Columbia, MO
Recent advances in genetic engineering have given clinicians a more holistic understanding of normal and pathological metabolic processes. Bio/Pharmaceutical companies have capitalized on this knowledge to develop a wide variety of new biological and gene therapy-based treatment options for infections and diseases.
The expansion of biological modalities has led to an ever-growing need for expertise in testing these unique drug candidates. Eurofins BioPharma Product Testing (BPT) is a global leader in CMC Testing Services, providing comprehensive testing for the biopharmaceutical sector throughout the drug development life cycle.
Technical Capabilities at Eurofins BPT Columbia
The Eurofins BPT facility in Columbia, MO, is an integral part of the global Eurofins BPT network of laboratories. Constructed in 2007, Eurofins BPT Columbia consists of a 100,000ft2 facility, including 38,000ft3 dedicated to stability suites with an emphasis on both small and large molecule bio/pharmaceutical testing support. Additionally, Eurofins BPT Columbia has a second location with approximately 6,800ft2 dedicated to the synthesis of 14C radiolabeled active pharmaceutical ingredients to be used in phase 0/1 clinical trials.
Eurofins BPT Columbia has state-of-the-art biochemistry and bioassay laboratories and additional laboratory spaces dedicated to cell culture and storage, viral testing, PCR, high throughput multiplex electro-chemiluminescence, flow cytometry, and analytical ultracentrifugation. All of the aforementioned laboratories are BSL-2 compliant. The facility has rigorous systems and processes in place to ensure sample and data integrity, and all studies are conducted in compliance with ICH (Q2A and Q2B), EU, JP, FDA, and USP guidelines. The biologics laboratory has supported the testing of raw materials, drug substances, intermediates, and drug products from early phases of development through post-marketing commercial programs.
The biologics program in Columbia began in 2009 and rapidly grew to be the largest service offering on-site. The site employs approximately 120 dedicated laboratory scientists who have worked on over 100 unique drug products. They have successfully completed testing of mAbs, bi-functional mAbs, antibody-drug conjugates, recombinant-fusion proteins, PEGylated proteins, biosimilars, and cell and gene therapy products including recombinant viral vaccines and nanoparticle-based therapeutic delivery systems.
Eurofins BPT Columbia provides comprehensive testing services in cell and gene therapy (CGT), biochemistry, and functional bioassays. Along with phase-appropriate method validations and long-term stability testing, the team also offers a comprehensive array of product characterization evaluations, including molecular weight determination, protein sequencing, peptide mapping, disulfide linkage, and other post-translational modification analyses. Studies requiring SEC with various detectors, including MALS, MFI, charge variants, product degradants, truncations, and amino acid substitutions are available. Services supporting In-Use clinical and compatibility studies as well as GLP test article characterization are also offered.
According to Nathan Whitford, Eurofins BPT Columbia President, “Our site works closely with our partners to design client-specific validation and stability programs. With an industry-leading integrated laboratory information management system (LIMS), we provide not only expertise in testing but also seamless delivery of accurate data to our clients through secure electronic portals in real-time via LabAccess.com. Additionally, the ability to partner with other global Eurofins BPT locations offers a tremendous advantage for us and value to our clients and their global supply chains.” Eurofins BPT Columbia continues to be a client-focused service provider with the facility, instrumentation, and expertise to address the evolving needs of the biopharmaceutical industry.
Eurofins BPT Columbia’s Response to the Global Pandemic
The Columbia site provided key analytical testing support for a major COVID-19 vaccine manufacturer during the pandemic. Loretta Sukhu, Director of Operations, noted, “Our success in pivoting to become the North American testing site for one of the COVID vaccines was due to our capability to leverage our technical expertise in bioassays, cell and molecular biology, and biochemistry. Previous investments in key instrumentation with redundancies meant that product testing could be executed without delay.” A key contributor to the success of this program was a newly implemented 5S LEAN initiative, which ensured good management and control of lab supplies and materials. Affiliates in the worldwide Eurofins network of laboratories came together to share materials and supplies to support this work.
Similar to other North American EBPT sites, the Columbia team validated methods and conducted release and long-term vaccine stability studies to support Emergency Use Authorization and IND submissions. The site also conducted batch release and stability studies to ensure product efficacy and safety. Comprehensive studies using quantitative and endpoint PCR, cell-based recombinant viral vaccine assays, ELISAs, spectroscopy, RP-HPLC, dynamic light scattering, protein fingerprinting, and monograph testing were completed to ensure product identity, potency, purity, and safety.
Efforts to minimize viral transmission within the facility, while at the same time maintaining near-normal operations, were also a challenge during the pandemic. To ensure the safety of employees and their families, the site implemented zoning strategies and alternate work schedules. This flexibility ensured success in achieving the 5-day identity and 10-day potency testing required by the client’s need for rapid product release.
