Action 23. Call on regulatory authorities to expedite and simplify the review of priority paediatric formulations and diagnostics, including by:
Making better use of sub-regional collaborative regulatory approval processes and the WHO Collaborative procedure for accelerated registration;
Increasing reliance on evaluations and opinions of stringent regulatory authorities (SRAs) and the WHO prequalification program, up to providing full waivers for high priority paediatric drugs;
Allowing compassionate use until drugs are registered; and
Ending requirements for local clinical trials when sufficient PK and safety data exists, even when no innovator equivalent exists.
Action 24. Develop a toolkit to set standards and support accelerated research, development, and introduction of priority paediatric formulations.
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 39. GAP-f partners develop a work plan for finalization, roll-out and increasing demand for and accelerating access to 2-3 high priority drugs planned for approval in 2018.
Action 40. Continue to refine the Global Accelerator for Paediatric Formulations concept as a key component of the AIDS Free work stream, including by establishing leadership, roles and responsibilities, and a financing mechanism.
GAP-f partners have been discussing with ViiV and regulatory authorities to determine the best regulatory pathways for pediatric DTG (10 mg scored and 50 mg scored tablets) and ways to accelerate registration and introduction of DTG and RAL at country level.
EGPAF and CHAI are beginning preparations for introduction of DTG and RAL (EGPAF), including production of a DTG introduction toolkit. DNDi is working with in-country partners on expand uptake of LPV/r solid formulations for the roll-out of introductory materials.
PEPFAR and WHO PQ have discussed how to implement CRP based on SRA approval, conversation ongoing. Countries among the AIDS FREE priority countries who are not included in CRP list were identified.
WHO and Unitaid in collaboration with IMPAACT (International Maternal Pediatric Adolescent AIDS Clinical Trials) network, PENTA (Paediatric European Network for Treatment of AIDS) foundation and experts from the Paediatric Antiretroviral Working Group launched Toolkit for research and development of paediatric antiretroviral drugs and formulations available as PDF at http://www.who.int/hiv/pub/research-dev-toolkit-paediatric-arv-drug-formulation/en/ is also available as online tool at https://globalhealthtrainingcentre.tghn.org/research-toolkit-paediatric-antiretroviral-drug-and-formulation-development/ . Following wide dissemination at AIDS 2018 and the Paediatric Workshop the toolkit is being further disseminated to industry and relevant stakeholder via a series of 6 webinars that will be completed by the end of the year (2 webinars already convened). Scientific papers for further dissemination are under development.
Set of milestones to highlight progress on the action plan, available onhttps://www.paediatrichivactionplan.org/
Progress Report on Implementation Rome Action Plan (June 2018) available in Updates and Library sections.
First webinar scheduled took place 24 April 2018 15:00-16:30 CET.
Second webinar scheduled to take place 17 October 2018 14:30-15:30 CET.
Concept Paper developed and planning ongoing
Concept note was revised, Lancet and IAS papers released, presentation of the principles behind the business plan at AIDS2018, business plan being finalized for presentation to key stakeholders by Rome 4
GAP-f was launched at AIDS2018; and the concept for GAP-f was laid out in an article in the Lancet, “Catalysing the development and introduction of paediatric drug formulations for children living with HIV: a new global collaborative framework for action partners.” GAP-f partners are finalizing a new business plan that will be released by December 2018.
A website is being established to facilitate the sharing of resources on pediatric formulation research, development, and introduction: http://gap-f.org/
GAPf progress share with stakeholders and updates timely provided on the http://gap-f.org/ website.
Note: Detailed Progress update of GAP-f is available in Library section (January 2018)
GAP-f has been formally established in WHO as an agile team (to be coordinated by Science Division), TOR and membership for the Secretariat and Advisory committee currently being finalized. Support to the GAP-f Secretariat is being discussed with PEPFAR (confirmed) and ELMA (proposal submitted). GAP-f is currently discussing partnerships and actively seeking funding to accelerate investigation and development of TAF/XTC/DTG and DRVr.
16. Seek and direct funding to support the additional clinical research required to inform development and use of PADO priority products.
17. Identify and facilitate the most suitable financial incentive for a given product included in PADO list, possibly including one or more of the following:
Support to development upon timely achievement of key milestones
Advance market commitments.
18. Promote donor coordination to cover the full spectrum of activities required to ensure accelerated research, development, registration, commercialization, roll-out, and appropriate monitoring of PADO priority products.
19. With the support of Unitaid, partner with Janssen and generic manufacturers to develop and register DRV/r 120/20 mg by Q4 2020.
29. Sustain and strengthen collaboration among relevant stakeholders to ensure the most efficient development and uptake of optimal paediatric ARV formulations, in close consultation with the community of people living with HIV.
31. Collaborate with PAWG to offer technical advice to national ERBs to accelerate the process.
30. With the support of Unitaid, provide visibility on the demand for formulations in the pipeline (LPVr solid formulations, DTG 10 mg scored DT, RAL granules and RTV 25 mg).
23. Jointly agree upon and execute next steps to optimize the availability and delivery of these formulations in 2019 including:
Timely and regular information sharing (including orders placed and timelines for deliveries)
Providing best possible demand forecasts
Collaborate on the optimization of limited supply within and among countries and joint prioritization among orders to ensure sustainable supplies to children once initiated
Support product uptake at country level
Regulatory filings as needed to support scale-up, timely responses to queries raised during the review, and implementation (re-validation as required) of post approval changes at risk during the review period.
Commitments 16, 17, 18, and 29:
GAP-f partners have met in March 2019 to agree on a product portfolio developed on the basis of the PADO priorities. For each product of the portfolio, a path to patient has been mapped and product specific briefs are being developed to identify opportunity for acceleration and key gaps in resources. GAP-f formally established in WHO as an agile team (to be coordinated by Science Division). The GAP-f business plan is being finalized to include details of the product portfolio and a more granular operational structure with clear roles and responsibilities of individual partner organizations. A TOR for the GAP-f secretariat and formal letters of agreement to define the relationship among partners are being drafted. Updates were formally shared with donors and a broader group of partners on March 26, 2019. Proactive dialogue with industry has been initiated and will be expanded in Q2 2019.
GAP-f discussing partnerships and actively seeking funding to accelerate investigation and development of TAF/XTC/DTG and DRVr
Delays on R&D for the adult market have held back pediatric formulation development. However, GAP-f is working to accelerate the development of two formulations of DRV/r (120/20), one using the standard approach that includes melt granulation and the second based on the Liverpool SDN methodology. While CHAI has a grant from Unitaid through December 2020, support from Liverpool, and a substantial incentive pool for a single generic manufacturer for the melt granulation formulation, additional funding from Q1 2021 through Q3 2022 is required to achieve regulatory filing. As such, the original commitment deadline cannot be met.
Commitments 23 and 30:
The APWG issued an updated memo on 10 January 2019 to Suppliers of paediatric LPV/r formulations, HIV program managers, and ARV logistics divisions “to provide information on global coordination efforts to ensure paediatric LPV/r formulations are appropriately distributed and utilized.” The APWG also continues to meet monthly with manufacturers and to develop a plan for increased supply by end 2019. It plans to develop a dashboard on the supply situation of LPV/r granules and pellets for the APWG website.