FAQs

Q. What does it cost to have nanomaterial characterized by the NCL?

A. If a nanotechnology strategy/material is selected for characterization, NCL’s services are provided at no cost to the submitting investigator. As part of its assay cascade, the NCL will characterize the nanomaterial’s physical attributes, their in vitro biological properties, and their in vivo compatibility using animal models. The time required to characterize nanomaterial from receipt through the in vivo phase is expected to be one year.

For more information on the NCL assay cascade, visit http://ncl.cancer.gov/working_assay-cascade.asp

Q. I’m studying nanomaterials but my application is not in the area of cancer. Can I still submit a proposal for characterization by the NCL?

A. The NCL serves as a national resource and knowledge base for researchers to facilitate the regulatory review of nanotechnologies intended for cancer therapies and diagnostics. The NCL generally does not accept proposals for characterization of nanomaterials intended for application in areas other than cancer . Cancer-related nanostrategies proposed to the NCL for characterization are ranked according to their projected impact on clinical cancer applications and/or furthering nanotechnology’s compatibility with biological systems. Specific evaluation criteria include, but are not limited to:

• Previously demonstrated efficacy in vitro and/or in animal models
• Advantages offered by the strategy over existing cancer therapies or diagnostics
• Previous physical characterization of the nanomaterial such as purity and stability
• The nanostrategy’s manufacturing process and compatibility with scale-up
• The material’s inherent toxicity and/or environmental concerns
• Plans or approach to transition the strategy to clinical trials such as filing the follow-on IND, IDE or pre-IDE

For detailed information on submitting a proposal for a cancer-related project, please visit http://ncl.cancer.gov/working_application-process.asp

Q. Does NCL provide funding?

A. No. The NCL is a resource enabling researchers in academia, industry, and government to transition their nanotechnology strategies to clinical applications. The NCL provides critical infrastructure and characterization services but does not fund research grants.

Q. If my proposal is accepted, how much material will I be required to submit?

A. We require ½ to 1 gram of your nanomaterial in order to complete all assays. Depending on the availability of resources during the application process, NCL may be able to assist researchers with scale-up in order to have enough nanomaterial to enter the assay cascade. To share and safeguard research material and proprietary information, NCL’s interaction with researchers is normally conducted under a Material Transfer Agreement (MTA), permitting the collaborative exchange of materials and associated information.

For more information on Material Transfer Agreements and intellectual property protection, please visit http://ncl.cancer.gov/working_intellectual-property.asp

Q: How does the NCL determine if an engineered nanoparticle is likely to be safe?

A: In short, the NCL examines the weight of the evidence from preclinical studies, looking for “consensus behavior”. A recently published study¹ demonstrated interference of carbon nanotubes with the MTT assay (see “NCL Protocols” in this issue of NCL News for a discussion of the MTT assay). The study showed that carbon nanotubes have the ability to absorb formazan dye, giving the appearance of a reduction in cell viability. This phenomenon helped to explain the lack of consensus behavior of carbon nanotubes in the in vitro toxicology literature where groups were using different cytotoxicity endpoints and arriving at contrasting conclusions regarding carbon nanotube cytotoxicity.

Even if the previous toxic responses attributed to carbon nanotubes in vitro were the result of MTT assay interference, this does not mean that carbon nanotubes are necessarily safe, as often in vitro results are not predictive of in vivo responses due to the complexities inherent in the whole organisms (i.e. exposure-dose-response relationships, cell-cell interactions, etc.). As such, it is important to look at the total body of evidence.

¹ Oops, they did it again! Carbon nanotubes hoax scientists in viability assays. Nano Letters 2006 June; 6(6):1261-8.

Q. Is the NCL relationship with the nanomaterial developer considered to be a collaboration? How much control does the nanomaterial developer have during the characterization process?

A. Yes! We view our interaction as a collaboration. Prior to the initiation of a project, the NCL staff and project developers engage in multiple interactions via teleconference, email and face-to-face meetings. Once the project begins, the collaborator receives an update at least once per quarter on the physical characterization, immunology and toxicology data generated from the NCL assay cascade.

The NCL and collaborators jointly work through any issues that might arise. For example, it is not uncommon for a nanoparticle formulation to have impurities in the first batches submitted to the NCL. In these situations, NCL staff work with collaborators to identify any contaminants; the NCL may then recommend methods to further purify the preparation.

Q. What are the deliverables provided to the collaborator by the NCL?

A. Updates and reports on the progress of the nanomaterial characterization are provided to NCL collaborators at regular intervals – at least once per quarter. Once characterization of the nanomaterial is complete, a formal report of data from the NCL assay cascade is provided to the collaborator. Nanoparticle characterization data presented in the report are peer-reviewed by the NCL Scientific Oversight Committee (SOC) consisting of experts from the supporting organizations (i.e., NCI, NIST, and FDA).

