One of the basic expectations of Quality Management System is to carry out Self Inspection to assess the level of compliance. Carrying out Self Inspection is mandated by almost all the regulators in the world be it USFDA, EU, MHRA, PIC/S, TGA, WHO, CDSCO and many more.

 

What is Self-Inspection/ Internal Audit…? Is there any difference??

 

In routine Pharma GMP vocabulary Self Inspection and Internal Audit are often considered as synonyms. Although this is not entirely incorrect but there are few differences between the extent, objective and execution of carrying out the two type of inspections.

Self-Inspection: This may be defined as an inspection of system, processes and product and their state of compliance with the GMP, In-house procedures and various National and International Guidelines as applicable. The inspection team consists of personnel identified from the same manufacturing site. During self-inspection as the inspectors are from the same site, hence, it is not possible to carry out the complete inspection of the site in one go. This may lead to conflict of interest on the part of the members from the self-inspection team.

 

Internal Audit: This may be defined as an inspection of system, processes and product and their state of compliance with the GMP, In-house procedures and various National and International Guidelines as applicable by the inspection team identified from the personnel within the organization but from the site other than the auditee site. The firm may also appoint any external agency or auditor to carry out the internal audit. The Internal audit is carried out to assess the compliance level of all systems, processes and products w.r.t. GMP and Quality Management Systems in one go (however, assessment of single or multiple system may be defined in the scope of audit).

Internal audit also bring in picture the “third eye” to review the systems and processes which might be overlooked by the self-inspection team. It also helps to eliminate bias if any as the audit is being carried out by external party. Independent audits by external experts who have more experience in inspecting more number of companies can help to identify blind spots and suggest good practices for further improvement of the system

Why to carry out Self Inspection?

A self-inspection if carried out thoroughly and without any bias shall be beneficial in following ways:

  1. Bring a clear picture of the level of compliance that a firm is meeting w.r.t. procedures, policies, processes adopted by the firm. A detailed self-inspection plan will highlight the non-compliances w.r.t. GMP in all aspects of production, quality control and quality management systems.
  2. To assess the effective implementation and maintenance of quality management system.
  3. The self-inspection will not only detect the non-conformance but will also help to identify corrective and preventive actions.
  4. Self-Inspection is considered as a proactive approach to identify the lacunas and take corrective actions accordingly.
  5. Gives an opportunity to address any issues internally and earlier therefore avoid potentially bigger problems in future.
  6. Create a sense of confidence among the employees.
  7. Leads a firm to the concept of “All time readiness for audit”
  8. Improve the level of understanding of the principles of GMP and QMS among the employees.
  9. Leads to continuous improvement.
  10. Brings Customer Satisfaction and decreases chances of market complaints
  11. As per regulatory requirement.

When to Carry out Self-Inspection?

As far as regulatory requirements are concerned, it is expected that the firm shall carry out self-inspection at least once a year. However, Self-Inspection frequency shall be decided based upon the risk assessment and on the basis of compliance level. Compliance level expectation of Production, Quality Control and Quality Assurance are high than the other departments. Also, the department with more non-conformances shall be inspected more frequently than the departments who are doing fairly well.

The firm shall prepare a detailed inspection planner and the same shall be approved by the management and/or quality assurance.

Additionally, product recalls, repeated rejections, market complaints, as a part of preparation for the upcoming audit etc. may trigger additional self-inspection.

Where to carry out Self-Inspection?

The self-inspection system shall cover but not limited to following items:

  • Personnel;
  • Premises, equipment including personnel facilities;
  • Maintenance of buildings and equipment;
  • Storage of starting materials and finished products;
  • Equipment;
  • Production and in-process controls;
  • Quality Control including OOS and OOT,
  • Quality assurance including Deviation Management, Investigations, Change Control etc,
  • Documentation;
  • Sanitation and hygiene;
  • Validation and revalidation programmes;
  • Calibration of instruments or measurement systems;
  • Recall procedures;
  • Complaints management;
  • Labels control;
  • Results of previous self-inspections and any corrective steps taken

 

Who to carry Out Self-Inspection?

