GAP-f progress update – February 2018
Limited treatment options and sub-optimal formulations have contributed to poor adherence and outcomes for children living with HIV. Despite the need for expanded and improved options for paediatric treatment, which are essential for sustained adherence and better treatment outcomes, barriers to incentivizing research and development remain. The GAP-f aims to promote a faster, more efficient and more focused approach to paediatric formulation development. It is a collaborative framework that can help get better paediatric products quicker and cheaper by prioritizing products, streamlining the generation of clinical evidence, incentivizing manufacturers, accelerating product development and introduction, and coordinating procurement. As shown in Figure 1 below, the GAP-f formalizes collaboration across sectors to ensure accelerated development and uptake of the most needed drugs and formulations for children.
Figure 1. The GAP-f formalizes collaboration across sectors to ensure accelerated development and uptake of the most needed drugs and formulations for children. SRAs, stringent regulatory authorities; NRAs, national regulatory authorities (in high-burden countries). Source: Penazzato et al. Shortening the decade-long gap between having optimal adult and paediatric drug formulations, JIAS, In press.
In November 2017, a High-Level Dialogue on Scaling Up Early Diagnosis and Treatment of Children and Adolescents was convened by His Eminence Peter Kodwo Appiah Cardinal Turkson, Prefect of the Dicastery for the Promotion of Integral Human Development, with PEPFAR, UNAIDS and Caritas Internationalis, and in close collaboration with the World Council of Churches-Ecumenical Advocacy Alliance, EGPAF and the WHO. Key principles of the GAP-f set the basis of discussion, which led to an action plan including an impressive list of commitments from industry, regulators, UN agencies and other stakeholders. The commitments from the Rome action plan promote three key principles: focusing on priority paediatric drugs and formulations; accelerating development, review, and introduction of paediatric formulations; and collaborating to expedite the development and introduction of paediatric products. These principles align with the foundations of GAP-f and give further opportunities to address challenges in paediatric drug formulation development, as shown in Figure 2 below.
Figure 2. The GAP-f represents an opportunity to address challenges in paediatric drug formulation development. Challenges are grouped around three areas: dependence on adult drug development, paediatric formulation requirements and paediatric ARV market. Progress to date in addressing these challenges is depicted along a funnel originating from precursor mechanisms (the existing initiatives that are unified under the GAP-f) and leading up to the GAP‑f collaborative model. Legal framework challenges are placed outside of the funnel because of the limited influence of the GAP-f to directly address these. Source: Penazzato et al. Shortening the decade-long gap between having optimal adult and paediatric drug formulations, JIAS, In press.
As part of GAP-f activities, a Research Toolkit for Paediatric Drug and Formulation Development is being assembled (with launch expected for AIDS 2018) to provide guidance to researchers and manufacturers (both originators and generics) as well as other organisations with an interest in drug development, and facilitate faster, more efficient and focused development of paediatric formulations. The toolkit will comprise 10 modules, each addressing key areas for the development of paediatric drugs:
- Pharmacokinetic (PK) studies and PK modelling
- Clinical trial designs
- Pregnant and breastfeeding women
- Community engagement
- Target product profile
- Forecasting and programme introduction
- Regulatory filing
Manufacturers will soon be invited to review the content covered in the research toolkit. Representatives of regulatory authorities will also have the opportunity to provide feedback and ensure alignment with existing regulatory framework and guidance.
Finally, the Paediatric ARV Drug Optimization (PADO) group recently reviewed its list of priority paediatric ARV formulations. The review focused on implementation considerations, accounted for key outcomes of the Conference on Drug Optimization (CADO) 3 meeting, and enabled preliminary discussion to inform the upcoming WHO ART guidelines revision (planned for Q2 2018). In collaboration with the WHO and CHAI, hosted a webinar to report on the PADO 3 review. This interactive session primarily aimed at industry covered the latest discussions around the list of priority paediatric ARV formulations and took place on 5 February 2018. The webinar recording can be found here; slide sets will be posted shortly.
Efforts to further develop the GAP-f concept and explore synergies are ongoing, and we welcome any input. Please do not hesitate to be in touch with any question or comment you may have.