2018 TREATMENT

REGULATORY

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).

The European Medicines Agency commits to:

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 US Food and Drug Administration (USFDA) commits to:

5. 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.

6. For PIPs/PSPs on ARVs identified as priority products by PADO, strive to ensure alignment with EMAon 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.

WHO Prequalification Programme commits to:

9. For ARVs identified as priority products by PADO and included in WHO EOI, strive to ensure alignment with USFDA on study requirements and approach to dossier review.

10. Increase support for harmonization, convergence, and work-sharing through regional regulatory networks and reactivate the Paediatric Regulatory Network by Q2 2019.

11. Initiate implementation of the agreement with USFDA to facilitate the CRP-lite pilot program of products with USFDA full approval or tentative approval by Q1 2019.

12. Encourage wider use of Collaborative Registration Procedures, in particular by the 21 AIDS Free WGpriority countries.

Pharmaceutical companies commit to:

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, Optimalformulary and Limited use lists.

15. Ensure all drug registration dossiers meet minimum requirements at the time of filing and thatresponses to specific queries are complete and provided in a timely manner.

FINANCING

GAP-f partners commit to:

16. Seek and direct funding to support the additional clinical research required to inform development and use of PADO priority products.

17. Identify and facilitate the most suitable financial incentive for a given product included in PADO list, possibly including one or more of the following:

  • Support to development upon timely achievement of key mileston2s

  • Catalytic procurement

  • Advance market commitments.

18. Promote donor coordination to cover the full spectrum of activities required to ensure accelerated research, development, registration, commercialization, roll-out, and appropriate monitoring of PADO priority products.

19. With the support of Unitaid, partner with Janssen and generic manufacturers to develop and register DRV/r 120/20 mg by Q4 2020.

Pharmaceutical companies commit to:

Pharmaceutical companies commit to:

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.

Donors commit to:

21. Support catalytic procurement of all or part of initial validation batches from manufacturers such that product availability is not delayed once approval or tentative approval is achieved.

22. Incentivize commercialization of new pediatric ARV products “at risk” to accelerate introduction and scale up of new paediatric ARV product such that product is available at time of approval/tentative approval/prequalification.

INTRODUCTION, UPTAKE AND PROCUREMENT

Manufacturers of heat-stable LPV/r formulations and all relevant stakeholders involved (ARV
Procurement Working Group, Unitaid, Ministries of Health, GAP-f partners) commit to:

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).

25. DNDi commits to continue supporting efforts to improve sustainable in-country access to 2-in-1 LPV/r by providing technical support on use of LPV/r pellets and granules through collaboration with Unitaid, APWG, other GAP-f partners, PEPFAR, MoHs, and HIV stakeholders in country.

26. DNDi, ICAP, and EGPAF commit to collaborate on product uptake for solid oral dosage forms of LPV/r (2-in-1’s and 4-in-1), including:

  • Development of healthcare workers’ training tools based on implementation research data generated by DNDi; and

  • Acceleration of product uptake in selected countries with engagement of all stakeholders including MOH, civil society, FBOs, and communities of people living with HIV, and to share the training toolkit and experience by disseminating information globally.

27. UNICEF commits to collaborate with GAP-f partners to develop, test, and disseminate training tools for treatment initiation with LPV/r and other optimal pediatric formulations.

PEPFAR, MSD, and EGPAF commit to:

28. Partner on the assisted introduction of RAL granules for neonates, starting with the MoH of Eswatini, followed by other countries beginning early 2019, donating sufficient supplies at the outset of the project and then selling at no profit in low income and sub-Saharan African countries to ensure sustainability of the initiative.

All GAP-f partners commit to:

29. Sustain and strengthen collaboration among relevant stakeholders to ensure the most efficient development and uptake of optimal paediatric ARV formulations, in close consultation with the community of people living with HIV.

30. With the support of Unitaid, provide visibility on the demand for formulations in the pipeline (LPVr solid formulations, DTG 10 mg scored DT, RAL granules and RTV 25 mg).

31. Collaborate with PAWG to offer technical advice to national ERBs to accelerate the process.

CHAI commits to:

32. Collaborate with WHO to house and incubate the GAP-f partnership through its start-up phase.

MPP commits to:

33. Inform all countries in the paediatric license group on the status of paediatric ARV patents.

PENTA and IMPAACT commit to:

34. Rapidly develop and implement research actions (including carrying out specific studies to generate high quality evidence for regulatory submissions and high quality pharmacovigilance studies where needed) in the framework of GAP-f to accelerate access to innovative, high quality, and affordable drugs for children worldwide.

