21 CFR Part 211 - Current Good Manufacturing Practice

Buildings used for manufacturing must be of suitable size, construction, and location to facilitate cleaning, maintenance, and proper operations including prevention of mix-ups and contamination.

• Facility layout drawings
• Flow diagrams (personnel/material)
• HVAC qualification records
• Room classification documents

• Material and personnel flows cross-contaminate
• No formal classification scheme
• Layout drawings outdated

Adequate ventilation must be provided. Air filtration systems with HEPA filters where appropriate must be used to control contamination, with environmental monitoring of pressure, temperature, humidity.

• HVAC IQ/OQ/PQ
• HEPA integrity test reports
• EM data trending
• Pressure differential logs

• No periodic HEPA integrity testing
• Pressure differentials not trended
• EM excursions not investigated

Each lot of components, drug product containers, and closures must be withheld from use until sampled, tested, and released by the quality control unit.

• Sampling plans
• CoA reviews
• Identity testing records
• Release decisions
• Supplier qualification files

• Reliance on supplier CoA without identity test
• Sampling plans not statistically justified
• Quarantine controls weak

Equipment must be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter safety, identity, strength, quality, or purity.

• Cleaning SOPs
• Cleaning validation protocols/reports
• Maintenance logs
• Equipment cleaning logs

• Cleaning validation only worst-case justification weak
• No documented dirty-hold and clean-hold times
• Maintenance overdue without justification

Automated systems including computers must be routinely calibrated, inspected, or checked according to written program. Controls must ensure changes are instituted only by authorized personnel.

• CSV documentation
• Calibration schedules
• Change control records
• Access control matrices
• Audit trail reviews

• Audit trails not reviewed
• Access roles not periodically reviewed
• CSV gaps for legacy systems

Written procedures must describe warehousing including quarantine of components and finished products, and storage under appropriate conditions of temperature, humidity, and light.

• Warehouse mapping studies
• Temperature/humidity logs
• Quarantine SOPs
• Storage condition alarms

• No formal warehouse mapping
• Alarm response not documented
• Mixed status materials co-located

Written procedures must describe distribution including oldest approved stock distributed first (FEFO) and a system to facilitate prompt recall of any lot from the market.

• Distribution records
• Mock recall reports
• FEFO procedures
• Lot trace databases

• Mock recalls not performed annually
• Distribution data not lot-level traceable
• FEFO exceptions undocumented

Each batch must be tested for conformance to final specifications including identity and strength prior to release. Sampling plans and test methods must be in writing and validated.

• Finished product specs
• Release CoAs
• Method validation reports
• Sampling plans

• Method validation lacks robustness data
• Sampling not representative
• Specifications not justified

A written stability testing program must be designed to assess stability characteristics of drug products. Results must determine appropriate storage conditions and expiration dates.

• Stability protocols
• Annual stability commitments
• Stability data trending
• Out-of-trend procedures

• No ongoing annual batch
• OOT criteria not defined
• Stability chambers not qualified

A quality control unit must exist with authority and responsibility to approve or reject components, in-process materials, packaging, labeling, and finished products. Written procedures must define its responsibilities.

• QCU charter
• Org chart
• Written QCU SOPs
• Approval/rejection logs
• Job descriptions

• QCU lacks documented independence
• No written approval authority matrix
• QCU SOPs not formally approved

Each person engaged in manufacturing, processing, packing, or holding must have the education, training, and experience to perform assigned functions. Training in cGMP must be ongoing and documented.

• Training matrices
• Curriculum vitae
• Job descriptions
• Annual cGMP training records
• Training effectiveness assessments

• No periodic refresher training
• Training records incomplete or unsigned
• No qualification criteria for specialized roles

Personnel must wear clean clothing appropriate to operations, practice good sanitation and hygiene, and report health conditions that may adversely affect product quality.

• Gowning SOPs
• Health self-reporting forms
• Hygiene training records
• Gowning qualification records

• No documented gowning qualification
• Missing health screening process
• Inadequate visitor controls

Written procedures for receipt, identification, storage, handling, sampling, examination, and testing of labeling and packaging materials must exist. Outdated or obsolete labels must be destroyed.

