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 6: Prioritize PADO products in research and development plans.
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.
9. (individual commitment) Mylan committed to submitting LPV/r granules for regulatory approval in 2017; “4-in-1” (ABC/3TC/LPV/r) granules in 2018; and a paediatric ABC/3TC/DTG formulation in 2019, subject to the WHO providing paediatric DTG dosing guidance in early 2018.
Mylan submitted its pediatric LPV/r formulation to WHO PQ in December 2017. Following WHO PQ submission in December 2017, LPV/r has been submitted to the GFATM ERP in January 2018 and to the FDA February 2018. The product was tentatively approved by FDA under PEPFAR in August 2018. See https://www.fda.gov/internationalprograms/pepfar/ucm119231.htm.
Mylan is scaling up production capacity of LPV/r granules, with support from PEPFAR and the Global Fund. Mylan’s capacity for the LPV/r 40/10mg granules now exceeds 200,000 packs/month (as of February 2020). FDA is finalizing review of additional manufacturing facility. Alongside Cipla, capacity is expected to meet demand by Q2 2020.
4-in-1” (ABC/3TC/LPV/r) granules: submission to WHO PQ and FDA now scheduled for Q2 2019.
Paediatric ABC/3TC/DTG formulation in 2019: Development of this product will commence following finalization of WHO pediatric DTG dosing guidance, which is still pending. Mylan’s development of this product has been pending final WHO guidance on its dosage. Mylan does not currently have a target submission date, but the earliest it could be submitted would be Q4 2020.
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.
24. Mylan commits to double its manufacturing capacity of LPV/r granules by Q4 2019 (to 5-6 million sachets/month)
42. Submit the dossier for DTG 10mg scored dispersible tablet in Q1 2020
Development of the “4-in-1” granule product (ABC/3TC/LPV/r) has been delayed as they ere not successful with bioequivalence testing and are reworking the product to try again. Plan to submit to the US FDA by September 2020, or earlier if possible. Educational materials being developed to enable scale-up in many countries with PEPFAR, WHO, ICAP and others.
Submission to US FDA expected by end-2020 or in Q1-2021. However, Mylan expects substantial shift beginning in 2021 among HIV-positive infants to the use of dispersible DTG formulations (see below).
Mylan is scaling up production capacity of LPV/r granules, with support from PEPFAR and the Global Fund. Mylan’s capacity for the LPV/r 40/10mg granules now exceeds 200,000 packs/month (as of February 2020). Alongside Cipla, capacity is expected to meet demand by Q2 2020. Investing substantially in capital so they can meet global demand. Increased capacity for 2-in-1 will apply to 4-in-1 (ABC/3TC/LPV/r) .
Mylan is on track with the supply of LPV/r granules for HIV-positive infants, following a recent FDA approval of an amendment needed to activate our increased production capacity (200,000 packs/month).
DTG 10mg development (with ViiV, CHAI, and Unitaid) proceding as expected. The submission of DTG 10mg is scheduled for Q2 2020, assuming successful results on the pivotal BE and stability.
Mylan is on track, working with ViiV and CHAI, to submit the dispersible formulation of dolutegravir to the FDA in May 2020.
Major milestone in moving towards improved pediatric HIV treatment with ViiV’s approval of dispersible DTG in June. Thanks to close collaboration, Mylan submitted its dispersible DTG to US FDA in May and hopes for approval by end of year. Goal is then for low-cost, optimal treatment (ABC+3TC + DTG, both in dispersible formulations) to be scaled up in 2021.
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.
44. Develop pediatric ARV products at a scale that will meet ultimate market demand as provided by GAP-f partners.