Change control is one of those systems every quality manual describes in careful detail and every SOP index lists near the top. It is also, according to two FDA warning letters issued roughly eighteen months apart, one of the systems most likely to exist convincingly on paper while barely functioning in practice.
Neither case involved a company that had never heard of change control. Both had procedures. Both, when FDA looked closely, could not show that those procedures had actually been followed when it mattered.
Your firm failed to establish adequate written procedures for production and process control designed to assure that drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and to follow all of your written production and process control procedures (21 CFR 211.100(a) and 211.100(b)).
What the two letters found
FDA inspected BioMylz Pvt. Ltd.'s Bengaluru, India facility from February 4 to 9, 2026. Investigators recovered a garbage bag containing original CGMP records, including executed batch records, environmental monitoring forms, and product complaint and change control log forms. The firm attributed the destruction to a single former employee acting alone. FDA's response noted that the evidence contradicted this, showing the individual had been repeatedly observed destroying records over time.
Separately, the same letter cited a failure to follow written production and process control procedures under 21 CFR 211.100(a) and (b), including inadequate validation of a manufacturing process after commercial scale-up. In its required response, FDA asked the firm to describe the steps in its change management system for introducing new manufacturing equipment or a new product, a request that only makes sense if the existing description was not credible.
Roughly eighteen months earlier, FDA issued a warning letter to Global Calcium Pvt. Limited following an inspection that found damaged flooring and signage failures in a production area. The firm's response claimed a change control had been initiated to cover a partial shutdown for facility upgrades. FDA's reply was direct: no information was provided during the inspection to support that a change control existed, and the firm had not adequately evaluated the potential quality impact to lots manufactured during the maintenance period.
Global Calcium's warning letter did not turn on whether a change control procedure existed in the quality manual. It turned on whether a specific, real change control record existed for a specific, real event, and whether anyone had assessed what that event might have done to product already made. FDA found neither.
What 21 CFR 211.100(b) actually requires
21 CFR 211.100 requires written procedures for production and process control designed to assure that drug products have the identity, strength, quality, and purity they claim to have. Paragraph (b) adds the operative requirement for change control: any deviation from those written procedures must be recorded and justified. A change to equipment, a process parameter, a specification, a supplier, or a facility is not compliant because a procedure describing how changes should be handled exists somewhere. It is compliant because a specific record shows that a specific change was proposed, assessed, approved, and evaluated for impact before and after it happened.
That distinction, between having a change control system and having evidence that a particular change went through it, is exactly where both warning letters landed.
What a defensible change control programme actually contains
A change control system that can survive an inspection has several parts that all have to be traceable to the specific change in question, not just described in general terms:
- A logged, numbered change request. Every proposed change, to equipment, a method, a specification, a supplier, a facility, or a process parameter, gets a unique record the moment it is proposed, before it is implemented.
- A documented risk and impact assessment. What could this change affect: product quality, other processes sharing the same equipment, validated states, regulatory filings, previously released batches.
- Cross-functional review and approval. Quality, and whichever technical function owns the area affected, sign off before the change is implemented, not after.
- Verification that the change achieved its intended effect. Post-implementation review confirming the change worked as planned and did not introduce a new problem.
- A retrospective look at product made before the change was formalised. If a change happened informally before the paperwork caught up, as in the Global Calcium case, that gap itself has to be assessed for impact on already-distributed lots.
Neither firm in these two letters was missing all of these elements. BioMylz had change control log forms, they existed, they were simply destroyed alongside other records. Global Calcium referenced a change control in its response but could not produce it. In both cases, the gap was not conceptual. It was evidentiary.
Why "we initiated a change control" is not a defense on its own
FDA's reply to Global Calcium is worth sitting with: the firm was not challenged on whether change control was the right mechanism for a maintenance shutdown. It was challenged on whether any evidence supported the claim that the mechanism was actually used. A firm that describes its process correctly in a written response, without being able to produce the record showing that process ran for the specific event under scrutiny, has effectively confirmed that the system is aspirational rather than operational.
Why record destruction turns a change control gap into something worse
The BioMylz case shows the other failure mode: records that did exist, including change control logs, were not retained. A change control system is only as strong as the durability of its records. FDA's data integrity guidance treats destroyed or altered records as evidence that a quality system as a whole cannot be relied upon, not as an isolated documentation lapse. Once that conclusion is reached, every other system in the facility, change control included, loses its credibility along with it.
Change control is not usually cited because a firm lacks a procedure for it. It is cited because, for a specific real change, at a specific real point in time, no one can produce a record showing the procedure was actually followed, or the record that once existed is gone. A change control system earns its credibility one traceable record at a time, not through the quality of its SOP.
Key regulatory references
- FDA Warning Letter 320-26-103, BioMylz Pvt. Ltd., July 13, 2026
- FDA Warning Letter 692000, Global Calcium Pvt. Limited, January 16, 2025
- 21 CFR 211.100 — Written procedures; deviations
- FDA Guidance: Data Integrity and Compliance With Drug CGMP: Questions and Answers
- ICH Q10 — Pharmaceutical Quality System
Our change control coursework covers this in full
Change request logging, risk and impact assessment, cross-functional approval, and retrospective evaluation, built from 21 CFR 211.100(b) and real enforcement cases. Certificate on completion.