Effectively Reviewing GMP Documents: A 10-Step Guide

Good manufacturing practice (GMP) documents are the backbone of pharmaceutical quality systems. It serves as controlled records that ensure consistency, traceability, and compliance with regulatory standards. We have prepared a comprehensive guide on how to review GMP documents systematically. This will help ensure regulatory compliance, product quality, and patient safety. Additionally, we have highlighted why GMP document review is critical.

What is GMP?

Good manufacturing practices (GMP) is a system that sets guidelines for consistently manufacturing products as per defined quality benchmarks. GMP covers every aspect of the manufacturing process to ensure patient safety and improved patient outcome as well as prevent cross-contamination, adulteration, and mislabelling. GMP guidelines are developed to minimize pharmaceutical production associated risks that cannot be eliminated only by testing the finished product. Good manufacturing practices provide detailed written guidelines for each step in the drug production process that could affect the quality of the final product. Aspects of production regulated by GMP are as follows:

• Manufacturing building, environment, and facilities
• Manufacturing equipment and instrument
• Raw materials
• Personnel
• Quality management
• Staff sanitation and hygiene
• Inspections and quality audits
• Product complaints
• Documentation and recordkeeping
• Validation and qualification

Implementing GMP in your production process can help reduce losses and waste. Additionally, you can avoid product recalls, fines, and legal action for manufacturing substandard products. Thus, GMP in pharma industry protects both patients and the company.

What are GMP documents?

GMP documents are controlled records demonstrating GMP compliance. They include Standard Operating Procedures (SOPs), batch manufacturing records, validation protocols, quality manuals, and deviation reports. All these documents are designed to capture every step of production and testing in a clear, accurate, and reproducible manner. GMP documents safeguard product quality, patient safety, and regulatory compliance. Moreover, they prevent errors, enable investigations, and provide evidence during audits. Thus, they are essential for maintaining integrity and reliability in pharmaceutical manufacturing.

Why reviewing GMP documents matter?

• Ensures data integrity and adherence to SOPs.
• Documents deviations and provides the basis for CAPA.
• Verifies product quality and compliance with FDA, EMA, WHO GMP standards.
• Regulatory agencies often cite poor documentation as a major cause of observations and warning letters. Hence, it is vital to thoroughly review the GMP documents.

10-Step guide to effectively reviewing GMP documents

We have provided a step-by-step guide to review GMP documents like a pro. A disciplined, risk-based review ensures data integrity, audit readiness, and patient safety.

1. Identify document type and purpose: For batch manufacturing records (BMRs), verify production steps, yields, and reconciliation. For standard operating procedures (SOPs), ensure clarity, consistency, and alignment with regulatory requirements. For validation protocols/reports, confirm reproducibility and adherence to approved methods. For deviation/change control reports, assess justification, root cause analysis, and CAPA linkage. Notably, each document type has unique compliance risks. Hence, knowing the purpose of the document will define how you review them.
2. Check version control and approvals: Confirm document number, revision history, and effective date. Ensure authorized signatures (QA, production, QC) are present. Verify obsolete versions are not in circulation. Missing or outdated approvals are a common FDA regulatory inspection observation. Hence, attention should be paid to revision history and approvals.
3. Apply ALCOA+ principles: Review the document according to Attributable, Legible, Contemporaneous, Original, Accurate (ALCOA+) principles. As per the principles, check who performed the action, is the writing legible, were the documents recorded at the time of activity, is it the first record and not transcribed, and does the data match actual observation?
4. Cross-check against SOPs and protocols: Ensure procedures match approved SOPs. Confirm that raw material IDs, equipment calibration, and environmental conditions align with protocols. Moreover, document deviations with proper justification. Notably, any mismatch will indicate potential data integrity gaps.
5. Verify good documentation practices (GDP): While reviewing the documents, check if the document follows the general GDP rules. There should be no overwriting or use of correction fluid. Moreover, corrections must be single-line strike-through, signed, dated, and justified. Use indelible ink to record data and avoid pencil. Additionally, there should be no blank entry. Use NA for not applicable. Use standardized formats, such as DD-MM-YYYY and 24-hour clock. Notably, GDP violations can be a huge roadblock to GMP compliance.
6. Check completeness: All fields should be filled and there should be no blanks. Additionally, attachments should be included. Verify operator initials, supervisor sign-offs, QA approvals. Notably, incomplete records undermine traceability.
7. Review consistency of data: Compare batch yields, timings, and equipment logs across documents. Spot anomalies like unrealistic timings or mismatched weights. Ensure reproducibility across multiple batches. Consistency checks will reveal hidden process deviations.
8. Evaluate deviation handling: Investigations must be root cause driven and not superficial (checking for “human error” alone is insufficient). CAPA must be specific, measurable, and time-bound. Link deviations to risk assessments and impact analysis. Weak deviation handling will undermine regulatory confidence.
9. Check sign-offs and authorization: Each section has to be signed by operators, supervisors, and QA. Electronic systems must show audit trails. Ensure dual verification where required (e.g., critical calculations). Missing QA approval invalidates the record.
10. Confirm traceability: Trace raw materials, intermediates, and finished product. Link deviations, investigations, CAPA, and effectiveness checks. Ensure test results can be traced back to source data. Thus, traceability is the backbone of regulatory compliance.

Common mistakes to look for while reviewing GMP documents

We have presented some typical errors that any GMP document reviewer should keep track of while reviewing GMP documents.

• Recording activities before they occur or backdating entries. Regulators see this as a data integrity violation because it undermines contemporaneous recording (ALCOA principle).
• Incomplete records, such as missing signatures, initials, or dates, blank fields left unaddressed, and attachments not included. This weakens traceability and raises questions about product quality.
• Inconsistencies between batch manufacturing records, equipment logs, and QC test results.
• Yield calculations not matching with input/output data. This suggests either poor oversight or potential falsification.
• Using shorthand or acronyms without a legend or SOP reference. This creates ambiguity and hinders reproducibility.
• Overwriting entries, using correction fluid, or erasing data.
• Corrections not signed, dated, or justified.
• Reusing templates without updating batch-specific details.
• Carrying forward incorrect data across multiple records. This leads to systemic errors and undermines electronic audit trails.
• Labeling issues as “human error” without root cause analysis.
• CAPA not linked to risk assessment or effectiveness checks indicates weak quality culture and poor risk management.
• Handwriting that cannot be read.
• Use of pencil or erasable ink to record data.
• Not checking against SOPs, calibration records, or raw material certificates. Missed discrepancies can cascade into product quality failures.
• Documents signed only by operators or supervisors, without QA approval.

Pharmadocx Consultants: Your trusted GMP documentation support

Thus, good manufacturing practices in pharma industry regulate all aspects of the drug-production process for patient safety and improved patient outcome. Proper documentation is necessary for GMP compliance. Hence, GMP documents are the backbone of pharmaceutical quality systems. Therefore, GMP document review ensures data integrity, regulatory compliance, and ultimately patient safety. By adhering to Good Documentation Practices and rigorously cross-verifying against SOPs and protocols, reviewers can transform documents into reliable evidence of quality. Furthermore, keeping track of common errors, such as incomplete records, backdating, or superficial deviation handling, will strengthen audit readiness and build confidence with regulators. A disciplined detail-oriented document review system not only prevents errors but also reinforces a company’s commitment to regulatory excellence. For any assistance with GMP document preparation, email at [email protected] or call/Whatsapp on 9996859227.