Notice of Concern
Most inspections reveal a certain degree of non-compliance and even if non-conformities are cited as being “critical”, matters can usually reach a satisfactory conclusion, sometimes involving extensive corrective and preventive action plans and follow-up inspections. A Notice of Concern is issued when a manufacturer, contract research organization (CRO) or medicines quality control laboratory (QCL) does not manage to resolve the cited significant non-compliances and to apply an appropriate corrective and preventive action plan which in turn may have a negative impact on the safety, efficacy/performance or quality of a prequalified product, and result in failure to comply with relevant standards and norms, or in the case of a laboratory, lead in failure to ensure the validity of test results and to comply with the relevant standards and norms. A Notice of Concern will also be issued if the inspection observations relate to misrepresentation of data, falsification or manipulation of data with the intent to deceive.
The aim of the Notice of Concern is to remind a manufacturer, CRO or QCL of its obligations to maintain quality management system procedures and continue applying good practices in accordance with international standards and norms, and to inform suppliers and procurement agencies of any potential risks associated with a given product, manufacturer, CRO or QCL.
A Notice of Concern is not necessarily cause for public health alarm. However, if WHO Prequalification does identify a public health risk linked to a given product, manufacturer, CRO or QCL, appropriate additional measures will be taken to safeguard public health and advise the public as well as WHO Prequalification stakeholders. Measures may include but are not limited to:
- suspension of products included on the WHO List of Prequalified Products
- suspension of a laboratory included on the WHO List of Prequalified Quality Control Laboratories
- issuing of a compulsory variation to temporarily or permanently suspend a manufacturing site of a prequalified product
- recall of product batches or a product on the WHO List of Prequalified Products that have been supplied by a manufacturer
- rejection of applications for prequalification assessment submitted by the manufacturer or Quality Control Laboratory
A Notice of Concern contains the factual non-conformities observed during an inspection; these would have been discussed during the inspection and cited in the inspection report. Generally, the facts that form the basis of the non-compliance are not in dispute. However, the manufacturer or CRO or QCL may disagree that a risk exists or with the level of risk identified by WHO Prequalification, and that has resulted in issuing the NOC. If the manufacturer, CRO or QCL disagrees with any aspect of the inspection report and subsequent Notice of Concern, it should contact by email (firstname.lastname@example.org, indicating Attention: Unit Head, WHO Prequalification in the subject line) WHO Prequalification, providing the basis for its disagreement. The matter will then be investigated, and a response sent to the site within 15 working days. Should the site not be satisfied with the response, the site is advised to email the Director, Regulation and Prequalification Department (RPQ) at RHTinfo@who.int, indicating Attention: Director, RPQ in the subject line. All feedback will be treated in confidence.
A Notice of Concern will remain on this website until WHO Prequalification is satisfied that an adequate and appropriate CAPA plan has been implemented effectively by the manufacturer, CRO or QCL concerned.
During the period that a Notice of Concern is in place, Inspection Services may perform additional and more frequent inspections, especially if the NOC relates to a manufacturing site that continues to supply prequalified product(s). If the manufacturing site has been suspended, the next inspection will be performed after the manufacturer informs Inspection Services that non-compliances leading to the NOC have been addressed. WHO Prequalification will withdraw the Notice of Concern upon inspecting and verifying that non-compliances were appropriately resolved, and improvements were effectively implemented. In addition, WHO Prequalification will recommend that the inspected site be reinstated in the relevant dossiers under prequalification or already prequalified. The NOC will be withdrawn from this website and archived, and a notice to this effect posted on this website.