What to Inspect During Self-Inspection in Pharmaceutical Companies

The Good Manufacturing Practices (GMP) framework includes self-inspections as a crucial part of ensuring companies involved in the manufacture and sale of drugs abide by both regulatory requirements and provide consistently good quality products.

Self-inspection allows manufacturers to find issues with their processes, records or equipment prior to being identified by an outside (regulatory) group.

With a well-structured self-inspection program, companies will not only ensure that they are in compliance with WHO, FDA, EMA and other regulatory groups, they will also create an environment of continual improvement.

In this article, you will find an explanation of what to inspect, how to properly conduct self-inspections and the specific areas in which you should pay special attention.

What Is Self-Inspection in Pharmaceuticals?

Self-Inspection is an internal audit of the pharmaceutical company's facilities that is performed by qualified personnel to demonstrate compliance with Good Manufacturing Practices (GMP), company standard operating procedures (SOPs) and applicable regulatory guidelines. This provides a mechanism for finding inefficiencies and implementing corrective and preventive actions (CAPA) necessary to prepare the operation for a regulatory or customer audit.

Self-Inspection typically occurs on a planned basis (quarterly, semi-annually or annually) based on the level of risk and/or frequency of activity.

Objectives of Self-Inspection

The three prime objectives of a self-inspection in the pharmaceutical industry are:

• To evaluate the level of compliance with GMPs and company SOPs.
• To identify areas where non-conformances exist or places where improvement could occur.
• To validate the control and validation of processes and systems.
• To confirm the accuracy and retrievability of records.
• To ensure readiness for external inspection and/or audit.

Conducting self-inspections in a systematic manner will provide product quality and safety for patients by allowing you to identify deviations before they impact production and release.

What to Look for When Conducting an Inspection: Key Areas of Concern

The World Health Organisation (WHO) and other regulatory bodies recommend covering all critical areas which have an effect upon product quality or compliance. The following will list major sections that should be assessed during a pharmaceutical self-inspection checklist.

A. Premises and Facilities

All assets used in the manufacture, storage and support of inventory must be inspected for cleanliness of facilities, maintenance and design. The following areas can be reviewed:

• Cleanliness records and pest control.
• Lighting, ventilation and temperature control.
• Segregation of sterile and non-sterile areas as well as the dispensing area.
• Air locks, pressure differentials or other means of preventing contamination from one area to another (cross-contamination).
• Access control and flow of personnel and materials.

B. Equipment and Instruments

Both equipment used for manufacturing and testing must have an established record of maintenance, calibration and qualification. Inspectors should review the following:

• Calibration and maintenance logs for equipment.
• Cleaning validation and status labels.
• Preventive maintenance schedules.
• Breakdown or repair records for equipment.
• Measurement device storage.

Failure to maintain equipment will result in inaccurate test results, contamination or failure to produce product.

C. Personnel and Training

Human error is one of the top reasons for non-compliance with GMP. At time of self-inspection evaluate:

• Employee hygiene and gowning practices.
• Availability of training records and evaluations.
• Job responsibilities clearly laid out in the organization chart.
• Health check and certification for medical fitness.
• Employee behavior and compliance with health and safety procedures in the manufacturing areas.

D. Documentation & Control

Documentation is foundation for Pharmaceutical Quality Management. Inspectors need to verify the following:

• Current Standard Operating Procedures (SOPs) are approved, up-to-date and controlled.
• Records must be contemporaneously created, legible and signed by authorized representative.
• Data integrity principles (ALCOA+) are continuously adhered to.
• Batch manufacturing records and batch packaging records are complete and easily traceable.
• Documentation is available for deviations, out-of-specification (OOS) and change controls.

Regularly conducted self-inspections are often used to identify documentation deficiencies; regulators generally consider these serious violations.

E. Production & In-Process Controls
The production environments must be compliant with GMPs to assure product consistency and quality. Inspect the following:

• Line clearance records are complete and available for review before attempting to start-up a new batch of product.
• Manufacturing instructions (BMRs/BPRs) are utilized appropriately in the manufacturing process.
• Methods of weighing, dispensing and labeling product are appropriate.
• Sampling method and in-process checks are suitable.
• Environmental monitoring is done in sterile environments.

Check for any cross-contamination possibilities, incorrect use of equipment and/or deviations from approved processing parameters.

F. Quality Control (QC) Laboratory

QC laboratories are responsible for ensuring that the product quality has been verified prior to its distribution. They must comply with Good Manufacturing Practices (GMP) and Good Laboratory Practices. Review by inspector(s) of QC laboratory for compliance will include:

• Validation of analytical methods along with documentation
• Calibration and qualification of analytical instruments (e.g. HPLC, GC, balances, etc.)
• Sample management and retention
• Storage and use of reference standards
• Data integrity and audit trails

A special emphasis on the electronic systems will be placed to ensure compliance with 21 CFR Part 11 and equivalent regulations.

G. Warehousing and Distribution

Maintaining product quality depends on both the warehousing and distribution of the product. The inspector(s) will review the warehouse for the following:

• Temperature and humidity monitoring record
• Proper stock rotation (FIFO/FEFO)
• Segregation of rejected, expired or returned items.
• Cleaning and pest control procedures
• Management of distribution records and transportation conditions

Storage must be consistent with Good Distribution Practices.