 

The team to carryout the self-inspection shall be carefully selected. As the team members are to be selected from within the site personnel special care shall be taken to avoid any conflict of interest among the team. Following basic qualities of inspector shall be there in the inspection team:

  1. The team should consist of personnel who can evaluate the implementation of GMP objectively.
  2. The team members should be well qualified and should be holding good experience of all relevant fields
  3. All the inspectors shall be trained on all the national and international guidelines applicable on the plant. He/ she should also be trained on Internal Self-Inspection SOP and other relevant SOPs.
  4. The inspector shall have good inspection experience.
  5. The inspector shall have good interpersonal skills
  6. Inspectors shall be updated with new advancements in the field of GMP by attending conferences, seminars, trainings or referring to various periodicals and journals.
  7. Inspectors shall also keep themselves updated w.r.t. warning letters or GMP concerns raised by various regulatory agencies to different manufacturers. The same shall be extended to their own site to identify possible gaps.
  8. Inspector shall be fair and shall not have any kind of conflict of interest.
  9. Inspector shall have good technical writing skills.
  10. Inspector shall have good analytical capability to identify and further classify the non-conformances on the basis of risk assessments.
  11. Inspector shall be humble but stern enough to receive the right information.

The inspection team shall have at least 2-3 members. None of the inspector shall be from the auditee department e.g. In case of self-inspection being carried out in oral solid dosage manufacturing, none of the inspector shall be from the same department. A lead inspector shall be identified among the team who shall lead the audit. In case of any discrepancy among the inspectors, he should have the last call.  Apart from the above-mentioned qualities of an inspector a lead inspector shall also have following qualities:

  1. Good leadership qualities
  2. Effective communication skills
  3. Logical and shall be paying attention to details
  4. Highly technical
  5. Decision making ability
  6. Accountability
  7. Shall be able to delegate duties

Qualification of Inspector: A firm should have a detailed procedure for qualification and requalification of the inspectors carrying out the self-inspection. An inspector shall be qualified on the basis of experience, knowledge, training, soft skills and number of inspections carried out which also includes all the above-mentioned qualities of an inspector.

All the new inspectors identified shall be first made a part of the inspection team as observers. They will participate along with the inspection team but only as an observer to learn the art of inspection. All the young inspectors shall be evaluated by the senior inspection team and on the basis of their evaluation they may be promoted to the self-inspection team for carrying out inspections independently. The inspectors may be demoted also in case their performance found non-satisfactory.

It should be noted that an inspector shall be regularly carrying out the inspections at certain level. Long gap between consecutive inspections may require the inspector to be requalified before carrying out the inspection.

How to carry out Self-Inspection?

The firm intending to create, implement and execute self-inspection system at their site shall follow following minimum steps to ensure that the self-inspection procedure is systematic, independent, objectively evaluated and thoroughly documented:

  1. The firm shall prepare a detailed Standard Operating Procedure covering all aspects of self-inspection programme viz. Scope, standards to be followed, frequency, Inspection planner, list of qualified inspectors, audit execution, evidence collection, report preparation, ensuring compliance to the observations and many more. The SOP shall be reviewed periodically to check if the same is meeting the revised standards if any.
  2. The firm shall prepare an inspection planner mentioning the departments, systems, processes or products to be covered during the year. The firm may decide if they wish to self-inspect all areas/chapters in one single self-inspection (annually) or; – have several self-inspections within a year (i.e. split the areas/chapters and perform self-inspections on several occasions).
  3. The frequency of audit shall be decided based on risk assessment. However, at least self-inspection shall be carried once in a year.
  4. As per the inspection planner, the Head-QA along with Management Representative as required, shall prepare a list of inspectors who shall be appointed to carry out the Self-inspection. The self-inspection team shall have multiple representatives from different areas of work/responsibility.
  5. A lead Inspector shall also be identified. The inspectors shall be identified from the list of qualified inspectors. Care shall be taken to address the issue of conflict of interest i.e. one shall not inspect his/her own work or area of work.
  6. The firm shall also clearly inform the standards to be evaluated during the self-inspection viz. standards set by WHO, USFDA, EU, PIC/S or local FDA besides the compliance to internal guidelines and other statutory requirements.
  7. Once the inspection team is finalized, the lead inspector shall share the tentative inspection plan with auditee department and convey the tentative inspection dates.
  8. On receipt of confirmation, the self-inspection team plans for the inspection.
  9. Before the date of inspection, the self-inspection team shall collect all the relevant information required for the effective self-inspection viz. market complaints, minutes of management review meetings, deviation records, open change controls, audit findings of previous inspection reports (internal or external) etc.
  10. During self-inspection, the inspection team shall follow the Good Inspection Skills and carry-out the inspection as per training. At the beginning of the inspection, the self-inspection team shall carryout an opening meeting with the auditee to explain scope of the inspection and the inspection process.
  11. The self-inspection team shall ask appropriate and right questions and shall focus on identifying flaws/gaps of processes and systems rather than finding faults on an individual. Use “who”, “what”, “where”, “when”, “why” and “how” rather than “closed questions” which will end up getting a “Yes” or “No” as an answer. It must be noted that superficial questions often produce superficial findings.
  12. Wherever, necessary the inspection team may refer to in-house checklists or aide memoir. the checklist shall be appropriately designed and, in a way, to allow the recording of any Non-Conformances. It is advisable to follow the checklist or aide memoir as provided by various regulatory bodies for their inspectorate staff viz. WHO, CDSCO etc. in absence of internal checklists.
  13. Inspection shall be thorough and shall cover all the aspects of the auditee department including compliance to the previous audit observations. Although it is recommended to carry-out the inspection within the scope of the self-inspection, however, if necessary, the lead inspector may allow the inspection to be extended to other related systems. departments or documentation.
  14. All the major or critical non-conformances shall be informed to the auditee department at the time of closure of self-inspection. It is expected that in few cases, auditee may provide some missing information or document related to non-conformity, which may lead to removal of draft observation.
  15. Collection of evidences through examination of documents, interviews of concerned, physical observation, measurements and records shall be thoroughly done.
  16. The entire self-inspection exercise shall be systematic and objective.
  17. Post Inspection, the self-inspection team shall place on the table all the non-conformities. There shall be detailed discussion among the inspectors to decide which observation shall be reported as non-conformance in the final report. In case of any ambiguity, the decision of lead inspector shall be accepted.
  18. The inspection report shall contain scope, purpose and the observations bot positive as well as negative.
  19. The report writing especially non-conformities shall be clear, precise and unambiguous. All the observations shall be supported with evidences.
  20. All the non-conformities shall be written to clearly indicate which regulation, guidance, or procedural requirement was not met by the auditee.
  21. All the non-conformances shall be categorized as Critical, Major, Minor and OFI based on the risk associated with the non-conformance. The three categories may be defined as:

