For some manufacturers, meeting requirements for WHO prequalification (PQ) or emergency use listing (EUL) can be challenging. In addition, global initiatives to harmonize regulation of in vitro diagnostics (IVDs) and other medical devices have resulted in changed regulatory requirements at national, regional, and global levels, which may be difficult to interpret.
WHO provides specialized technical assistance to help recipients achieve compliance with international regulatory norms and standards, so that they can attain WHO PQ for priority products, or EUL for unlicensed products to be used in the context of a public health emergency, and/or they can supply quality-assured products required by United Nations (UN) Agencies, their partners and procurement agencies serving WHO Member States; and/or for risk assessment for the Expert Review Panel for Diagnostics (ERPD) for IVDs. In particular, WHO can assist manufacturers by providing Specialized Technical Assistance to:
- help recipients understand requirements for WHO PQ or EUL, and how to meet them
- identify any major shortcomings in achieving compliance with international regulatory norms and standards.
WHO CAN APPLY?
Technical assistance is restricted to manufacturers of IVDs that meet the prequalification eligibility criteria or those for which eligibility of unlicensed product for assessment under the EUL procedure has been established by WHO, including IVDs for WHO priority diseases and that have a high public health impact (e.g. self-tests, point-of-care tests, and/or tests adapted and suitable for the different health care levels in low- and low-middle income countries). These manufacturers include those who:
- produce IVDs eligible for prequalification
- produce IVDs eligible for EUL
- intend to participate in tenders issued by UN-procuring organizations
- have submitted or have a plan to submit an IVD to the Expert Review Panel for Diagnostics (ERPD) for risk assessment
- any manufacturer who has made a pre-submission to WHO PQ but whose product did not pass pre-submission screening
- under certain circumstances, manufacturers of innovative products that are still under research and development stage; the products concerned are reviewed on a case-by-case basis.
Specialized technical assistance will be prioritized for:
- manufacturers from low- and middle-income countries (LMICs)
- manufacturers who have submitted or have a plan to submit to PQ within 2 years
- IVDs intended to face a public health emergency
- IVDs that are under-represented in the PQ list or pipeline.
WHAT AREAS ARE COVERED?
Technical assistance experts work with manufacturers to develop capacity to achieve compliance with international and WHO norms and standards to attain WHO PQ or EUL.
Technical assistance may include:
- selection of optimal products for PQ or EUL and agreement on a product development plan
- a quality management system (QMS) audit or WHO pre-inspection
- development of a corrective and preventive action plan
- preliminary review of data intended to be submitted as part of an application for PQ or EUL
- compilation of a product dossier for submission to WHO for evaluation for PQ or EUL
- organization of training workshops on specific topics requested by manufacturers.
WHAT IS THE PROCEDURE FOR REQUESTING TECHNICAL ASSISTANCE?
A manufacturer may forward a request for specialized technical assistance by emailing to localproduction@who.int, or by completing a request form for specialized technical assistance.
Alternatively, Specialized Technical Assistance may be initiated by WHO's Local Production and Assistance Unit (LPA):
- After a request has been made by an IVD PQ assessor following product dossier review or by a PQ inspector following manufacturing site inspection.
- When the ERPD secretariat informs LPA about a manufacturer that manufactures a product of interest to procurers, which has the potential to deliver significant public health benefit, but which does not yet meet ERPD requirements for categorization as eligible for procurement.
- Technical assistance can also be proposed by other parties such as international procurers or government ministries.
Whichever case applies, the recipient will be requested to provide a signed Letter of Agreement for Specialized Technical Assistance prior to the provision of technical assistance.
Potential recipients are expected to:
- declare their intent to submit their IVD product to WHO PQ or EUL after the necessary improvements have been implemented
- be transparent regarding any similar technical assistance that is being or will be provided by other organizations or under donor-driven projects
- designate a focal point for communication with LPA regarding the technical assistance visit that will be organized and coordinate all aspects of the visit, including follow-up activities, if needed
- facilitate the visit of the technical assistance expert(s), by providing: administrative support (in the form of an invitation letter) for visa applications; transportation between the relevant site and accommodation; provision of a modest lunch/refreshments and a small meeting room for team discussions and/or review of documents on the days of site visits; a skilled interpreter, and translation of relevant documents, if required
- provide the technical assistance expert(s) with the necessary information and documentation before, during and after the technical assistance visit, and cooperate with the expert(s) and WHO on all matters relating to the technical assistance
- agree that WHO can make public their names as recipients of technical assistance
- provide WHO with an evaluation of the conduct and usefulness of the technical assistance provided.
