Steps in Managing the Pharma Audit
To achieve its’ objective efficiently and cost-effectively an audit should be thoroughly planned, carefully structured, systematically performed, faithfully reported, and remedial actions progressed to a timely and satisfactory conclusion. As with most issues involving people, clear and effective communication with the relevant stakeholders is essential if business benefits are to be maximised through strengthening all aspects of the customer/supplier relationship.
Issues for remedial action will be a prominent feature of the audit report. If these are ignored the audit will have incurred a significant failure (and lost opportunity) cost to both auditor and auditee.
The collection, collation and analysis of relevant information is an essential prerequisite for successfully planning a quality audit. It is important to clearly establish the reason for performing the audit (e.g. new supplier; outsourcing; defect/recall investigation; routine re-audit; remedial action follow-up; etc.) in order to determine the type, scope and specific objective(s) of the audit. There should also be a clear business benefit to justify the cost, to both auditor and auditee, of undertaking the audit. This may, for example, be to satisfy a regulatory requirement, or to gather information to justify reduced analytical testing upon future receipt of a raw material (Clarification: This in no way absolves the manufacturers (supplier and receiver) from performing all necessary tests prior to release and dispatch).
A major source of information is the pre-audit questionnaire which, if well constructed,sufficiently comprehensive and used in a timely manner, can be an extremely valuable tool if responses are analysed carefully (see template annex 1).
Experience of previously received product, particularly problem deliveries (in the case of a supplier audit), together with earlier audit reports (if they exist) can add value to the preparation for a quality audit.
Dependant on the scope of the audit the audit team can be composed of one or more auditors. If special expertise is required the team can be expanded by the inclusion of (a) specialist(s). If there is more than one auditor a lead auditor should be assigned and responsibilities should be agreed. It is advisable to interchange auditors from time to
time for a given area in internal audits. This will combine the benefits of a detailed understanding of the areas/activities with the broader expertise and experience of different auditors.
Contact with the auditee should be made well in advance of the audit to allow adequate time for the necessary arrangements to be made, and initial information gathering to take place.. A Primary Contact within the Quality Assurance department of the Auditee should be defined at the outset for a Customer or Third Party Audit and regulatory inspection. The lead auditor or Inspector will then be in direct communication to make the necessary arrangements and agree the agenda in advance of the audit.
When a pre-audit questionnaire (appendix B) is used, and this is strongly advised,responses should be studied carefully by all relevant stakeholders, and clarification requested as appropriate. This will allow the audit proper to concentrate on areas of uncertainty and/or perceived weakness thereby saving time and reducing inconvenience,
to the benefit of both auditor and auditee.
Previous audit reports are another valuable source of information. Similarly, discussing experiences, good and bad, with recipients (e.g. internal customers in the case of an internal audit; your raw materials testing laboratory in the case of an external raw materials supplier audit) can provide useful information such as batch/lot numbers for
challenging traceability etc.
The agenda for the audit should be communicated to, and agreed with, the auditee. This could also identify key reference documents (e.g. GMP; Quality Manual, etc.) and relevant working documents such as checklist(s), etc. to be used during the audit.
The auditor should be aware of any sensitive issues, for example Highly Confidential information and, should any conflict arise during the audit, the auditor should take care to handle the issues in a way that will not jeopardise the relationship with the auditee.
Performing the Audit
The audit should commence with an opening meeting to introduce auditor(s) to relevant auditee staff and Senior Management Representatives (especially relevant for an external audit or inspection); review scope and objectives, and finalise and agree the agenda and timetable. The opening meeting also provides an opportunity to explain the
audit rationale, clarify the audit plan, agree communication channels and clarify ambiguous replies in the pre-audit questionnaire.
In the case of an external audit the opening meeting also provides an ideal opportunity for the auditee to explain Company rules concerning e.g. safety, taking photographs,confidentiality of information, taking samples, talking with operators, making recordings, etc.
The auditor should decide in advance whether to use a detailed checklist or (less detailed) ‘Aide Mémoire’ (see annex 2), or simply rely on memory and experience. If the former, then it is a courtesy to explain this approach to the auditee. The Aide Memoire has the advantage of maintaining focus by providing structure to the questioning
sequence and ensuring that all listed issues are covered. However the auditors should feel free to spend more time on specific topics where compliance issues are becoming apparent and so should used the Aide Memoire as a guide from which the auditors can deviate if a concern arises over an issue not covered by the checklist.
