ICH Q7 clause 6: Documentation and records

Auditors should verify the existence of a comprehensive document management system covering the full document lifecycle from creation through retirement. For API manufacturers, this system must handle both paper and electronic documentation with equivalent controls. Key areas to probe include whether the system tracks revision history with clear supersession trails, whether obsolete documents are promptly removed from points of use, and whether there is a master document list or equivalent index. The system should extend to all GMP-critical documents including specifications, SOPs, master batch records, and laboratory methods.

This clause specifically addresses the approval workflow and retention periods. Auditors should verify that every GMP document has evidence of preparation by a qualified author, review by a subject matter expert, and approval by an authorized person (typically QA). The retention periods are critical compliance points: 1 year post-expiry for APIs with expiry dates, or 3 years post-complete-distribution for APIs with retest dates. Whichever is longer should apply. Verify retention through sampling batch record archives.

Focus on the complete lifecycle trail for document revisions. Every revision must have a documented reason (not just 'updated' or 'revised'). The same organizational function that originally approved the document must approve changes — this prevents production from unilaterally changing QA-approved specifications. Auditors should sample several key documents and trace their revision history to verify consistent application.

This clause goes beyond simply keeping records — the retention procedure must cover ALL GMP-relevant document types with specific retention periods for each. The list in the guidance is illustrative, not exhaustive. Key considerations for API manufacturers include maintaining development history (for regulatory submissions), technology transfer records (for site changes), and distribution records (for recall capability). Auditors should request the retention schedule and verify it against actual practice.

This is one of the most frequently cited clauses in API inspections. The two retention rules are not alternatives — you must apply whichever results in a longer retention period. For APIs with expiry dates: all records retained for at least 1 year after the expiry date. For APIs with retest dates: at least 3 years after the batch is completely distributed. 'Completely distributed' means when the last portion of the batch leaves the manufacturer's control. Local regulations may require longer periods. Storage conditions must maintain legibility — this applies to thermal paper, ink, and electronic media degradation.

Data integrity fundamentals for GMP records. Every entry must be: (1) indelible (no pencil, no erasable ink), (2) made at the time of the activity (not recorded later from memory), (3) attributable to a specific person (signature or initials), and (4) dated. This is the ALCOA+ principle applied to API manufacturing. Blank spaces should be lined out to prevent retrospective entries. Auditors should examine actual batch records for evidence of contemporaneous recording, single-line corrections with initials/date/reason, and absence of white-out or overwriting.

Complements clause 6.15 with specific correction requirements. The four elements of a compliant correction are: (1) original entry remains readable (single-line strikethrough for paper), (2) corrected value clearly written, (3) date of correction, (4) signature/initials of person making correction, and (5) reason for correction. The reason must be specific — 'error' alone is insufficient; it should explain what was wrong (e.g., 'transcription error — correct value per equipment readout'). For electronic systems, the audit trail must capture all five elements automatically.

Specifications are the quality benchmarks against which materials and products are evaluated. Every material that contacts or could impact the API must have written specifications with defined acceptance criteria. This includes obvious items (raw materials, APIs) and less obvious ones (process aids, filter gaskets, lubricants). In-process controls need documented acceptance criteria even if they are not formal specifications. Auditors should verify that specifications are current, approved by QA, and referenced in batch records and test methods.

If an API manufacturer uses electronic signatures (e-signatures), the system must be validated per applicable regulations (FDA 21 CFR Part 11, EU Annex 11). The e-signature must be legally equivalent to a wet signature, which requires: unique to the signer, under sole control of the signer, linked to the record such that any change invalidates it. The underlying electronic records must have audit trails, be tamper-resistant, and remain retrievable for the full retention period. System validation should cover IQ/OQ/PQ with emphasis on security controls.

Equipment logbooks (or electronic equivalents) must maintain a complete chronological record of what was processed, when it was cleaned, and by whom. This supports product-to-product cross-contamination risk assessment and cleaning validation. For non-dedicated (shared) equipment, the logbook is critical for traceability. For dedicated equipment, the logbook may be integrated into the batch record. Auditors should review equipment logbooks for completeness and verify that cleaning status is clearly indicated before each use.

Complete receiving records establish the traceability chain from supplier through to finished API. Each receipt must create a documented record with sufficient detail to trace back to the supplier's manufacturing batch. The assigned internal lot number is the link between the supplier material and internal production records. Auditors should trace a raw material from receiving record through to its use in a specific batch to verify end-to-end traceability.

Extends 6.30 by requiring that test results and CoAs are formally linked to the receiving record and ultimately to the batch record that consumed the material. When supplier CoAs are accepted in lieu of full testing (per clause 7.31), those CoAs must be filed with or cross-referenced to the batch record — not simply kept in a separate supplier file. Re-evaluation records for materials held beyond their re-evaluation date must also be maintained. This ensures a complete quality dossier for each batch.