• Label reconciliation records
• Destruction records
• Label specifications
• Receipt logs

• Reconciliation tolerances not justified
• No formal label destruction witness
• Online label printing not validated

Packaging and labeling operations must include prevention of mix-ups and cross-contamination, identification of containers, examination of materials, and inspection of facilities before use.

• Line clearance records
• Pre-use inspection logs
• Reconciliation documentation
• Coding records

• Line clearance not independently verified
• Inadequate segregation between lines
• Code/expiry date checks missed

Written procedures for production and process control must be designed to assure drug products have identity, strength, quality, and purity they purport to possess. Deviations must be documented.

• Master batch records
• Process validation reports
• Deviation logs
• SOP index

• Deviations not trended
• MBR changes lack control
• Process validation lifecycle incomplete

Procedures must describe in-process controls and tests to be conducted on appropriate samples to monitor output and validate performance of critical manufacturing processes.

• IPC specifications
• Control charts
• Sampling SOPs
• Test result records

• Statistical limits not justified
• OOS in-process not investigated
• Sampling locations not representative

Appropriate written procedures must be established to prevent objectionable microorganisms in non-sterile drug products and to ensure sterility of products purporting to be sterile.

• Bioburden monitoring
• Environmental monitoring program
• Sterilization validation
• Microbial limits testing

• Objectionable organism list not defined
• Media fill frequency inadequate
• Trending of EM excursions weak

Records required by Part 211 must be retained for at least one year after expiration date of the batch. Records must be readily available for authorized inspection.

• Retention schedules
• Archive index
• Records destruction logs
• Electronic records backup

• Retention period not enforced
• Electronic records not protected from loss
• Archive access not controlled

Production and control records must be reviewed by the quality control unit before any batch is released or distributed. Discrepancies must be investigated whether or not the batch is already distributed.

• Batch review checklists
• Investigation reports
• Release decisions
• CAPA records

• Batch review is checkbox only
• Investigations close without root cause
• Trend data not feeding CAPA

Written procedures must describe handling of written and oral complaints regarding drug products. Files must include investigation and reply to the complainant.

• Complaint logs
• Investigation reports
• Trend analyses
• Field alert reports

• Complaints not trended
• Field alert reports late
• Closure without CAPA linkage

Returned drug products must be identified and held. If condition casts doubt on safety, identity, strength, quality, or purity, products must be destroyed unless examination establishes otherwise.

• Returns log
• Disposition records
• Destruction certificates
• Examination reports

• Returns mixed with saleable stock
• No formal disposition decision authority
• Destruction not witnessed

The regulations in this part contain the minimum current good manufacturing practice for preparation of drug products for administration to humans or animals.

• cGMP applicability statement signed by Quality
• Product portfolio register flagging human vs veterinary drug products
• Regulatory inventory mapping each SKU to 21 CFR Part 211
• Site master file referencing Part 211 scope

• OTC and Rx product lines treated under a single SOP set without scope differentiation
• Contract manufacturing arrangements not explicitly bound to Part 211 scope
• Veterinary products inadvertently excluded from cGMP coverage
• No documented scope review when new dosage forms are introduced

Definitions of key terms including act, batch, component, drug product, fiber, lot, representative sample, active ingredient, and in-process material.

• Controlled glossary of cGMP terms (batch, lot, component, active ingredient)
• Definition cross-reference table linking SOPs to 211.3 terms
• Training record on cGMP terminology
• Document control register enforcing standardised terminology

• Local plant terminology drifting from 211.3 definitions
• Inconsistent use of lot vs batch across SOPs and batch records
• Definition of representative sample not aligned with sampling SOPs
• Active ingredient terminology not reconciled with ICH Q7 API definitions

A quality control unit with authority and responsibility to approve or reject all components, drug products, in-process materials, and procedures affecting the identity, strength, quality, and purity of the drug product.

