# Presentation: 205914

## NanotechnologyFDA Public HearingJay M. Ansell, PhD, DABT

**Nanotechnology****FDA Public Hearing****Jay M. Ansell, PhD, DABT**

- September 8, 2008

## Agenda

- Introduction
- ICCR - Background
- Definition
- Survey Results

## FDA Nano Task Force - Challenges

- Nanomaterials present regulatory challenges similar to other new technologies FDA has dealt with in the past
- There is a need to develop standard particle characterization methods.
- Rendering appropriate regulatory decisions requires up-to-date training and information.
- New analytical methods
- Didn’t recommend formal, fixed definitions of  terms for regulatory purposes.

## FDA Nano Task Force - Testing

- Existing information does not appear to indicate a need for revision to all tests.
- Tiered or staged approach to evaluation would seem appropriate.
- Issue is not so much one of whether the tests are valid...rather the familiarity with the predictive value of the tests.

## FDA Nano Task Force - Labeling

- Use does not mean that a product’s safety or effectiveness is necessarily increased, decreased, or affected in any way.
- Because the current science does not support a finding that classes of products with nanoscale materials necessarily present greater safety concerns than classes of products without nanoscale materials, the TF does not believe there is a basis for saying that, as a general matter, a product containing nanoscale materials must be labeled as such.

## FDA Nano Task Force - Safety

- Agency oversight capacity is less comprehensive for products not subject to premarket authorization. However, manufacturers are still responsible for ensuring that the products they market are safe.
- Whether subject to premarket authorization or not, drugs, must be safe and effective; and color additives, and cosmetics **must be safe.**

## Broadly agree with Task Force

- Risk Assessment paradigms are robust
- Testing is reliable
- Testing approaches remain realistic
- Challenges remain
- Materials characterization
- Regulations should be Technology Neutral
- No Labeling; Safety Assessments
- Definitions are intrinsically difficult when assuming the role of hazard/ risk assessment
**Products Must be Safe (& Effective) **

## International Cooperation on Cosmetics Regulations (ICCR)

## International Cooperation on Cosmetics Regulations (ICCR)

- Voluntary group of cosmetics regulatory authorities from the U.S., Japan, the EU, and Canada
- Will consider some U.S. OTC drugs that are regulated as "cosmetics" outside the U.S.
- Remove regulatory obstacles among the regions, while maintaining the highest level of global consumer protection.

## ICCR – Mission

**Agree to implement** decisions and subsequent actions recognizing the boundaries of member’s legal and institutional constraints.
- Agree to promote the documents reflecting the consensus within their own jurisdictions and to **seek convergence of regulatory policies and practices **among the members.

## Industry Participation

- The trade associations of each region will gather input to **represent all affected industry** sectors on specific issues at ICCR meetings.
- Prior to ICCR meetings, industry will **suggest items** for priority actions.
- During the ICCR meeting, industry trade associations will enter in a constructive dialogue with the members and **give their opinion and directions** for future work.

## ICCR-1; September 2007 Proposed Priorities

- Good Manufacturing Practices
- INCI
- Substantiating that U.S. consumers understand the meaning of trivial names.
- Nanotechnology
- Develop a common definition of nanotechnology and set up an inventory of current application of nanotechnology.
- Market surveillance
- Keep each other apprised of emerging product-related safety issues.
- Authorized substances
- Global harmonization of risk assessment.
- Animal testing and alternative methods
- Develop and validate scientific alternatives to animal testing.

## ICCR-1; Nanotechnology

- Nanotechnology, ICCR invited industry to:
- develop common definitions for nanotechnology in the field of cosmetics; and
- set up an inventory of current application of nanotechnology in this field.
- ICCR will use this information in order to determine the path forward in this area.

## Associations Working Group

- Canadian Cosmetic Toiletry and Fragrance Association (CCTFA)
- COLIPA
- Japanese Cosmetic Industry Association (JCIA)
- U.S. Personal Care Products Council (Council)

## Scope

- Nanotechnology broadly covers materials, techniques and applications
- Not all are relevant
- Characterization of *Nanomaterials*
- Relevant in the context of cosmetic products too
- Enable generation of the Inventory

## Survey: Inclusive while Remaining Focused on Cosmetics

- Inventory should include all materials of interest:
- U.S. OTCs & Japanese Quasi-Drugs
- Those scientific community wishes _distinguished_ from the universe of materials all agree have been adequately addressed within existing scientific and regulatory frameworks.
- Gases, fumes, aerosols, liquids, solids are all routinely addressed
- Document to Inform the Participants
- Detail why size alone is insufficient -Stability, Solubility, Manufactured Intentionally and Form

## Inventory Limitations

- Does not implicitly or explicitly suggest any safety conclusion on materials listed.
- Is Not Hazard Identification
- Is Not Exposure Analysis
- Is Not Risk Assessment
- “As with many other new technologies, the use of nanotechnology does not mean that a product’s safety or effectiveness is necessarily increased, decreased, or affected in any way.”*
- * “Nanotechnology: A Report of the U.S. Food and Drug Administration Nanotechnology Task Force, July 25, 2007”

## Inventory Limitations 

- Others also developing definitions related to Nanotechnology - May differ to some extent
- ASTM (American Society for Testing and Materials): Committee E56;
- ISO (International Standards Organization): Technical Committee 229;
- OECD (Organization for Economic Cooperation and Development) Committee on Scientific and Technological Policy’s Working Party on Nanotechnology
- Used within the scope of the ICCR

