QMS-155 External Audit Procedure

1.0 DOCUMENT OWNER

Technical/Quality Manager

2.0 PURPOSE

This objective is to describe the method for regular audits of suppliers, distributors, service providers, and contract laboratories for the GMP manufacturing facility.  The purpose of the procedure is to ensure that the suppliers comply with the current Code of GMP and/or other GMP Quality Standards and that action is taken to correct any deficiencies.

3.0 SCOPE

This SOP covers audits of:

3.1 Suppliers and distributors of printed packaging components, primary, secondary and tertiary packaging materials, raw materials, and bulk materials.

3.2 Service Providers for example but not limited to calibration services, documentation storage providers, sterilization services, and warehouses.

3.3 Contract Laboratories for example but not limited to those used to test raw materials, finished goods, intermediate products, microbiological samples, and validation samples.

3.4 This SOP does not cover audits for contract manufacturers or those suppliers that are under global purchase agreements.

4.0 RESPONSIBILITY

4.1 Supplier status shall be determined based on the audit rating of the scheduled audit conducted by the Quality Assurance Associate or delegate.

4.2 The Quality Manager has the responsibility of ensuring that the audit program is conducted to schedule and to the requirements of this SOP.  Other unscheduled audits may be required to be added during the year either because they are proposed new sub-contractors / suppliers or due to quality problems that have arisen. This is at the discretion of the Quality Manager.

4.3 It is the responsibility of the Quality Assurance Associate or delegate to publish and manage external audit schedule.

4.4 Members of the Quality Assurance group together with other suitable GMP staff should conduct audits.  One person on each audit team should have completed the GMP supplier auditor course.  Other audit training and experience may be considered in lieu of this training.  A list of auditors should be available in “Approved Site Auditors” list.

4.5 Maintenance of audit files is the responsibility of the Quality Assurance Associate or delegate.

4.6 New supplier, new materials from an already approved supplier, or new supplier-manufacturing site shall be assessed and approved by means of the following:

– Perform Supplier Audit;

– Conduct full raw material testing of at least three representative raw material lots;

– Conduct pilot laboratory use testing;

– Perform plant trial;

– Evaluate Packaging materials; and

– Evaluate product stability.

4.7 Evaluation and approval of prospective new suppliers and new materials from the already approved supplier shall be processed through the Change Control system.

Logistics – Procurement department shall initiate the Change Control and advise Quality Assurance Associate or delegate for liaison with Supplier for audit scheduling.

4.8 No new supplier is to be used without a satisfactory audit.  When an audit rating of unacceptable supplier is assigned and there is no alternative source of material, it is the responsibility of the site Quality team to review and approve the corrective action plan of the relevant supplier.

4.9 Suppliers with unacceptable audit rating and/or supply history should be audited at a higher frequency.

4.10 The target date for closure of audit action items is three months after the issue of the final report or as determined by the audit action plan agreed between the supplier and GMP Auditor.

4.11 All action items are tracked through GMP tracking system. Closure of action items will be tracked by Quality Assurance Associate or delegate on a regular basis to ensure closeout is within agreed time.

4.12 Audit reports should be completed according to the timeframes in Appendix 2.

5.0 PROCEDURE

5.1 Determine Yearly Audit Schedule

5.1.1 At the beginning of each year, a review and update of the supplier list in conjunction with the logistics – Procurement team is to be established. This is to ensure that suppliers are still current for that year.

5.1.2 Determine which suppliers should be audited based on the approved supplier list, previous audits, issues that have arisen through the year and the frequency of audit required (see Appendix 1 for risk categories and frequencies).

5.1.3 The schedule then is reviewed with Quality Manager.

5.1.4 An auditor or audit team with a lead auditor is then allocated.

5.1.5 If, through the year an audit needs to be rescheduled, a risk assessment may be conducted if necessary to assess the risk of deferring the audit for another year or for the need to reschedule in the same year.

5.2 Schedule the Audits

5.2.1 To schedule the audit, contact the relevant persons at the supplier and determine an agreed time, date, venue and duration for the audit.

5.2.2 Determine the scope of the audit and discuss the agenda with the other auditor(s) or the Quality Manager.

5.2.3 Send out audit agenda as specified below to the supplier.  A template of the audit agenda, questionnaires etc. can be downloaded from www.gmpsop.com website. Vendor Audit questionnaire.  

5.2.4 Confirm Audit agenda.

5.2.5 Collect pre audit questionnaire (to be sent back to site before the audit date).

5.2.6 Review Audit Guideline (provides a checklist of the area of focus).

5.2.7 Prepare document list (to request which documents are required to have ready on the date of the audit).

5.2.8 Review previous audit reports, noting findings and comments for review during the audit. Additional resources for preparing for the audit may include relevant standards, material test reports, registration documentation and supplier specifications, etc.