Q. How do you protect the collaborator’s proprietary information?

A. The exchange of confidential information and the materials between the provider and NCL is protected by the terms of the Material Transfer Agreement (MTA)

(http://ncl.cancer.gov/working_application-process_annex2.pdf). All confidential/proprietary information disclosed to the NCL is strictly protected and will not be disclosed.

Q. What happens if the NCL determines nanoparticles are toxic or cannot reproduce a collaborator’s results? Does the NCL publish "unfavorable" results?

A. The NCL works closely with its collaborators to address any safety/efficacy issues or inconsistencies. Development of a collaborator’s nanotech strategy is an iterative process and the NCL will attempt to offer suggestions as to how to further optimize a sponsor’s nanoparticle. The NCL will then characterize the improved “batch” of nanoparticles.

If the scope of improvements to a nanoparticle’s formulation is drastic, such as a change in the targeting modality, the NCL would require the sponsor to reapply for evaluation. The new material would need to demonstrate efficacy and would require the characterization to start from scratch.

Q. How is an NCL collaborator’s intellectual property safeguarded by the NCL?

A. The NCL takes the same security measures for protection of NCL sponsor intellectual property as for NCL data; every effort is made to ensure security and confidentiality. To share and safeguard research material and proprietary information, the NCL’s interaction with sponsors is normally conducted under a Material Transfer Agreement (MTA) which includes a non-disclosure clause. The MTA permits the collaborative exchange of materials and data between the NCL and the sponsor. In certain circumstances, NCL–sponsor inter­action is conducted under a Cooper­ative Research and Development Agreement (CRADA).

Q. How does the FDA use NCL data when an NCL collaborator submits an Investigational New Drug (IND) filing?

A. Data derived from the NCL assay cascade are intended to be included in an investigator-led filing of an Inves­tigational New Drug (IND) with the FDA. Since the NCL sponsor initiates and files the IND, the sponsor decides if and how NCL data are presented to the FDA in the IND filing. NCL data alone, however, will not be sufficient to meet the FDA’s requirements for an IND. If the NCL’s assays predict favor­able in vivo safety and efficacy, NCI and the NCL anticipate the sponsor will pursue the translation of the tech­nology into clinical applications.

Q. What information about the nanomaterials the NCL characterizes does the NCL provide to the FDA?

A. As a formal collaboration between the National Cancer Institute (NCI), the National Institute of Standards and Technology (NIST), and the Food and Drug Administration (FDA), the NCL makes an effort to maintain transpar­ency to its governing institutions. In that spirit, all NCL characterization data are available to the FDA. The NCL and FDA work together on many aspects of nanomaterial characteriza­tion, and the FDA is informed about the properties of NCL nanomaterials as data are being generated. Charac­terization data that appear in NCL reports are peer-reviewed by FDA scientists who serve on the NCL’s Scientific Oversight Committee (SOC). Biannually, NCL scientists formally present characterization information and data related to NCL nanomaterials to the NCL’s SOC, which includes representatives from the FDA.

However, as mentioned previously, if an NCL sponsor initiates and files an IND with the FDA, the sponsor decides what NCL data are included in the IND and how the NCL information is presented.

Q. Does the NCL publish proprietary information provided to them by their collaborators?

A. Absolutely not! The NCL does not publish information provided by its sponsors without their express written permission.

In contrast, data generated by the NCL from characterization of a material may be presented in scientific and public forums if such data are deemed to benefit the cancer research community. This public disclosure, however, pertains only to data generated by the NCL; a sponsor company’s proprietary/confidential information is protected and will not be disclosed under any circumstances. Furthermore, the NCL and its sponsors agree to treat in confidence any written information about the research materials that is indicated as confidential.

Q. How does the NCL safeguard nanomaterial samples during and after characterization?

A. The nanotechnology samples represent significant investments on the part of the laboratories and investigators submitting to the NCL. Many of these samples took years to develop and optimize. The NCL is cognizant of this, and is careful to retain control of the samples. NCL samples are not transferred to anyone not under the direct supervision of the NCL without advance notification to the sponsor. The samples are used only for research purposes, not for commercial purposes such as production or sale. When NCL characterization is complete, the NCL archives a sample of each submitted nanomaterial. Any remaining sample is disposed of or returned to the sponsor.

Q. Can I publish data generated by NCL?

A. Certainly. NCL scientists greatly appreciate the opportunity to collaborate on publications. NCL data are intended to be used in regulatory filings, in publications, and to garner interest from venture capital.

To submit a question to NCL, please click here.