Regulatory Guide
21 CFR Part 211 Compliance Checklist
February 2025 · 14 min read
21 CFR Part 211 — Current Good Manufacturing Practice for Finished Pharmaceuticals — is the foundational regulation governing pharmaceutical manufacturing in the United States. Every FDA inspection of a drug manufacturing facility evaluates compliance against this regulation. Every 483 observation cites specific sections. Every warning letter traces enforcement action back to these requirements.
This checklist covers each subpart of 21 CFR Part 211 with the specific compliance requirements that FDA investigators evaluate, the most commonly cited deficiencies, and how AI-powered compliance analysis can automate gap detection for each area.
Subpart B — Organization and Personnel (§211.22–211.34)
The quality control unit must have the authority and responsibility to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products. This authority must be documented and exercised independently from production management.
Compliance Requirements
Quality unit responsibilities are documented in writing with clear authority to approve/reject materials and products
§211.22(a)
Adequate number of qualified personnel for manufacturing, processing, packing, and holding
§211.25(a)
Personnel training in cGMP and specific job functions, with documented training records
§211.25(a)
Training conducted by qualified individuals with sufficient education, training, and experience
§211.25(b)
Personnel hygiene practices established, documented, and followed
§211.28
Consultants have sufficient qualifications; records maintained of name, address, qualifications, and service provided
§211.34
Most common 483 finding: Failure to have an adequate quality unit with authority to approve/reject materials. In practice, this often manifests as quality decisions being overridden by production management, or quality unit responsibilities that are documented but not consistently exercised.
Subpart C — Buildings and Facilities (§211.42–211.58)
Facilities must be of suitable size, construction, and location to facilitate cleaning, maintenance, and proper manufacturing operations. Environmental controls must prevent contamination and cross-contamination.
Compliance Requirements
Adequate space for orderly placement of equipment and materials to prevent mix-ups and contamination
§211.42(a)
Separate or defined areas for each manufacturing operation to prevent cross-contamination
§211.42(c)
Adequate lighting, ventilation, heating, cooling, and sanitation in all areas
§211.44, §211.46
Plumbing designed to prevent backflow and contamination; drains adequately sized and maintained
§211.48
Written procedures for facility sanitation with defined schedules, methods, and responsibilities
§211.56
Written maintenance procedures for facility and equipment systems
§211.58
Subpart D — Equipment (§211.63–211.72)
Compliance Requirements
Equipment of appropriate design, adequate size, and suitably located for intended use
§211.63
Equipment construction does not alter safety, identity, strength, quality, or purity of drug product
§211.65
Written cleaning and maintenance procedures established and followed; cleaning validation performed
§211.67
Automatic, mechanical, and electronic equipment calibrated, inspected, and checked per written program
§211.68
Computerized systems validated; controls in place to prevent unauthorized access and changes
§211.68(b)
Equipment cleaning and use logs maintained showing date, time, product, and lot number
§211.182
Subpart E — Control of Components (§211.80–211.94)
Compliance Requirements
Written procedures for receipt, identification, storage, handling, sampling, testing, and approval/rejection of components
§211.80
Each lot of components identified with a distinctive code and tested for conformance with specifications
§211.84
Components stored under appropriate conditions and handled to prevent contamination
§211.80(b)
Containers and closures tested per written procedures before use; meet USP or NF requirements
§211.94
Subpart F — Production and Process Controls (§211.100–211.115)
This is the subpart that generates more 483 observations than any other. Production and process controls must ensure that drug products have the identity, strength, quality, and purity they are represented to possess.
Compliance Requirements
Written procedures for production and process control designed to assure drug product quality
§211.100(a)
Written procedures drafted, reviewed, and approved by appropriate organizational units and QA
§211.100(a)
Deviations from written procedures documented and justified; significant deviations investigated
§211.100(b)
Actual yields compared with theoretical yields at each appropriate processing step
§211.103
In-process sampling and testing at defined intervals
§211.110
Time limitations on production established where appropriate for product quality
§211.111
Process validation demonstrating reproducibility and consistency of manufacturing process
§211.113
Critical citation — §211.100(b): "Written production and process control procedures shall be followed in the execution of the various production and process control functions and shall be documented at the time of performance." This is the regulatory basis for the majority of production-related 483 observations.
Subpart G — Packaging and Labeling Control (§211.122–211.137)
Compliance Requirements
Written procedures for labeling issuance with strict control and reconciliation
§211.122
Examination and verification of labeling materials prior to use
§211.125
Adequate labeling inspection during and after packaging operations
§211.130
Expiration dates established and supported by stability testing
§211.137
Subpart I — Laboratory Controls (§211.160–211.176)
Compliance Requirements
Written laboratory testing procedures that are scientifically sound and appropriate
§211.160(b)
Laboratory controls include establishment of specifications, standards, sampling plans, and test procedures
§211.160(a)
Complete laboratory records including test data, calculations, and analyst identification
§211.194
Out-of-specification results investigated per written procedures with scientific justification
§211.192
Stability testing program with written procedures and adequate sample storage
§211.166
Reference standards properly qualified, stored, and documented
§211.160
Reserve samples retained and stored under conditions consistent with labeling
§211.170
Subpart J — Records and Reports (§211.180–211.198)
The records subpart is where documentation practices are evaluated — and where data integrity issues are most commonly identified.
Compliance Requirements
Records maintained for at least 1 year after expiration date of the drug product batch
§211.180(a)
Complete batch production and control records for each batch, including reproduction of master production record
§211.188
Production record review by quality unit before batch release
§211.192
Investigation of any unexplained discrepancy or failure of a batch, with written record
§211.192
Distribution records maintained with sufficient information to facilitate lot recall
§211.196
Complaint records maintained and reviewed; complaints regarding identity, strength, quality, or purity investigated
§211.198
The #1 citation — §211.192: "Any unexplained discrepancy (including a percentage of theoretical yield exceeding the maximum or minimum percentages established in master production and control records) or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated." This single citation appears more frequently in 483 observations than any other. AI compliance analysis specifically evaluates the thoroughness, timeliness, and scientific rigor of investigations against this requirement.
Automating 21 CFR 211 Compliance with AI
Manually evaluating compliance against every section of 21 CFR Part 211 across all manufacturing and quality documentation is a massive undertaking. Most internal audit programs sample a subset of records against a subset of requirements — leaving gaps undetected until an FDA investigator applies a more comprehensive review.
AI compliance platforms like Clinplex AI automate this evaluation by analyzing every quality record against the complete regulatory framework. SOPs are evaluated for procedural completeness against applicable 211 subparts. Deviation investigations are assessed for the thoroughness required by §211.192. Batch records are checked for documentation completeness per §211.188. CAPA records are evaluated for root cause adequacy and effectiveness verification.
The result is a continuous compliance posture that covers every requirement in this checklist — not as a one-time assessment, but as an ongoing operational capability that updates with every new or revised document in your quality system.
Evaluate Your 21 CFR 211 Compliance Now
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