4. Maintain and scale-up a sustainable and affordable collaborative registration procedure for diagnostics and support national regulatory bodies to make use of it to streamline their national regulatory procedures.
5. Develop and disseminate clearer procurement guidance for countries regarding the proposed and suggested remaining shelf-life of molecular diagnostic tests.
6. Expedite release of recent clinical and service delivery diagnostics-related guidance and recommendations in Q2 of 2021.
17. Develop and implement a sustainable and affordable collaborative registration procedure for diagnostics in 2019 and support national regulatory bodies to make use of it to streamline their national regulatory procedures.
18. Subject to support from donors (see 16 above), reinforce the capacity of its Prequalification of In Vitro Diagnostics programme, so that additional staffing can help to optimise process efficiencies and support transparent and predictable timelines for the review of HIV diagnostic products (in particular EID and VL products, and in alignment with WHO guidance).
19. In order to facilitate reduction of national evaluation studies (see points 9 and 12 above), provide relevant additional information within the public reports of products achieving prequalification status for increased data sharing to countries.
20. Provide additional guidance and support implementation on post-market surveillance and quality assurance to manufacturers, countries, and national regulatory authorities.
21. Develop guidelines and tools to support multiplexing of diagnostic technologies as well as viral load frequency for pregnant and breastfeeding women and children and consider novel interventions with patient impact evidence for review in next guidance review processes, including upgrading the POC EID recommendation.
The collaborative registration procedure for IVDs is being further extended in 2020.
The 2nd draft of the guideline document: Collaborative procedure between the World Health Organization (WHO) and National Regulatory Authorities in the assessment and accelerated national registration of WHO-prequalified In Vitro Diagnostics (IVDs), has been prepared to facilitate timely access to WHO-prequalified products in countries, to ensure that the product in countries is the same as the one which is WHO-prequalified and to provide a model for regulatory information exchange between countries. The document has undergone 2 rounds of public consultation and is on-track to be published by the end of the year.
One additional country (Ghana) has joined the CRP for IVD pilot.
A workshop was held with participants from the national regulatory authority in Uganda to support the facilitated registration of HIV self-tests. A second workshop is planned with the Mozambique NRA later in October.
The CRP-IVD pilot was implemented in 2019 in 5 countries. The procedure is being further extended in 2020 whereby WHO will be working with 7 countries to support the facilitated registration of HIV self-tests. The CRP-IVDs guidelines are published for public consultation.
The pilot is ongoing, all 5 pilot countries have signed the CRP agreement with WHO and the manufacturer is filing the submissions in each country. By end of 2019 we will be able to draw conclusions on the experience with the pilot.
To date no additional resources were made available to PQT/IVD, although discussions following transformation and RPQ relocation study included needed resources and phased prioritization of recruitments. PQDx timelines are transparent; - published a guidance on timelines on their website.
Regulators and end-users of IVDs in three sub-regions have been trained:
• Sub-regional work shop for Anglophone Africa in Arusha (2016)
• Sub-regional workshop for Francophone Africa in Dakar (2017)
• Sub-regional workshop for Russophone countries in Minsk (2018)
• National workshop in Ukraine (2018).
A replacement for a staff who left in 2019 is coming on board in November 2020. Beyond this, any additional resources are subject to approval by DG.
PQ Public reports have been amended and include extensive additional information to assist countries in leveraging PQ assessment outcomes. In Q3 2020 PQT will also split the current Public Report into two reports; the WHOPAR will capture the dossier assessment and performance evaluation outcomes and the WHOPIR will outline the site inspection findings.
The PQ public report was adjusted to provide more data on performance evaluations. At the next GDWG meeting this will be discussed again and input from GDWG will be sought.
The WHO normative guidance on post-market surveillance of in vitro diagnostics is available in English, French and Russian. A 2-day workshop that describes how to implement the guidance exists in each of the languages. There is no current HQ funding for these activities; however, additional funds are being sought to support further post-market surveillance trainings and workshops.