Critical: The non-fulfilment of a requirement that represents a high level of risk to the quality, safety and efficacy of the product, integrity of the Quality Management System or regulatory compliance.

Major: The non-fulfilment of a requirement that represents a medium level of risk to the quality, safety and efficacy of the product, integrity of the Quality Management System or regulatory compliance.

Minor: The non-fulfilment of a requirement that needs to be corrected but onle represents a low level of risk to the quality, safety and efficacy of the product, integrity of the Quality Management System or regulatory compliance.

Opportunity for Improvement (OFI): An opportunity to improve the quality system that does not rise to the level of a finding.

  1. The self-inspection team shall submit the report in a timely manner and the copy of the same shall be provided to the auditee.
  2. It is also expected that the auditee department submits the compliance report in a timely manner. If compliance submission timeline is not mentioned in the SOP, then self-inspection team may seek compliance within the time frame decided by them.
  3. The auditee is responsible to initiate the corrective action and all the corrective actions shall be time bound. The priority may be given to addressing the critical observations first followed by major and minor.
  4. Each corrective action should be specific and shall mention responsibility and the target completion date.
  5. No open-ended corrective actions submitted by the auditee shall be accepted.
  6. The compliance review is normally a desk exercise by reviewing all the supporting evidences submitted by the auditee against the closure of non-conformances.
  7. If required QA Head may ask for the follow-up inspection to verify the effectiveness of the corrective actions taken as per the compliance report.
  8. It is important to note that non-conformances of one department or system or process may be extended to other departments, systems or processes within the organization as it may be an indication of systemwide gap.
  9. On the basis of self-inspection report and the non-conformances observed, it may be decided that the auditee department shall be placed in more frequently inspected or less frequently accepted categories.
  10. There shall be proper tracking of the executed audits.

Important Considerations:

  1. Self-inspection shall not be considered a tool for fault finding. It shall be considered as a tool for finding gaps and carrying out subsequent improvements w.r.t. GMP and regulatory requirements. This process shall be considered as an opportunity for continuous improvement.
  2. It should be noted that as per regulatory expectation, all the records related to planning, execution and closure of self-inspection system are auditable. This includes self-inspection report. However, it is to be noted that any regulatory auditor will appreciate the detailed and transparent self-inspection reports. One should not be afraid of showing the self-inspection reports to the auditor.
  3. The role of senior management is important in a way that how much free hand is given to the self-inspection in performing their duty.
  4. In rare cases if auditee department does not cooperate during inspection process at any stage, the same shall be escalated to the higher management for necessary intervention.

References:

  1. Chapter 9 of PIC/S guide to Good Manufacturing Practice for Medicinal Products Part I (PI009-14 (Part I))
  2. Annexure 2 of WHO Technical Report Series no. 986.
  3. Schedule M, Part I of Drugs and Cosmetics Act
  4. ASEAN Guidelines on GMP for Traditional Medicines / Health Supplements – 2015, Chapter 10 – Self Inspection