Background, Introduction, Statutory Authority, Introduction to Risk ...

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22 Οκτ 2013 (πριν από 3 χρόνια και 11 μήνες)

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Background, Introduction,

Statutory Authority,

Introduction to

Risk
-
Based Approach

Larisa Rudenko, PhD, DABT

What is Animal
Biotechnology?



Assisted Reproductive Technologies


Help distribute genetics beyond natural matings


AI, semen sexing,
in vitro

fertilization,
embryo transfer, embryo splitting


1300s
-
present


Cloning


More rapid distribution of naturally occurring desirable traits in
breeding stock


1990s
-
present in livestock


Genetic Engineering


Introduces/modifies genes not naturally occurring to introduce
new traits


1980s
-
present in livestock

Animal Biotechnology (from the
Regulator’s Perspective)

Genetic Engineering

GE Animals with

Heritable Constructs


Animals with

Non
-
Heritable

Constructs

Natural

Breeding

AI
±

Frozen

Semen

Cloning

Embryo

Split

in vitro

Fertilization

Selective


Breeding

Animal cloning is on a continuum with other ARTS……...

Genetic engineering is a distinctly different
technology

Animal Biotechnology (from
the Regulator’s Perspective)


The previous slide presents a series of boxes on a horizontal axis
that indicate a continuum of assisted reproductive technologies
currently in use in US commercial agriculture ranging from natural
breeding, selective breeding, artificial insemination/frozen semen,
in vitro fertilization, embryo splitting, and ending up with cloning. It
is intended to show that cloning falls on that continuum. On the
horizontal below is a dotted line and a box saying "genetic
engineering,” which indicates that genetic engineering does not
fall on that same continuum. Finally, the slide indicates a
bifurcation of the term "genetic engineering" to indicate that GE
animals can contain both heritable and non
-
heritable constructs.



Challenges for the Technology


Funding (basic research and commercialization)


Effective communications


Unbiased, credible sources of information


Not overpromising the technology


A tool in the toolbox


No panaceas


Faith in the regulatory system


Public acceptance


Challenges for the Agency


Getting the word out


Educating investigators


Staying in touch with stakeholders


Follow
-
on guidances


Coordination across USG


Continuing international outreach


Continuing to have faith
in the regulatory system maintained

Possible Solutions


Do the work


Work harder at constructive engagements


Abandon stale arguments


Hazards vs risks


“Scientists” vs “the public”


Consider new approaches to sustainability


Avoid reductionist approaches

Transparency


“Agency interested in increasing transparency”
(Guidance 187)

What does that mean?


Transparency of processes


Data acquisition?


Interpretation?


Transparency of deliberations


Conclusions?


What do they mean?


Public VMAC meeting prior to approvals


Review of Basic Concepts in
Hazard…Risk…Safety

Definitions, Relationships, Standards

Harm

≡ an adverse outcome

Hazard
≡ substance or activity that has the potential to cause a harm

Risk

≡ conditional probability of an adverse outcome provided that
exposure to a
receptor

has occurred

…or

Risk


f
outcome

(exposure, hazard),


or

“the likelihood of harm”



Receptor

≡ individual or population experiencing risk


Safety
….reasonable certainty of no harm (established standard)

Intended, Unintended, Direct,
Indirect Effects/Risks

Terms used to sort outcomes


Direct/Indirect

categorize based on
mechanism of action


Intended/Unintended

categorize based on
objective of modification



Hazard to What, Risk to
Whom?

rDNA construct produces
potential hazard(s) in rDNA
animals. These may pose
health risks to the animals.


Humans/animals consuming
edible products from GE
animals may/may not
experience food consumption
risks.

GE Animal
Guidance


Final 1/15/2009


Guidance for Industry #187
-

Regulation of
Genetically Engineered Animals Containing
Heritable Recombinant DNA Constructs


http://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/GeneticEngineeri
ng/GeneticallyEngineeredAnimals/default.htm


Goal/Structure of Draft
Guidance

Three parts



Clarification of FDA’s continued regulation of GE
animals under NADA provisions of FFDCA



Congruence with existing regulations (21 CFR 511
(INAD) and 21 CFR 514 (NADA)



Recommendations on how sponsors can prepare
data and information for FDA to review

Scope


All GE animals covered; specific
recommendations for those with heritable
rDNA constructs


Explicitly includes biopharm animals


Enforcement discretion possible for low risk
applications


INAD/NADA processes


Post
-
approval responsibilities


Key Concepts
-
1

Statutory/Scope


Definition of “article”


rDNA construct intended to affect the structure or
function of the animal



“All GE animals derived from the same tx event contain
the same article, and subject to evaluation under a
single new animal drug application.”

(Guidance 187 p 6)



No products in commerce without FDA approval
(minor exceptions


enforcement discretion)



Key Concepts
-
2

Risk
-
Based Approach


Each GE Animal/rDNA construct event poses
unique risk(s)


Specific set of risk questions


Specific set of data/information driven responses


Case
-
by
-
case evaluation for each transformation
event (i.e., each “article”)



Two Paths


Default assumption: INAD/NADA approach


All species traditionally consumed as food


All scenarios not considered “low risk”



Certain low risk scenarios may be eligible
for enforcement discretion