# Presentation: 120330

## FDA Nanotoxicology Workshop

- Topics to Address
-   Harmonization
-  “Nano-hype”
-   Redbook Considerations
-   Stability Assessments
-  “Stealth” Nano

| Robin Guy, MS, DABT RQAP(GLP)
Robin Guy Consulting, LLC
Toxicology and GLP Consulting
PO Box 830, Lake Forest, IL  60045
and President, Roundtable of Toxicology Consultants |
| --- |

- FDA Nanotoxicology Workshop  September 8, 2008

## Harmonization

-  Due to the worldwide regulatory reaction to nanomaterials, it would be prudent to develop, validate and harmonize specific aspects of toxicology/safety testing (e.g., dose expressions) to avoid unnecessary retesting, especially with animals.

- FDA Nanotoxicology Workshop  September 8, 2008

## Harmonization

-  Due to the number of potential uses and innovative nature of nanoscience, approaches to the safety assessment of nanomaterials and products containing nanomaterials should be taken on a case-by-case basis.
-  However, we should not be too restrictive, as nanomaterials appear to offer valuable advances that may not be completely appreciated or understood at this time.

- FDA Nanotoxicology Workshop  September 8, 2008

## Nano-Hype

-  The toxicologic community and nano industry are becoming increasingly cognizant of and concerned with literature and presentations of a scientific nature that appear to present safety concerns for nanomaterials based on studies in progress or nonvalidated methods and results.
-  Such studies are typically not conducted under GLPs.
-  FDA should not utilize or support such information in guidance or regulation of nano materials.
-  Guidances should be developed according to scientifically sound, valid and well-documented procedures.

- FDA Nanotoxicology Workshop  September 8, 2008

## Redbook Considerations

-  As nanomaterials have a much higher surface area to mass than conventional materials, and the FDA has experience with a number of previously approved products containing nano materials, there is a strong need from the Redbook for general guidance on
-  Dosage expression
-  Conduct and reporting of dosage stability for CMC,
-    pharmacology, toxicology and clinical studies
-  ADME, especially absorption and distribution assessments
-  ADI, as the current expression of ADI is based on mass
-  Cumulative Human Exposure to assess Concern Levels
-  Safety Factors
-  Adding these to the “Emerging Issues” Section would separate any nanomaterials and nanoproduct guidances from conventional guidances.

- FDA Nanotoxicology Workshop  September 8, 2008

## Redbook Considerations

-  Considerations for nano material handling and storage for safety testing need to be well defined in safety assessment protocols and study reports
-  Vehicle
-  Containers
-  Shipping methods/conditions
-  Other potential considerations

- FDA Nanotoxicology Workshop  September 8, 2008

## Stability Assessments

-  More extensive stability testing appears necessary because nanomaterials generally have chemical, particle and surface properties that relate to their mechanisms of action, biodistribution and pharmacokinetics.
- Nanomaterials have been known to change particulate properties under different storage and handling conditions.

- FDA Nanotoxicology Workshop  September 8, 2008

## Stability Assessments

-  Considerations for Stability Testing
-  Same frequency as ICH guidances,
-  Validate or justify the relevance of elevated storage temperatures and its utility in making stability projections
- There is a need to add to traditional chemical analysis, including assays for:
-  Potential for forming aggregates
-  Particle size
-  Particle shape
-  Surface chemistry (including zeta potential)
-  Surface area determinations
-  TEM and/or SEM documentation and verification of the
-    particle under formulated stability conditions

- FDA Nanotoxicology Workshop  September 8, 2008

## “Stealth” Nano

-  Many companies, including food companies, would rather their nano ingredients be “stealth”, to avoid consumer apprehension on a level comparable to genetically modified or irradiated foods.
- A definition of nano should take into consideration toxicologic or safety parameters and not just size, so that a material that is over 100 nm doesn’t slip under the radar (ex: if particle sizing under 250 nm changes the characteristics of the material).
-  Proper safety testing and publication of those data would help to dispel concerns as well as increase the public database on nano safety.

- FDA Nanotoxicology Workshop  September 8, 2008

## Thank you!

**Robin Guy, MS, DABT, RQAP(GLP)**
**Robin Guy Consulting, LLC**
**Toxicology and GLP Consulting**
**PO Box 830 **
**Lake Forest IL  60045**
**(847) 295-9250**
**rcg@robinguy.com**
**and**
**President, Roundtable of Toxicology Consultants**

- FDA Nanotoxicology Workshop  September 8, 2008