Procedures are the most-cited problem in drug GMP
Two of the three most-cited drug GMP observations in FDA’s FY2025 data are about written procedures (GMP Insiders):
- 211.22(d), quality unit procedures missing or not followed: 243 citations (first)
- 211.100(a), missing or inadequate written production procedures: 162 citations (third)
Cleaning procedures not established or followed (211.67(b)) added another 70. For a plant quality manager, the SOP system is the single biggest inspection exposure on site.
What Part 211 expects of procedures
- Production and process control procedures must exist, be drafted and approved by the right units, and be reviewed and approved by the quality control unit; they must be followed and documented, and any deviation recorded and justified (21 CFR 211.100).
- The quality control unit’s own responsibilities and procedures must be in writing and followed (21 CFR 211.22).
- Laboratory control mechanisms follow the same pattern: QC unit approval, followed, documented, deviations justified (21 CFR 211.160).
The repeated pattern is written, approved, followed, documented, deviations justified. An SOP review should test all five.
Four ways an SOP fails an inspection
| Failure | What the investigator sees | Typical cause |
|---|---|---|
| Missing | A GMP activity with no procedure | New equipment or process added without documentation |
| Inadequate | Procedure lacks a required element or decision criterion | Written by someone outside the process; not updated after change |
| Not followed | Records or observation differ from the SOP | Workarounds on the floor; procedure impractical |
| Undocumented deviation | Departure from the SOP without record or justification | Culture of informal fixes |
A five-step SOP review method
1. Build the inventory against the process
List every GMP activity on site (from receipt to release) and map each to a procedure. Gaps in the map are “missing” findings.
2. Check content against requirements
For each SOP, check it covers the regulatory requirements for that activity and your commitments in applications. Look for clear acceptance criteria and decision points.
3. Compare procedure to practice
Walk the floor with the SOP in hand. Watch the task, then compare records to the procedure.
4. Check deviations and changes
Look at deviations raised against the SOP and changes made to the process since its last revision. Repeated deviations often mean the procedure, not the operator, is wrong.
5. Prioritize by risk
Fix SOPs for sterile operations, cleaning, release and investigations first; these sit in FDA’s top ten.
Making periodic review meaningful
Many sites review SOPs on a fixed cycle and simply re-sign them. A meaningful periodic review records what was checked: requirement coverage, practice comparison, deviations and changes since last revision, and training impact.
The plant quality manager’s role
- Set the standard: what a good SOP looks like on this site.
- Allocate review effort by risk, not alphabetically.
- Hold process owners accountable for practice matching procedure.
- Make the quality unit’s own procedures exemplary: they were the most-cited area in FY2025.
- Report SOP health (overdue reviews, repeat deviations) in site management review.
Who you work with
- Production, engineering and QC managers: SOP owners.
- Document control: inventory, workflow and periodic review.
- Training: retraining after revisions.
- Corporate quality: global procedures and local adaptations.
- Operators and analysts: whether the SOP works in practice.
Common weaknesses
- SOP inventory not linked to actual site processes.
- Periodic review as signature only.
- Global procedures adopted without local detail.
- Repeated deviations treated as operator error.
- Quality unit SOPs weaker than production SOPs.
Checklist
- Process-to-SOP map complete with no gaps
- High-risk SOPs checked against requirements and practice
- Deviations and changes since last revision reviewed
- Quality unit procedures reviewed first
- Periodic review records show what was checked
- SOP health reported to site leadership
How AskDona helps
Reviewing hundreds of SOPs against requirements and against each other is slow. AskDona reads your SOPs against Part 211, your commitments and related records, and flags missing elements, conflicting instructions between procedures and deviations that point to the same SOP, with page citations. Run a sample SOP review on your cleaning or batch release procedures. AskDona shows the evidence; your site quality team decides.
Editor’s note: CFR text is paraphrased from LII. FY2025 counts come from GMP Insiders’ analysis of FDA’s 483 data, which does not cover every inspection. The review method is a practical framework, not an FDA requirement. Not legal advice. The LinkedIn count was supplied by the client.
FAQ
Which CFR sections cover written procedures? 211.100 for production and process control, 211.22 for the quality unit, and 211.160 for laboratory controls, among others.
What was the top drug GMP observation in FY2025? 211.22(d), quality unit procedures, with 243 citations.
How often should SOPs be reviewed? On a cycle your quality system defines, and whenever processes change or deviations show a problem.
Who owns an SOP? The process owner writes and maintains it; the quality unit reviews and approves it.
References
All pages opened and checked by October 23, 2026.
| Source | Type | Used for |
|---|---|---|
| GMP Insiders: FY2025 FDA inspection observations | Industry analysis | Citation counts |
| 21 CFR 211.100 (LII) | Regulation | Written procedures |
| 21 CFR 211.22 (LII) | Regulation | Quality unit |
| 21 CFR 211.160 (LII) | Regulation | Laboratory controls |