Issue link: https://www.e-digitaleditions.com/i/1462272
www.biopharminternational.com Quality and Regulatory Sourcebook eBook March 2022 BioPharm International 9 the overgeneration of deliverables with questionable value. Documentation generation, as opposed to critica l thinking, has played a much bigger role in the CSV process. The goal of CSA is to switch the focus during the CSV planning process. With CSA, additional inputs such as vendor audit results, system criticality (i.e., does it directly or indirectly impact product quality/patient safety), and addi- tional upstream and downstream con- trols in the production process should be considered when assessing risk, which drives the assurance/validation plan. In addition to ensuring critical think- ing is an essential part of validation planning, CSA introduces alternative testing techniques such as unscripted and ad-hoc testing where there is no longer the expectation to generate detailed step by step instructions for medium and low risk features. This makes protocol generation more effi- cient and less prone to documentation related issues, while increasing protocol test coverage. CSA also recommends that the routine use of capturing screen- shots and the recording of Actual Results is curtailed and is instead lim- ited to situations where these activities add value, such as when a test case fails. In summar y, CSA is ver y much part of CSV—they are not two sepa- rate processes. CSA is used to ensure critical thinking is applied during the CSV lifecycle and that the resulting validation evidence is captured (i.e. 'documented') and appropriate. This streamlined documentation approach leads to a significant reduction in CSV time (and consequently, time to begin realizing value from the soft ware), fewer documentation issues, and poten- tially more robust testing. UPCOMING FDA GUIDANCE BioPharm: FDA is planning to draft a guidance on CSA in 2022. What are some of the key aspects of this guidance expected to be? Can you share any of the drivers going into development of this guidance from the FDA-industry work groups you are involved in? FISCA: As part of the FDA's Case for Quality program, the FDA encour- aged stakeholder participation from the life science manufacturers in identifying how to drive higher quality. As part of a 2015 Siemens Digital Industries Medical Device Executive Roundtable event, executive participants identified CSV as a major barrier for realizing value from their technology investments for continuous improvement and innova- tion. Common pain points included: • CSV takes a long time to complete. • A mounta in of documentat ion needs to be created to meet auditor expectations. • A multitude of detailed test scripts need to be generated. • The management of test script errors is burdensome. • CSV creates significant non-value overhead. The FDA's intent of the current General Principles of Software Validation (2002) was not to create these overly burdensome activities. As both the US government and the life sciences industry looked to drive more adop- tion of automation, digital technol- ogies, and advanced manufacturing to improve product quality and help protect patients, the FDA began to develop a new guidance to help reset expectations and clarify mispercep- tions on what a value-added risk-based CSV approach could look like. Some key aspects we have recom- mended and hope to see in this guid- ance include: • The promotion of critical thinking when validation planning. • Leverage vendor audit results to scale internal validation activities. If the vendor has an acceptable SDLC and conducts rigorous testing of their software, then use this information for test planning and execution. • Documentation/deliverable rigor based on whether the features of a system have a direct or indi- rec t impac t on pat ient sa fet y/ product quality. • The introduction of such test- ing techniques as unscripted and ad-hoc testing, which will ensure that the appropriate record detail has been established. • T he promot ion of autom ate d test tools. UNDERSTANDING CDRH BioPharm: It looks like this initiative is being led by FDA's Center for Devices and Radiological Health (CDRH) with the support of the Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER). Can you clarify this and comment on how pharma manu- facturers might expect this to apply to their work? Are there particular aspects of pharmaceutical manufacturing they should/could be applying CSA or does it apply to any digital system? FISCA: Our understanding is that the effort is being led by CDRH, and other centers within the FDA are aware and are internally collaborating on the upcoming CSA guidance document or are aligned with similar principles outlined in the International Society for Pharmaceutical Engineering's Good Automated Manufacturing Practice (ISPE GAMP), as there is a realization that more regulatory guidance is needed across the life sciences industry given the desired increase in automation and digital technology adoption. Pharmaceutical manufacturers are well acquainted with GAMP5, as it was originally created for the pharma- ceutical industry, and is considered the global gold standard when it comes to compliant good quality (GxP) systems. The concepts and principles in CSA are aligned with GAMP5; however, CSA highlights some of these princi- ples which are sprinkled throughout GAMP5. Any type of business pro- cess application where pharmaceutical Quality and Regulatory Sourcebook Quality: Validation Contin. on page 36