35. Ensure appropriate evidence generation from ongoing DTG studies to enable ViiV regulatory submissions by end 2019.

Cipla commits to:

36. Bring RTV 25 mg to the market, producing first batch beginning in June 2019.

Gilead commits to:

37. Prioritize development of low dose F/TAF dispersible tablet and complete investigation of low dose paediatric dose for 15-25kg by end of 2019.

38. Undertake a bioavailability study for dispersible tablets of F/TAF by mid-2019 and begin enrolment of children under 15kg by end 2019, using parallel enrolment of weight bands where feasible.

Hetero commits to:

39. Submit LPV/r taste-masked pellets before end 2019.

40. Begin development of DTG/3TC/ABC when data available to inform dosing and ratio.

Janssen commits to:

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).

Macleods and Mylan commit to:

42. Submit the dossier for DTG 10mg scored dispersible tablet in Q1 2020.

ViiV Healthcare commits to:

43. Continue to work closely with FDA & EMA, IMPAACT and PENTA to strive to meet target submission date of December 2019 for DTG 5mg dispersible tablet and expanded weight band indication for 50mg.

Generic companies commit to:

44. Develop pediatric ARV products at a scale that will meet ultimate market demand as provided by GAP-f partners.

PEPFAR commits to:

45. Contribute to the funding of the secretariat of the Global accelerator for 2 years, plus additional funding upon achievement of milestones.

Elma commits to:

46. Contribute to the funding of the secretariat of the Global Accelerator and its activities as outlined in the product portfolio of the GAP-f business plan.

Unitaid commits to:

47. Provide financial incentives for the development of child-friendly formulations for ARVs, including DTG 10 mg dispersible tablet and LPV/r fixed-dosed combinations.

48. Continue to strategically support GAP-f and the relevant participation of Unitaid-partners, and engage with Unitaid Executive Board in 2019 to explore funding new investment cases for paediatric ARV optimization and access.

UNICEF commits to:

49. Support Ministries of Health to expand paediatric care and treatment within broader MCH services.

Ministries of Health (Kenya and Zimbabwe) commit to:

50. Accelerate transition to more optimal regimens and formulations as described in WHO Guidelines and 2018 Optimal formulary by:

  • Developing transition plans by Q1 2019

  • Introducing DTG 50 mg for children above 25 kg by Q2 2019

  • Fully phasing out NVP based regimens by Q3 2019 in children older than 3 years and by Q2 2020 in children younger than 3 years.

  • Optimizing the use of LPVr solid formulations by prioritizing infants and children that most need them as well as using LPVr tablets as soon as a child can swallow them

  • Transitioning stable children to optimal regimens as outlined by in the WHO treatment guidelines and in the Optimal Formulary and Limited Use List

51. Increase viral load monitoring of children and ensure linkage of children failing first line drugs to 2nd and 3rd line drugs, working with donors and manufacturers to ensure availability of drugs in line with WHO guidelines.

Faith Based Organizations commit to:

52. Ensure FBO participation in local and national forecasting of optimal paediatric drug formulations.

53. Collaborate with GAP-f partners to develop, test, and disseminate training tools for treatment initiation with LPV/r and other optimal pediatric formulations.

54. Support and increase family treatment initiation and retention for children, adolescents, and families by:

  • Increasing identification and provision of same-day/same-appointment mother/infant pair treatment through FBO clinics;

  • Promoting male/father engagement in EMTCT programmes; and

  • Increasing stigma reduction interventions through mobilized faith leaders and faith communities

  • Providing social work interventions to assist fathers to support treatment and adherence of

  • their partners and children living with HIV.

55. Foster and more actively participate in coordinated and collaborative advocacy to:

  • Increase funding for research & development, introduction and scale-up of priority pediatric drugs and formulations;

  • Accelerate regulatory processes for rapid adoption and uptake of optimal paediatric drugs and formulations; and

  • Ensure sustainable access to optimal testing and treatment for infants and children.

GNP+ commits to:

56. Support treatment preparedness programs, ensure improvement of treatment awareness among caregivers of children of all ages and adolescents, and work jointly with other stakeholders on treatment literacy and demand creation for new pediatric formulations.

All partners commit to:

57. Advocate for and support Ministries of Health to quickly adopt and implement WHO Pediatric HIV Testing and Treatment Guidelines.

58. Advocate for and support Ministries of Health to rapidly transition to optimal paediatric formulations as outlined by the WHO guidelines, provide coordinated support for the development and implementation of transition plans, inform clinicians and patients of the value of transitioning to new formulations, and ensure communication of reliable information on the availability of new formulations in-country.

59. Tackle the stigma and discrimination in communities, schools, and healthcare settings that prevent children living with HIV from accessing testing and treatment.

60. Promote awareness of, political and financial support for, and full implementation of the Action Plan among all relevant stakeholders.