An amendment to the ‘Improving the quality of HIV-related point-of-care testing: ensuring the reliability and accuracy of test results’ handbook is ongoing to support improved quality assurance with POC NAT
WHO (HIV and TB) co-convened in July 2019 a global meeting with ASLM including 15-20 countries and key stakeholders in diagnostics to identify concrete ways to improve and increase access to integrated multiplex technologies, to determine how they can be translated into public health policy, and ultimately have global patient impact. The integration toolkit developed from this meeting will ideally be released by the end of 2019.
An amendment to the ‘Improving the quality of HIV-related point-of-care testing: ensuring the reliability and accuracy of test results’ handbook is ongoing to support improved quality.
Planning underway for updated consolidated guidelines on diagnostics for the first half of 2020, including POC EID and viral load considerations
26. Provide guidance to manufacturers, donors, and other stakeholders on the diagnostic approval processes to ensure a consistent baseline level of evidence for WHO-convened expert reviews.
27. With appropriate evidence, prioritize the timely review of additional urine-based lateral flow assays, molecular technologies (both point-of care and laboratory-based), alternative (non-sputum-based) specimen types, and novel testing approaches to provide better tools for pediatric TB detection and encourage and introduce market competition.
28. Support national regulatory bodies to develop or leverage regulatory procedures based on WHO assessments.
29. Develop more simplified pediatric case-finding algorithms and implementation guidance for collecting, processing and testing various non-sputum specimens, in collaboration with the Global Laboratory Initiative and Child and Adolescent TB Working Group.
30. Generate target product profiles for diagnostic assays needed for children.
31. Consider clinical scoring and symptom-based diagnostic algorithms while awaiting bacteriologic confirmation.
56. Through the Unitaid Optimal grant, accelerating access to optimal pediatric ARVs for children, including DTG 10 mg dispersible tablets, across focal countries.
57. With the support of Unitaid, support catalytic procurement of generic DTG 10 mg dispersible tablets across several focal countries to rapidly bring this optimal product to children by late Q1 2021.
1. Accelerate the national drug registration process to enable registration of any ARV listed by WHO EOI in around 40 participating countries within 1 year by ensuring that:
FOR PRODUCTS WITH PQ APPROVAL:
Company submits for registration in countries requesting use of the CRP (based on PQ approval) and process completed within around 4-5 months (country decisions within 3 months, plus submission processing time)
FOR PRODUCTS THAT HAVE NOT YET RECEIVED PQ APPROVAL:
Company submits with USFDA for full approval or tentative approval and process completed
within 6 months;
USFDA approval or tentative approval review shared with WHO for Collaborative Registration Procedure-lite (CRP-lite), a pilot program at first allowing FDA to share up to 5 minimally redacted reviews.
Company submits for registration in countries requesting use of the CRP (based on WHO PQ, FDA (CRP-lite) or other SRA review) and process completed in around 4-5 months (country decisions within 3 months, plus submission processing time)
9. For ARVs identified as priority products by PADO and included in WHO EOI, strive to ensure alignment with USFDA on study requirements and approach to dossier review.
10. Increase support for harmonization, convergence, and work-sharing through regional regulatory networks and reactivate the Paediatric Regulatory Network by Q2 2019.
11. Initiate implementation of the agreement with USFDA to facilitate the CRP-lite pilot program of products with USFDA full approval or tentative approval by Q1 2019.
12. Encourage wider use of Collaborative Registration Procedures, in particular by the 21 AIDS Free WG priority countries.
9. Efforts to facilitate alignment between the three regulatory bodies (USFDA, EMA, WHO-PQ) continue. A meeting among PQ, EMA, and FDA to align and triangulate is planned for November, and discussions occur regularly on alignment of specific dossiers.
10. The Paediatric Regulatory Network was reactivated in December 2019 and will be used as a platform to facilitate information sharing for registration of paediatric medical products.
11. The pilot for collaborative registration procedure for diagnostics was finalised successfully and the proposed first draft of the Collaborative procedure between the World Health Organization (WHO) and National Regulatory Authorities in the assessment and accelerated national registration of WHO-prequalified In Vitro Diagnostics (IVDs) is out for public consultation until 15 July 2020 (https://www.who.int/biologicals/Collaborative_Procedure_for_IVDs_for_PC.pdf?ua=1).
