1. Purpose
To provide the minimum mandatory requirements for notification, conduct, reporting and follow-up action associated with inspections by regulatory authorities and also to outline recommendations on how to achieve compliance.
2. Scope and Applicability
This guideline covers GLP, GCP and GMP inspections of a manufacturing functions, departments, clinical investigation facilities, Pharmacovigilance programs, and R&D or manufacturing sites by Regulatory Authorities including ‘Notified Bodies’ in the case of medical devices and diagnostics.It also includes Information Services (and any associated third party providers) in support of the GXP regulated computerized systems.
3. Definitions
None
4. Responsibilities
The Quality Assurance/Compliance/Qualified Person (QP) in EU and functional management at the site inspected are responsible for the preparation, conduct and follow-up of inspections. Clinical Quality Management will provide the key contact for regulatory inspections of clinical studies or of Clinical Development systems. For inspections that involve Information Services (and any associated 3rd party providers), there may be a need to also involve IS Compliance group. The Out Sourcing and Procurement Group play a significant role in inspections at contract facilities.
5. Guideline
5.1 Minimum Mandatory Requirements
5.1.1 It is essential that management develop, document and implement procedure(s) for managing inspections by Regulatory Authorities in order to protect the legal rights of the business (and the Regulatory Authorities to perform repeated inspections) and,at the same time, to maintain a professional relationship with the regulatory authority conducting the inspection.
5.1.2 Senior Management at a site or function must be present during key parts of an inspection.
5.1.3 Inspection notification, ongoing highlights of the inspection, and the final results of an inspection must be communicated to relevant Senior Management in a timely manner.
5.1.4 There must be a local SOP describing the actions and responsibilities associated with an inspection. The SOP must address the local legal requirements for taking photographs; the use of tape recorders or other electronic equipment; the listening to, reading and signing of affidavits by company personnel; the review of internal audit reports and allowing access to computer databases.
5.1.5 An accurate and detailed record is to be maintained of events, significant comments or recommendations from the inspector(s), documents and/ or reviewed/copied for the inspector, product samples, and any other information deemed important to the inspection.
5.1.6 At the conclusion of an inspection, local management must assure that any inspection observations are clearly understood, that any factual errors are brought to the attention of the inspector(s) and that there is a clear understanding of what will be addressed by the site in written communication to the Authority.
5.1.7 Any commitments included in a response impacting on the regulatory submission must be discussed with and reviewed by the Regulatory Affairs team
5.1.8 Copies of all inspection reports, observations and the company responses submitted to Regulatory Authorities must be documented.
5.1.9 For all inspection observation written responses, the person whose name appears on the observation form/inspection report must sign the written response letter. For FDA inspections, this letter must indicate that the Observations and Responses should be supplied together when a request for documentation concerning the inspection is made under the US Freedom of Information Act.
5.2 Recommended Practices
To Meet Minimum Mandatory Requirements
5.2.1 Local SOP(s) On Regulatory Inspections
The management and administration of inspections by Regulatory Authorities should be subject to a local SOP(s). Personnel associated with the inspection process should be trained against the SOP(s). The SOP(s) should describe the main activities of key roles such as primary contact, inspector escorts, scribes, document runners, subject experts, etc. Security and site reception personnel should be aware of their responsibilities to notify management upon arrival of any Regulatory Authority. There should be a list of names and phone numbers immediately available for this purpose. A temporary area should be established for storage and collation of documents expected to be reviewed during the inspection. The primary contact should determine the purpose and scope of the inspection.
5.2.2 Senior Management Presence and Support
The most senior management of the department, function or site should be present during at least the opening and closing of a Regulatory Authority Inspection. For inspections of clinical investigator facilities, this is the Principal Investigator. It is customary for Senior Management to give a brief introductory presentation covering the department, function or site. The Qualified Person (QP) in the EU should participate for the entire inspection.
5.2.3 Communication
Senior Management and all relevant Corporate Quality functions should be notified as soon as an inspection has been scheduled or announced. A short summary, phone call or e-mail should be prepared daily during the inspection highlighting any significant issues or concerns raised. This summary should be sent to appropriate Senior Management. On the day the inspection concludes, appropriate Senior Management should be notified when the inspector departs. A brief, immediate summary of events should be provided and, if observations were issued, a copy should be immediately sent to Senior Management of the department, function or site inspected.
5.2.4 Photographs, Tape Recordings, Affidavits, Internal Audit Reports
The taking of photographs; the use of tape recorders or other electronic equipment; the listening to, reading and signing of affidavits (sworn statements) by company personnel; the review of internal audit reports and allowing access to computer databases should all be subject to a policy that meets local legal requirements. In general, it is usually best to remain silent on these issues until it becomes apparent that the inspector intends to invoke these tools during the inspection process. If local requirements allow flexibility, then the initial position should be not to permit any of these activities. Senior Management should approve any deviation from local legal requirements and this must be documented. Duplicate records of any pictures, recordings, etc. are to be retained.
5.2.5 Accurate Record of the Inspection Proceedings
The inspection escort team should keep accurate, detailed notes documenting those issues, products, operations, studies (pre-clinical and clinical), and other areas covered during the inspection. All comments or observations made by the inspector and a listing of all documents reviewed or supplied should be documented. It is essential that those responsible for escorting the inspector clearly understand any concerns raised during the inspection and that these be discussed with Senior Management if appropriate. Any documents provided to the inspector should be stamped CONFIDENTIAL, the only exceptions being those documents publicly available. The purpose of any samples requested by the inspector should be determined. The inspection team should ensure that sufficient duplicate samples remain for in-house use.
5.2.6 Inspection Conclusion and Follow-up
Written responses to inspection observations should be submitted to the Authority within 30 calendar days maximum. The inspector should be asked to clarify for which observations a written response is expected. Any proposed written responses to be submitted to the Regulatory Authorities should be agreed by the relevant Senior Management and. It may be appropriate to provide evidence of the corrective action taken, for example a copy of a revised SOP, with the written responses. After the close of an inspection, it is suggested that the personnel involved should prepare a detailed report to be sent to functional Senior Management. The report should minimally include: Site, inspecting authority/inspector(s)/details/ duration/dates, hosts, reason/type of inspection/ scope, areas covered, inspector’s recommendations, official observations, responses/outcome, learning points, issues, listing of any samples and documents given to inspector, report author.