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www.biopharminternational.com June 2018 BioPharm International eBook 21 Single-Use Systems Qualification BPSA: The qualif ication steps and order may vary depending on if the single-use system is going to replace an older process or if it is brand new. In addition, some activities may be run in parallel, some may not be required depend- ing on the circumstances (e.g., sin- gle-use in upstream applications versus downstream of the final sterilizing filter). With the intro- duction of a brand-new process, after selection of a supplier (NB: may require a user requirement specification), prototype has been tested, and drawing and proposal is final, the following steps would be typical: • Ve n d o r a u d i t a n d q u a l i t y agreement template (1) • Vendor documentation check (c e r t i f i c a t i o n o f a n a l y s i s , c e r t i f ic at ion of i r r ad iat ion, particulates testing, pyrogen- free claims, stressed conditions st ud ies a nd shel f-l i fe/e x pi r y c la i m s, compat ibi l it y [V H P, gamma, product, E/L], animal- free claims, TSE/BSE Statements, materials of construction and design, product sheets • Raw material specification, QC release process • Va l id at ion (may i nc lude a n assessment of vendor data on E/L , integrit y tests, bacterial challenge tests, rupture tests, sterilization validation, etc.) • Standard operating procedure • Training • I ncor p or at ion of si ng le - u s e process in batch record. Modifying an existing process would require a change control. Pora (Pall Biotech): For each sys- tem, the user must be sure that [the system] has been qualified and validated for the function/applica- tion it is meant for. Each of the quality attributes must be defined, and all necessary regulatory and end user requirements must be met. It is easiest to start with com- ponents, and then validate the complete system. The best way to do this is often through sup- ply chain qualification. Risk assess- ment will play a significant role in evaluating the extent of validation which is requested. B u l p i n ( M i l l i p o r e S i g m a ) : T h e process for qualifying single-use systems can var y based on the complexity of the single-use sys- tem, the criticality of the process step where the system is being used, and the phase (e.g., clini- cal Phase I, II, or III, or commer- cial manufacturing) of the process where it's being used. The quali- fication strategy and plan should be d r iven by a r isk assessment that considers the f luid contact materials of construction and the application where the system is being used. In addition, the risk assessment needs to consider the a mou nt of h istor ica l data a nd knowledge that already exists for components within the system, the method of sterilization, shelf- life of the system, and the data and documentation provided by the single-use supplier. At a high level, the process to qualify a new single-use system is as follows: • Demonstration that the single- use system is 'fit for purpose'— whether the system meets your pre-defined requirements and whether you are able to process at t he de si r able cond it ion s (temperature, pH, pressure, time, etc.) w ithout impact to your process or the integrity of the single-use system. • Identification of fluid contact materials of construction. • C h e m i c a l c o m p a t i b i l i t y a s s e s s m e nt — i n s o m e c a s e s supplier data can be leveraged. In other cases, additional testing may be required. • E&L assessment—in some cases supplier data can be leveraged. In other cases, additional testing may be required. • Supplier qualif icat ion— Have you worked with the supplier before? Do they have a strong reput at ion i n t he i ndu st r y? A re t hey able to meet you r r e q u i r e m e n t s ? H a v e y o u performed a technical visit or aud ited t heir manufac t u r ing f a c i l i t i e s a n d / o r q u a l i t y systems? These are all questions that should be asked prior to purchasing a new single-use system. • R aw m ate r i a l s p e c i f ic at io n review and approval. • Tox icolog y a ssessme nt w it h c ustomer's process and dr ug product. • P r o c e s s q u a l i f i c a t i o n w it h customer's process. Hower and Lu (SGS): The qualifi- cation of single-use systems is a s c ie nc e - d r ive n a nd r i sk- ba s e d approac h. It was desc r ib ed i n United States Pharmacopeia (USP) <665> and <1665> drafts published on Pharmacopeial Forum (PF) 43 in 2017 (2,3). A risk assessment needs to be performed on all compo- nents used in the manufacturing of pharmaceuticals. The testing requirements are based on the results of the risk assessment. The initial assessment exam- ines whether the single-use sys- tem is fit for its intended use with respec t to pat ient sa fet y w it h- out characterization. It evaluates whether there is meaningful con- tact between a component and a process stream. The later step will consider whether the mater ial, component, or system has been used to manufacture an approved and marketed API, drug substance, or drug product. When a compara- tor has been established for the component under assessment, fur-