Master Production Instructions (MPIs), also called Master Batch Records, are the template from which all individual batch records are generated. They must be prepared by a qualified person (typically production) and independently verified by QA. 'Independently checked' means a separate person reviews the MPI for accuracy and completeness — not the same person who wrote it. The MPI must be sufficiently detailed that a trained operator can execute the process without needing to consult additional undocumented instructions. Every change to an MPI must go through change control.

This clause specifies the minimum content requirements for MPIs. Auditors should use this as a checklist when reviewing actual MPIs. The seven required elements ensure that the MPI is a complete, self-contained instruction set. Expected yield ranges are particularly important — they serve as the basis for yield deviation investigations per clause 8.12. Storage instructions for intermediates prevent degradation during hold periods. Reprocessing instructions, where included, must be validated per Section 14.

Each batch must have its own batch production record (BPR) generated from the current, approved Master Production Instruction. Before issuance to production, someone (typically QA or document control) must verify that: (1) the BPR was generated from the correct MPI version, (2) the reproduction is legible and accurate (no missing pages, no cut-off text), and (3) all blank fields are present for completion during production. This pre-issuance check prevents use of obsolete instructions. For electronic batch records, system controls should enforce version currency automatically.

This clause defines what data must be captured in every BPR during production execution. The batch number must be unique across the site to prevent confusion. Every significant step must have both a date and time recorded (not just date). Major equipment must be identified by its specific unit number (not just type). Raw material lot numbers establish forward/backward traceability. Actual yields documented at appropriate phases enable comparison to expected ranges. Signatures at critical steps confirm both the operator and supervisor/verifier witnessed the operation.

This is the contemporaneous recording requirement — entries must be made 'at the time the specific activity is performed.' Copying data from sticky notes, personal notebooks, or scratch paper to the batch record after the fact is a significant data integrity violation. Deviations from the MPI must be captured in real-time on the batch record (not hidden or documented separately without cross-reference). QA must investigate and approve all deviations before the batch can be released. This clause is among the most frequently cited in FDA warning letters to API manufacturers.

Goes beyond simply documenting deviations — requires investigation with documented conclusions, root cause analysis, and evaluation of impact on associated batches. 'Associated batches' is a critical concept: if a deviation involves contaminated equipment or a faulty instrument, all batches processed on that equipment or measured by that instrument must be evaluated. CAPA must be implemented to prevent recurrence. Auditors should verify that deviation investigations are thorough, timely, and that associated batch impact assessments are documented.

Laboratory records must capture the complete analytical dataset — not just pass/fail results. This includes raw data (chromatograms, spectra, weighing printouts), calculations, and final results compared against specifications. Lab records are integral to the batch record review process (clause 6.71). Any result outside acceptance criteria must trigger a formal OOS investigation per a written procedure (clause 11.15). Auditors should review lab records for completeness of raw data, proper calculation documentation, and timely OOS trigger recognition.

This clause provides the definitive checklist for laboratory record content — 8 mandatory elements. Auditors should use this as a point-by-point checklist when reviewing lab records. Element (5) — complete record of all raw data — is the most frequently deficient, especially when instrument data is stored electronically but not linked to the lab record. Element (8) requires two signatures: the analyst who performed the test AND a second person who reviewed the data. This dual-signature requirement is a key data integrity control.

ICH Q7 §6.70 verbatim establishes two load-bearing obligations: (1) written procedures for review and approval of batch production AND laboratory control records (including packaging/labelling) determining compliance with specifications before release/distribution, and (2) QA review and approval of critical-step records before API batch release. The standard does not prescribe a review checklist, reviewer-qualification framework, or specific approval mechanism — those are at the organization's discretion. The 'critical process steps' qualifier means the QA review obligation specifically attaches to critical steps, not necessarily all steps.

The review must confirm three things: (1) all required testing is complete and results meet specifications, (2) the batch was manufactured according to the current MPI, and (3) all deviations have been investigated and resolved (or a justified rationale exists for releasing with known deviations). 'Resolved' does not necessarily mean the CAPA is closed — it means the impact assessment is complete and the batch has been evaluated as safe for distribution. No partial releases without full review of completed steps.

This clause makes clear that deviation investigation is a prerequisite for batch release — not something that can be completed retroactively. For critical deviations, both the investigation AND the corrective actions must be implemented before release. For minor deviations, the investigation must be complete but CAPA may be tracked separately as long as the impact assessment demonstrates no risk to the batch. The batch record must contain the complete audit trail: what deviated, the investigation reference number, and the final disposition decision.

When a batch fails, the investigation scope must extend beyond the failed batch to identify all potentially affected batches. 'Associated' means batches that share common factors with the failure: same raw material lot, same equipment, same operator, same environmental conditions, same time period. The investigation must explicitly evaluate whether other products manufactured on shared equipment could be affected. This clause drives thorough root cause analysis and prevents the release of compromised batches that happened to pass specification by chance.