38. Continue to include target countries NRAs as observers in the EMA assessment procedure for new paediatric ARVs.

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2. Release an official communication to reflect that the review of Paediatric Investigation Plans (PIP)s, while maintaining that each PIP is evaluated on a scientifically justified case-by-case basis, will continue to ensure that the following points are always considered:

  • Paediatric formulation development must be integrated from the beginning in the planning and implementation of the overall paediatric drug development starting at least by the time of completion of phase 1 studies in adults taking into account paediatric dose finding and clinical studies;

  • Adolescents should be included in initial pivotal efficacy and safety trials in adults, or adolescent trials should be conducted in parallel with adults unless otherwise scientifically justified;

  • When scientifically appropriate studies of drugs across the paediatric spectrum of ages/weights (at least down to the age of 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.

3. Work on measures to improve the handling of PIP applications including to facilitate the modification process as agreed in the EMA-EC action plan published in October 2018.

4. Continue to discuss with USFDA prior to and during the review of PSPs and PIPs in order to align on content as much as possible, specifically also for ARV products identified as priority products by PADO.

The Paediatric Committee at the EMA (PDCO) endorsed the commitments as outlined in the enclosed letter. This letter was adopted at the Plenary meeting of the PDCO end of March 2019.

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.

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63. Continue the review of Paediatric Investigation Plans (PIPs) specifically taking into account the following points, always bearing in mind that PIPs are evaluated on a scientific case-by-case basis:

  • Paediatric formulation development must be considered in an integrated way right from the beginning of the planning process together with the whole paediatric drug development after completion of phase 1 studies in adults, taking into account dose finding and clinical studies.

  • Adolescents should be included in adult trials or adolescent trials should be conducted in parallel with adults unless scientifically justified.

  • Studies of medicines across the paediatric spectrum of ages/weights should be conducted in parallel rather than in serial age-staggered approach, taking into account for example the pharmacological characteristics of the particular medicinal product, e.g. specific safety or drug disposition factors which may warrant a different approach.

  • PIPs for new TB medicines should consider including systematically children with HIV and other common co-infections found in children affected by TB, taking into account safety or drug-drug interaction issues.

 

64. Provide guidance about when clinical trials for efficacy have to be done in children and when extrapolation of efficacy based on PK is sufficient.

 

65. For planned regulatory submissions to provide guidance on pathways for paediatric drug development programmes without reference products and/or TB indication in adults.

 

66. Continue to work with other non-EU regulatory authorities and WHO to foster alignment on development programmes for TB in children.

 

67. Identify specific mechanisms as defined by the legal framework to facilitate access to WHO Prequalified paediatric TB formulations in their countries/regions through specific mechanisms as defined by the legal framework.

 

68.Continue to offer the opportunity to target countries to participate as observers in the EMA evaluation.

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