INADs and Beginning the Review Process

Larisa Rudenko, PhD, DABT

GE Animal: Investigational Use

Outlines obligations and responsibilitiesOpens path for confidential communications21 CFR § 511.1b

INAD = file; not authorizationAllows for certain activities during development

Animal (drug) shipments/labeling Record keeping Disposition

• No investigational animals/products in food/feed supply without prior authorization

First look at environmental considerations for animal/product

Qualified investigators/collaborators

The NADA/INAD Review Process aka “Ziggy”

Hierarchical, weight-of-evidence, risk-based Satisfies statutory requirements for safety,

effectivenessFollows NADA regulations, with adaptations

for technology/expertise

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Early Interactions w Sponsor

Usually occurs right after opening INAD to ensure confidentiality

Sponsor provides some information prior to meeting

Generally starts with open seminar, then closed session with review team

Discusses nature of submissions; data/information to prepare

Follow up includes MOC

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In House Review of Submissions

Group composition determined by subject area issues, availability

Convene Review Group Group Discussion of issues

Suitability, Completeness

Assignment of reviews to subject area experts

Prepare preliminary review by in-depth reviewers

Peer review by group Issue response to Sponsor

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Our First Approval: GTC’s ATryn® Producing GE Goats

ATryn Goat Approval (2/6/09)

2 Separate Legal Actions CVM NADA approval

rDNA construct in GE goat to produce rh antithrombin in milk

CBER BLA approval for ATryn Anticlotting agent for individuals with

hereditary clotting disorders in high risk situations

Approval Path

Describes the animal, construct, and proposed claim

Product Definition

Product Definition

Broad statement identifying the GE animal, its proposed product or traits (Animal/rDNA construct + claim)

Suggested format: An [x-ploid][n-zygous] [animal common name/breed, line]

[genus, species] containing [copy number] copy/ies of the [construct name] construct at [genomic location] in the [animal breed/line] that [claim].

GTC 155-92 Product Definition

A specific hemizygous diploid line of domestic goats (Capra aegagrus hircus) containing 5 copies of the Bc6 transgene located at the GTC 155-92 site directing the expression of the human gene for antithrombin (which is intended for the treatment of humans) in the mammary gland of goats derived from Founder 155-92.