Action 27. Mobilize their networks and work with communities to help build treatment literacy, generate demand, and expand access to ARVs among children.
Action 34. Increase efforts to share information on the roll-out of new paediatric formulations, including lessons learned.
Paediatric HIV & TB : Rome Action Plan
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.
On May 16, 2022, FDA reclassified HIV serological and NAT diagnostic and supplemental tests from class III to class II. The reclassification went into effect on June 15, 2022. All currently approved HIV diagnostic and supplemental PMA tests are reclassified to class II.
The reclassification does include HIV sample collection devices. It does not include HIV self-testing devices.
HIV viral load tests will be reclassified when the proposed order is finalized.
FDA is in the process of reclassifying HIV Viral Load monitoring devices from class III to class II. The proposed order, which includes both lab-based and point-of-care tests, published for comments on November 24, 2021 and closed January 24, 2022. It is now in the process of being finalized.
8. Work with diagnostics manufactures to use all regulatory tools available, such as breakthrough designations and leveraging existing data from outside the US, to expedite review of early infant diagnostics for HIV.
5. Continue to meet with EMA prior to and during the review of PSPs and PIPs to try to align on content.
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.
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. 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 2020 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.
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.
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.
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.
39. Continue supporting the pediatric HIV priority ARV drugs research and development agenda, as outlined in Rome Action Plan.
Dolutegravir (Tivicay, Tivicay PD) is now approved for the treatment of HIV infection, inclusive of pediatric patients 4 weeks and older, and weighing at least 3kg
Triumeq (abacavir/dolutegravir/lamivudine FDC) is now approved for the treatment of HIV infection, inclusive of pediatric weighing at least 10kg
FDA remains committed to continue to meet with EMA prior to and during the review of PSPs and PIPs to try to align on content and strive to ensure alignment with EMA on study requirements and approach to dossier review.
FDA continues to support pediatric drug development programs for antivirals, as outlined in Rome Action Plan. FDA remains committed to expedite pediatric protocols review, and continue to work with other regulatory authorities to seek early alignment on development programs.
FDA continues to support the prioritization of the research and development agenda for pediatric ARV drugs, as outlined in Rome Action Plan. FDA is committed to working with diagnostics manufacturers to use all regulatory tools available, such as breakthrough designations and leveraging existing data from outside the US, to expedite review of early infant diagnostics for HIV.
FDA continues to work and support these commitments to review pediatric-related data to support use of ARVs for the treatment of HIV infection in children during the COVID-19 pandemic without delay.
54. Expand use of the Collaborative Registration Procedure based on PQ or SRA approval to expedite national review of paediatric TB drugs and formulations.
55. Use the Paediatric Regulatory Network for advocacy of use of the Collaborative Registration Procedure and to explore models of regulatory reliance to promote equitable access to paediatric TB formulations.
56. Expedite and simplify the review of priority paediatric formulations including by:
Making better use of sub-regional collaborative regulatory approval processes and the WHO Collaborative Registration Procedure for accelerated registration;
Increasing reliance on evaluations and opinions of SRAs and the WHO PQ programme.
57. End requirements for local clinical trials when sufficient PK and safety data exists, even when no equivalent innovator product exists.
58. Minimize/remove country-specific packaging and labelling requirements for paediatric formulations.
69. Observing the following principles in its regulatory review process:
Extrapolating efficacy from adults to children is acceptable for most children with TB.Extrapolation of adult efficacy to paediatric populations for the treatment of pulmonary TB may be appropriate for most paediatric populations, other than the very young as they can have different clinical and pathophysiologic characteristics. Pharmacokinetic (PK) and safety information in paediatric patients will be needed to support the appropriate dose for treatment of children.
Adolescents with pulmonary TB can be included in phase 3 clinical trials, if appropriate.
Paediatric patients can be enrolled in trials if sufficient safety and antimycobacterial activity data in adults are available and appropriate dosing regimens have been characterized.
Studies of drugs across the paediatric spectrum of ages/weights can be conducted in parallel rather than sequentially unless there is a specific safety or pharmacokinetic properties that warrants a different approach.
Paediatric development plans for new TB medicines could include children living with HIV and other common co-infections provided there are no safety or drug-drug interaction issues.
Cohorts for paediatric studies can be defined based on chronological age or weight-based criteria, particularly for oral drugs.
Paediatric formulation development should begin soon after adult Phase 2-b trials and dose selection.
70. Continue to work with other regulatory authorities to seek alignment on development of products for TB in children.
71. Continuing engagement on development of products and age appropriate formulations for treatment of TB in children
March 2022 & June 2022
FDA continues to support the prioritization of the research and development agenda for pediatric TB drugs, as outlined in Rome Action Plan. FDA remains committed to expedite the review of pediatric TB formulations and to work with other regulatory authorities to seek alignment on development of products for TB in children.