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8 BioPharm International eBook July 2021 www.biopharminternational.com nity to implement faster, more-efficient means to develop, produce, analyze and review new pharmaceutical products, all while maintaining a critical eye on safety and quality," he states. For a n a l y si s of biot he r ap e ut ic product CQAs, the advent of rapid m i c r o b i o l o g i c a l m e t h o d s , r a p i d high-throughput screening methods, rapid release and stability methods— in particular rapid bioassay methods that mimic the in-vivo functionality of the product—are all areas where enhanced turnaround times will be critical to getting new products to market, Wolman emphasizes. "The ability of the industry to meet rapid manufacturing and testing turn- around times will def ine the success and availability of promising autologous cell-based therapies," Wolman adds. For example, to support an autologous cell therapy, a patient's cells must be harvested and modified, and the mod- if ied cells must be rapidly tested for structure, function, identity, purity, and safety-related CQAs before the patient can be inf used w ith the modif ied cells. "The analytical testing requires coordination of sample shipping and receipt with critical handling, execution of assays and data review, and quality assurance approval of the samples' test- ing report," Wolman explains. "This monumental effort may have a limited timeline of one to two weeks given the short shelf life of the ex-vivo modified cells and the patient's life-depending need to receive the therapeutic." BP Biopharmaceutical Analysis Analytical Evolution Novel biotherapeutics are expected to have higher heterogeneity (variants); learning and understand- ing what these variants are will increase assurance of product consistency, says Pedro Morales, director, Catalent Biologics. He explains that massive genomics and proteomics data will need to be correlated with functionality data to identify what is truly critical to set specifications for release. "The establishment of proteomics and genomics databases are also a chal- lenge as one needs to consider not only the product, but the genetic makeup of the patient as part of the correlation. Next-generation sequencing will be cru- cial to the implementation of cell and gene therapies (CGTs) because of the nature of personalized medical approaches," Morales says. As the industry moves gradually towards more personalized biotherapeutics, the ability to craft a biotherapeutic for each patient in real-time becomes more of a reality, asserts Christopher Colangelo, biopharma business development leader, Agilent Technologies. He states that there is a need, however, to scale and commoditize lab analytical workflows so that the same robust purification and critical quality attributes characterization can be performed at a lower cost per sample, without compromising sample or data quality. Decreasing the cost of developing immunotherapeutic modalities, especially those based on CGT approaches, will be essential for their broad adoption, says Jana Hersch, scientific consultant, Genedata. "Innovative digitalization and new manufacturing practices will provide key solutions. New and enhanced digital solutions are already becoming available to support CGTs. Since cell and gene therapies often serve relatively small patient populations, miniaturization with patient- scale manufacturing represents another tangible step towards lowering costs," she says. "While these technologies predated the therapeutics, mechanisms to manage the data generated from these analytical approaches and to validate the instruments' software for GMP [good manufacturing practice] testing is lacking. For nucleic acid sequencing, whole genome and single cell-based sequencing platforms continue to evolve with new, powerful software tools to support data analysis," Marc Wolman, principal scientist at PPD Laboratories' GMP Lab says. These tools, however, require substantial manual intervention and analyst interpretation when performing the analysis or retrieving sequencing data from tangential databases, he specifies. "If techniques like AUC [analytical ultracentrifugation] and NGS [next-generation sequencing] are to become mainstream GMP methodologies, then innovations in data management and analytics regulations must be developed and implemented to meet CFR 21 compliance," Wolman concludes. The methods used to characterize, inform, and select the best biologic drug candidates are becoming more complex, requiring different analytical parameters to be assessed, observes Campbell Bunce, chief scientific officer at Abzena, who reinforces the need for speedy analysis with emerging drug platforms. For example, in the context of personalized cell therapies, a fast turnaround time from cell collection, modification, scale up, and treatment are critical to the patient outcome. "Innovative means of applying sophisticated analytics to these complex therapeutics in a fast and efficient way is required to help streamline the manufacturing process to increase the chances of success and pre-empt or reduce safety risks" he says. —Feliza Mirasol Meeting future analytical requirements for novel biotherapeutics