In a 31 October 2019 “Ask the Expert” presentation, Nicole Wakes (group leader of Abzena’s cell-line development team) observed that drug sponsors often outsource their early upstream activities to a few different contract research organizations (CROs). But that strategy can thwart short timelines and introduce regulatory and financial risks. Wakes described Abzena’s upstream approach, illustrating how partnering with a single, multicompetent CRO from cell line construction through manufacture can streamline workflows. Integrating cell line development and manufacturing in this way promises to ease process transitions, reduce the incidence of process variability, and prevent resource duplication.
Sponsors often need a few third parties to get through upstream activities. In a typical workflow, one vendor handles research cell bank (RCB) development, then passing clone candidates to another for expression stability assessment. Only after that does the original vendor — or another — start good manufacturing practice (GMP) production. But such arrangements can hamper later, more costly processing stages. Sponsors lose valuable time waiting for stability testing to conclude. More troubling is process variability. Each organization selects its own equipment and follows its own protocols. Significant differences in process parameters can raise red flags for quality control and compliance.
Abzena leverages a global analytical workflow to secure and streamline bioprocessing efforts. Teams in Cambridge, UK, support cell line development. Meanwhile, a sister site in San Diego, CA, focuses on antibody manufacturing development and quality control testing, including assessments of antibody stability and method qualification and execution. A unit in Bristol, PA, addresses antibody–drug conjugate (ADC) manufacturing. Because of that multidisciplinary network, Abzena can harmonize all units’ methods, instrumentation, and documentation, limiting process variability — and the need for repeated runs to check scale-up conditions.
The company’s carefully integrated network also gives sponsors a unique opportunity to speed therapies to clinical trials. Rather than waiting for another party to complete stability testing before transferring the RCB and initiating GMP manufacturing, Abzena can ship relevant materials and documents to San Diego to perform those steps simultaneously. Sponsors can save four to five months compared to typical timelines with that capability.
Structured communication channels facilitate transitions between sites. Abzena designates a single project manager during cell line development. Because of that person’s direction, and because the company’s various sites all are on the same team, analytical method development can begin during RCB cultivation — earlier than it would in a multivendor approach. Upon completion of RCBs in Cambridge, the project manager supervises transfer to San Diego, as does an onsite cell line development scientist who oversaw the Cambridge production process. Standardized forms — listing specifications for cell line performance, culture parameters, feed/media regimes, and product purification — bolster the knowledge those representatives bring from their sister site, providing for seamless transitions into the San Diego facility. Sterility testing certificates, stability report findings, assay development reports, and other such documents — all produced in harmonized templates — accompany technology transfer materials to ensure GMP compliance.
Sticking with a single CRO from vector construction through manufacture is invaluable because it begets familiarity. Abzena teams gain deep understanding of sponsor materials and requirements. Thus, it can accelerate timelines and transfer technology seamlessly. Close, consistent collaboration ultimately is what decreases operational and regulatory risks while saving time, effort, and cost.
Questions and Answers
How does Abzena’s acceleration plan differ from accepting the risk of transferring without an expression-stability study? By initiating stability study while starting process optimization for high-producing clones, we can scale up as soon as we have selected the most stable clone. We also will have started analytical method development and formulation study early, reducing timelines later in the workflow.
Have you encountered cases in which product quality was different than clone quality? Differences in quality usually are insignificant. Quality attribute testing sometimes reveals different glycan profiles between clones and their products, but such discrepancies are slight and usually quantitative rather than qualitative.
What criteria do you recommend for evaluating cell-line stability? Abzena uses industry-standard, expression-based criteria. First, we develop a cell line out 60 generations. Then we determine whether its expression is ±30% from original titer.
The full presentation of this webcast can be found on the BioProcess International website at the link below.