• Quality Control Unit charter with authority statement
• QCU organisation chart and reporting lines independent of production
• Batch disposition log with QCU signatures
• Procedure register approved by the QCU
• Annual product review reports signed by the QCU

• QCU reporting line not independent from manufacturing
• QCU sign off captured in email rather than controlled records
• Authority to reject components not exercised consistently across sites
• QCU not involved in approving change controls affecting quality
• Inadequate QCU resourcing during peak production periods

Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience to enable that person to perform the assigned functions.

• Job descriptions defining cGMP responsibilities
• Training matrix mapped to roles and processes
• Training completion and effectiveness records
• Qualification records (education, experience, certifications)
• Refresher training schedule

• Training records not signed or dated by trainee and trainer
• On the job training not formally assessed for effectiveness
• Refresher training overdue for long tenured staff
• Contractor and temporary staff omitted from the training matrix
• Role changes not triggering retraining

Personnel shall wear clean clothing appropriate for duties, practice good sanitation and health habits, and not have illness that may adversely affect drug products.

• Gowning and hygiene SOPs
• Health screening and return to work records
• Visitor and contractor gowning logs
• Hygiene training records
• Periodic gowning qualification assessments

• Self reporting of illness not enforced or anonymised effectively
• Gowning qualifications expired but operators still in classified areas
• Visitor logs missing gowning compliance entries
• Jewellery and cosmetics policy not enforced consistently
• No documented evidence of gowning verification before entry

Consultants advising on cGMP shall have sufficient education, training, and experience to advise on the subject for which they are retained.

• Consultant qualification dossiers (CV, certifications, references)
• Consultant scope of work and quality agreement
• Consultant activity log
• Confidentiality and conflict of interest declarations

• Consultant qualifications not retained for the required retention period
• Scope of work not signed by the QCU
• Consultant deliverables not subject to formal quality review
• No periodic re evaluation of long term consultants

Any building or buildings used in the manufacture, processing, packing, or holding of a drug product shall be of suitable size, construction and location to facilitate cleaning, maintenance, and proper operations.

• Facility design qualification (DQ) documentation
• Flow diagrams for personnel, materials, waste, and product
• Room classification register with environmental monitoring limits
• Segregation and containment risk assessment
• As built drawings approved by Quality

• Personnel and material flows crossing without controls
• Penicillin or sensitising products not segregated as required
• Room classifications not aligned with the actual operations performed
• Pressure differentials documented but not routinely verified
• Changes to layout not reassessed for contamination risk

Adequate lighting shall be provided in all areas.

• Lighting level survey results by room
• Preventive maintenance plan for luminaires
• Lighting design specification per area classification
• Lux measurement records during requalification

• No documented lux measurements at the work surface
• Lighting checks not part of the preventive maintenance schedule
• Emergency lighting not tested or documented
• Visual inspection stations without verified illumination levels

Adequate ventilation, air filtration, air heating and cooling shall be provided where appropriate.

• HVAC qualification protocol and report (IQ, OQ, PQ)
• Air filter integrity testing records
• Pressure differential monitoring trend data
• Air change rate calculations per room
• Smoke study videos and reports for aseptic areas

• HEPA filter integrity tests overdue
• Air change rates not recalculated after layout changes
• Pressure cascades inverted during fault conditions
• Smoke studies not repeated after major HVAC work
• Recovery time testing missing after start up events

Potable water shall be supplied under continuous positive pressure in a plumbing system free of defects that could contribute contamination to any drug product.

• Water system P&IDs
• Backflow prevention test records
• Plumbing maintenance logs
• Cross connection control survey

• Dead legs in water distribution not eliminated
• Backflow preventers not tested at the required frequency
• Drain traps in classified areas not maintained
• Cross connections between potable and process water not surveyed

Sewage, trash, and other refuse shall be disposed of in a safe and sanitary manner.

• Waste segregation and removal SOPs
• Waste disposal vendor qualification records
• Sewage system maintenance logs
• Waste route flow diagrams

• Waste accumulation points located too close to product flows
• Hazardous and general waste streams not segregated at source
• Waste contractor approvals expired
• No verification that waste removal frequency matches production volumes

Any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in a clean and sanitary condition.

