BioPharm March eBook - Outsourcing Resources

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Page 22 of 34 March 2018 BioPharm International eBook 23 Outsourcing Resources Process Validation Hastings: As a CDMO, FUJIFILM Diosynth Biotechnologies has seen quite a variety of validation strate- gies. Some strategies are influenced by indication, regulatory designa- tion, or client platform. Some com- mon themes have shown themselves to aid in success of many of these projects. These themes include build- ing clear attribute‒parameter link- ages, taking a systematic approach to validation, and leveraging data- driven risk management. Clear attribute‒parameter linkage begins with a fundamental understanding of the molecule attributes, the mea- surement systems, and the potential points of variation and ambiguity therein. This knowledge of the mea- surement can then be applied to the process control strategy including any ambiguity and interaction with other attributes. A team's focus on required control becomes increas- ingly clear by applying a logically mapped linkage from attribute to the controlling parameters. A systematic approach to valida- tion that is based on consensus on both definitions and readiness crite- ria and is aimed at long-term com- mercial execution is recommended. We have refined our validation-read- iness process to achieve a balance between lean efficiency and sustain- ability. This development required careful attention to details such as definition subtleties, systematic documentation linkage, quantita- tive assessment including leveraging previous data, and systematic manu- facturing execution standards. This focus on mechanistically applying pre-built tools has proven to be suc- cessful with numerous clients effi- ciently driving their projects to success. We also recommend building an iterative and logical risk-management program that is based on data-driven decisions. As progress continues toward validation, teams can often be influenced by process history (both recent and past), which can lead to decision making with unintended consequences. We push teams to itera- tively refine risk-management docu- ments when new data come available thereby allowing them to make deci- sions based on data, even in the 'heat of the moment.' To guide teams, we have built a series of risk-manage- ment tools that range from simple and focused on one problem to large and involved FMEA [failure mode and effects analysis]. This focus on regu- larly reviewing and documenting risk and data evolution has expedited proj- ect execution in a reliable manner. BioPharm: What tools are used in process validation of biologics com- pared with solid-dosage drugs? Hastings: Biologics, when com- pared with solid-dosage product, can be a sea of parameters and attributes, many with a high degree of variabil- ity. We have a systematic approach to process validation that draws on experience from more than 300 mol- ecules; this allows us to focus atten- tion on what matters most. We first begin with high-level process map- ping intended to focus attention on parameter-attribute pairings. The next step, which includes smart use of a proprietary FMEA-like software tool, can help focus characterization and equipment adjustments to help improve process reliability. Finally, our platform quantitative assessment tool for parameter-attribute pairs confirms readiness for process valida- tion. Taking this systematic approach, we have been successful in cutting through a large number of variables to reduce variation and ensure right- first-time success for validation cam- paigns with tight timelines. UTILIZING PROCESS VALIDATION DATA BioPharm: How can the data obtained during process validation be used elsewhere? Hastings: Process validation should be designed to demonstrate the capa- bility of the process to support com- mercial manufacturing. To this end, the data generated during process validation should be the forerunner to the commercial control charts. A primary question when reviewing an initial set of commercial data should be: how do these data compare with the expected variation from my validation-preparation activities? Ideally, we expect commercial man- ufacturing to flow seamlessly from validation, but due to the artificial- perfection that can accompany vali- dation, some changes are expected. Recognizing these subtle changes, and mitigating them as early as pos- sible, can substantially improve long- term manufacturing reliability. SUPPLY CHAIN CONSIDERATIONS BioPharm: How can process validation help companies ensure their biolog- ic's supply chain is reliable? Hastings: Process validation is not just about three batches in a row. It is about launching a reliable commer- cial process. This is why we design process validation campaigns around an expectation that sustained com- mercial supply must be planned for. The quantitative pre-validation statistical guidelines and system- atic tool-sets we use for validation- readiness have been developed and built around the expectations that projects must have data to support sustainable commercial success. Approaching statistical risk manage- ment with more pre-validation runs is a common practice for many com- panies, but our [process validation] philosophy extends beyond that to leverage a large body of pre-existing data and rigorous process-agnostic testing to augment process-specific data. To our clients, this means improved knowledge of their supply chain expectations prior to process validation. BP

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