WHO medicines prequalification is in a unique position given its in-depth experience of assessing finished pharmaceutical products (FPPs) and active pharmaceutical ingredients (APIs) across a range of therapeutic areas. Experience in prequalifying quality control laboratories (QCLs) has also proved invaluable when working with countries to increase their capacity to monitor the quality of medicines circulating on their markets.
Hands-on training for regulators
WHO passes on its experience in assessing FPPs and APIs to regulators through hands-on training. This includes opportunities for:
- participation in assessment sessions or in the annual prequalification assessment training, held at UN City, in Copenhagen, Denmark
- rotational fellowships at WHO Headquarters in Geneva, Switzerland for assessors of low- or middle-income countries
- participation in the WHO Collaborative Procedure for Accelerated Registration
- participation in hands-on assessment training organized by individual national regulatory authorities or by regulatory networks.
The training offered benefits not only regulators but also WHO prequalification since the regulators trained bring their own insights into regulatory issues and the problems that may be faced by manufacturers or QCLs when seeking to attain prequalification. And on returning to their own countries, they continue to promote and support WHO prequalification.
Regulators working with a national medicines regulatory agency who are interested in hands-on training should contact Dr Matthias Stahl if interested in inspection training. Regulators interested in the WHO Collaborative Procedure for Accelerated Registration, or in training organized by national regulatory authorities or by regulatory networks, should contact Dr Luther Gwaza.
Hands-on training for QCL staff
WHO has developed a peer audit system within the network of QCLs involved in WHO prequalification. Through peer audits QCLs can identify gaps in their technical competence and/or activities, and work towards eliminating these. Peer audits also provide training opportunities for QCL auditors. Further information or a request to participate in a mutual audit can be sent to firstname.lastname@example.org.
Over 100 quality control laboratories (QCLs) participate in WHO prequalification. More than 50% of these QCLs are already prequalified with the remainder working towards WHO prequalification.
In January 2015, WHO introduced a peer audit scheme whereby mock WHO prequalification inspections and in-situ training are organized. Based on WHO norms and standards, the scheme is robust, transparent and pragmatic. It is both helping QCLs to improve the quality of their laboratory testing and facilitating QCL networking.
Peer audit objectives
- Assist laboratories to be better prepared for prequalification inspections by: identifying gaps in their quality management system (QMS) and/or compliance with WHO norms and standards; providing advice and recommendations for corrective actions and/or improvement; training their staff; and strengthening their internal audit schemes.
- Train QCL auditors and create a pool of auditors that practices harmonized application and common interpretation of relevant quality standards.
- Promote harmonized interpretation of standards by QCLs and mutual confidence in proficiency and competencies.
- Promote work-sharing and mutual recognition of testing results.
- Serve as an information resource for QCLs aiming at WHO prequalification.
Principles of participation
- Participation is voluntary: a QCL simply has to express its interest in participation.
- Audits are performed only at QCLs that have applied for prequalification and that have not yet been prequalified. Applications from laboratories that are affiliated with a manufacturer of pharmaceutical products – particularly those that have an interest in having one or more of their products prequalified by WHO, or whose products is/are already prequalified by WHO – may be assigned a lower priority for participation.
- A national, university/nongovernmental organization and/or independent commercial QCLs, either prequalified or undergoing WHO prequalification, can nominate an auditor for participation but not more than three nominations can be considered from any single laboratory.
- The costs of participation are funded principally from resources made available by WHO.
Expression of interest
QCLs that are interested in being audited should submit a letter to email@example.com indicating when they would be available to participate, the language in which the audit should be conducted and the scope of the audit that they would like to be considered. Audits will always cover the laboratory’s QMS, but the interested laboratory can decide whether the audit should cover chemical testing only, or both chemical and microbiological testing.
QCLs who would like to nominate their staff as auditors should submit – for each nominee – a completed nomination application form, together with contact details and a professional CV to firstname.lastname@example.org . Each CV should include details of the nominee’s auditing experience and an indication of the languages of which s/he has a working knowledge. No direct individual or personal requests can be accepted.
The audit team
Each audit team will consist of 3‒4 persons :
- expert appointed by WHO
- staff auditor from a prequalified QCL
- staff auditor from a QCL currently undergoing prequalification
- and, when available, a WHO representative.
