26. Ensure innovation to improve the health of children by supporting CHAI and PENTA in their commitment to accelerate development, registration and catalytic launch of DRV/r 120/20 mg optimal pediatric fixed dose combination and provide DRV API from 2021-23.
27. Support approaches that track access to pediatric patients and to continued transparency around its HIV & TB pediatric work.
28. Enhance collaboration and facilitate knowledge-sharing to promote development of new technologies to enhance effectiveness and acceptability of paediatric medicines, including long-acting injectables for infants and adolescents (Rilpivirine).
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.
45. In collaboration with EGPAF and other key partners, broaden the impact of the New Horizons Advancing Pediatric HIV Care Collaborative (NHC). The NHC currently provides support to its participating countries with health systems strengthening and access to Darunavir (DRV) & Etravirine (ETR) through donations (from Johnson & Johnson subsidiary Janssen Products LP). Starting in 2021, these two pillars of the program will be enhanced through further expansion of technical assistance in identifying and managing HIV treatment failure in children and adolescents, capacity building, evidence generation, supply chain management, and support for harmonized TB co-infection screening. Johnson & Johnson and the NHC team commit to seek additional stakeholders to support the expansion of these critical initiatives.
46. Continue to work with PEPFAR on catalytic procurement of DRV 75mg for children in the developing world.
41. Ensure availability of DRV paediatric formulations in LMIC countries until DRVr FDC is available, and partner with GAP-f partners to develop transition plans to generic products once the generic FDC is available (expected in Q4 2020).
Johnson & Johnson through Janssen Pharmaceutical NV, part of its Janssen Pharmaceutical Companies, is working with PEPFAR on a catalytic procurement project for children in the developing world. The parties have agreed on the quantity of Darunavir 75 mg required to support the initiative for 2019/2020, as such manufacturing and shipments have commenced and product needs continue to be collected from countries. Q4 2019 and January 2020 orders have shipped, and additional bottles are ready to ship in February 2020. Open orders have also been placed for Q2-Q4 2020, and manufacturing is planning production needs accordingly.
To support Darunavir forecasting and production planning, the parties have agreed to share their respective pediatric demand/order forecast summaries with CHAI & the ARV Procurement Working Group (APWG). The first APWG forecast view was shared in January 2020, and has provided greater visibility to the collective pediatric Darunavir forecasted demand.
Since the last update, Q1 and Q2 2020 orders have shipped, and orders for Q3 and Q4 2020 will be postponed until Q3 and Q4 2021 due to insufficient demand from the countries. Johnson & Johnson production has planned accordingly, and PEPFAR HQ is working with countries to identify eligible patients.
To support Darunavir forecasting and production planning, the parties have agreed to share their respective pediatric demand/order forecast summaries with CHAI & the ARV Procurement Working Group (APWG). This has provided greater visibility to the collective pediatric Darunavir forecasted demand.
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.
32. Ensuring ongoing access to the 20mg bedaquiline tablet, which Johnson & Johnson, in partnership with Stop TB Partnership's GDF Pediatric DR-TB Initiative, has already made available for over 130 countries, following US FDA approval in May 2020.
33. Continue efforts in exploring additional clinical trial sites to ensure timely completion of study investigating the use of bedaquiline in children below 5 years of age.
34. Engage early and regularly with GAP-f and other WHO-convened expert groups on pediatric indication development.
35. Engage with the Medicines Patent Pool and/or generic companies to evaluate licensing agreements for pediatric formulations, where appropriate.
36. Make pediatric formulations and data available to research networks advancing pediatric PK and safety studies, where appropriate under collaborative agreements. Rapidly submit data to regulatory authorities and the WHO to facilitate updating of labelling and recommendations.
37. Use the following best practices for the design and implementation of research studies:
Engage with regulators to explore options for pediatric studies as soon as a given drug shows promising efficacy and safety in Phase IIa adult studies.
Consider Including adolescents when conducting initial adult efficacy trials or conduct parallel trials with the goal of providing information to support licensing for adolescents at or near the same time as adults, when appropriate from a scientific and ethical perspective and allowed by regulations.
In the design of paediatric PK and safety studies, when appropriate from a scientific and ethical perspective and allowed by regulations, consider studying weight-based dosing and enrolling all children above 4 weeks of age concurrently (i.e., no age de-escalation).
Assess acceptability and palatability of formulations, including for use in low-resource settings, at the earliest appropriate stage of the formulation’s development.
38. Support the development of drug susceptibility testing (DST) and methods in parallel to new molecule development and make pure drug substance available for DST at the same time as the introduction of a new molecule.
87. Consider the use of the CRP for national registration of paediatric TB products.
88. Ensure all drug registration dossiers meet requirements at the time of filing and that responses to specific queries are complete and provided in a timely manner.
89. Consider facilitating existing joint assessment procedures by planning the submission in different countries/regions to allow for joint assessment in existing networks.
90. Provide multilingual Patient Information Leaflets or Instructions for Use to facilitate appropriate use by Healthcare workers and caregivers
91. Consider prioritizing registration submission of new TB pediatric products in high burden countries where import waivers cannot be granted.