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.
6. (individual commitment) ViiV Healthcare committed to deploy people, resources and technical expertise to speed up as much as possible the generation of data for regulatory approval of medicines for children living with HIV, including the ongoing development of Dolutegravir for children.
7. (individual commitment) ViiV Healthcare committed to make paediatric Dolutegravir available at cost of production in low income countries, least developed countries and across Sub-Saharan African countries until generics are available.
ViiV has committed additional resources to Pediatrics and has convened a cross‐functional team to address possible ways to accelerate development of DTG for pediatrics. Delivery against our commitments in paediatric HIV is a key objective for ViiV globally.
ViiV has appointed a Paediatric Medicines Development Lead (MDL) who will further increase resource and focus in paediatrics. The MDL will work across the whole of ViiV’s R&D portfolio to bolster the portfolio approach to ViiV’s efforts in paediatric ARV development.
ViiV had a productive meeting with the FDA in June 2018 to inform clinical development plans and regulatory approach for paediatric DTG as planned.
On 18 July 2018, ViiV and CHAI/Unitaid made a joint announcement to paediatric HIV stakeholders to announce the launch of a partnership to speed up development and introduction of optimized pediatric formulations of dolutegravir for children living with HIV in resource‐limited settings. The initiative provides Mylan and Macleods (who both have voluntary licences for paediatric DTG through the Medicines Patent Pool) with a financial incentive award from Unitaid via CHAI, as well as the technical expertise of ViiV Healthcare, to catalyze thedevelopment, manufacture and supply of generic formulations of pediatric dolutegravir. https://www.viivhealthcare.com/media/press‐releases/2018/july/innovative‐publicprivate‐partnership‐initiative‐to‐accelerate‐development‐of‐optimal‐pediatricformulations‐of‐dolutegravir‐to‐improve‐the‐lives‐of‐clhiv.aspx.
ViiV confirmed (in a meeting with PEPFAR) their intention to provide paediatric drugs at access pricing until generics are available, and potentially beyond in LMIC.
43. Continue to work closely with FDA & EMA, IMPAACT and PENTA to strive to meet target submission date of December 2019 for DTG 5mg dispersible tablet and expanded weight band indication for 50mg.
ViiV filed regulatory submissions to both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for a 5mg dispersible-tablet formulation of dolutegravir (DTG), as well as a simplified dosing regimen to optimise use of the existing DTG 50mg film-coated tablet in paediatric HIV patients.
ViiV/CHAI/Unitaid partnerships with Mylan and Macleods to expedite generic development of a scored 10mg dispersible tablet formulation of DTG - all activities are on track including confidential, official correspondence with the FDA regarding the filing strategy.
Engagements with donors, Governments and implementers have commenced to enable product introduction planning for the new dispersible formulation(s) – ViiV’s and the Gx - but more to be done here – we count on collaboration with partners to make implementation successful.
Unprecedented collaborative efforts between PENTA/ODYSSEY, WHO, VIIV and IMPAACT: deep and intimate involvement and collaboration to facilitate the submission by December 2019.
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.
14. Explore use of CRP mechanism for DTG dispersible tablets: had productive meeting with the CRP team in January where made it clear that ViiV intends to use CRP mechanism, while hoping to tweak it so they can initiate the process more quickly because need to use it with EMA as a reference rather than FDA. Next stage is to discuss with EMA if that will be possible prior to full EU approval. Would happen in 2020.