2. Facilitate the Clinical Development and Regulatory Review of Nanomaterials for Cancer Clinical Trials
In order to accelerate the transition of basic nanotechnology research to clinical applications, the NCL must also work closely with regulatory bodies, primarily the FDA, as it assists industry to navigate through pre-clinical tests and clinical trials. The FDA refers to this multidimensional product development and evaluation in terms of "critical path" and "critical path research." The former refers to the path from discovery or design concept through clinical evaluation to widespread clinical application; the latter is directed toward improving the product development process itself by establishing new evaluation tools. The NCL seeks to facilitate both the critical path itself and the development of critical path evaluative tools for medical product development.
In support of the critical path, the NCL will perform the pre-clinical characterization of nanomaterials intended for clinical trials. The rigorous and thorough analytical cascade used by NCL will contribute to the scientific quality of data submitted in the IND/IDE application package; the lack thereof is the major cause of delays in IND/IDE approval. More specifically, the NCL will generate quality data in support of paragraphs (7) "Chemistry, manufacturing, and control information" and (8) "Pharmacology and toxicology information" in 21 CFR 312.23, "IND Content and Format." Relevant to the multidimensional critical path (Figure 2), the NCL will assess safety through the in vivo portion of the analytical cascade. It will also address medical utility during the in vitro characterization and by developing modeling tools that help engineer and predict effectiveness of nanomaterials. Similarly, it will address scale-up and manufacturability in the physical characterization phase, by virtue of its close association with NIST.
Adapted from Challenge and Opportunity on the Critical Path to New Medical Products
One mechanism for the enhanced relationship between the NCL and FDA is already in place with the NCI/FDA Interagency Oncology Task Force (IOTF). The IOTF is an interagency working group representing the leadership of NCI and FDA enabling efficient sharing of knowledge and resources to facilitate the development of new cancer drugs and speed their delivery to patients. A nanotechnology subcommittee to the IOTF has been formed to address issues related to using nanotechnology in cancer therapies and diagnostics. By interfacing with these working groups, the NCL will gain valuable insight into the regulatory review process, and affords the NCL an ongoing opportunity to improve the analytical cascade based on inputs from the FDA.
The relationship with the FDA is also crucial for NCL interaction with industry. Industry presently assumes significant risk in R&D for nanomaterials intended for clinical applications; the regulatory guidelines for nanomaterials are presently undefined. A standardized analytical cascade, developed in collaboration with NIST and FDA, is intended to "incentivize" industry to submit nanomaterials to the NCL for characterization, thereby reducing the high risks associated with regulatory approval. FDA itself, as a result of changes introduced by the Modernization Act of 1997, has increased flexibility in classifying new medical devices (including diagnostics), a technique called de novo classification. The FDA also has a broadened tool box of regulatory tools including modular PMAs, special and abbreviated 510(k)s, real-time reviews, and expedited reviews.
It is also anticipated that much of NCL's pre-clinical characterization will be amenable to the use of Drug Master Files (DMF), a submission to the FDA that permits other users to reference the study (see 21 CFR 314.420). The NCL, through the NCI, could therefore submit core nanoparticle analysis and characterization results to a DMF. Subsequent nanotechnology strategies that rely on that core nanoparticle (e.g., dendrimers) could then reference the DMF in their INDs.
A Service of the National Cancer Institute