• Master sanitation schedule
• Cleaning SOPs and detergent qualification records
• Pest control contract, inspection reports, and trend analysis
• Sanitation training records
• Environmental monitoring results linked to cleaning events

• Cleaning frequencies set without scientific rationale
• Pest control trend data not reviewed by Quality
• Sanitation gaps during plant shutdowns
• Detergent residue not included in cleaning validation
• No periodic effectiveness review of the master sanitation schedule

Any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in a good state of repair.

• Preventive maintenance plan for facilities
• Building condition survey reports
• Repair and corrective maintenance logs
• Facility change control records

• Roof leaks and wall damage not closed out in CMMS
• Maintenance work in classified areas not under change control
• Repairs performed without restoring qualified state
• Building services preventive maintenance overdue

Equipment used in the manufacture, processing, packing, or holding of a drug product shall be of appropriate design, adequate size, and suitably located.

• Equipment URS, FAT, SAT documentation
• DQ, IQ, OQ, PQ protocols and reports
• Equipment location and layout plans
• Capacity and scale up rationale documents

• Equipment placed too close to walls preventing cleaning
• URS missing cGMP requirements such as cleanability
• Design qualification skipped on legacy equipment
• Scale up rationale not documented after process changes

Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter safety, identity, strength, quality, or purity.

• Materials of construction certificates (316L, USP Class VI)
• Surface finish and roughness measurements
• Lubricant compatibility assessment
• Equipment qualification records

• Lubricants in product contact zones not food grade or USP qualified
• Surface roughness above 0.8 micrometre Ra on product contact surfaces
• Non documented welding repairs on stainless steel
• Gaskets and elastomers not on a controlled spares list

Equipment and utensils shall be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination.

• Cleaning SOPs per equipment train
• Cleaning validation master plan and reports
• Equipment cleaning logs
• Preventive maintenance schedules
• Visual inspection and swab sampling records

• Cleaning validation worst case rationale not justified
• Hold times (clean and dirty) not validated
• Manual cleaning steps with high operator variability
• Cleaning logs missing operator and verifier signatures
• Maintenance breaching cleaned status without requalification

Automatic, mechanical, or electronic equipment used for manufacture, processing, packing, or holding shall be routinely calibrated, inspected, or checked according to a written program.

• Computerised system inventory with GAMP categorisation
• Validation lifecycle documents (URS, FS, DS, IQ, OQ, PQ)
• Audit trail review records
• Access control matrix and periodic user reviews
• Data backup, restore, and archival evidence

• Audit trails not reviewed at the required frequency
• Shared user accounts on GxP systems
• Backup restore tests not performed periodically
• Spreadsheets used in batch release without validation
• Legacy systems lacking ALCOA+ controls

Filters for liquid filtration used in the manufacture, processing, or packing of injectable drug products intended for human use shall not release fibers into such products.

• Filter qualification and extractables and leachables studies
• Filter integrity test records (pre and post use)
• Filter change control and lot traceability log
• Fibre release assessment

• Asbestos containing filters not formally banned in specifications
• Pre use post sterilisation integrity testing not performed
• Fibre releasing filters used without downstream non fibre releasing filter
• Filter validation not refreshed when product formulation changes

Written procedures describing receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers and closures.

• Component receipt SOP and inspection checklist
• Material status labels (quarantine, approved, rejected)
• Vendor approval list
• Sampling plans

• Material status labels missing or illegible
• Quarantine area not physically segregated
• Receipt SOP not aligned with the vendor approval process
• No reconciliation between deliveries and purchase orders at receipt

Upon receipt and before acceptance, each container or grouping of containers of components shall be examined visually for appropriate labeling and damage.

• Quarantine storage map
• Temperature and humidity monitoring records
• Receiving log
• Container damage inspection records

• Quarantine and approved stock co mingled on the same rack
• Temperature excursions in receiving bay not investigated
• Damaged containers released to production without disposition
• No verification of supplier seals at receipt

Each lot of components shall be withheld from use until the lot has been sampled, tested, or examined and released for use by the quality control unit.

