Pharmaceutical Technology - May 2018

Pharmaceutical Technology eBook - Biologics and Sterile Drug Manufacturing

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Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 53 FDA's 1987 process validation guideline defined validation as "Establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a prod- uct meeting its pre-determined specifications and quality attributes" (5). In 2000, ICH Q7A defined validation as, "A documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting pre-determined acceptance criteria" (9). Process validation The concepts presented in the definitions of vali- dation and process can be combined to form a meaningful definition of process validation ap- plicable to the production of pharmaceuticals and biopharmaceuticals. FDA's 2008 draft process validation guidance document defined process validation as "the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products" (6). The 2008 definition falls short in several areas, not the least of which is that the process is capable of delivering quality products instead of that it does deliver quality products—and does so con- sistently and reproducibly. Also, the term "quality products" is nebulous. Does quality relate to meet- ing regulatory requirements? Or, does it relate to product safety and efficacy? ICH Q8(R2) provides an excellent description of process validation vis-à-vis product develop- ment (10). Process validation, based on the combination of the definitions of the words process and valida- tion, is establishing, documenting, and verifying that the inputs, operating through the processing system, result in outputs that consistently meet pre-determined acceptance criteria and quality attributes. This definition is remarkably similar to FDA's original 1987 definition of validation. In essence, process validation is documented process understanding. Why validate? Validation is necessary throughout a product's life- cycle, from initial development through commer- cialization, to ensure it is safe and effective. The molecule originally identified as possibly having clinical significance must be fully characterized and its synthesis routes developed with the aim of scalability. Formulations to be used in clinical trials must be developed. The clinical formula- tions must be scalable to commercial production, retaining their effectiveness and safety attributes. Commercial production processes must be robust and reliable to ensure consistent product quality, maximize efficiency, and minimize cost. Process validation should—read must—begin at the very beginning to ensure the finished product can be manufactured and controlled to provide requisite levels of clinical effectiveness and patient safety. Products manufactured with validated processes almost invariably meet all regulatory expectations and quality requirements. How to validate Start by thinking about the goals: What is the pur- pose of the study; what should it show, or prove, or demonstrate? Successful validation efforts often follow the 80-20 rule—80% of the effort should be thinking, evaluating options, and planning, and

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