FDA ties process control to shortages

The U.S. Food and Drug Administration’s January 2025 draft guidance on 21 CFR 211.110 is being read by industry specialists as a manufacturing document, not just a compliance one. The rule itself requires written procedures for in-process controls, tests and examinations on appropriate samples of each batch to assure batch uniformity and drug product integrity. FDA said the guidance, when finalized, will describe considerations for complying with 21 CFR 211.110 and related quality issues for products made with advanced manufacturing. ### Why is a rule about sampling being linked to drug shortages? Pharmaceutical Technology said in an April 2, 2025 article that the guidance matters because stronger in-process controls can help reduce production failures and, in turn, drug shortages. The article by Susan J. Schniepp and Rona LeBlanc-Rivera framed the issue as one of manufacturing discipline, with quality built into the process rather than checked only at the end. (fda.gov) FDA’s draft guidance says manufacturers must maintain the process in a state of control over the life of the process to ensure drug product quality even as materials, equipment, the production environment and personnel change. That language ties supply continuity to process consistency, because batches that drift out of control are more likely to fail, be rejected or require rework. ### What does 21 CFR 211.110 actually require on the plant floor? Section 211.110 requires written procedures describing the in-process controls and the tests or examinations to be conducted on samples of in-process materials from each batch. (pharmtech.com) The regulation also says those procedures must be followed, and that valid in-process specifications consistent with drug product final specifications must be derived from previous acceptable process average and process variability estimates where possible and determined by application of suitable statistical procedures where appropriate. (fda.gov) FDA’s guidance adds detail around where companies should sample, how they should monitor the process and when they should intervene. Pharmaceutical Technology’s coverage said the document stresses monitoring, sampling plans, intervention rules and stronger in-process testing as practical tools to prevent failures before they become finished-product problems. ### Why does FDA keep emphasizing “batch uniformity” and “drug product integrity”? (ecfr.gov) FDA said the draft guidance is intended to help ensure batch uniformity and drug product integrity. Those terms matter because the agency is not describing quality as a final laboratory event; it is describing quality as something supported by controls during manufacturing. Pharmaceutical Technology’s later coverage said stakeholders focused on the same themes, including advanced manufacturing, batch uniformity, drug product integrity and the use of process models in commercial control strategies. (pharmtech.com) That broadens the discussion beyond manual checks to include model-based monitoring and other controls embedded in production. ### Does this stop at upstream production, or reach storage and release too? (fda.gov) The draft guidance applies to human drug products and biologics, though not to active pharmaceutical ingredient manufacturing, and discusses commercial manufacturing control strategies. That scope supports the view that control has to extend across the production system, including downstream handling and the steps that support release decisions. (pharmtech.com) Pharmaceutical Technology’s April 2025 article argued that quality should be treated as embedded across the workflow rather than as a final inspection step. That framing puts responsibility on the manufacturing process itself — from in-process sampling through later handling decisions — instead of relying on end-of-line testing to catch problems after they have already been created. ### Where does this leave manufacturers now? (pharmtech.com) FDA issued the document as draft guidance on January 6, 2025 through docket FDA-2024-D-5374, and the agency says it is meant to describe considerations for complying with 21 CFR 211.110. Manufacturers reviewing the document are being asked to examine whether their control strategies, sampling plans and intervention criteria are robust enough to keep processes in control over time. (pharmtech.com) The current text of 21 CFR 211.110 remains in the electronic Code of Federal Regulations, and FDA’s draft guidance remains posted on the agency’s guidance page for companies tracking the next step toward finalization. (ecfr.gov) (hhs.gov)