• Component specification documents
• Sampling SOPs
• Analytical test methods and validation reports
• Certificates of analysis from vendors
• Component release records

• Reliance on supplier CoA without periodic confirmatory testing
• Identity test missing for each container
• Specifications not reviewed when pharmacopoeial monographs change
• Sampling plan not statistically justified
• Failing component lots not formally rejected in the system

Components shall be rotated so that the oldest approved stock is used first (FIFO). Deviation from this requirement is permitted if such deviation is temporary and appropriate.

• FEFO and FIFO inventory rules in the ERP
• Component allocation reports
• Retest date management procedure
• Inventory transaction audit trail

• Manual overrides of FEFO without justification
• Retest dates not visible at picking
• Aged components consumed beyond retest without retesting
• ERP rules not aligned with the quality release status

Drug product containers and closures shall not be reactive, additive, or absorptive so as to alter safety, identity, strength, quality, or purity of the drug beyond established requirements.

• Container closure specifications
• Extractables and leachables study reports
• Container integrity test records
• Supplier qualification for primary packaging
• Resin and tooling change control records

• Extractables studies not refreshed when resin grade changes
• Container closure integrity testing missing for sterile products
• Tooling changes at suppliers not communicated under quality agreement
• No periodic container quality risk assessment
• Closure torque verification not part of in process controls

There shall be written procedures for production and process control designed to assure that drug products have the identity, strength, quality, and purity they purport or are represented to possess.

• Master Batch Records (MBR)
• Standard Operating Procedures
• Deviation management procedure and records
• Change control records
• Periodic process review reports

• Deviations closed without robust root cause analysis
• MBR updates lagging behind validated process changes
• SOP review cycles overdue
• Repeat deviations not escalated to CAPA
• Production proceeding under temporary deviations for extended periods

Written production and control procedures shall include the following: The batch shall be formulated with the intent to provide not less than 100 percent of the labeled or established amount of active ingredient.

• Dispensing SOP
• Weigh log with double verification signatures
• Calibrated scale records
• Material reconciliation forms

• Second person verification performed retrospectively
• Tare and gross weights not recorded contemporaneously
• Scale calibration overdue at the point of dispensing
• Component reconciliation tolerances not justified

Actual yields and percentages of theoretical yield shall be determined at the conclusion of each appropriate phase of manufacturing, processing, packaging, or holding of the drug product.

• Theoretical and actual yield calculations in MBR
• Yield trend analysis reports
• Investigation reports for out of limit yields
• Material reconciliation records

• Yield limits set so wide they cannot detect loss events
• Out of limit yields not investigated
• Yield trends not periodically reviewed across campaigns
• Reconciliation discrepancies attributed to process loss without evidence

All compounding and storage containers, processing lines, and major equipment used during production shall be properly identified at all times.

• Equipment identification numbering scheme
• Status labelling SOP (clean, in use, out of service)
• Equipment use logs
• Line clearance checklists

• Status labels missing date and signature
• Two products in adjacent equipment without clear identification
• Equipment IDs reused after decommissioning
• Line clearance checklists signed without independent verification

To assure batch uniformity and integrity, written procedures shall describe in-process controls and tests to be conducted on appropriate samples.

• In process control (IPC) sampling plans
• IPC specifications
• IPC test results in batch records
• Trend analysis and CPV reports
• Method validation for IPC tests

• IPC limits set wider than registered specifications
• Out of trend IPC results not flagged
• Sampling plans not statistically justified
• Process capability not trended over time
• IPC test methods used without validation

When appropriate, time limits for completion of each phase of production shall be established to assure the quality of the drug product.

• Validated maximum hold times per process stage
• Hold time study reports
• Batch record entries for hold start and end times
• Deviation reports for hold time excursions

• Hold time studies missing for intermediates
• Holds extended without revalidation evidence
• Hold start and end times not contemporaneously recorded
• Microbial limits at end of hold not verified

Appropriate written procedures designed to prevent objectionable microorganisms in drug products not required to be sterile shall be established and followed.

• Microbial contamination control strategy
• Environmental monitoring (EM) program and trend reports
• Sterilisation validation reports
• Bioburden monitoring records
• Endotoxin testing records

• EM excursions not investigated to species identification
• Sterilisation cycles not requalified after equipment changes
• Bioburden trending limits not statistically derived
• Aseptic process simulations less frequent than required
• Contamination control strategy not formally documented

Written procedures shall be established and followed prescribing a system for reprocessing batches that do not conform to standards or specifications.

