WHO Prequalification aims to ensure key medical products meet international standards of quality, safety and efficacy, in order to optimize use of health resources and improve health outcomes. To this end, Inspection Services supports the work of and collaborates with Product Streams in the prequalification of priority health products (in vitro diagnostics, medicines, vaccines, active pharmaceutical ingredients, vector control products, immunization equipment and devices and male circumcision devices) by conducting inspections or desk assessments to evaluate compliance of manufacturers, contract research organizations and laboratories with good practices, international standards and norms and information submitted in the dossier. In addition, Inspection Services promotes collaboration and sharing of information with and among national regulatory authorities and partner organizations in order to:

• maximize the use of inspection resources
• leverage international inspection experience, expertise and information
• maximize the usefulness of the inspection outcome
• minimize the regulatory burden on those inspected.
• minimize registration time and
• improve access to priority health products

Inspection principles

In general, the following principles guide the organization, planning and conduct of WHO prequalification inspections:

• Quality risk management: All inspections shall be planned, conducted, and, in the case of routine inspections, scheduled at a frequency and level of detail taking into account risk-based principles and considering the nature and availability of the products and the compliance history and complexity of the respective site.
• Transparency and sharing of information: The outcome of an inspection shall be published on the Inspection Services webpage as “WHO Public Inspection Report” (WHOPIR) or in case of non-compliance as “Notice of Concern” (NOC). Inspection reports shall be shared with national regulatory authorities and partner organizations, upon their request. Similarly, the experience of national regulatory authorities operating to equivalent standards and stringency to those of WHO Prequalification, shall be leveraged where recent, relevant and reliable information of compliance is available to Inspection Services. Where satisfactory inspection evidence is available, it shall be considered in the planning of on-site inspections and inspections may be waived or deferred or otherwise modified.
• Resources and competence: Inspection resources shall be appropriate in terms of education, auditing skills, experience in regulatory requirements, technical background and expertise, time allocation and access to external scientific and other information, thereby contributing to the reliability of the inspection results
• Independence and confidentiality: Members of the inspection team shall be impartial and free from any conflict of interest or influence that could negatively affect their objectivity. The inspectors shall maintain confidentiality regarding information and documentation related to the inspection and shall comply with the defined WHO standards of conduct.
• Roles and responsibilities: Roles and responsibilities of all personnel involved in the inspection shall be clearly defined so that expectations can be met and the accountability of each is understood. Similarly, the role of representatives of the national regulatory authorities, procurement agencies and other WHO employees who may accompany the inspection team to the site(s) as observers or for training purposes, shall also be defined.
• Consistency of procedures: The inspection shall be performed according to defined WHO guidelines and led by a WHO Prequalification inspector to ensure consistency during the inspection. The WHO Prequalification inspector with overall responsibility for inspections shall ensure consistency between inspections of the same type and scope.
• Inspection objectives and scope: The inspection objectives and scope shall be defined. Generally, a tentative inspection plan shall be provided to the site and agreed upon with the representatives of the site before the inspection. The plan may be amended upon agreement by both sides, to accommodate the site processes and to enable audit trails to be followed.
• Adequacy of inspection documentation: Documentation associated with each inspection, such as inspection reports, shall provide adequate information related to the prequalification assessment of the product, for ensuring continuity between successive inspections and to assist the site in making quality improvements.
• Inspection results and conclusions: The results and conclusions of the inspections shall be consistent and accurate, subject to the normal limitations of an inspection, and considering the objective evidence collected during the inspection.

Organization of on-site inspections

Logistics for the inspection

Dates and time allocated for inspection

The dates and time scheduled for an inspection are to be agreed upon by all participants under the guidance of the lead inspector and documented in an inspection plan. In the case of a manufacturer, the dates proposed for the inspection should be during a time when:

• the production line of the product undergoing prequalification assessment is active (if several products are inspected during the same inspection, the production line for at least one of them should be active)
• quality control activities are being performed
• key personnel for the quality management system, quality control and production line will be present.

In the case of a contract research organization (CRO), the dates proposed for the inspection will be based on the recommendation of the head of medicines assessment, and during a time when both the clinical and bioanalytical aspects of the study concerned can be covered.

In the case of a quality control laboratory (QCL), the dates for the inspection will be proposed after acceptance of the laboratory information file, and during a time when the QCL's physico-chemical, instrumentation and microbiology sections can each be inspected.

Time allocated to the inspection will vary according to the scope of the inspection, the complexity of the site and the products.

The inspection plan is usually provided one to two weeks before the inspection and it will include:

• scope and purpose of inspection
• identification of inspection team members and of the contact person representing the site
• date and place of inspection
• expected time and duration of each inspection activity including meetings to be held with the site’s management team

Language of on-site inspections

All inspections are conducted in English. To enable a smooth and effective inspection, the relevant higher-level quality management documents must be available in English. Translation and interpretation needs, will be discussed with the site well ahead of the inspection.

Travel and accommodation arrangements

The WHO lead inspector is responsible for organizing the travel and accommodation of the inspection team. This responsibility will not extend to the observers, except under particular circumstances, such as when WHO is providing training or education. If requested by WHO, the manufacturer will use its local knowledge to assist with safe travel and accommodation arrangements for the inspection team.

Meetings during the inspection

Opening meeting

An opening meeting is held so that the inspection team and the team on-site can exchange information about the inspection process and site/study or quality control laboratory (QCL) to be inspected, as well as to confirm the inspection scope, objectives and plan, and the availability of contact persons on site.

Inspection team meeting

Inspectors will meet, as necessary, throughout the inspection to discuss findings and the progress of the inspection. They will also meet to prepare the daily inspection summary and on the last day of the inspection to prepare the closing meeting and paperwork, where appropriate.

Daily wrap-up meeting

Issues of potential concern identified during document review, and observations made during review of production and laboratory activities, or during interviews, will be communicated, normally on a daily basis.

During the daily wrap-up meetings, the manufacturer, CRO or QCL can express comments or any issues of concern on the performance of inspection and/or the findings. Comments on issues of concern and on the performance of the inspection allow the manufacturer, CRO or QCL to demonstrate their understanding of any inspection finding, to contest part, or all the facts of the observation/ non-conformity, or to provide additional clarification, if necessary. If the manufacturer, CRO or QCL wishes to contest the observation, a rationale must be provided to support their view, including full supporting evidence.

Closing meeting

The closing meeting concludes the inspection and is held in the presence of the complete inspection team and the senior management team of the manufacturer/CRO/QCL. Other staff members may be invited by the senior management team, as appropriate.

The outcome of the inspection, including areas covered and not covered, limitations of the inspection, or the product/CRO/QCL will be presented. The lead inspector will summarize the inspection findings and issues of concern and present the observations. The site’s management team will have the opportunity to comment on and seek clarification from the inspection team on issues raised during the closing meeting.

The list of findings will allow the site to start working on any immediately required corrections. The timeframe for the issuing of the final inspection report and the implementation of corrective actions should follow Inspection Services procedures, should be communicated to the senior management team and be agreed upon at the closing meeting.