene therapy products historically, fully customized methods were required to address safety and characterization, resulting in longer development timelines.

Our strategic R&D team evaluated the complete gene therapy development and testing process and identified key assays that could shift from a fully custom approach to a platform approach. These assays have been developed and validated as a platform allowing for specific parameters to be customized, for example the gene of interest, requiring minimal additional qualification work to maintain the validated state.

We have extensive experience with key vectors including:

• Adeno-Associated Virus (AAV)
• Retroviral/Lentiviral vectors
• Adenovirus

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The BioReliance® Testing Services Advantage

Acceleration The optimal balance between speed and customization will give you the confidence to get products to market quickly and safely	Expertise Our R&D team is continuously innovating to optimize existing assays and establish new platform assays that can be tailored to meet client-specific needs
Flexible Approach Client-specific testing programs utilize a unique set of pre-developed assays, customizable to your specifications, and will help you meet your critical development timelines	Proven Results Our cell and gene therapy assays have been included in regulatory filings with various agencies worldwide

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Gene Therapy Testing Requirements

	Plasmids	Cell Banks	Virus Seed	Unprocessed Bulk Harvest	Purified Bulk Harvest	Final Lot	Transduced Cells
Cell Line Characterization		✔
Adventitious Agents	✔	✔	✔	✔	✔	✔	✔
Identity	✔	✔	✔	✔	✔	✔
Titer			✔	✔	✔	✔
Biological Activity					✔	✔
Residuals					✔	✔
Product Characteristics i.e. Osmolarity, Appearance, pH						✔
Replication Competent Virus Testing				✔	✔
Gene Expression					✔	✔	✔
Vector Integration							✔
Plasmid Monitoring					✔

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Flexibility and Innovation in Vector Characterization Methods

Testing Category	Traditional Methods		Novel Methods
Safety	Sterility Mycoplasma Spiroplasma in vitro and in vivo assays for adventitious viruses	Replication competent virus (co-cultivation assays with infectivity, PERT or qPCR endpoints) Endotoxin	Rapid sterility by BAC-T/Alert® 3D Rapid Microbial Detection System Pinnacle Q-PCR™ assay for rapid mycoplasma and spiroplasma detection Replication competent virus assay for lentivirus, adenovirus, AAV, etc.
Genetic Characterization	Sanger sequencing qPCR		Next Generation Sequencing (NGS) Droplet digital PCR (ddPCR)
Purity	PCR for: Residual plasmids Residual host cell DNA DNA sizing E1A and SV40 (293T cells) ELISA assay for: Host cell protein Residual Benzonase® endonuclease Residual BSA Appearance Particulates		ddPCR Pinnacle Q-PCR™ assay AUC for empty/full capsid
Identity	PCR identity assay Immunochemical methods Restriction enzyme analysis		Vector identification by qPCR NGS Mass Spec
Potency	Titer (infectious virus & genomic titer) Potency of expressed protein		ddPCR (genomic titer)

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Gene Therapy Development Pathway

Open each step below to learn more about the testing solutions necessary to meet regulatory requirements.

Raw Materials Raw Materials: For many new therapies, especially cell therapies, it is very difficult to remove human or animal-derived products from the manufacturing process. If these materials are used in the process, then it is essential that they be thoroughly tested to ensure the absence of adventitious agents.	Process Clearance Process Clearance: Unlike traditional biopharmaceuticals and non-enveloped viral vectors (e.g. AAV and Adenovirus), enveloped viral vectors, such as Retro and Lentivirus, as well as cell therapies cannot claim viral clearance for their manufacturing processes. Given the nature of the product, it is not possible to separate or inactivate potential viral contaminants without adversely impacting the product. Viral inactivation and removal steps can be included in the manufacturing process for non-enveloped viral vectors, and the viral reduction can be claimed for many such processes.
Cells Cells: Cell banks used to manufacture biological therapies must be thoroughly characterized according to regulatory guidelines for biologics, and tested to ensure the absence of adventitious agents. This testing may include verification of the cell type, tests for bacteria, fungi, mycoplasma and possibly mycobacteria, broad specificity viral assays as well as assays for specific viruses, and assays for retroviruses.	Purified Bulk Purified Bulk: Purified bulk should include a verification of identity, such as confirmation of the gene of interest, confirmation of AAV serotype, etc. Quantitation of infectious titer, genome titer and potency are appropriate at this stage. The absence of microbial contamination and replication competent vector should also be confirmed. Verification of the absence of residual product and process impurities is also advised.
Unpurified Bulk Unpurified Bulk: Testing of unpurified bulk, which may include transfected producer cells, should include verification of identity, and may involve confirmation of the gene of interest. The titer of the vectors should also be determined at this stage. The absence of replication competent viral vectors should also be confirmed. Tests for microorganisms (e.g., bacteria, fungi, and mycoplasma) are appropriate for this material, as are broad specificity assays for adventitious viruses.	Final Product Final Product: The identity of the final vector product must be confirmed, and this testing may include the sequencing of the gene of interest, infectivity titer, genomic titer and potency testing. Sterility and levels of endotoxin should be analyzed. In addition, characteristics of the final product should be determined, this may include vector aggregation, pH, osmolality, appearance and particulates.