PHARMACEUTICALS

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Uribe - Look for most specifically applicable regulation

‣ where implementing compliance was also an opportunity to streamline an extremely complex process . Changes were therefore made . “ In the future state mapping , we basically decided that he wanted to take a more holistic CAPA plan rather than individually issued CAPA documents .” The CAPA process optimisation was demonstrated using retrospective data against the new process to show increased performance potential . CAPA data from January 2019 to January 2021 using the existing CAPA process was compared against the optimised process flow . The output of that assessment revealed a 29 % reduction in the CAPA-related documentation issued if the new process had been used over the last year , demonstrating an overall reduction in terms of the numbers of requests submitted , InfoCards created and workflows processed . In addition , although the new process is more comprehensive and

overall processing takes longer to close each CAPA , it is expected to greatly reduce the total time needed by eliminating process steps and the number of CAPAs needed , potentially over 4,400 hours less of processing and review time over almost two years . “ The CAPA Plan in the future state will be developed and approved in parallel with the deviation and non-conformance document ,” Dillion said . “ Under this approach , the CAPA Plan is a lifecycle document and final CAPA closure in the streamlined process closes the full CAPA lifecycle . “ This eliminates the potential for any auxiliary activity to remain open when the CAPA is closed . It also reinforces the importance of the CAPA . The final process that Alcami ended up with was considerably simpler , as well as being more compliant .” This is all shown in Figure 2 .

FDA view

When the FDA decides whether to classify a combination product as a drug , biologic or device , it looks at the primary mode of action ( PMOA ). This , in Uribe ’ s view is the essential element in determining a regulatory strategy for combination product submissions , including which FDA review centre will be the primary one for the application review . “ What they are looking at is the action of a combination product ,” Uribe said . If the PMOA is that of a drug , the agency centre charged with the pre-market review will be CDER ; for a device , CDRH ; for a biologic , CBER or possibly CDER . Where the

Figure 2 – CAPA process flow – future state ( draft )

Effec5veness check fail & CAPA closed

Secondary assessment – inves5ga5on or new CAPA

PMOA is not clear , the FDA will look at past precedents , primary safety concerns and its own expertise . For companies who have little experience of working with combination products and who wish to understand how product classifications and jurisdictions are assigned , Uribe continued , there are three sources of informal advice . This is usually where such companies start . “ You can simply email the FDA Office of Combination Products , who deal with simple issues , uncertainty and process concerns ,” she said . “ They can help in determining whether a request for designation ( RFD ) or a pre- RFD meeting is needed .” The pre-RFD is the most common option for firms routinely working the combination product space . It leads to feedback but this is non-binding . The last stage is the RFD , a formal , binding determination process that generally takes about 60 days . This is the preferred option where complex issues are involved or if there is any dispute and / or uncertainty associated with the combination •

Brianna McElfresh

SALES & BUSINESS DEVELOPMENT MANAGER

ALCAMI

k + 1 910 604 4688 J brianna . mcelfresh @ alcaminow . com j www . alcaminow . com

MAY / JUN 2021 SPECCHEMONLINE . COM

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