CRPlite: the lessons learned from the pilot are being evaluated.
USFDA/WHO agreement on CRPlite established and 2 products are being piloted.
12. Priority countries actively encouraged to join CRP list
Action 1. Continue to host the Paediatric ARV Drug Optimization (PADO) process and update the list of priority products with a view to providing a consistent, clear, and harmonized set of products that will be communicated to industry and regulators in a timely manner, and ensure inclusion of PADO priority products in the WHO Expression of Interest list as soon as dosing is provided.
Action 2. Update treatment guidelines in a timely manner to ensure that more effective drugs are recommended for children as soon as pharmacokinetic (PK) and safety data is available.
Action 3. Continue to use the Pediatric ARV Working Group (PAWG) mechanism to provide recommendations on optimal dosing and ratios for formulation development
Action 4. In collaboration with other partners, continue to revise the Optimal ARV Formulary and ensure its inclusion in Essential Medicine List
Action 10. Increase support for harmonization, convergence, and work-sharing through regional regulatory networks and reactivate the Paediatric Regulatory Network by Q2 2019.
Action 11. Continue to convene the PAWG to provide advice to innovators prior to submission of PSPs/PIPs, communicate technical opinions to SRAs in a timely manner, and provide dosing and ratio recommendations to generics for development of new FDCs.
Action 12. Reestablish the Paediatric Regulatory network to accelerate national registration and facilitate in-country registration of specific products under the Collaborative procedure established by WHO.
Action 37. Take responsibility for monitoring implementation of the Action Plan and holding actors to account, including monthly calls of principals, tracking progress towards milestones, and regularly communicating with participants about progress on their commitments and overall implementation of the Plan.
Action 38. Develop a set of milestones in 2018 to highlight progress on the Action Plan and establish opportunities for stakeholders to take on more specific commitments.
Action 41. Organize a follow-up meeting focused on diagnostics for children in Q1 2018
WHO convened a virtual meeting of the Pediatric ARV Drug Optimization (PADO) group in December 2017 to review the list of PADO3 pediatric ARV formulations and develop implementation considerations related to current priority products. list of priority paediatric ARV formulations. A summary report on the PADO3 review (held December, 12 2017) was sent to representatives from pharmaceutical companies and to PADO members which include key stakeholders, regulators and key funders. The meeting report is available for dissemination (see document PADO3 review summary). http://www.who.int/hiv/pub/meetingreports/pado3-review/en/. PADO 4 is planned for December 10th to 12th 2018.
Two webinars were held on Feb 5th by ILF/IAS in collaboration with WHO to disseminate the key outcomes of the PADO3 review to manufacturers and key stakeholder. Recordings and slides from webinars are available from ILF/IAS - http://www.iasociety.org/HIV-Programmes/Programmes/Industry-Liaison-Forum/Events/ILF-Webinar-Report-back-on-PADO-3-review . A summary report on the PADO3 review (held December, 12 2017) was sent to representatives from pharmaceutical companies and to PADO members which include key stakeholders, regulators and key funders. The meeting report is available for dissemination (see document PADO3 review summary)
The EML will be updated by the end of 2018.
WHO shared the PADO 3 Review Summary Report with industry and regulators on first March 18. A webinar for dissemination to industry and regulators is scheduled for the week of Dec 19th 2018.
The PADO 4 meeting was held on December 10-12, 2018. A PADO4 list of priority products was promptly disseminated to industry and regulators as well as other relevant stakeholder on December 17th 2018 http://gap-f.org/Events/Webinar-Outcomes-of-the-Paediatric-ARV-Drug-Optimization-4 . A revised EOI list aligned with the PADO priorities was launched in February 2019 https://extranet.who.int/prequal/sites/default/files/documents/EOI-HIV_February2019_0.pdf.
PADO4 report was released and now available at https://www.who.int/hiv/pub/meetingreports/paediatric-arv-optimization-pado4/en/
WHO updated guidelines in July 2018 guidelines with inclusion of more potent regimens for neonates and children.