H. Validation and Qualification

Self-inspections should verify that validated and qualified systems, utilities and processes are properly functioning. These include but are not limited to:

• Validation reports for processes, cleaning and computer systems.
• Qualification records for the HVAC, water and compressed air systems.
• Impact assessments of changes to qualified systems.
• Periodic schedules for revalidation and reports.

Systems that are either unvalidated or out-of-date pose quality risks.

I. Handling Complaints, Recalls and Deviations

Evaluate how the company manages quality issues that arise after a product has been brought to market:

• Procedures for handling complaints and conducting investigations.
• Processes for recall of non-conforming products, including records from mock recalls performed during reviews.
• Documentation for deviation and Corrective Action/Preventive Action (CAPA) including root cause analysis reports for deviations.

The effectiveness of a company's anticipation of issues and implementation of systems to prevent the occurrence of such issues can be determined from analysis of the above documentation.

J. Self-Inspection and Internal Audit System

The self-inspection process itself must be evaluated in terms of its effectiveness.

• Defined scope of self-inspection, schedule of inspections and responsibilities for self-inspections.
• Qualifications of self-inspection personnel.
• Timely completion of CAPA actions.
• Effectiveness of the management review and follow-up to the self-inspection process.

A self-inspection program should be proactive and not reactive.

Frequency and Planning of Self-Inspections

The frequency of inspections is based off of the type of product, risk level of a product and how complex the operations are.

• For departments that have critical areas like sterile production, QC and warehousing, the inspections are to be on a 3-6 month basis.
• For supporting departments like HR or administration, inspections are to be conducted on a yearly basis.

According to WHO GMP guidelines, there are to be inspections on all departments at least once every year as per the Inspection Schedule.

When planning inspections, the following should be included:
- Defined Inspection Scope
- Defined Inspection Objectives
- Use of Inspection Checklists
- Trained & Independent Inspectors from the area being inspected
- Documentation of Inspection Findings and Implementation of Corrective Action Plan (CAPA)

Common Deficiencies found during Self-Evaluations

Typical issues that can be identified include:
- Outdated procedures
- Non-calibrated equipment
- Incomplete batch records
- Cleaning validation issues
- Unlabeled or improperly stored materials
- Incomplete training records
- Lack of follow-up on CAPAs
If identified early in an internal audit, they can help prevent significant findings during a regulatory audit.

Reporting and CAPA Management

Once the Inspection is completed, a detailed report should be developed and must include the following items:

• All Observations (categorized) critical, major and/or minor.
• Root Cause Analysis for all findings.
• CAPA's (Corrective and Preventive Action) for all findings including responsible person(s) and timelines for completion.
• Review and Approvals from Senior Management.

Timely implementation of CAPA and follow-up reviews shows a strong culture of quality.

Regular Self-Inspection Benefits

• Continuous adherence to current Good Manufacturing Practices (cGMP).
• Improved accuracy of documented processes; increased discipline among employees.
• Preparedness for external audits by regulatory agencies.
• Reduced potential for product recalls and/or denials by customers.
• Demonstrated ownership of processes and accountability.

An organization that has a successful self-inspection program places a high priority on quality and safety of patients.

Self-Inspection is not only a regulatory requirement, but it is also a key element of pharmaceutical Quality Assurance. As a result of proper Self-Inspections, companies can identify potential risks and correct deficiencies in their operations, thereby increasing their GMP compliance across all operational areas.

Focusing on elements such as premises, documentation, production, quality control and warehousing, companies will have the means to continually improve and foster confidence with Regulatory Agencies, Health Care Providers and Patients.

In the pharmaceutical industry, the primary focus of Self-Inspections is to establish trust with the public by assuring that every product released from the company is safe, effective and of the highest quality.

Frequently Asked Questions (FAQs) on Self Inspection

Q1. What is self-inspection in pharmaceuticals?

Answer: Self-inspection refers to an internal audit conducted by a company to determine its compliance to the Good Manufacturing Practice (GMP) and whether there are areas for improvement.

Q2. How often should self-inspections be conducted?

Answer: Self inspections are typically done once a year for all departments and at least twice per year for those areas with the highest risk.

Q3. Who conducts self-inspections?

Answer: Self inspections are conducted by personnel of the company's own employees who have been specifically trained in performing audits or by cross functional teams.

Q4. What areas should be inspected?

Answer: Self inspections can be conducted on the following areas: premise, production, quality control (QC), documentation, warehouse and personnel.

Q5. What is the outcome of a self-inspection?

Answer: The end result of doing a self inspection is to produce a report that includes all of the non-conformities and include recommendations for corrective and preventative action (CAPA).

Q6. Why is self-inspection important?

Answer: Self inspections are important in that they provide a means to ensure that your company is in compliance and producing products of high quality as well as preparing your company for regulatory inspections.

Q7. What documents are reviewed?

Answer: The following documentation should be reviewed during the course of the self inspection: standard operating procedures (SOP), batch records, training logs, validation records and equipment logs.

Q8. How are findings categorized?

Answer: Categories of findings include critical, major and minor based on their potential impact on the overall product quality.

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