Auditing of GMP Facilities: An Overview of GMP Audits

Why is Auditing Required?

1. Compliance with Regulations: Regulatory agencies like the FDA, European Medicines Agency (EMA), Health Canada, Therapeutic Goods Administration (TGA), and others mandate GMP compliance. Auditing ensures that manufacturing practices meet these agencies’ requirements.
2. Product Quality Assurance: Regular audits help verify that the manufactured products are of consistent quality and meet all safety and efficacy standards.
3. Risk Mitigation: Audits identify potential risks in the manufacturing processes, such as contamination, deviations, or lapses in control measures, which could lead to defective products or health risks.
4. Continuous Improvement: Audits provide valuable insights into areas of improvement for processes, procedures, and systems, enabling ongoing enhancement of operations.
5. Legal and Market Access: Manufacturers must demonstrate GMP compliance during regulatory body inspections to maintain market access and avoid legal sanctions or product recalls.

Different Types of Audits in GMP Facilities

Audits can be broadly categorized based on their purpose, scope, and the entity performing the audit. Here are some of the primary types:

1. Internal Audits: These are audits conducted by the organization itself to ensure that its systems and operations comply with GMP regulations. Internal audits are typically performed regularly in the company’s quality management system.
2. External Audits: Conducted by third parties or regulatory bodies, external audits assess the facility’s compliance with GMP standards and are often mandatory for regulatory approvals. Regulators or third-party audit firms can perform them.
3. Supplier Audits: These focus on evaluating suppliers’ practices and quality systems that provide raw materials, components, or services critical to the product’s manufacturing process.
4. Regulatory Audits: These are conducted by regulatory bodies like the FDA, EMA, or TGA to evaluate compliance with regulatory requirements. These audits typically involve extensive inspection of manufacturing, quality control, and documentation practices.
5. Certification Audits: Organizations like ISO or other certification bodies carry out these to verify compliance with specific standards, such as ISO 9001 or ISO 13485.
6. Pre-Approval Inspections (PAIs): These audits are conducted before a new drug or product is approved for marketing. The regulatory body inspects the manufacturing facility to ensure it meets GMP standards.
7. For-cause audits are triggered when concerns about a facility’s compliance are raised. They may occur in response to a complaint, investigation, or previous audit findings.

Auditing Procedures by Different Regulatory Bodies

Specific standards and regulations govern the key GMP regulatory frameworks and their auditing procedures. Let’s look at each of them:

US FDA (Food and Drug Administration)

• Audit Scope: The FDA audits GMP facilities to ensure compliance with the Code of Federal Regulations (CFR), precisely 21 CFR Part 210 (Pharmaceuticals), Part 211 (Drug Manufacturing), Part 820 (Medical Devices), and related guidelines.
• Procedure: The FDA conducts routine inspections of drug manufacturing plants (CGMP inspections) to verify the company’s adherence to GMP. The audit process includes:
  • Reviewing manufacturing practices and documentation
  • Verifying the integrity of data, equipment, and facilities
  • Sampling products for testing
  • Investigating records and reports on deviations, complaints, and recalls

EU GMP (European Union)

• Audit Scope: The EU’s GMP standards are outlined in Directive 2001/83/EC and related guidance documents. These focus on the quality, safety, and efficacy of medicines.
• Procedure: The European Medicines Agency (EMA) and national regulatory bodies conduct inspections according to EU GMP guidelines. Inspections include:
  • Verification of compliance with manufacturing standards
  • Review of documentation and manufacturing practices
  • Inspection of raw materials, storage conditions, and distribution processes
  • Examination of lab and testing procedures
  • Random sampling for quality testing

Health Canada

• Audit Scope: Health Canada’s GMP requirements are defined in the Food and Drug Act, its regulations, and the “Guideline on Good Manufacturing Practices” for pharmaceutical products.
• Procedure: Health Canada conducts inspections and audits to the US FDA and EU standards. The audit involves:
  • Verifying compliance with GMP regulations
  • Ensuring that manufacturers follow standard operating procedures (SOPs)
  • Reviewing records, training, and calibration reports

TGA (Therapeutic Goods Administration, Australia)

• Audit Scope: The TGA’s GMP inspection requirements are based on the Australian Code of Good Manufacturing Practice for medicinal products.
• Procedure: TGA audits follow a systematic approach, focusing on:
  • Assessing risk management practices
  • Reviewing facilities, equipment, and process validation
  • Ensuring that records are maintained and compliant with regulatory standards

MCC (South Africa)