HOW IS TECHNICAL ASSISTANCE PROVIDED?
Following receipt of a Letter of Agreement, technical assistance is initiated with a discussion with the intended recipient about a plan for attaining PQ or EUL. This may be followed by a two‒ or three‒day gap analysis visit to the recipient's premises by a group of experts, including QMS specialists and product-specific laboratory technical experts. Where appropriate, the national regulatory authority (NRA) may be invited to participate in or observed the visit.
During the gap analysis visit, the entire workstream flow — from incoming goods to outgoing IVDs — is followed and assessed. If needed, particular workflow elements may be assessed in depth. By the end of the visit, the manufacturer will have gained a good understanding of which manufacturing processes are compliant with PQ or EUL and regulatory requirements and those that require improvement. The gap analysis report will guide the manufacturer as to what action must be taken in order to achieve full compliance with regulatory requirements.
A review of existing documentation for an IVD that it is intended to be submitted for PQ or EUL may be organized, and an agreement reached on data completion, if necessary. Advice on data completion can be organized by correspondence.
Generally, a manufacturer can implement many of the improvements indicated without assistance from external parties. However, in some instances, the manufacturer may be advised to contract external expertise, relating, for example, to development of the product dossier, product quality control, analytical and/or performance studies, or the manufacturing processes and procedures of the production plant and/or warehouses.
Care is taken to ensure avoidance of any conflict of interest with WHO PQ and with respect to individual sites covered by the technical assistance. In particular, technical assistance experts that have provided, or are providing, technical assistance to a recipient are not permitted to participate in the assessment of any IVD or site inspection for WHO PQ or EUL of IVD manufactured by that recipient.
Site inspections and evaluations of product dossiers performed for WHO PQ are independent of the outcomes of technical assistance. Information gathered during provision of technical assistance is not shared with WHO PQ staff and remains confidential.
Technical assistance is currently provided free of charge, although recipients may be requested to contribute towards the local costs associated with the visits of technical assistance experts, as described above. The following conditions apply:
- Technical activities may be combined — such as site visit and documentation review — aimed at assessing the intended recipient's potential to achieve technical assistance milestones. A combination of remote, on-site support and training may be used when providing technical assistance
- Provision of technical assistance to a manufacturer may be combined with capacity building of other parties. For example, the NRA may participate in or observe the visit of the technical assistance expert(s)
- Provision of specialized technical assistance may be prioritized, for example, for IVDs that would have a high public health impact if prequalified, or if less than three urgently needed products have been prequalified and less than two such products are under assessment.
WHO ensures that the confidentiality of commercially-sensitive and other information obtained during a technical assistance visit is respected. The observations and recommendations of the technical experts are shared with the recipient (but excluding those specifically addressed to WHO). Any information obtained during the provision of technical assistance can be made available to third parties only with the recipient's consent.
WHO reserves the right to request additional information from the organization that has requested assistance and to decide whether to meet the request, taking into account the need for the relevant IVD(s), availability of WHO resources and any other relevant factors. WHO will respond within 60 days (excluding any time required to request and receive additional information) to the request for technical assistance.
WHAT ARE THE EXPECTED OUTCOMES?
Technical assistance is deemed successful if it enables a recipient to submit a dossier for WHO IVD PQ or EUL and pass the initial screening without any critical or a high number of major observations. In so doing, the recipient will have improved the quality of its IVD and reduced the time to PQ or EUL.
More generally, technical assistance can be seen as a means of improving the quality of locally-produced IVDs and of promoting adherence to international and PQ standards.
Experience to date has also shown that provision of technical assistance can increase a government’s awareness of the value of strengthening regulatory requirements and the commitment of manufacturers to meeting them.
For further information about provision of Specialized Technical Assistance, please contact localproduction@who.int.
