Chapter <665> of the United States Pharmacopeia (USP), which focuses on single-use systems (SUS) and container closure systems storing pharmaceutical and biopharmaceutical products, stands on the precipice of significant change, and biomanufacturers need to prepare now before it’s too late.
The revisions to the chapter represent a significant shift in how SUS and container closures are regulated. Currently, USP <665> has no mandatory requirements for compliance, but that is about to change. The revisions to the chapter were formally approved in 2023, but the USP General Chapters–Packaging and Distribution Expert Committee extended the official effective date to May 1, 2026, to give the industry time to comply with the new regulation properly.
For most biopharma manufacturers, 2026 seems a long way off, but that date will quickly come around. Those failing to prepare for this change may be at the back of the line. The change will make USP <665> mandatory, and no products currently on the market will be grandfathered in.
How Biopharma Manufacturers Can Prepare
As this regulatory evolution looms, the importance of early preparation cannot be overstated. The chapter’s forthcoming revisions herald a significant shift in regulation for single-use systems (SUS), moving from guidance to mandatory compliance.
The extension is a grace period for adaptation, not a delay for action. Starting now ensures compliance readiness, avoiding the rush and potential backlog as the deadline approaches. The fact that all biopharma manufacturers must be certified from the start underscores the urgency for manufacturers to act promptly to ensure their products remain on the market. Current biopharma manufacturers are likely to fall into one of three categories:
Those who have done no testing on their single-use systems. These manufacturers are starting from the ground up and, in many ways, have the most straightforward task. They should seek to understand what the revised version of USP <665> will require and get in line with a testing partner now. As this group does not have processes established, nor has it identified appropriate lab partners or earmarked budget, it may have a challenging path to compliance. Fortunately, there is plenty of time as long as they’re proactive.
Those who tested based on BPOG guidelines. Many manufacturers took it upon themselves to conduct testing based on the best practices strategy of the BioPharma Operations Group (BPOG). If manufacturers used the BPOG protocols, then it is likely their data will comply with the new USP <665> requirements. The new guidance resulted from years of collaboration between USP and members of BPOG, but compliance is not guaranteed, and a gap assessment is the first step. Manufacturers would do well to put in the work now to make sure they’re not left behind.
Those who conducted their own internal testing. Some manufacturers will have conducted their own testing using old or outdated test methods. This group won’t know where they stand concerning USP <665> and should take a very active approach to avoid a lot of time-intensive work further down the line.
Regardless of which category to fall into: Engaging a trusted lab partner now will get you concrete answers to your questions and ensure you aren’t left behind as the 2026 deadline nears. The cost of pulling non-compliant products from shelves could be significant compared to the time and effort required to get the work done beforehand.
The Advantages of Planning Now Rather Than Later
Embracing early preparation for the USP <665> revision offers a strategic advantage. Manufacturers with the foresight to address these changes head-on can prevent significant backlogs, navigate inevitable regulatory shifts, and manage substantial financial implications with strategic budgeting. Acting promptly will ensure a smooth transition and mitigate interruption to market demands. Additional advantages to proactive planning include:
Avoiding big backlogs
There will be no exceptions to the new rules once they come into effect and no grandfathering of existing products. That means there’s likely to be gigantic queues to get products compliant.
A second timing concern biomanufacturers must consider is the extension period for Europe’s MDR compliance for medical devices. In 2023, EU states voted to extend the transition period to May 2026 for class III implantable custom-made devices and December 2027 for class III and implantable class IIb devices. Skilled laboratories are likely serving both segments, so timing will undoubtedly be tight.
Moreover, American regulators issued a statement in February 2024 urging all medical device sponsors and manufacturers to scrutinize and verify third-party data. After several instances of testing data was found to be fabricated, duplicated or unreliable, regulators are reminding manufacturers to do their due diligence when selecting lab partners. Choosing a laboratory that has ISO 17025 accreditation and is registered with the appropriate regulatory agency is a must do first step.
The bottom line is, biomanufacturers waiting until 2026 to comply with <665> will likely find themselves at the back of a very long line if additional testing is required. This could result in costly delays for biomanufacturers and frustration for patients waiting for products.
Embracing the inevitable
The implementation date may have been pushed back to 2026, but the new USP <665> requirements are inevitable, and some regulators may adopt them before that date. China has already started asking for USP <665> compliant data, and while Europe and the United States do not currently, it’s only a matter of time. This makes thoughtful planning prudent and necessary.
Proactive budgeting
Complying with the revised USP <665> may be expensive, depending on the current state of your data. This expense can’t be left as a budgetary surprise, and undertaking compliant testing now will allocate resources in advance, helping biomanufacturers manage their budgets effectively.
There may also be a role for trusted lab partners here, too. A laboratory that has regulatory knowledge and proven experience in developing test strategies and performing gap analyses could prove to be a valuable partner in saving time and money.
The journey towards USP <665> compliance is not just a regulatory requirement but a strategic imperative for the biopharma industry. Early action transcends mere preparedness; it’s a proactive measure to safeguard market presence, financial stability and patient trust.
A Final Word
With the impending enforcement of USP Chapter <665>, biopharma manufacturers face a pivotal moment. Delaying preparation could lead to significant setbacks, as the new guidance is inevitable. This transition period offers a prime opportunity for those ready to embrace the new standards, setting themselves apart in a competitive landscape. Collaborating with experienced laboratory partners now is not just about compliance; it’s about securing a strategic edge, ensuring uninterrupted market presence, and confidently navigating the future of pharmaceutical manufacturing.
