1. Purpose
This Procedure defines the procedure for performing Distribution Site (DS) audits and includes selecting, preparing for, conducting, reporting and documentation archiving of DS audits. The primary purpose of these audits is to evaluate the operational use of the DS for compliance with the company procedural documents, GMPs, GCPs, and applicable (local) regulatory requirements.
2. Scope and Applicability
It should be in the policy that each DS, used for distribution of Study Drug, will be audited as part of the quality assurance process. This includes any DS located within the same premises, as well as any DS at a Contract Research Organization Audits of Distribution Sites should be carried out by QA group working for contracts.
3. Definitions
3.1 Critical Observation
“Deficiencies with Company Standards, and/or current regulatory expectations that provide immediate and significant risk to product quality, patient safety or data integrity, or a combination/repetition of major deficiencies that indicate a critical failure of systems. “Immediate corrective action and reporting to Management is required
3.2 Major Observation
“Deficiencies with Company Standards and/or current regulatory expectations that provide potentially significant risk to product quality, patient safety or data integrity, or could potentially result in significant observations from a regulatory agency, or a combination/repetition of “other “deficiencies that indicate a failure of system(s).”
3.3 Minor Observation
Observations of a less serious or isolated nature that are not deemed Critical or Major, but require correction, or suggestions given on how to improve systems or procedures that may be compliant, but would benefit from improvement (e.g. Good Practice seen elsewhere).
3.4 DS
Distribution Site
4. Responsibilities
4.1 General
QA Systems Strategic Planning and Re-sourcing Coordinators are responsible for:
Management of the overall audit program for DS audits
* Preparing an annual audit program
* Planning and scheduling of DS audits Allocation of auditors
* The DS Subject Matter Expert in QA is responsible for:
Technical review of DS audit reports issued by QA
* Overseeing the issuing of Audit Reports
* Issuing on annual basis a summary of audit findings
* DS audit training
The auditors are responsible for:
* Preparing, conducting, reporting the audits of the DS as detailed in the Procedure.
4.2 Identification/Selection of Audits
The QA Systems/Support Strategic Planning and Re-sourcing Coordinator prepare the overall audit program for DS audits. The selected DS audits for each year are stated in the annual audit program. Audit programs will be made available on the DS website.
4.3 Composition of Audit Team
Whenever possible, two auditors will comprise the audit team, one of whom will be the Lead Auditor who will facilitate organizing, conducting and reporting of the audit. The Lead Auditor must have been trained in conducting audits of a DS. The presence of a management representative at the opening meeting and feedback meeting (see section 5.3) is recommended.
5. Guideline
5.1 Frequency of the Audit Program
The frequency of DS audits will be one every 3 years, as initial assessment. Thereafter the assessment may be based on audit (i.e. visits), questionnaire, or other information.
5.1.1 Prioritization of Audits
Prioritization of audits is potentially based on:
* Clinical study activities (number of studies) at DS
* External Inspections
* Scope of licensed activities, e.g. manufacturing license or distribution activities
* Compliance risk, based on previous DS audits, reported compliance issues, or another knowledge
5.2 Preparing for the Audit
5.2.1 Planning the Audit
The Lead Auditor and Co-Auditor will: Decide the practical arrangements for conducting the DS audit
5.2.2 Initial Contacts and Confirmation
The Lead Auditor will:
* Inform the responsible DS Manager or the responsible person at the DS. Once the audit date is confirmed, the Lead Auditor will:
* Confirm the planned audit to the DS contacts via electronic mail or by letter. The e-mail or letter, will introduce the audit team, confirm the agenda of the audit, and state the documents to be sent to the auditors preceding the audit.
5.2.3 Preparatory Reviews and Preparation of Working Documents
The Auditor(s) will:
* Complete preparatory work before the DS audit will be performed. Activities should include, where possible, a review of supplementary Sops, organization chart(s), and job descriptions. Activities should also include, where possible, a review of (a sample of) Compliance Issue Notification forms and Compliance Issue Reports, which have been completed since e.g. last audit. Investigational Products and/or QA from the site that is responsible for the investigational products for which study drug documentation will be reviewed during the audit, should be contacted ahead of the audit for any relevant input (including, for example, information on compliance issues). If the DS audit is in conjunction to planned investigator site audit(s) or systems audit, activities should also include, where possible, a review of study drug supply information. For example, information on study drug supply as stated in the clinical study protocol, monitoring reports.
