WHO provides specialized technical assistance to help recipients achieve compliance with international regulatory norms and standards, so that they can attain WHO prequalification (PQ) for priority products or services, or emergency use listing (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 risk assessment for the Expert Review Panel (ERP) for medicines. Products eligible for WHO PQ are listed in Invitations to Manufacturers to Submit an Expression of Interest for Product Evaluation (EOIs). Products eligible for EUL are those for which eligibility of unlicensed product for assessment under this procedure has been established by WHO.
WHO CAN APPLY?
Manufacturers who are eligible for specialized technical assistance are those who:
- produce priority active ingredients (APIs) or finished pharmaceutical products (FPPs) as listed in the current EOIs for PQ
- produce products eligible for EUL
- intend to participate in tenders issued by UN-procuring organizations
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
- medicines intended to face a public health emergency
- APIs or FPPs that are under-represented in the PQ lists or pipeline
- manufacturers who do not have prior experience with the PQ process or did not proceed pass the screening stage after one or more submissions
Contract research organizations (CROs) that provide services to manufacturers of LMICs, and who conduct or plan to conduct clinical studies for FPPs found eligible for PQ or EUL.
Commercial or third-party Medicines Quality Control Laboratories (QCLs) that provide quality control testing services to LMIC manufacturers that produce or plan to produce APIs or FPPs listed on the current EOIs for prequalification.
WHAT AREAS ARE COVERED?
Technical assistance experts work with manufacturers, CROs or QCLs to develop capacity to achieve compliance with international and WHO norms and standards to attain WHO PQ or EUL. For example, for manufacturers this may relate to preparation of product dossiers and/or their achieving compliance with WHO Good Manufacturing Practice (GMP) while QCLs may require assistance to achieve adherence with WHO Good Practices for Pharmaceutical Quality Control Laboratories and CROs with Guidelines for good clinical practice (GCP) for trials on pharmaceutical products and Good Laboratory Practices applicable to bioequivalence testing.
For manufacturers 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 GMP pre-inspection, which may include the QCL
- 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.
For CROs technical assistance may include:
- an audit of the QMS
- analytical methods that would be applied in generating data relating to FPPs invited for WHO PQ or EUL
- audit of a study already conducted by the CRO and that would be similar to a study to be conducted for an FPP invited for WHO PQ or EUL
- preparation of documentation to be included in an FPP dossier to be submitted for evaluation for WHO PQ or EUL.
For commercial or third-party QCLs technical assistance may include:
- a focus on QMS implementation in the laboratory
- a focus on test methods, such as microbiological testing, that would be considered during an evaluation for PQ of the QCL
- training in special topics of current interest for meeting WHO and other international norms and standards
- development of a corrective and preventive action plan
- advice on the design of laboratory premises.
WHAT IS THE PROCEDURE FOR REQUESTING TECHNICAL ASSISTANCE?
A manufacturer, CRO or QCL may forward a request for Specialized Technical Assistance by emailing to localproduction@who.int, or by filling a request form for specialized technical assistance.
Alternatively, following review of a product dossier or laboratory information file, or inspection of a manufacturing site or QCL, assessors or inspectors of the WHO Prequalification Unit may propose that technical assistance be provided to a manufacturer, CRO or QCL. 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 medicine 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 WHO's Local Production and Assistance Unit (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 three‒ to five‒day visit from a technical expert to the recipient's premises. The visit will begin with an audit (evaluation of current deficiencies) and be followed by consultation on the plan of corrective action and on any needed training. In the case of technical assistance to manufacturers, a review of existing quality documentation for an FPP that it is intended to be submitted for PQ or EUL is organized, and an agreement reached on data completion, if necessary. Advice on data completion can be organized by correspondence. Where appropriate, the national regulatory authority (NRA) may be invited to participate in provision of technical assistance.
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 API or FPP or site inspection for WHO PQ or EUL of the API and/or FPP manufactured by that recipient. The same applies to QCLs undergoing WHO PQ.
Site inspections and evaluations of product dossiers performed for WHO PQ are independent of the outcomes of technical assistance. Information gathered during the technical assistance visits is not shared with WHO PQ staff and remains confidential.
Technical assistance is currently provided free of charge, but 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 pre-inspections and data 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 with capacity building of other parties may be combined, for example, inviting NRA inspectors to participate in or observe audits
- provision of specialized technical assistance may be prioritized, for example, for APIs and/or FPPs 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 provision of technical assistance 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 FPP(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 an API or FPP dossier for WHO PQ or EUL and pass the initial screening and/or successfully undergo WHO inspection without any critical or a high number of major observations. In so doing, the recipient will have improved the quality of its API or FPP, or its testing services, and reduced the time to PQ.
More generally, technical assistance can be seen as a means of improving the quality of locally-produced medicines and of promoting adherence to international pharmaceutical 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.