5.3 Conducting the Audit

5.3.1 Conduct the audit according to the guidelines as specified in “Site Quality Auditor Training Program Manual”.  Also refer to “Audit Open / Close meetings guideline”.

5.3.2 Commence the audit with an opening meeting during which the audit method, scope, timetable, resources will be confirmed.

5.3.3 Note all observations and recommendations for reference at the closure meeting.

5.3.4 Discuss all action items that will be included in the audit report with the subcontractor / supplier / manufacturer management at the closing meeting.

5.3.4.1 Review observations with reference to internal GMP standards where applicable.

5.3.4.2 Agree on corrective action and time frames for closure of observations.

5.4 Audit Reporting

5.4.1 A supplier audit report shall be drafted by the auditor for Quality Manager ’s approval and issued within 30 working days of the audit.

5.4.2 The audit report shall be written in a way that the body of the report is free from proprietary, speculative, or potentially controversial comments and stating only actual facts observed during the audit.

5.4.3 The audit report shall be written in accordance with the given format as indicated in Section

5.4.4.  An agreed closure date from the audit closure meeting shall be entered in the audit report. If a closure date has not been established a closure date will be assigned based on the classification of the action, by the Lead Auditor.

5.4.4 The report format shall include, but not be limited to the following information:

– Supplier name, address, type of operation, name of product or service supplied and principal contact;

– Date of audit and date of last audit, if applicable;

– Purpose of audit;

– GMP auditor and audit participants;

– Audit findings;

– Supplier audit rating;

– Executive Summary (for GMP use only); and

– Recommendations for possible corrective actions for each finding.

5.4.5 An Executive Summary containing proprietary information shall be included in each Supplier Audit Report to inform the GMP recipients of the audit results. This Executive Summary shall not be included with the copy of the Supplier Audit Report that is sent to the audited supplier location representative. The Supplier Audit Report shall be considered GMP-proprietary information.

5.4.6 The Supplier Audit Executive Summary shall include, but not be limited to the following:

– Purpose of the audit

– Information regarding the supplier, such as:

History of the supplier

Any regulatory inspection received;

Any certification received (e.g. ISO); and

A brief synopsis of the type of operation.

– Summary of the ASC (area of special concern), Major, and Minor findings;

– ASC and Major findings;

– Information regarding the use of materials;

– Information comparing the audited supplier location to its competitor (if applicable);

– Current audit rating (if available) and;

– Next recommended audit.

5.4.7 All action items shall be reported in accordance with the severity of the findings, they are categorized:

ASC (Area of Special Concern): Item observed is extremely serious. Immediate corrective action by Supplier is required.

MAJOR – Item observed is serious, or a significant number of minor observations have occurred in the same area or system. Prompt corrective action by Supplier is required.

MINOR – Item observed is not yet serious but could become a problem if not corrected in a timely manner. Supplier Management follow-up is required to assure that a systematic problem does not exist.

Comment – This is a suggestion for improvement of a weakness that is not necessarily a deficiency. The subject area is acceptable but could be improved.  No response from Supplier is required.

5.4.8 Any observations that are deemed of special concern should be addressed immediately. The QA Manager must be informed within one business day. A preliminary action plan must be put in place within one week of the audit, to address the potential area of special concern.

5.4.9 A copy of the final audit report will be reviewed by the Lead Auditor.

5.4.10 The final audit report shall be approved by the Quality Manager and shall be sent for reference to internal stakeholders:

5.4.11 A copy of the final approved report detailing findings, ratings and timings for observation closure as agreed to at the audit closure meeting will be sent to the company audited.

5.4.12 The audit rating will be indicated in the audit report. The rating is determined based on the audit findings.  The audited supplier shall be rated as follows:

i. Acceptable – Materials or services specified may be ordered from the supplier.

ii. Conditionally Acceptable – Materials or services may be ordered from the supplier however specific restrictions (such as a GMP representative in the plant, extra testing and extra manufacturing steps) may apply. A periodic re-evaluation of the supplier performance should be conducted.

iii. Unacceptable – The materials or services specified cannot be purchased from the supplier.

5.4.13 Where the supplier audit rating is Conditionally Acceptable, the supplier is required to develop an action plan to address the action items in the report. The action plan should specify the actions that will be taken to address the ASC and major observations and have a timeline for completion. The action plan should be completed by the supplier and sent back to GMP Site within 30 days of the issue of the report.

5.4.14 When a Supplier Status or Supplier Audit Rating has been downgraded, within one (1) working day of the status change, The Lead Auditor shall notify the Quality Manager & Logistics-Procurement Manager.