## Definition

## Nanotechnology

***The knowledge and expertise to manipulate materials at the nanoscale.**** *

## Nanotechnology

- Need to go Further:
- Within ICCR -- Need to Characterize Nanomaterial to inform inclusion/ exclusion criteria

## Key Characteristics: Stable & Insoluble

- Two Groups
- Labile nanoparticles which disintegrate upon application into molecular components
- Insoluble particles (e.g. TiO2, ZnO, fullerenes, quantum dots).
- SCCP & SCENIHR _exclude_ labile and soluble materials
- vesicle-type formulations, liposomes, microemulsions, nanoemulsions

## Key Characteristics: Manufactured Intentionally

- Exclude naturally occurring nanoscale materials
- Ambient air 1 to 5 x 1010 nanoparticles / m3
- Exclude unintentional by-products
- ~ 103  - 105 carbon nanotubes / m3 above gas stove burner
- UK Dept Environ, Food and Rural Affairs:
- Voluntary Reporting Scheme “are deliberately engineered”.
**Materials have to be the product of Nanotechnology **

- L.E. Murr, et. Al., Int. J. Environ. Res. Public Health, 2006, 3(1), 48 – 66.

## Key Characteristics: Nanometic Form - Shape

- Shape
- Nanoparticle is typically used in discussions of nanotechnology
- A common understanding of particle would have all three dimensions generally comparable in size.
- Particles, Rods & Tubes
- Aggregates – Strong Forces
- Agglomerates – Weak Forces (Van der Waal)
- Not all are Expected in Cosmetics

## Key Characteristics: Nanometic Form - Size

- 10-9 meter. Introduced in 1951, from the Greek nanos, meaning dwarf.
- Behavior, Not Size in itself, is at Issue
- "aerodynamic diameter"
- Novel properties be <1 nm or >100 nm
- Nanoparticle reinforced polymers ~ 200-300 nm
- Intrafollicular penetration 300nm
- Biological activity may even be reversed
- No chemical or physiological bright line

## Key Characteristics: Nanometic Form - Size

- Approximations
- US NNI, “control of matter at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel applications”.
- Woodrow Wilson Project has used “*in the realm of* 1-100 nanometers”.
- Even differing limits
- UK Dept Environment, Food and Rural Affairs, nanoscale materials as having two or more dimensions up to 200nm
- Royal Society selected a size range typically from 100nm down to the atomic level (approximately 0.2 nm)

## Key Characteristics: Nanometic Form - Size

- Further complicated by Analytics
- Different methods give different sizes.
- Agglomerates or aggregates of the primary particles
- Number Average vs. Weight Average
- In recognition of the value of a uniform, if arbitrary, limit the panel accepted the more commonly referenced range “on the order of 1 to 100 nm.”

## US FDA Nanotechnology Task Force Report

- Moreover, while one definition for "nanotechnology," "nanoscale material," or a related term or concept may offer meaningful guidance in _one context_, that definition may be too narrow or broad to be of use in another. Accordingly, the Task Force does not recommend attempting to adopt formal, fixed definitions for such terms for regulatory purposes at this time.

- US FDA Nanotechnology Task Force Report, “Nanotechnology: A Report of the U.S. Food and Drug Administration Nanotechnology Task Force”, July 25, 2007

## Nanotechnology is a Knowledge Base

- Like the ‘Bronze Age’ knowledgeable manipulation says nothing about the materials made.

## Survey Results

## Survey Approach

- Provide Discussion Paper to Lead Associations
- Survey Key Committees/ Companies
- Major multinationals - Most significant users
- Second Level Survey of all relevant members of each association.
- Outreach to potentially thousands of companies
- It is our expectation that the final result will not differ significantly.

## Survey Limitations

- First Level Survey
- Major players, Most significant users
- Second Level Survey
- Still only reach Associations members
- Recognize will not include every cosmetic product, worldwide
- May miss some ingredient advertised as “Used”
- Members still represent vast majority of products sold worldwide.

## Survey Limitations

- Characterization - Multifaceted
- “Reported” to be Nanosized
- Not confirmed or subject to any real scrutiny
- Analysis Dependent
- May be Nano in only one analysis method
- May be a minor fraction
- May be in only one stage of manufacture
- There may not be any Nanoscale materials in the definitional “Nano” material.

## Preliminary Survey Results:Reported as ‘Used’ in US - Alphabetical

- Alumina
- Carbon Black
- Iron Oxides
- Silica
- Titanium Dioxide
- Zinc Oxide

## Preliminary Survey Results:Reported as ‘Used’ in US – Major Function

- Drug
- Titanium Dioxide ; Zinc Oxide
- Colors
- Carbon Black; Iron Oxides
- Cosmetic
- Silica; Alumina

## Cosmetics - Preliminary Survey Results:Survey Limitation 

- Recognize will not include every cosmetic product, worldwide
- May miss some ingredient advertised as “Used”
- Reported but ‘Used’ Outside US:
- Cerium Oxide
- Fullerene
- Platinum

## Conclusions

- Risk Assessment paradigms are robust
- Testing is reliable & approaches remain realistic
- Challenges remain
- Materials characterization
- Regulations should be Technology Neutral
- No Labeling; Safety Assessments
- Move beyond Size - Definitions
**Products Must be Safe (& Effective) **