NIH Grants, ICCVAM Alternatives, Organizations, AAALAC

What is 21st Century Cures Act?

Public Law 114-255

designed to help accelerate medical product development and bring new innovations and advances to patients who need them faster and more efficiently

Specifies both male and female animals should be used

NIH Research Project Grant Program

Generally awarded for 3 -5 years

no specific dollar limit unless stated

R01

1 multiple choice option

Limited funding for pilot studies, development of new research technology, etc. Only 2 years of funding

Direct costs generally up to $50,000 per year

Not renewable

R03

3 multiple choice options

awards are for post-doc study at an eligible institution

T32

1 multiple choice option

awards can be for pre- or post doctoral training programs

F32

1 multiple choice option

Research Program Project Grants provide support for integrated multi-project, multi-investigator research projects

P01

3 multiple choice options

Center Core Grants provide support for shared resources and facilities for multidisciplinary approach to a joint research effort by multiple investigators

P30

3 multiple choice options

NIH Support for Conferences and Scientific Meetings

R13

3 multiple choice options

Repair, Renovation and Modernization of Existing Research Facilities

G20

1 multiple choice option

Research Facilities Construction Grant

Provides matching Federal funds up to 75% for construction or major remodeling to create new research facilities

C06

1 multiple choice option

The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) is a permanent committee of _________

NIEHS.

What is the FDA "Animal Rule"?

If all of these criteria are met, it is reasonable to expect the effectiveness of the drug in animals to be a reliable indicator of its effectiveness in humans.

A - generally know how the substance/agent and treatment work

B - demonstrate effect in 2+ animals that are kind of similar to humans or 1 animal very similar to humans (i.e. NHPs)

C - benefit is clearly desirable (i.e. survival vs. otherwise lethal condition)

D - PK/PD data allows selection of an effective dose in humans

What is Murine Local Lymph Node Assay?

To identify substances that could cause allergic contact dermatitis in humans

Replaces Guinea Pigs Maximization Test and Buehler Test methods

Requires fewer animals

Less time to perform

Provides dose-response information

Typically eliminates pain and distress

The LLNA measures cell proliferation in the draining auricular lymph nodes of the mouse by analyzing incorporation of a radioactive marker into newly synthesized DNA.

Measures cell proliferation by assessing the level of ATP using bioluminescence

What is Draize test?

involves applying 0.5mL or 0.5g of a test substance to the eye or skin of a restrained, conscious animal, and then leaving it for set amount of time before rinsing it out and recording its effects.The animals are observed for up to 14 days for signs of erythema and edema in the skin test, and redness, swelling, discharge, ulceration, hemorrhaging, cloudiness, or blindness in the tested eye. (rabbit)

What is In Vitro Eye Irritancy Tests (Ocular Corrosivity and Irritation)

Replaces live animal testing of corrosives and irritants of Draize test

using isolate rabbit, chicken eye or bovine corneal, hen egg

What is used to replace Pyrogen Testing?

Measures cytokine levels

What is Limulus Amebocyte Lysate (LAL) Assay?

Screens for the presence of LPS/endotoxin (gram-negative)

Species: Limulus polyphemus (horseshoe crabs)

Replaces: Rabbit pyrogen testing

Procedure:

Blood drawn and amebocytes (blood cells) are lysed producing the lysate

Sample mixed with lysate and reagent

Coagulation = presence of endotoxin

Why is haemolymph of Limulus polyphemus (horseshoe crabs) blue?

Hemocyanin (contains copper, binds to oxygen, turns blue) vs. hemoglobin

What is Koken rat?

Replicates pharynx, larynx, trachea, stomach, and tail vein of the rat

Specifications mimic a 9 week old male Sprague Dawley rat

What does AAALAC do? How often is the site visit conducted?

Confidential peer-review through triennial site visits (performance based)

How many site visitors should be present for AAALAC site visit? What's the qualification of site visitors?

All accreditable units shall initially be evaluated by a team of not less than 2 site visitors

Cannot be employed by unit visited or agency

Cannot visit unit if employed by a competitor

Cannot visit unit if employer has financial interest in unit to be visited

What is considered a mandatory item?

a serious deviation from the recommendations of the Three Primary Standards and/or AAALAC International's Reference Resources that must be corrected to achieve or continue accreditation. The significance of a mandatory item is ordinarily based on the Council's assessment of its potential to adversely affect the health, well-being or safety of animals or humans.

What are the potential outcomes of a new AAALAC application?

Award Full Accreditation

With or without SFIs

Award Accreditation with Condition

Unit retains at least one mandatory item to be reported during the next annual report or at another time specified by Council

Award Provisional Status

One or more mandatory items with required response, up to 24 months for correction

Not accredited

Withhold Accreditation

Institution can appeal the decision

What are the potential outcomes of a Re-accreditation AAALAC application?

Continued Full Accreditation

With or without SFIs

Conditional Accreditation

Unit retains at least one mandatory item which requires follow-up report

Deferred Accreditation

Unit retains one or more mandatory items with a two month deadline for response, with or without additional SFIs. Failure to correct will result in probation

Probationary Accreditation

Previously accredited facility may not revert to provisional

12 month period to correct deficiencies

If adequate correction of the mandatory item(s) is not achieved within the allotted time, proceedings to Revoke accreditation are initiated.

Additional 12 months period optional if more deficiencies found

Revoke Accreditation

Occurs after unit has been placed on probation and fails to correct deficiencies

Appeal process available