• Reprocessing procedure with QCU approval
• Reprocessing validation reports
• Risk assessment for reprocessed batches
• Stability commitment records for reprocessed lots

• Reprocessing performed under deviation rather than validated procedure
• No stability commitment for reprocessed lots
• Reprocessing pathways not described in the master batch record
• Lack of QCU pre approval for the specific reprocessing event

There shall be written procedures describing the receipt, identification, storage, handling, sampling, examination, and/or testing and approval or rejection of labeling and packaging materials.

• Packaging and labelling material specifications
• Receipt and inspection records for labels
• Label proofreading and approval records
• Obsolete label destruction certificates

• Label revisions implemented without controlled destruction of superseded versions
• Receiving inspection of labels limited to count only
• Master artwork not under version control
• Multi market labels with insufficient differentiation controls

Strict control shall be exercised over labeling issued for use in drug product labeling operations.

• Label issuance and return records
• Label reconciliation forms per batch
• Authorised issuer signature list
• Excess label destruction logs

• Label reconciliation tolerances too wide to detect mix ups
• Excess labels returned to stock rather than destroyed
• No independent verification of label issuance
• Issuance records not reconciled with packaging line counters

There shall be written procedures designed to assure that correct labels, labeling, and packaging materials are used for drug products.

• Packaging line SOPs
• Line clearance checklists
• In process controls during packaging (fill weight, torque, code verification)
• Reconciliation of components, labels, and finished units
• Vision system qualification records

• Line clearance not verified between runs of different products
• Vision systems used without challenge testing
• Reconciliation discrepancies signed off without investigation
• Manual code printing without independent verification
• Changeover SOPs lacking explicit residual product checks

Each manufacturer and packer who packages an OTC drug product shall package the product in a tamper-resistant package.

• Tamper resistant packaging design specification
• Statement on the label describing tamper evident feature
• Tamper feature qualification reports
• OTC product packaging compliance register

• Tamper evident feature statement missing from the label copy
• Tamper feature qualification not refreshed after supplier changes
• OTC SKUs not flagged in the system for tamper evident requirements
• Tamper feature integrity not tested across the shelf life

Packaged and labeled products shall be examined during finishing operations to provide assurance that containers and packages have the correct label.

• Finished product visual inspection SOP
• AQL sampling plans for finished packaging
• Inspector qualification and requalification records
• Defect classification library

• Inspector requalification overdue
• AQL plans not aligned with criticality of defects
• Defect library outdated and missing newly observed defects
• Visual inspection performed under non standard lighting

To assure that drug products meet applicable standards of identity, strength, quality, and purity at the time of use, an appropriate expiration date shall be determined.

• Stability protocols and reports supporting expiry
• Expiry calculation procedure
• Label expiry verification records
• Stability commitment list for new products

• Expiry on label not matching stability supported shelf life
• Stability data not updated for formulation changes
• Expiry calculation rules differ between sites
• Ongoing stability commitments not on a tracked schedule

Written procedures describing the warehousing of drug products shall be established and followed. They shall include instructions for storage conditions including temperature, humidity, and light.

• Warehouse layout and storage zone maps
• Temperature mapping and monitoring records
• Quarantine, released, and rejected stock segregation evidence
• Pest control records for warehouse
• Inventory cycle count reports

• Temperature mapping not repeated after warehouse layout changes
• Released and quarantine stock co located
• Monitoring sensor calibration overdue
• Cycle count discrepancies not investigated
• Pest activity trends not reviewed by Quality

Written procedures shall be established and followed describing distribution of drug products. They shall include a procedure to ensure oldest approved stock is distributed first (FIFO).

• Distribution SOP
• Lot traceability records customer level
• Mock recall test reports
• Cold chain shipping qualification reports
• Transit excursion investigation records

• Mock recalls not performed at the required frequency
• Distribution records cannot reach end customer level
• Cold chain shippers not requalified annually
• Transit excursions accepted without impact assessment
• Returns reintroduction process not documented

Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures.

