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 41. Organize a follow-up meeting focused on diagnostics for children in Q1 2018

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 1

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/

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Action 2

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.

Action 3

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

Action 4

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.

Action 10

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 being re-established (Consultation in Dec 2019).

Efforts to facilitate alignment between the three regulatory bodies (USFDA, EMA, WHO-PQ) continue.

Action 11

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.

Action 12

Note: WHO to include next steps and milestones for the Paediatric Regulatory network and the collaborative procedure.

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.

Commitment 17

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 eb able to draw conclusions on the experience with the pilot.

 

 

Commitment 18

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.

Commitment 19:

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.

Commitment 20

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

Commitment 21

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