In 2004, FDA published a landmark report entitled, “Innovation or Stagnation: Challenge and Opportunity on the Critical Path to Medical Products”. The report concluded that the process of drug development and the availability of new therapies were not fully benefitting from the many advances in biomedical science. To address this challenge, FDA launched the Critical Path Initiative (CPI) to encourage powerful scientific and technical innovations for more efficient drug development. Some of the areas of focus of the CPI are to encourage the development of a variety of tools, methodologies, and approaches to enhance medical product development.
What are Drug Development Tools (DDTs)?
DDTs are methods, materials, or measures that have the potential to facilitate drug development. Examples of DDTs may include, but are not limited to: a biomarker used for clinical trial enrichment, a clinical outcome assessment (COA) used to evaluate treatment benefit, or a disease specific animal model used for efficacy testing under the Animal Rule.
Because the substantial time and effort involved in developing these types of tools is often beyond the capabilities of a single entity, the FDA encourages the formation of collaborative groups to work together to increase the efficiency of DDT development. One such group is a public-private partnership (PPP), which is a collaboration involving at least one non-profit organization and one for-profit organization. A variety of projects undertaken by various PPPs have demonstrated the usefulness of this approach.1
To support these development efforts and make the outputs publicly available, the FDA created programs and initiatives that aid in the evaluation of some types of DDTs. These programs and initiatives, along with resources that support them, are described below.
DDT Qualification Programs
Three types of DDTs include: biomarkers, clinical outcome assessments and animal models for use under the Animal Rule. The FDA has established programs for formal qualification of each of these types of DDTs, wherein a formal package is voluntarily submitted for evaluation and review by FDA staff. Qualification is a regulatory decision that means that within a stated context of use (COU), a DDT has been demonstrated to reliably support a specified manner of interpretation and application in drug development. Once qualified, a DDT can be used under its qualified COU across multiple programs, thereby facilitating more efficient drug development and review. DDT Qualification Programs are currently available for biomarkers, COAs, and animal models for use under the Animal Rule.
Letter of Support (LOS) Initiative
Often, biomarkers that are in development for use as potential DDTs are not ready for formal qualification review. To support these development efforts, FDA established the LOS Initiative to enhance the visibility of promising biomarker(s) that may be appropriate for future qualification, encourage data sharing, and stimulate additional studies. An LOS describes FDA’s thoughts on the potential value of a biomarker for use in drug development, encourages further evaluation, and is posted publicly on the FDA LOS Initiative website.
Critical Path Innovation Meeting (CPIM)
CPIMs provide an opportunity to request a meeting with CDER to discuss a proposed methodology or technology and obtain general advice from CDER on how this methodology or technology might enhance drug development. Through this program, FDA expects to become more familiar with prospective innovations in drug development, broadening its regulatory perspective. The discussions and background information submitted through the CPIM are drug product-independent and are nonbinding for both the FDA and CPIM requesters.
FDA has established qualification programs for three types of DDTs: biomarkers, COAs, and animal models for use under the Animal Rule. There are other types of DDTs that include methodologies, in silico disease models, etc. Due to the dynamic nature of these types of DDTs and the inability to establish formal qualification, FDA has established the Fit-for-Purpose Initiative. Through this initiative, a DDT may be deemed fit-for-purpose based on a regulatory evaluation of the information provided. The fit-for-purpose determination is publicly posted on the Fit-for-Purpose Initiative website in an effort to facilitate greater utilization of these tools in drug development programs.
Over the past several years, FDA has engaged with external stakeholders to develop powerful resources that can be utilized to bring efficiency into the overall drug development and regulatory processes. Examples of such resources by program are:
Data Standards Program
- CDER Data Standards Program - A comprehensive program within CDER to identify and prioritize data standards needs and to implement good practices for standards development.
Biomarker Qualification Program
- BEST (Biomarkers, EndpointS, and other Tools) Resource - A glossary of biomarkers and endpoints in basic biomedical research, medical product development, and clinical care.
COA Qualification Program
- COA Compendium - A table that summarizes COA information for many different diseases and conditions into a single resource.