Invitation to submit a product dossier
For a prequalification assessment of a male circumcision device (MCD), WHO will formally invite the manufacturer to submit a product dossier together with a signed letter of agreement and proof of payment of the dossier screening fee.
Prequalification assessment cannot start until the manufacturer has:
- compiled and submitted the product dossier (see Guidance documents section below)
- completed, signed and returned to WHO the letter of agreement
- provided WHO with proof of payment of the applicable prequalification doissier screening fee.
Manufacturers should not submit a product dossier or pay the prequalification fee, unless invited to do so by WHO. Dossiers that are submitted in the absence of a formal request from WHO will be destroyed without prior notice.
Information that was previously submitted in the application form will also be considered by WHO during the review of the product dossier.
About the dossier
The manufacturer is expected to prepare, and either hold or provide timely access to, technical documentation that shows how each male MCD was developed, designed and manufactured. This technical documentation, typically controlled in the manufacturer's quality management system (QMS), is often extensive and sections of it may be held in different locations. The documentation is revised to reflect any changes made during the life cycle of the MCD through normal application of the manufacturer's QMS.
The product dossier is a selection of records and documents from this entire collection of records and documents that a manufacturer holds for a particular product. Manufacturers compile a product dossier from their existing technical documentation to provide evidence that the MCD conforms to the internationally recognized set of safety and performance principles described in the Essential Principles of Safety and Performance of Medical Devices of the International Medical Devices Regulators Forum. On this website they are referred to as the Essential Principles. The information provided may include, for example, abstracts, high-level summaries, or existing controlled documents, as appropriate, sufficient to communicate key relevant information and allow a reviewer to understand the subject to assess the validity of that information. Furthermore, the dossier should contain an Essential Principles checklist (EP checklist). The content of the submitted product dossier should be traceable by the manufacturer for future reference.
Note 1: Many terms are used internationally to describe a product dossier. They include: standard technical documentation; technical file; summary technical documentation; product summary file; and product master file. For the purpose of MCD prequalification, WHO uses only the term "product dossier".
Note 2: A "product" for MCD prequalification means a specific product name, the respective product code(s), manufacturing site and regulatory version. All information submitted within the product dossier must refer to the specific “product”.
Manufacturers must ensure that the content of the product dossier is consistent with the information submitted in the application form and that any changes in the information submitted in or as part of the application form are promptly notified in writing to WHO. The product dossier should only include information in support of the product name, product code(s), regulatory version and manufacturing site(s) indicated as eligible by WHO.
Once the product dossier has been received by WHO, it will be screened for completeness by WHO staff before being reviewed. This screening is aimed at ensuring that all requisite sections of the product dossier have been submitted and as such does not take into consideration the technical appropriateness of all the information provided in the product dossier. If the product dossier is incomplete, the manufacturer will be informed in writing that an incomplete dossier has been received and will be requested to provide supplemental information to complete the dossier within a specified deadline.
The manufacturer will have two opportunities to submit the required supplemental information within the deadlines set by WHO. In the event of noncompliance, the product dossier will be rejected on grounds of incompleteness and the application will be cancelled.
Dossiers that are considered complete following the screening will be retained by WHO for dossier review.
WHO will inform the manufacturer in writing on the outcome of the dossier screening.
Components of assessment
The prequalification assessment process for MCDs includes the following components:
- review of the application form;
- review of the product dossier, including review of clinical evidence;
- inspection of the manufacturing site(s);
- labelling review.
WHO reviews the product dossier to:
- assess the product and how it performs
- assessing the product manufacture
- determine whether the manufacturer's QMS is of an adequate standard to warrant a WHO prequalification site inspection.
Review of clinical evidence
Assessors will also review clinical evidence that WHO may obtain directly from principal investigators conducting independent clinical trials on the MCD in the intended use settings. The product dossier should contain clinical evidence that demonstrates conformity of the device with the Essential Principles that apply to it. Clinical evidence is an important component of the technical documentation of an MCD for use in public health male circumcision programmes for HIV prevention, which along with other design verification and validation documentation, device description, labelling, risk analysis and manufacturing information, is needed to allow a manufacturer to demonstrate conformity to the Essential Principles. A clinical study (also called clinical investigation or clinical trial) is a systematic investigation or study in or on one or more human subjects, undertaken to assess the safety and/or performance of a male circumcision device. The undertaking of a clinical study is a scientific process that represents one method of generating clinical data. The objective of a clinical investigation is to assess the safety and performance/efficacy of the device in question and evaluate whether the device is suitable for the purpose(s) and the population(s) for which it is intended.
The Essential Principles of Safety and Performance of Medical Devices of the International Medical Device Regulators Forum include essential safety and performance criteria for a medical device that allow the manufacturer to demonstrate that the product is suitable for its intended use.
Data from at least one randomized controlled trial that compares the performance of the device with standard procedures (currently surgical), and at least one non-comparative field study in settings of intended use will be required for review.
Any deficiencies in the documentation submitted and/or in the data that are identified in the product dossier review will be communicated in writing to the manufacturer by WHO. A corrective action plan that details the amendments needed to correct the deficiencies (i.e. responses to comments, provision of documentation and/or data that is missing) and deadlines for their submission must be provided by the manufacturer to WHO. The manufacturer will have the opportunity to submit up to two corrective action plans and, provided that the corrective action plan is accepted by WHO, only one amendment to the original product dossier will be permitted. The prequalification assessment procedure is usually suspended (i.e. WHO will not undertake any further action) until a corrective action plan has been submitted by the manufacturer and accepted by WHO. In certain cases, WHO may agree to permit the manufacturer to correct specific nonconformities after prequalification provided that the manufacturer commits in writing to correct them by an agreed upon deadline. Such a "commitment to prequalification" will be reflected in the WHO prequalification public report and will be verified during the re-inspection.
The manufacturer may request a hearing or meeting with WHO to clarify issues identified during dossier review. WHO may provide technical guidance and specifications to manufacturers to facilitate compliance with WHO requirements. If the product successfully meets the WHO prequalification requirements, a summary of the product dossier review will be included in the WHO prequalification public report. If the product dossier does not meet WHO prequalification requirementsthe prequalification application will be cancelled.