nanotechnology regualtory perspectives, challenges & issues 13 february 2014 post

Nanotechnology: Regulatory Perspectives, Challenges & IssuesAJAZ S. HUSSAIN, PH.D. | INSIGHT, ADVICE & SOLUTIONS, LLC

2/15/2014 [email protected] 1

Keynote address: NanoSciTech 2014, Punjab University, Chandigarh, India

Nanotechnology

Dimensions in 1 and 100 nm

range

Unique phenomena

Understanding Control Benefit >> Risk


National Nanotechnology Initiative Website, http://www.nano.gov/htmVfacts/whatIsNano.html

“Proactive Risk Management in a Dynamic Society”*: Many nested levels of decision-making

Government Regulators Company Management Staff Work


Politicalclimate &

public opinion

Changing marketconditions and

financial pressure

ChangingCompetency & levels

of education

Changing product mix, technologies, and

regulatory requirements

Environmental pressure

Laws (e.g., FDASIA) Regulations

JudgmentCompany Policy Plans Action

Judgment Judgment JudgmentJudgment

Political Science;Law; Economics;

Sociology

Economics;Decision Theory;Organizational

Sociology

IndustrialEngineering;

Management &Organization

Psychology;Human factors;

Human-MachineInteraction

Chemistry;Pharmacy;

Biotechnology; Engineering,…

Research disciplines

Analysis Public opinion Incident or accidentReport Observations, DataLogs, ReportsOperations review

*Jens Rasmussen & Inge Svedung (2000)

A ‘process of migration’ to explain how accidents can occur


Boundary to unacceptable

workload

Boundary to economic failure

Boundary to functionally acceptable

performance

Safety Zone

Gradient towards least effort

Gradient towards cost effectiveness

Rasmussen (1997)

Perceived risk in the present controversy-free period


NATURE NANOTECHNOLOGY | VOL 4 | NOVEMBER 2009

• unfamiliarity (contrary to expectations) not strongly associated with risk aversion

• reduced ‘knowledge deficits’ are correlated with positive perceptions

Nanotechnology risk perceptions appear to contradict traditional findings:

Risk-Benefit Perceptions: Effect of Information, Familiarity and Cultural Worldviews


Cultural Cognition of the Risks and Benefits of Nanotechnology. Nature Nanotechnology, 4(2), 87-91. (2009)

Emerging dynamics ofnanotechnology commercialization

• published about 52,100 scientific articles and

• applied for about 45,050 patents

• 18,000 patents granted to corporate assignees

From 1990 – 2008, ~ 17,600 companies

worldwide (and 5,440 US companies)

• Considering the ratio of corporate nanotechnology patent applications to corporate nanotechnology publications by year

A relative shift in emphasis from discovery to

application: 1999


The Journal of Technology Transfer December 2011, Volume 36, Issue 6, pp 587-60

http://link.springer.com/journal/10961

http://link.springer.com/journal/10961/36/6/page/1

Social science perspective

High priority in various national agenda for science and technology development

• Expected to impact an entire range of industries

• Significant implications on human health, the environment, sustainability, ….

Not a single homogenous science or technology field

• Researchers from different disciplines are involved

• Most firms specialize in a particular technology

Importance of access to tacit knowledge

• Scientists engaged in both scientific research and technology development tend to have an advantage

• Large firms expand their knowledge by building up new capabilities; small firms rely on their existing capabilities


J Technol Transf (2011) 36:145–172

Key pointsIn the current phase (controversy-free period) traditional risk-aversion to new technology is muted

The ‘pendulum shifted’ towards commercialization about a decade ago

The need for, and adequacy of, risk-assessment and risk-management in commercial setting is highly variable

Nanoscience and nanotechnology publications often tout ‘transdisciplinary’; evidence from social science perspective suggests much of the research is ‘uni-disciplinary’

Tactic knowledge plays a significant role in science to technology transfer; ability to do both within a group or organization is advantageous

A transdisciplinary approach to regulatory policy development would be important for efficient standardizations of frameworks, concepts, tools and vocabulary