The staff-auditor from the prequalified QCL will have the appropriate qualifications, competence, knowledge and skills for performing QMS functions as well as chemical and/or microbiological testing. S/he should also be involved in internal auditing of the QCL at which they are employed.
The staff-auditor from the QCL undergoing prequalification will have appropriate qualifications, competence, knowledge and skills for performing QCL functions. S/he will preferably be currently involved in QMS management and currently have audit responsibilities at the QCL at which s/he is employed, or likely to have such responsibilities in the future.
Members of audit teams will be required to sign confidentiality agreements for each peer audit in which they participate.
- Each audit will be of 3‒4 days duration (depending on the scope of the audit) and extent of operations and facilities of the audited laboratory. Some time for training may be allocated on request.
- Only those activities proposed by the audited QCL for WHO prequalification will be audited.
- Each audit will be led by the WHO-appointed expert.
- The audit report will be prepared with the cooperation of each of the participating auditors, under the leadership of the WHO-appointed expert, and submitted to the audited QCL within 2 months of the final day of the inspection.
- The audit report will be shared between the audited QCL, WHO and the audit team. It will remain confidential.
- An evaluation report on implemented corrective actions and/or plan of corrective actions (CAPAs) will be prepared by the audited QCL and submitted to WHO within 2 months from its receipt of the audit report.
- The WHO-appointed expert will evaluate CAPA implementation; the results of the evaluation will be provided to the audited QCL.
- The CAPAs, and the expert's evaluation of CAPA implementation, will be shared with the audit team.
Peer audit activities will be reported at network seminars. Experience and lessons learned will be shared through the Co&lab platform.
Training workshops for regulators, manufacturers and QCL staff
WHO organizes training workshops for regulators and for manufacturers. Topics are varied but may cover regulatory data requirements, assessment, principles and specific requirements relating to Good Manufacturing Practices, Good Clinical Practices and/or Good Laboratory Practices, WHO’s Collaborative Registration Procedures, pharmaceutical development and WHO prequalification requirements.
Some workshops are organized for a combined audience of regulators and manufacturers since each group can find it informative to better understand the perspectives and challenges in regulation or manufacturing of the other group. Training workshops are generally by invitation only, but workshop PowerPoint presentations are made publicly available on the Events section of this website. (WHO training modules on GMP and QCL topics can also be of great value when seeking to improve staff competencies.)
Provision of feedback and support to manufacturers during prequalification process
During evaluation of an API or FPPs submitted for WHO prequalification a manufacturer may receive valuable guidance that will assist it in quality-assured production of not only the product undergoing evaluation but any other products that it produces. Surveys of manufacturers have indicated that this feedback is highly valued. Feedback may take the form of written communication or one-to-one meetings (held during a Copenhagen assessment session, at WHO Headquarters in Geneva, or during the annual prequalification meeting with manufacturers).
Organization of specialized technical assistance for manufacturers, CROs and QCLs
WHO provides technical assistance to help recipients develop the capacity to achieve compliance with international regulatory norms and standards, so that they can attain WHO prequalification for priority products or services. It is available for:
- manufacturers who produce or plan to produce priority APIs or FPPs, as listed on current Invitations to Manufacturers to Submit for Product Evaluation
- CROs that conduct or plan to conduct clinical studies for FPPs listed on current Invitations to Manufacturers to Submit for Product Evaluation
- national QCLs that conduct or plan to conduct quality control testing for of priority FPPs, as listed on current Invitations to Manufacturers to Submit for Product Evaluation.
Medicines prequalification guidance
During the process of prequalification – be these of finished pharmaceutical products, active pharmaceutical ingredients or QCLs – WHO learns which issues are the source of greatest difficulty. One of the ways in which it seeks to provide support to overcome these is by producing prequalification guidance documents. Much of this guidance is developed with feedback from manufacturers and regulators, thereby ensuring its relevance and clarity.
Dissemination of prequalification information
Additionally, WHO makes Public Assessment Reports, Public Inspection Reports and reports on medicines quality monitoring projects available on this website, and regularly publishes peer-reviewed articles on assessment findings, to further facilitate transfer of medicines knowledge and expertise.