25. Explore collaborations with GAP-f partners to accelerate the generation of evidence on child-friendly formulations of DOR and ISL, using weight bands and with concurrent testing of age groups making use of GAP-f input on PSPs and PIPs.
43. Through PENTA and IAS CIPHER, work together to develop an enhanced monitoring and safety data platform for new and existing paediatric ARV drugs.
44. Convene or participate in a series of virtual consultations of key stakeholders in 2020-2021 to develop a model and mobilize resources for the platform.
Doravirine is approved for administration to individuals >12 years of age and weighing at least 35kg by the US FDA
Pediatric studies with islatravir are on pause pending resolution of the FDA clinical hold.
A pediatric study (MK-1439-066) evaluating DOR (plus 2 NRTIs) and DOR/3TC/TDF is currently enrolling children/infants <35 kg and >4 weeks old, with all 6 WHO weight bands opening concurrently, and utilizing an age-appropriate mini-tablet formulation. The study is part of the agreed PIP and PSP for DOR.
The pediatric program for DOR/ISL has been initiated with a study (MK-8591A-028) in participants <18 yo and weighing at least 35 kg, which is currently enrolling. Development of an age appropriate formulation for ISL is underway (minitablet, same formulation approach as for doravirine) for the next planned pediatric study in participants <35 kg and >28 days old (lowest weight band 3-6 kg). For this second DOR/ISL pediatric study, all weight bands will open concurrently as per the PIP and PSP.
28. Partner on the assisted introduction of RAL granules for neonates, starting with the MoH of Eswatini, followed by other countries beginning early 2019, donating sufficient supplies at the outset of the project and then selling at no profit in low income and sub-Saharan African countries to ensure sustainability of the initiative.
Merck & Co., Inc., confirmed (in a meeting with PEPFAR) their intention to provide paediatric drugs at access pricing until generics are available, and potentially beyond in LMIC.
MSD confirmed RAL granules and chewable tablets will be available for use by end Q2 2019.
All pediatric formulations available at no profit. Now working with key procurement organizations to improve lead time. Working with PEFAR and EGPAF on RAL granules for neonates; will be launched when first country is selected
Pharmaceutical companies, SRAs, WHO Prequalification Programme (PQ) and NRAs commit to:
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)
13. Share their methodological approaches to acceptability studies (including palatability and ease of administration) and contribute to a repository held by GAP-f partners to guide future investigation of acceptability for paediatric products.
14. Consider the use of the CRP for national registration of pediatric ARV products on PADO, Optimal formulary and Limited use lists.
15. Ensure all drug registration dossiers meet minimum requirements at the time of filing and that responses to specific queries are complete and provided in a timely manner
20. Manufacture new PADO priority pediatric ARV products “at risk” such that the new product is available for supply at time of approval/tentative approval/prequalification, including validation of manufacturing process during regulatory review.
Action 6: Prioritize PADO products in research and development plans.
Action 13: In pre-clinical and clinical development, initiate paediatric formulation development as soon as a given drug shows potential public health impact in adults, soon after Phase II trials are completed.
Action 14: Include adolescents when conducting initial adult efficacy trials, where possible and practical, or conduct parallel trials with the goal of providing information to support licencing for adolescents at the same time as adults.
Action 15: In the design of paediatric PK and safety studies, use weight-based dosing and enroll all children above 4 weeks concurrently, unless a strong rationale exists for not doing so.
Action 16: Assess acceptability and palatability of formulations for low-resource settings at early stages of the formulations development.
Action 17: Engage in early and regular consultations with the PAWG on PIP/PSPs, as well as recommended dosing and ratios for FDC development.
Action 18: Take all possible measures to rapidly complete development of priority paediatric drugs and formulations in the pipeline, with the goal of providing the maximum number of new formulations by end of 2018, especially for infants and young children.
Action 30: Strengthen and expand collaboration to overcome intellectual property challenges and otherwise facilitate technology transfer and knowledge sharing that can promote faster paediatric formulation development, including on challenges like taste-masking.
5. (individual commitment) Merck & Co., Inc., is committed to make pediatric Raltegravir available at no profit in low income, least developed countries and across Sub-saharan African countries until generics are available.