WHO provides technical assistance to help recipients achieve compliance with international regulatory norms and standards, so that they can attain WHO prequalification for priority products or services and/or supply quality-assured products called for the UN Commission on Lifesaving Commodities for Women and Children (UNCoLSC).
Who can apply for technical assistance?
Technical assistance is available for:
- manufacturers from low-income countries who:
- produce or plan to produce priority active pharmaceutical ingredients (APIs) or finished pharmaceutical products (FPPs), as listed on current Invitations to Manufacturers to Submit for Product Evaluation, or called for by UNCoLSC
- are interested in seeking prequalification so that they can participate in tenders issued by United Nations-procuring organizations
- contract research organizations (CROs) that provide services to manufacturers of low-income countries, and who conduct or plan to conduct clinical studies for FPPs listed on current Invitations to Manufacturers to Submit for Product Evaluation
- national quality control laboratories (QCLs) that have applied for WHO prequalification, and who conduct or plan to conduct quality control testing for of priority FPPs, as listed on current Invitations to Manufacturers to Submit for Product Evaluation.
What areas are covered by technical assistance?
Technical assistance experts work with manufacturers, CROs or national QCLs to develop capacity or expertise that they currently lack. 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 WHO Good Clinical Practices for Trials on Pharmaceutical Products and Good Laboratory Practices applicable to bioequivalence testing.
For manufacturers technical assistance may include:
- selection of optimal products for prequalification and agreement on a product development plan
- a quality management system audit (see Capacity building) or WHO GMP pre-inspection (see Inspections)
- drafting and agreement on a corrective action plan
- preliminary review of data intended to be submitted as part of an application for prequalification
- compilation of API or FPP dossier for submission to WHO for evaluation for prequalification or, with respect to UNCoLSC products, to a national/regional approval mechanism
- organization of training for staff on specific topics such as prevention of cross-contamination, heating, ventilation and air-conditioning or water systems, or issues relating to sterile production.
For contract research organizations technical assistance may include:
- an audit of the quality management system (QMS)
- a focus on the analytical methods that would be applied in generating data relating to FPPs invited for WHO prequalification or of interest to UNCoLSC
- 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 prequalification
- preparation of documentation to be included in an FPP dossier to be submitted for evaluation for WHO prequalification and/or to a national regulatory authority for registration.
For national 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 prequalification of the QCL
- training in use of relevant test methods for QCL staff
- advice on the design of laboratory premises.
What is the procedure for requesting technical assistance?
A manufacturer, CRO or QCL can contact WHO directly to request technical assistance.
Alternatively, following review of a product dossier or laboratory information file, or inspection of a manufacturing site or QCL, the medicines assessment group or inspection group of the WHO Prequalification Team 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, a Request for/Proposal of Technical Assistance form should be completed. The recipient of technical assistance will be requested to provide a Letter of Agreement. (See below.)
Potential recipients are expected to:
- declare to WHO their intent to submit an API or FPP for evaluation for prequalification (in the case of manufacturers), or confirmation of readiness for inspection for prequalification (in the case of QCLs), following conclusion of technical assistance
- 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 each technical assistance mission and coordinate all aspects of the mission, including follow-up activities
- facilitate the visits of technical assistance experts, by providing administrative support for visa applications, transportation to the relevant site and/or accommodation, a skilled interpreter, and translations of relevant documents, if required
- provide the technical assistance expert(s) with the necessary information and documentation before, during and after the technical assistance, and cooperate with the expert(s) and WHO on all matters relating to the technical assistance
- agree on mutually-acceptable technical solutions and steps to be followed with the technical expert(s), and provide WHO with progress reports within the agreed deadlines, if requested
- 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?
Technical assistance generally starts after a discussion, with the intended recipient, about a plan for attaining prequalification. 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 any needed training, In the case of technical assistance to manufacturers, a review is organized of existing quality documentation for an FPP that it is intended to submit for prequalification, and agreement reached on data completion, if necessary. Advice on data completion can be organized by correspondence. Where appropriate, the national medicines regulatory authority can be invited to participate in the technical assistance.
Care is taken to ensure avoidance of any conflict of interest with WHO prequalification and with respect to individual sites covered by the technical assistance. In particular, technical assistance experts are not permitted to participate in the assessment of any API or FPP or inspection of any site that has been the subject of technical assistance in which they have been or are involved personally. WHO inspections and evaluations of product dossiers are independent of the outcomes of technical assistance.
Technical assistance is provided free of charge but recipients may be requested to contribute towards the local costs associated with the visits of technical assistance experts. Given that resources that WHO has available for provision of technical assistance are limited, the use and potential impact of those resources is maximized by:
- leveraging the resources and capacities of other stakeholders to provide support
- combining activities — such as pre-inspections and data assessment — aimed at assessing the intended recipient’s potential to achieve technical assistance milestones.
- using a combination of remote, on-site support and customized training when providing technical assistance
- combining provision of technical assistance with capacity building of other parties, for example, by inviting NMRA inspectors to participate in or observe audits.
WHO ensures that the confidentiality of commercially-sensitive and other information obtained during provision of technical assistance is respected. The observations and recommendations of technical experts (but excluding those specifically addressed to WHO) are shared with the recipient. Any information obtained during 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 on 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 hoped-for outcomes of technical assistance?
Technical assistance is deemed successful if it enables a recipient to submit an API or FPP dossier for prequalification evaluation and pass 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 products, or its testing services, and reduced its time to prequalification.
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 prequalification 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.
Model letter of agreement with recipient of technical assistance