In the event of the only available supplier receiving an Unacceptable Audit Rating, and no alternative exists other than to use that supplier, the following actions shall be completed to upgrade the Supplier Audit rating:

A corrective audit action plan shall be prepared by the supplier and submitted to and review and approved by Site Quality Team.

Upon completion of the items listed in this action plan, the supplier shall notify the Lead Auditor and a follow up audit shall be conducted, and;

After a successful follow up Supplier Audit, a new audit rating shall be assigned of either acceptable supplier or conditionally acceptable supplier.

5.5 Commitments and Corrective Actions

5.5.1 Raise all action items (ASC, Major and Minor) in GMP tracking system as an Action (child of the Event).

5.5.2 Supplier corrective actions require documented evidence of the completion of the action.

5.5.3 File report in a master file together with correspondence and the responses from the supplier.

5.6 Audit Follow-Up

5.6.1 All action plans shall be reviewed and approved by Lead Auditor and Quality Assurance Associate or delegate. All queries found shall be followed up with Supplier for clarification.

5.6.2 The Lead Auditor or delegate shall be following-up with Supplier on open action items on a regular basis to ensure close out of action items within the agreed timeframe.

5.6.3 When all the action items have been addressed according to the agreed action plan consult with the Quality Manager or delegate to determine if the audit can be closed.

5.6.4 Conditionally acceptable suppliers require a follow-up audit. Restrictions must be communicated to relevant personnel (Logistics, QO) to ensure that the supplier will only be used on a conditional basis.

5.6.5 When audit action items have been closed by the supplier written acknowledgement will be sent to the Supplier that the audit has been satisfactorily closed.

5.6.6 Close audit action items in GMP tracking system.

5.7 Reviews

5.7.1 The number of audits completed, outstanding versus scheduled are included in the Quality Assurance quarterly report.

5.7.2 Any unacceptable or conditionally acceptable suppliers are reviewed at the Site Quality Review meetings.

5.7.3 In the yearly report a summary of the external audits conducted versus scheduled is prepared.  Any unacceptable, conditionally acceptable suppliers are documented and recommendations given.

5.7.4 When all action items are closed by Supplier with Unacceptable Rating or Conditionally Acceptable Rating, the Quality Manager shall review and determine whether to approve, conditionally approve, or disapprove the supplier. The decision and rationale shall be documented and distributed to the Site Leadership Team and Logistics – Procurement Manager.

5.7.5 From supplier audit review, the Quality Manager shall determine if an approved supplier of a specific production material requires another audit before supplying a similar and/or different product type.

6.0 DEFINITIONS

Audit – A verification activity evaluating the conformance of the design, product, process or system to specified standards or guidelines.

Supplier – Used in this SOP to denote any supplier of raw materials, packaging materials service providers or laboratories used by GMP site.

Supplier Status – A status assigned to supplier to indicate whether a specific Production Material manufactured at a specific location may or may not be purchased from the supplier.

Approved Supplier – Supplier status that indicates production materials specified may be ordered from the supplier when manufactured at a specific location.

Conditionally Approved – Supplier status that indicates production materials specified may be purchased from the supplier when manufactured at a specific location only when certain conditions have been satisfied, as defined in Supplier Audit Report.

Unapproved Supplier – Supplier status that indicates production materials specified may not be purchased from the supplier when manufactured at a specific location.

ASC – Area of Special Item observed is extremely serious. Immediate corrective action by Concern sSupplier is required.

Indicate a significant risk that product could or would be harmful to a consumer.

Have previously been documented as an ASC or major deficiency by a Licensing authority.

Would result in adulteration or mis-branding of a product.

Would result in product not meeting final specifications.

Major Action Item – Item observed is serious, or a significant number of minor observations have occurred in the same area or system.  Prompt corrective action by Supplier is required.

Could produce product not complying with product’s submission, registration or listing.

Contravenes the provisions of GMP’s Manufacturing Licence to a significant effect e.g. authority levels, advertising, formulations, product stability, etc.

Contravenes written instructions or procedures without proper justification or authority.

Allows process control loss so that the process outcome is not consistent or predictable.

Minor Action Item – Item observed is not yet serious but could become a problem if not corrected in a timely manner. Supplier Management follow-up is required to assure that a systematic problem does not exist.

Many minor deficiencies or the same type that could become a major deficiency.

Appendix 1 – Vendor Risks and Frequency Categories

The audit frequency (years) is based on the vendor risk category

            1          =          High

            2          =          Medium

            3          =          Low

Appendix 2 – Timeframe for Completion of Reports / Audits