• Laboratory control SOPs
• Specifications for components, in process materials, and finished products
• Reference standards and reagents management procedure
• Laboratory instrument inventory and qualification records

• Specifications not aligned with the registered dossier
• Reference standards used past expiry or recertification date
• Laboratory SOPs without revision dates or owners
• Instrument qualification status not visible at the bench

Each batch of drug product required to be free of objectionable microorganisms shall be tested and determined to be in compliance before release.

• Finished product specifications
• Method validation reports
• Release testing SOPs and worksheets
• OOS and OOT investigation procedures and records
• QCU release certificates

• OOS investigations closed without unequivocal lab error assignment
• Method validation not extended to all dosage strengths
• Release worksheets missing analyst and reviewer signatures
• Sampling plans not aligned with USP requirements
• Repeat OOS events not trended

There shall be a written testing program designed to assess the stability characteristics of drug products. Results shall be used to determine appropriate storage conditions and expiration dates.

• Stability protocols (ICH Q1A R2 aligned)
• Stability schedule per product and pack configuration
• Stability data trend reports
• Stability chamber qualification and monitoring records
• Annual stability commitment review

• Ongoing stability commitments not initiated for new products
• Stability chamber excursions not formally investigated
• Trend analysis not performed across batches and conditions
• Pack variants not all on stability
• Stability sample pull schedule slippage

For each batch of drug product purporting to be sterile and/or pyrogen-free, there shall be appropriate laboratory testing to determine conformance to such requirements.

• Sterility test SOPs and validation reports
• Bacterial endotoxin test method validation
• Particulate matter testing records
• Ophthalmic and injectable specific test procedures

• Sterility test method suitability not redone after formulation changes
• Endotoxin limits not recalculated for paediatric indications
• Particulate testing instruments not qualified periodically
• Isolator or RABS used for sterility test without smoke study evidence

An appropriately identified reserve sample shall be retained for each lot of each drug product. The reserve sample shall be stored under conditions consistent with product labeling.

• Reserve sample SOP and inventory
• Reserve sample storage conditions monitoring
• Annual visual examination records
• Reserve sample destruction logs at retention end

• Reserve samples not retained for the required period beyond expiry
• Annual visual examination not documented
• Reserve sample quantity insufficient for two full specification tests
• Storage of reserve samples not in final marketed container

Animals used in testing components, in-process materials, or drug products for compliance with established specifications shall be maintained and controlled in a manner appropriate.

• Animal care and use SOPs
• Veterinary oversight records
• Animal facility environmental monitoring
• Identification and traceability records for animals used in QC tests

• Animal facility monitoring records incomplete
• Veterinary oversight not formally documented
• Animal identification not unique and traceable
• Health screening of supplier colonies not verified

If a reasonable possibility exists that a non-penicillin drug product has been exposed to cross-contamination with penicillin, the non-penicillin drug product shall be tested for presence of penicillin.

• Penicillin segregation policy and facility design evidence
• Penicillin testing procedure for non penicillin products
• Dedicated equipment register
• Personnel flow restriction records

• Shared HVAC between penicillin and non penicillin areas
• Penicillin contamination testing not performed on suspect lots
• Personnel transfers between zones without controls
• No periodic risk reassessment of cross contamination controls

Any production, control, or distribution record that is required shall be retained for at least 1 year after expiration date, or 3 years after distribution for OTC drugs without expiry.

• Record retention schedule
• Document control SOP
• Data integrity policy and ALCOA+ training records
• Archive facility environmental controls
• Electronic records audit trail review evidence

• Retention schedule not aligned with the regulation (one year past expiry)
• Paper records archived without protection against degradation
• Audit trails not reviewed before batch disposition
• ALCOA+ training not refreshed periodically
• Inconsistent retention rules across global sites

A written record of major equipment cleaning, maintenance, and use shall be included in individual equipment logs.

• Equipment cleaning and use logs
• Logbook control procedure
• Logbook reconciliation at batch release
• Electronic logbook validation records (if applicable)

• Logbook entries not contemporaneous
• Pre printed times in logbooks
• Gaps in equipment logbooks not investigated
• Cleaning entries missing operator signature and verifier

Records shall include the name of the component, the supplier's name, lot number, information relating to conformance with specifications, and disposition.

