Drug delivery
RS) wrote that the guidance does not provide enough definition of terminologies: “The terminology surrounding Design Inputs, EDDOs, Essential Performance Requirements, and Primary Functions should be clearly defined to ensure there are no discrepancies in application, and to provide clarity versus existing FDA requirements and definitions.” The International Society for Pharmaceutical Engineering (ISPE) suggested changing the title of the document, to make it clear that it applies to future therapies like cell and gene therapies too. Meanwhile, the Parenteral Drug Association (PDA) suggested modifying the scope to exclude ‘standalone medical devices that are indicated for general delivery’. The CPC, say Odom and Robertson, have commented on many specific parts of the guidance. But above all, they want the FDA to afford the industry greater flexibility in terms of how they implement the new measures.
Industry leaders have urged the FDA to clarify and refine its draft guidance on drug-device combination products.
of determining what the product can withstand. Helpful though it is, Odom and Robertson suspect it may not be appropriate across the board. “Rather than being subject to a default expectation here, the industry would prefer to have the discretion to determine when, and for which EDDOs, preconditioning is appropriate,” they say. On top of that, there are some question marks around whether EDDOs/EPRs are ‘inputs’ or ‘outputs’. (Design inputs are the starting point for product design, ensuring the design requirements address what the product is meant to do. Design outputs are the tangible results of the design inputs.) As Odom and Robertson point out, the clear framing of EDDOs as ‘outputs’ came as a surprise to many companies. “Companies that have, to date, referenced EPRs as ‘inputs’ within their established quality management systems have raised concern that significant adjustments to these systems would be needed to accommodate the EDDO framework set forth in the draft guidance,” they say. “These adjustments could drive potential inconsistencies in company development processes across regions and add complexity to company compliance efforts more broadly.” There have also been some surprises around how the FDA approached the subject of design validation. “Specifically, there is some industry concern that FDA’s current language conflates acceptance criteria for EDDOs with design validation of a finished combination product or device,” say Odom and Robertson.
The way forward It’s no wonder that the industry’s response to the draft guidance has been mixed. In the months following its publication, the FDA solicited public comments. The level of stakeholder response was significant, with many asking the FDA for further clarification. The International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-
28
“CPC also strongly suggested that FDA host or actively participate in public forums to further discuss and receive additional input from industry on key tenets of the draft guidance,” they say. “CPC believes this FDA-industry dialogue will be critical in informing FDA’s development of final, or revised draft, guidance.” This kind of discussion would serve both parties well. Industry would be able to add further colour to comments submitted, while the FDA would be able to offer insight on the reasoning behind its approach. In the meantime, while it is possible that concepts from the draft guidance could come up during product reviews, recommendations from FDA guidance (even final guidance) are technically not binding on FDA or industry. In any event, companies will be crossing their fingers for a revised document that deals with the concerns they’ve raised. The final document is expected to be released in 2026 or 2027 – although Odom and Robertson caution there might be delays. “It’s unclear if this anticipated timing will hold given potentially shifting priorities under the new administration,” they say. “In addition, because this was one of the most ‘highly commented on’ FDA combination product-focused guidance documents, FDA will likely need time to carefully work through those written comments.”
In short, the industry could be facing continued uncertainty for some time to come. Not that manufacturers are deterred – innovation is progressing fast, and the FDA is receiving ever more submissions for drug device combination products. But it could be a while before we have the final word on what exactly the Agency is looking for. “CPC’s ultimate hope is for the final guidance to provide for an approach to EDDOs that allows for more streamlined submission content and reviews without compromising industry flexibility in determining the best path to meet FDA’s expectations,” say Odom and Robertson. ●
World Pharmaceutical Frontiers /
www.worldpharmaceuticals.net
Numstocker/
www.shutterstock.com
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58
