Issue link: https://www.e-digitaleditions.com/i/1375981
20 BioPharm International eBook May 2021 www.biopharminternational.com a quality manner, but they can give great insight into how well the site is ready to host an inspection. In addi- tion to a mock pre-approval inspec- tion, it is valuable to review internal audit f indings and make sure issues identif ied have been appropriately addressed. Finally, as the application or sup- plement for the new line moves for- ward, the t wo parties should start to discuss how they will manage the actual pre-approval inspection. Will the sponsor be onsite at the CMO or will they be remote? Onsite is always the ideal because you can work col- laboratively in real time, rather than over a phone or video call, to respond to investigator requests and questions. Since the CMO has other products for other companies being made at their plant, the sponsors usually won't be allowed in the front room because the regulators usually get into other areas, not just the sponsor's products. BEST PRACTICES FOR CMO/CDMO OVERSIGHT BioPharm: How do you select the most appropriate CMO/CDMO? Lynn (RCA): It must be the right fit the sponsor, as well as the CMO. The sponsor needs to ensure that the CMO/CDMO can adequately man- ufacture your product, and the CMO needs to ensure they can produce the product in the quantities and time- lines the sponsor mandates. A lso, before entrusting the CMO with pro- ducing the product the sponsor needs to perform thorough due diligence in their overall capabilities and capacity from an operational, as well as a qual- ity perspective. This diligence can't just be someone from commercia l operations calling the head of quality saying, 'we found the CMO and need to move forward fast'. If that is the case, run to another company. The diligence must take a multitude of factors into consideration, more than can be detailed in this response. At a high-level, you, as the sponsor, need to ensure that the CMO can manu- facture your product and their facility and equipment is fit-for-use. In selecting a CMO, make certain that you do an onsite audit. Look into the f it-and-f inish of the facil- ity. Does it present well or are there stains in the ceiling, paint peeling or holes in the wall? How does the equipment look? Are they clean and look ne w or do t hey look ba nged up a nd old? L ook i nto how t he y handle changes, investigations, and other v ita l operationa l and qua lit y processes. Look at past reg u lator y inspections and their outcome(s) and response(s). You can gather a lot of intel from seeing how well (or not) a f irm responds to an inspection. One big point here is don't get snowed i nto t he p otent ia l ly fa l s e a s s u mp t ion t h a t a C MO 's c l e a n regulator y histor y means they don't h a v e a n y p r o b l e m s . A u d i t s a n d inspec t ions a re just snap shots in t ime and t he big issue(s) may not have come up … yet. A lso, ever y- b o d y h a s p r o b l e m s . I f y o u h a v e humans working in your f irm, your pro c e s s e s a nd s y stems a re i n her- ently fallible. It's how a f irm deals with those problems that separates the good from the not-so-good. G et dow n i nto t he w e e d s a nd rev iew some dev iat ions/invest iga- t ions, change cont rols, etc. If t he CMO prevents you from doing this, it could be a f lag that there are prob- lems. Why? Because the CMO can easily redact any commercia l con- f identia l information out of these records and make them available. Bot tom l ine, when the due d i l- igence is all said and done and it's time to decide, it has to be a right f it. In tota lit y, did you have more f lags that raised potentia l risks or did the diligence come out well? If there's more risk f lags, I'd venture to guess that you may not want to move for w a rd . W he r e t he r e i s s mok e , there's usually f ire. If you're tr ying to f ind a pa r t ner to ma nu fac t u re your precious product, having a big f ire isn't conducive to having reliable production capability and capacity. BioPharm: What is required for oversight? W here do gaps in over- sight happen? Ly n n ( R C A ) : R e m e m b e r, t h e sponsor or marketing authorization holder (MAH) is ultimately respon- sible for the qualit y of the product. Whether the product is produced at t hei r ow n inter na l ma nu fact u r ing site or a CMO a cont inent aw ay, the responsibi l it y f irm ly sits w ith t he sponsor/ M A H. Nex t, how do you and CMO assure qualit y? The qu a l it y a g re ement shou ld b e one fo c a l p oi nt . O ut l i n i n g rol e s a nd re sp onsibi l it ie s , how t he sp onsor a nd CMO i nter ac t , how c h a n g e s a re m a n a g e d , how i nv e s t i g at ion s are managed, what gets escalated to the sponsor (and what is esca lated a nd when its esca lated) a re a few items. I f you're look i ng for some baseline regulator y guidance in this area, I suggest you check out FDA's G u i d a n c e f o r I n d u s t r y , C o n t r a c t M a n u f a c t u r i n g A r r a n g e m e n t s f o r Drugs: Quality Agreements. Partnerships for Outsourcing Quality/Regulations "Get down into the weeds and review some deviations/ investigations, change controls, etc." —Steven Lynn, Regulatory Compliance Associates