Pre-Clinical and Clinical Sciences Workgroup (PCS-WG) Q4-2015 Update
The PCS-WG is focused on the evidence-based evaluation of translational tools to support effective decision-making and advance new agents from the pre-clinical to clinical development space. These tools represent innovative approaches to address pre-clinical issues, including pre-clinical in vitro and in vivo efficacy, pre-clinical drug safety, and toxicology, pre-clinical PK/PD analyses involving the use of appropriate biomarkers, pre-clinical drug metabolism, drug interaction potential and pharmaceutical profiles. These tools may be submitted to regulatory authorities for regulatory review and/or qualification as appropriate. The PCS-WG also addresses other issues such as pharmaceutics and clinical PK/PD analyses of concentration vs. pharmacologic response data from clinical studies.
4Q, 2015 Progress:
- The PCS-WG, in conjunction with the Health Authorities Submission team, reviewed the ease and cohesiveness of FDA’s multiple guidance documents in supporting TB combination drug development processes. The team’s review provided comments and suggested areas of clarification to enhance the ease at which they can be navigated to support TB drug regimen development. Per FDA’s request, CPTR inserted comments into FDA’s “Draft Guidance Pulmonary Tuberculosis: Developing Drugs for Treatment” for consideration. This round of comments supplements CPTR’s original comments to the docket which were submitted in February, 2014. The FDA is reviewing these comments and will determine next steps with the PCS-WG team in February, 2016.
- Proceedings from the CPTR-NIAID in vivo Pharmacology Workshop titled “Toward an Evidence-Based Nonclinical Roadmap for Evaluating the Efficacy of New Tuberculosis (TB) Drug Regimens: Proceedings of a Critical Path to TB Drug Regimens-National Institute of Allergy and Infectious Diseases In Vivo Pharmacology Workshop for TB Drug Development” (AAC02041-15) was accepted for publication in Antimicrobial Agents and Chemotherapy (AAC) and is now available. The paper has been scheduled to appear in the following journal issue: Antimicrobial Agents and Chemotherapy, Volume 60, Issue 3.
- The PCS-WG’s sterilizing mouse model sub-team has completed the data inventory , which includes published and unpublished data, PK information. Access to IMI/PreDiCT-TB’s pre-clinical and clinical bactericidal activity data will be an important element of this project. The team has refined the current draft context of use (COU) statement for this model and a statistical analysis plan is being drafted