1. (individual commitment) The USFDA committed to a number of adjustments to the regulatory approval process for paediatric formulations and to make them public on World AIDS Day:
Paediatric formulation development should begin soon after adult Phase 2-b trials and dosing selection;
Adolescents should be included in initial registrational efficacy (Phase 3) trials in adults or adolescent trials should be conducted in parallel with adults;
Studies of drugs across the paediatric spectrum of ages/weights (at least down to age 4 weeks) should be conducted in parallel rather than in series (unless a particular product has a specific safety or drug disposition factor that warrants a different approach).
Drug development studies in children should be based on weight rather than age and should align with the WHO weight bands.
Action 7: Prioritize the review of Pediatric Study Plans (PSPs) and Paediatric Investigation Plans (PIPs) for paediatric ARVs on the list of PADO priority products over lower priority drugs.
Action 20: Accept and encourage the accelerated steps outlined in Actions 14-18 when evaluating paediatric development plans and reviewing drug applications and encourage formulation development to begin soon after Phase II dosing selection.
FDA reiterated its commitment to more efficient drug development pathways for children in a letter to PEPFAR (See Library section), and in updated Guidance for Industry on Pediatric HIV Drug Development, finalized in March 2019.
Action 7: USFDA already has a pediatric committee framework and timeline that prioritizes reviews of all PSPs.
1. (individual commitment): Companies are following the recommendation that adolescents should be included in initial registrational efficacy (Phase 3) trials in adults or adolescent trials should be conducted in parallel with adults. Regarding the studies of drugs across the paediatric spectrum of ages/weights, USFDA hasn't seen a big change yet to include all age/weights bands at the same time – still doing 6-12 and then 6 and below – may be due to additional need for formulation development. In regards to drug development studies in children should be based on weight rather than age and should align with the WHO weight bands, USFDA is recommending weight bands when the PSPs come in and also for protocols. In generalUSFDA tries to align with WHO weight bands. However, thihs may not always be possible.
59. Reclassify HIV diagnostic devices from class III PMA to class II 510(k) to expedite patient access to these tests per the July 19, 2018 Blood Products Advisory Committee recommendation.
7 . Initiate implementation of the agreement with WHO to facilitate the CRP-lite pilot program of products with USFDA full approval or tentative approval by Q1 2019.
8. Consider requests for the further deferral of pediatric assessments in PSPs of paediatric ARVs thatare not identified as priority products by PADO.
6. For PIPs/PSPs on ARVs identified as priority products by PADO, strive to ensure alignment with EMA on study requirements and approach to dossier review.
5. Continue to meet with EMA prior to and during the review of PSPs and PIPs to try to align on content.
6. Two meetings have been held with GAP-f to discuss alignment among SRAs
7. CRP-lite initiated. On June 18, 2019, FDA shared two reviews (minimally redacted) for the first CRP-Lite pilot applications with WHO, and has sent a senior project manager to WHO to learn more about WHO’s approach to these applications and to provide regulatory advice from FDA. Will send clinical reviewer to WHO in January to discuss approaches to the CRP lite review.
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.
1. Outreach to a number of countries on use of CRP, who are very interested.