• Component receipt, sampling, testing, and release records
• Material movement transaction logs
• Inventory ledgers reconciled to physical counts
• Label and packaging issuance records

• Material movement records not reconciled to batch usage
• Inventory adjustments without root cause analysis
• Linking from batch record to component lot not maintained
• Records of rejected components not retained for required period

To assure uniformity from batch to batch, master production and control records shall be prepared, dated, and signed for each drug product.

• Master Production and Control Records
• Document approval workflow with QCU signature
• MBR change control records
• Master formula files

• MBRs not approved by the QCU before use
• Multiple uncontrolled copies of MBRs in production
• MBR changes implemented without revision history
• Master records lacking detailed in process control limits

Batch production and control records shall be prepared for each batch of drug product produced and shall include complete information relating to the production and control of each batch.

• Executed Batch Production and Control Records
• Batch record review checklist
• Deviation entries within batch records
• Yield and reconciliation calculations
• Electronic batch record (EBR) audit trail outputs

• Batch records signed before steps were completed
• Missing values back filled without contemporaneous note
• EBR audit trails not reviewed as part of disposition
• Reconciliation discrepancies signed off without comment
• Batch record review queue exceeding internal SLAs

All drug product production and control records including packaging and labeling shall be reviewed and approved by the quality control unit.

• Production record review SOP
• Batch record review and disposition log
• Investigation reports for batch record exceptions
• Trending of recurring batch record exceptions

• Batch records released with open deviations
• Repeat exceptions not trended for systemic root cause
• Review depth varies between reviewers
• Investigation timelines exceeded without escalation

Laboratory records shall include complete data derived from all tests, examinations, and assays of components, in-process materials, and drug products.

• Laboratory notebooks or electronic equivalent
• Raw data files with audit trails
• OOS investigation records
• Instrument use logs
• Reagent and standard preparation records

• Raw data files deleted or overwritten on standalone instruments
• OOS investigations missing phase 1 lab error assessment
• Instrument logs missing entries between calibrations
• Reagent preparation lacking second person verification
• Audit trail review on chromatography systems not enforced

Distribution records shall contain the name and strength of the product, description of dosage form, name and address of the consignee, date and quantity shipped, and lot or control number.

• Distribution records by lot and consignee
• Recall procedure
• Mock recall exercise reports
• Customer master data controls

• Distribution data cannot resolve to consignee within target recall window
• Mock recalls not performed at least annually
• Customer master data quality issues delay recall execution
• Recall procedure not tested for global lots

Written procedures describing the handling of all written and oral complaints regarding a drug product shall be established and followed. A written record of each complaint shall be maintained.

• Complaint handling SOP
• Complaint intake and triage records
• Complaint investigation reports
• Complaint trend analysis
• Interface with pharmacovigilance and Field Alert Reports

• Complaints not triaged within defined timelines
• Investigation depth not commensurate with severity
• Trends not reviewed in management review
• Field Alert Reports not assessed for every reportable complaint
• Customer complaints not reconciled with adverse event data

Returned drug products shall be identified as such and held. If conditions under which they have been held, stored, or shipped are such that quality, safety or effectiveness may have been impaired, they shall be destroyed.

• Returned product handling SOP
• Returns quarantine area records
• Returned product disposition decisions
• Investigation records for returns related to quality

• Returns reintroduced into saleable stock without quality assessment
• Returns disposition decisions not signed by the QCU
• Storage history of returns not verified before disposition
• Returns related to quality complaints not linked to complaint files

Drug products that have been subjected to improper storage conditions shall not be salvaged and returned to the marketplace. Appropriate test methods and documentation must verify product integrity.

• Drug product salvaging SOP
• Salvage event records with environmental history
• Salvage decision risk assessment
• Testing protocol for salvaged products

• Salvage attempted on products exposed to fire, smoke, or water without robust risk assessment
• Salvage decisions not approved by the QCU
• Testing for salvaged products limited to release tests only
• No formal prohibition list for non salvageable categories