• Audit Scope: The Medicines Control Council (MCC) of South Africa enforces GMP compliance to ensure that drugs are safe, effective, and manufactured according to international standards.
• Procedure: The MCC audit includes:
  • Checking product quality controls
  • Verifying SOPs, equipment calibration, and environmental conditions
  • Conducting manufacturing and batch record reviews

 ANVISA (Brazil)

• Audit Scope: ANVISA enforces GMP in Brazil, which is aligned with international standards.
• Procedure: Audits focus on:
  • Reviewing manufacturing, quality control, and distribution practices
  • Ensuring compliance with Brazilian pharmaceutical regulations
  • Inspecting facilities and operational controls

ANVISA (Mexico)

• Audit Scope: Similar to ANVISA in Brazil, ANVISA in Mexico follows GMP standards to ensure product quality and patient safety.
• Procedure: Audits review manufacturing facilities, testing processes, and regulatory documentation.

ISO Standards (ISO 9001, ISO 13485)

• Audit Scope: ISO certification audits focus on the quality management system (QMS). ISO 9001 applies to general manufacturing, while ISO 13485 applies to medical devices.
• Procedure: The audit process typically includes:
  • Assessment of the QMS, policies, and procedures
  • Document review to ensure compliance with the applicable ISO standard
  • On-site inspection of production, testing, and distribution processes

Significance of External Auditing

External auditing is critical because it offers an unbiased, third-party evaluation of a facility’s adherence to regulatory and quality standards. The key benefits include:

1. Objectivity: External auditors provide an impartial assessment, which helps ensure that facilities meet international standards and regulatory requirements.
2. Expertise: External auditors are often specialists with in-depth knowledge of GMP requirements and industry best practices.
3. Regulatory Acceptance: Regulatory bodies rely on third-party audits for compliance verification, and an audit by a recognized firm can expedite product approvals and market access.

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Detailed Auditing Procedure by an External Regulatory Body

1. Pre-Audit Preparation:
   • Review relevant documents such as licenses, previous audit reports, and corrective actions.
   • Scheduling and notifying the facility in advance.
   • Determining the scope of the audit (e.g., manufacturing process, quality control, documentation).
2. Audit Execution:
   • Opening meetings with key stakeholders to define audit scope and clarify any requirements.
   • On-site facility inspection, including production lines, storage areas, and labs.
   • Interviews with key personnel (e.g., quality managers, operators, and supervisors).
   • Review of documentation, including SOPs, batch records, and validation reports.
   • Collection of product samples for quality testing (if applicable).
3. Audit Findings:
   • Identification of non-compliance issues, risks, or areas for improvement.
   • Categorization of findings into critical, major, and minor deficiencies.
   • Discussion of any immediate corrective actions needed to mitigate risks.
4. Closing Meeting:
   • Presentation of audit findings to the facility’s management team.
   • Review of any corrective actions taken during the audit.
   • Agreement on timelines for addressing deficiencies.
5. Audit Report:
   • A formal report documenting the audit findings, including identified non-conformities and the agreed-upon corrective actions.
   • Recommendations for improvement and next steps.
6. Follow-up:
   • Follow-up inspections may be scheduled to verify corrective actions are taken.
   • Ongoing monitoring and re-evaluation based on the nature of the findings.

In summary, GMP audits are essential to ensure compliance with regulatory standards and guarantee pharmaceutical products’ safety, quality, and efficacy. Different regulatory bodies have auditing procedures, but the core elements of auditing—documentation review, facility inspection, risk assessment, and corrective action—are common. External audits provide an objective and expert evaluation crucial for maintaining GMP compliance and ensuring product integrity in the global market.

Contact Us

GxP Cellators Consultants Ltd. is a respected contract services organization that provides comprehensive Good x Practices (GxP) auditing services across manufacturing, laboratory, distribution, engineering, and clinical practices. Our expertise spans a range of industries, including pharmaceuticals, biopharmaceuticals, medical devices, and cannabis. We are committed to collaborating closely with our distinguished clients in the life sciences sector to conduct thorough GAP assessments of their ongoing operations against applicable regulatory standards.

Our team is comprised of highly qualified professionals with specialized knowledge in Good Manufacturing Practices (GMP), Good Laboratory Practices (GLP), Good Clinical Practices (GCP), Good Distribution Practices (GDP), cleanroom operations, and engineering operations. Each Subject Matter Expert (SME) undergoes rigorous training to ensure they possess the necessary expertise to excel in their respective areas.

If you need assistance with GAP assessments, vendor audits, or evaluations of ongoing studies and operations, please do not hesitate to contact us at .