Whitford adds, “Looking back, our success was largely due to the resiliency of our team, the depth of their experience, and their desire to make a difference during one of the most challenging times in recent history. Combining this with our strong client partnerships and their commitment to patients aligns well with our mission to contribute to a safer and healthier world.”
Challenges Facing the Cell and Gene Therapy Industry
There are currently 32 FDA-approved cell and gene therapy (CGT) treatments.1 Although the development of this class of drugs is still extremely customized, highly complex, and very expensive, the therapeutic benefits are indisputable. While the market is still in its infancy, it is rapidly growing with estimates that the global CGT market will surpass $93.78 billion by 2030.2
Because CGTs are produced in living cells and may contain genetic and other biological material foreign to the patient, testing of these drugs poses a unique set of challenges. Accurate determination of product purity and residual contaminants from the manufacturing process are essential testing components in the development of all drugs, and CGTs are no exception. In addition, CGTs require additional bioassay-based analyses to ensure adequate and specific drug delivery to target tissues. Additional methods must also be developed to assess vector and transgene immunogenicity and potential off-target specificity. A thorough understanding of testing parameters, the development of highly robust testing methods, and compliance with evolving cell and gene therapy regulatory guidelines also present challenges during the development of CGTs.
To address these challenges Eurofins BPT Columbia employs their well-established expertise in cell-based functional and biochemical assays and protein chemistry. Although the specific methodologies in use are product-specific, product purity and the presence of degradants have been quantified by biochemical techniques. The presence of residual contaminants, such as host cell DNA and proteins or excipients, is determined by molecular, immunological, and biochemical techniques. Characterization of transgene expression, including infectivity titer, gene expression in target and off-target cells, cytokine production, apoptosis, and antibody-dependent cytotoxicity evaluations have been done at Eurofins BPT Columbia via quantitative PCR, electrophoretic techniques (including capillary electrophoresis), size exclusion chromatography, cell culture assays, ELISAs, particle sizing, and mass spectrometry.
The CGT testing services offered by Eurofins BPT Columbia have been strengthened by recent capital investments in key instrumentation. In addition to the endpoint and quantitative PCR offerings, Droplet Digital PCR (ddPCR) is available to provide the ultrasensitive and absolute nucleic acid quantifications needed by CGT applications. A state-of-the-art flow cytometer is also available to support clients who need to multiplex up to 13 individual targets in a single sample and a Bac-T rapid microbial identification system to support sample testing requiring quick turnaround times. Additional instruments include an analytical ultracentrifuge for characterizing viral particles, as well as instrumentation to determine the physical properties of large macromolecules using SEC-MALS. As previously discussed, the Columbia site is equipped with full peptide mapping, protein purity, and identity determination capabilities.
Regulatory guidance to ensure product safety and quality requires the accurate qualification of all custom components, matrices, and ancillary materials used in CGT product manufacturing. The Columbia site has onboarded a Biologics Raw Materials testing group to support these regulatory requirements. Due to the criticality of these materials for the manufacturing process, the site currently offers platform methods for raw materials testing with a strong emphasis on meeting the rapid turnaround times required by our clients. Select offerings in raw materials testing encompass cell-based assays for functional activity, cytokine assays, ELISAs, as well as protein concentration, and product identification utilizing an array of methodologies including, spectroscopy, qPCR, HPLC, FTIR, AAA, and capillary electrophoresis. Eurofins BPT Columbia has supported raw materials testing of components needed for the production of a CAR-T-based therapeutic. This testing was accomplished using electrophoretic, enzymatic, and cell-based assays to evaluate both identity and activity.
Outlook on Cell and Gene Therapies
Over the last decade, Eurofins BPT Columbia has seen the rapid evolution of effective cell and gene therapies. The market space for new CGT products is projected to expand dramatically in the near future due to these early clinical successes. New therapeutic interventions, delivery systems, therapeutic enhancers, and production methods are constantly emerging. In order to meet the current and future needs of this important biopharmaceutical sector, product testing facilities have to remain agile and focused on emerging targets and testing methodologies.
To serve this industry, Eurofins BPT Columbia has made significant investments in personnel, facilities, and instrumentation. With its strong technical team and state-of-the-art instruments, coupled with LEAN and automation initiatives, Eurofins BPT Columbia is well-positioned to meet the testing needs of this rapidly growing sector. While the industry has standardized some of the well-studied processes, CGT technologies are often times ahead of prevailing regulatory guidelines. Together with Eurofins’ BPT global network, Eurofins BPT Columbia is well-positioned to navigate this complex regulatory environment in order to continue providing comprehensive and expert services to customers.
References
1. BioInformant. List of U.S. FDA Approved Cell and Gene Therapy Products (32). August 16, 2023 By Cade Hildreth
2. Global Newswire Nov.30, 2022
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