Regulation and oversight that ensure the fulfillment of legitimate objectives

Protection of safety, health and the environment while avoiding unjustifiably inhibiting innovation, stigmatizing new technologies, or creating trade barrier

• Executive Order 13563, to guide the development and implementation of policies for oversight of emerging technologies at the agency level

• The White House Emerging Technologies Interagency Policy Coordination Committee: Principles for Regulation and Oversight of Emerging Technologies (March 11,2011)

Principles Scientific Integrity

Public Participation

Communication

Benefits and costs

Flexibility

Risk Assessment and Risk Management

Coordination

International Cooperation


Nanoscale materials


Size

Shape

Composition

Surfacemodificaiton

Surface charge

Adsorptivecapacity

Degradationmechanism

Route,Exposure &Duration

Risk mitigation

To protect workers

Hazard identification

Exposure assessment

Risk characterization

Risk management

What we know today

Health effects of industrial

ultrafine, fibers and air pollution

Nanoparticle can be

measured

Animal models for human exposure-response

Good practices to control exposure

What we don’t know

Applicability to engineered

nanoparticles

What are the most relevant

measures

Exposure-response

relationships

Appropriate OELs for

engineered nanoparticles


http://www.cdc.gov/niosh/topics/nanotech/

Weight of evidence

• multiple studies on even basic material properties often result in varying data

• pointing in different directions when data interpretation is attempted.

• Need WOE approach that explicitly integrate expert evaluation of data quality of available information.

Given the emerging

nature of the field and

complexity of nanomaterials


Nanotoxicology Feb 2014. http://informahealthcare.com/doi/abs/10.3109/17435390.2012.750695

Regulating drug products based on nanotechnology

Evaluations of safety, effectiveness or public health impact of such

products should consider the unique properties and

behaviors that nanomaterials may exhibit

FDA will ask:◦ Whether an engineered material or end product has at least

one dimension in the nanoscale range (approximately 1 nm to 100 nm); or

◦ Whether an engineered material or end product exhibits properties or phenomena, including physical or chemical properties or biological effects, that are attributable to its dimension(s), even if these dimensions fall outside the nanoscale range, up to one micrometer.

◦ These considerations apply not only to new products, but also may apply when manufacturing changes alter the dimensions, properties, or effects of an FDA-regulated product or any of its components.


http://www.fda.gov/RegulatoryInformation/Guidances/ucm257698.htm#conclusion

Dimension-dependent properties used forfunctional effects

For example

• Increased bioavailability, Decreased dosage,

• Increased potency of a drug product, Decreased toxicity of a drug product

• Better detection of pathogens

Due to altered chemical, biological, or magnetic properties, altered electrical or optical activity, increased structural integrity, etc. (not normally observed in their larger counterparts).

• These changes may raise questions about the safety, effectiveness, performance, quality or public health impact of the products.

• In addition, considerations such as routes of exposure, dosage, and behavior in various biological systems (including specific tissues and organs) are critical for evaluating the wide array of products under FDA’s jurisdiction.


http://www.fda.gov/RegulatoryInformation/Guidances/ucm257698.htm#conclusion

FDA’s Initiative on Pharmaceutical Quality for the 21st Century

• Process Analytical Technology

• Increased emphasis on design and risk-based approaches

• ICH Q8 - 11

• New update to process validation emphasizing statistical confidence

Initiated more that a decade ago with

clear recognition on the need to be

prepared to address increasing complexity


http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm128080.htm

An important lesson on measurement


Has the measurement system capability been verified?


Calibration & Gauge R&R


My conclusion in 2004 at the USP’s Annual Scientific Meeting - "The Science of Quality"


September 26–30, 2004 Sheraton at Woodbridge Place, Iselin, NJ

Is still relevant today. Fundamental approach that utilizes QbD is the way forward.

Given that today I am speaking at the Punjab University that has a unique, award winning program on QbD, I very much look forward to learning what you are doing in the area of QbD of nanotechnology based products.

Thank you for the kind invitation.

nanotechnology regualtory perspectives, challenges & issues 13 february 2014 post

Education