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.
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. Mono DTG under development with ViiV and through partnership with UNITAID.
Q1 2019 update: ABC/3TC/DTG - initiating development of generic version in close collaboration with ViiV to develop as soon as possible. Committed to providing LPV/r products in the meantime.
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
On track to submit 4-in-1 to FDA by middle of 2019. LPV/r granules for infants until DTG available; educational materials being developed to enable scale-up in many countries with PEPFAR, WHO, ICAP and others.
Will increase production capacity for LPV/r granules far beyond the amount committed to (doubling by end 2019); working with Global Fund and PEPFAR on how much and by when. 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) .
In consultation with PEPFAR and the Global Fund, Mylan hase committed to increasing capacity by 10-fold, to 200,000 packs/month, by the beginning of 2020. This is substantially more than previously communicated. The capacity will apply to both the LPV/r granules product and the 4-in-1, which Mylan is submitting in the next couple months.
DTG 10mg development (with ViiV, CHAI, and Unitaid) proceding as expected. Mylan contributes to develop pediatric formulations of DTG as mentioned by ViiV. ViiV/CHAI/Mylan/McLeods partnership for 10 mg scored on track for filing in early 2020.
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.