* Prepare appropriate working documents (checklists)
5.3 Conducting the Audit
5.3.1 Opening / Introductory Meeting
The Auditor(s) will: Hold an opening meeting to introduce the audit team, and to provide information on the purpose and details of the DS audit. The Lead Auditor will also inform the auditee on the issuing of a (draft) audit report and requirements for responses to the draft report. This information may also be provided during the feedback meeting (see section 5.3.3).
5.3.2 Audit Activities
The Auditor(s) will continue with:
* Interview(s) with the DS management and other appropriate personnel of the concerning organization, personnel of the facilities, DS documentation, and non-routine operations.
* A tour of facilities at the DS.
* A review of DS documentation.
* A review of selected Study Drug (if applicable) Documentation.
5.3.3 Feedback Meeting
At the end of the audit, the Lead Auditor will:
* Present audit observations to the DS management at the DS site.
* Discuss any follow-up corrective actions, where appropriate
* Thank those involved for their assistance during the audit
5.3.4 Follow-up Activities
The Lead Auditor will:
Send an e-mail to the DS site personnel thanking them for their assistance during the audit. This e-mail may be combined with the e-mail for issuing the Draft Audit Report (see section 5.4.1). If critical findings are identified during the course of audit activities, they will require reporting in an accelerated manner and must require immediate action. Critical findings, identified during the audit, will be reported as soon as possible to the Head of QA Systems/Support.
5.4 Reporting the Audit
5.4.1 Preparing / Issuing the Draft Audit Report
The Lead Auditor will:
* Prepare a Draft Audit Report.
* Obtain the DS audit number from the QA Systems/Support. The audit number should be available at the time the Draft Audit Report is issued.
Before being issued, the report will be circulated for review. Reviewers will bathe Co-Auditor, and technical reviewers in QA. Reviewers comments will be returned to the Lead Auditor, who will:
* Incorporate comments as appropriate.
* Issue the Draft Audit Report, normally within 15 working days after the audit. The Draft Audit Report will be issued, as an attachment to an e-mail. Relevant primary and secondary (cc) recipients will be stated in the e-mail.
5.4.2 Audit Responses
The DS management contacts will be requested to respond to the observations in the Draft Audit Report within 15 working days. When audit observations are not immediately resolvable, an action plan created by the DS responsible contacts acceptable.
5.4.3 Preparing / Issuing the Final Audit Report
Once audit responses have been received, the Lead Auditor will:
* Review the responses for acceptability
* Incorporate responses into the report When only minor observations have been reported, the audit will be considered closed, and the Final Audit Report will be issued. When major or critical observations have been reported, the audit will be considered closed after the lead auditor has obtained confirmation that follow-up commitments to major or critical observations (as specified in the action plan) have been completed. The Final Audit Report will be issued after obtaining the required confirmation. If longer term corrective/preventative actions will be transferred to a Compliance Improvement or Enhancement Plan for the DS, the Final Audit Report may be issued after receiving the Compliance Improvement or Enhancement Plan.
* Obtain confirmation that follow-up commitments to major or critical observations have been completed (or obtain the Compliance and Enhancement Plan for longer-term corrective/preventative actions).
* Issue the Final Audit Report. The Final Audit Report will be issued, as an attachment to an e-mail. The recipients will be the same as for issuing the Draft Audit Report.
5.4.4 Annual summary of audit observations
The head of the QA Systems/Support and the DS Subject Matter Expert will review the audit observations on an annual basis, and prepare a summary of the observations. The summary will be shared within QA, and DSs to facilitate learning, and to promote enhancements in compliance within the DSs. Summaries of audit observations should be made available on the DS website.
5.5 Archiving of Audit Documents
The audit report and all relevant documents will be archived. The following documents will be stored electronically, according to QA routines, on shared drive:
* E-mail for issuing Final Audit Report
* Final Audit Report
The following documents will be archived locally, according to local routines, format least 15 years:
* Copy of E-mail for Confirmation of DS Audit
* Copy of E-mail for issuing Final Audit Report
* Copy of Final Audit Report
The following documents will be archived locally, according to local routines, format least two years:
* Working documents that have been filled in during the audit, such as DS Audit Checklists.