During the audit it is usual to walk through relevant parts of the facility to observe the operation at first hand, to gather information, to assess the cleanliness and condition of facilities and the risk of potential contamination. Some auditors prefer to undertake a brief ‘tour’, following the introductory meeting, in order to familiarise themselves with
the size and complexity of the operation and achieve a clearer understanding of workflow and relative location of different activities. They may subsequently re-visit relevant areas to review GMP/systems compliance in greater detail.
During the audit evidence of compliance, or otherwise, will be obtained through observation, questioning, examining documentation and records, and challenging issues of concern. All relevant observations should be recorded clearly and concisely together with supporting evidence. Concerns should be discussed with the auditee as they arise to
avoid surprises in the Closing Meeting.
The closing meeting is particularly important since it allows the auditor (or audit team) to communicate the audit findings and conclusions in a logical and co-ordinated manner to the auditee’s management. It is, therefore, useful to provide a simple agenda and a short written summary of observations. It is important to emphasise the good news as
well as highlight the areas for improvement together with supporting evidence. Audit deficiencies should also be classified to highlight the priority for actions to the auditee and their Senior Management. The Audit Report Template (Appendix D) includes a Classification definition based on the EU GMP Inspection Report Format and this is used as standard in the APIC Audit Programme.
Deficiencies are classified as follows:-
1. Product Quality / Patient Safety Related deficiency (Critical)
2. Significant cGMP Deficiency but with no direct impact on Product Quality /Patient Safety (Major)
3. GMP deficiencies that are either considered to be minor isolated examples or there is insufficient information to classify them as Major (Other)
As stated above, the deficiencies should contain no surprises for the auditee, as all concerns should have been raised during the audit. The auditee should be given the opportunity to clarify and fully understand the evidence for the deficiencies. In this way there will be an acceptance of the findings and the auditee can then plan to fully address the audit findings rather than replay the audit.
While it is the auditors role to identify what needs to be achieved when a problem is identified, in the case of Second or Third Party Audits he/she should not be prescriptive in ‘how’ to achieve it, although advice may be offered, if specifically requested.
Reporting the Audit and Auditee Response
The single most important product of an audit is the audit report. It provides a record which identifies and may be useful for prioritising (e.g. Critical, Major, Other) areas for improvement. The audit report should be drafted, and the final version issued, as soon as possible after completion of the audit for reasons of both accuracy and effectiveness.
Suggested timings are within a maximum of 3 weeks. It is recommended that a draft of the report be supplied to the auditee for comment and check on the factual accuracy and to avoid misunderstandings arising over observations and recommendations.
Confidentiality of internal audit reports are subject to company policy. These reports are normally not made available to external auditors and inspectors from regulatory authorities.
Follow Up Of Progress with Remedial Actions
The timely implementation of corrective actions, and verification of their effectiveness,is essential to the concept of continuous improvement.
The efficiency and comprehensiveness with which agreed remedial actions are progressed is often a good reflection of the auditee management’s true commitment to quality. While minor remedial actions may be followed up at the next routine audit,progress with major issues should be reported within an agreed timeframe. It may also be necessary to re-audit to ensure that serious remedial action has been satisfactorily completed for Critical or Major deficiencies.
Failure of the auditee to actively progress major and/or serious actions should be referred to senior management (in both companies in the case of an external audit).
Responsibility for Follow Up and to decide timing of next audit lies with the customer or stakeholder responsible for initiating the audit and specifically with the QP of The Manufacturing Authorisation Holder for Human and Veterinary Medicinal Products in the case that the audit is done as part of ensuring effective GMP Compliance for Active Substances used in the manufacture of Medicinal Products in Europe.
Possible Audit Breakdown
The breakdown of an audit should be an exceptionally rare occurrence. However, it may be the result of poor planning/preparation, failure to clearly define and agree scope and objectives, an inadequately trained auditor or one lacking the appropriate personal characteristics, poor communication before and during the audit; and/or lack of commitment/co-operation/understanding on the part of the auditee. In such circumstances the scope for action to improve the situation is usually limited to either trying to identify and resolve the root cause (usually with the help of senior management) and endeavouring to continue with the audit or, as a final resort, to abort the audit.
Reference: AUDIT GUIDE -ACTIVE PHARMACEUTICAL INGREDIENTS COMMITTEE (APIC)