Guidelines were launched in Amsterdam with a dedicated satellite at AIDS2018 and at the Pediatric Workshop. Several webinars for dissemination have already occurred in collaboration with UNICEF and APWG. Support to country adoption and adaptation is ongoing.
WHO Guidelines were updated in July 2018 and rapidly disseminated in all AIDS FREE priority countries via regional workshop, dedicated webinars and specifically convened meetings of the national paediatric technical working group. Dosing recommendations on DTG were further updated in January 2019 as a result of new evidence from the ODYSSEY trial.
WHO guidelines were updated in early June and will be released at IAS 2019.
Ongoing conversation on dosing and ratio for DTG/TAF/XTC.
PAWG bi-monthly meetings for 2018 restarted on February 12th, 2018. A follow-up call with Gilead is being planned to review implementation of their paediatric plan for TAF.
PAWG continues to meet every two months, in particular to explore what work is needed with IMPAACT, PENTA-ID and other networks to generate key evidence to inform development and use of drugs. It developed dosing guidance for WHO guideline update. A 2019 workplan was agreed upon in March and activities are undergoing.
PAWG continues to meet regularly and interact with industry partners as needed
Optimal formulary and limited used list were revised in June 2018 along with a policy brief on: TRANSITIONING TO AN OPTIMAL PAEDIATRIC ARV FORMULARY: IMPLEMENTATION CONSIDERATIONS. They were included in the AIDS FREE toolkit for broad dissemination. A number of webinars have enabled dissemination and a dedicated one will be convened in early 2019.
Note: APWG to consider more frequent updates (outside of formal meetings)
Requests for modifications to the EML were made in December 2018 and a meeting to consider these modifications was held by WHO in April 2019.
EML was updated in April with input on ensuring alignment with products included in the 2018 ARV Optimal formulary and limited used list.
AMDS annual meeting held 17-18 April 2018. APWG annual meeting held 16 April 2018.
Notes: In 2017, optimal orders were 70% of total pediatric products
Documents: APWG April 2018 update
WHO Paediatric Regulatory Network is re-established (Consultation in Dec 2019).
Efforts to facilitate alignment between the three regulatory bodies (USFDA, EMA, WHO-PQ) continue.
WHO/PAWG sent a letter to EMA including considerations for implementation of existing PIPs. Letter includes feedback from PAWG on PIPs for EMA. The messages of the letter will be communicated to relevant companies on dedicated calls with PAWG members to facilitate dialogue. PAWG members will remain available to discuss specific products with relevant innovators.
Note: PSPs not publicly available for review
These considerations were also shared with members of the FDA technical team.
PAWG continues to meet every two months. Previous recommendations on dosing and ratio of ALD were confirmed. No further requests have been raised.
PAWG continues to meet regularly and interact with industry partners as needed.
The Paediatric Regulatory Network was reactivated in December 2019 and will be used as a platform to facilitate information sharing for registration of paediatric medical products.
7. Convene technical discussions to provide advice to innovators prior to submission of PSPs/PIPs, communicate technical opinions to SRAs in a timely manner, and provide dosing and ratio recommendations to generics for development of new formulations.
8. Update treatment guidelines in a timely manner to ensure that more effective drugs are recommended for children as soon as pharmacokinetic (PK) and safety data is available.
9. In collaboration with Stop TB Partnership (STBP)/Global Drug Facility (GDF) and the TB Procurement and Market-Shaping Action Team (TPMAT), continue to revise the minimum set of pediatric formulations to guide national procurement and ensure their inclusion in Essential Medicine List for Children (EML-C).
10. As convener of the Paediatric Drug Optimization for TB (PADO TB) process, set the research agenda for product development, update the list of priority products as needed; communicate outcomes to industry and regulators in a timely manner; and ensure inclusion of PADO priority products in the WHO PQ Expression of Interest list as soon as dosing is identified.
128. Support countries to collect and report data on TB-HIV co-infection and TB treatment initiation and outcomes in children living with HIV.