New! Change in Process for Qualification of Drug Development Tools
The process for qualification of drug development tools is changing under new FD&C Act Section 507. FDA is posting information about these updates to the DDT submission processes.
Qualification of an animal model through FDA’s Animal Model Qualification Program (AMQP) is voluntary (i.e., not required for product approval or licensure under the Animal Rule). The AMQP is jointly supported by CDER and CBER. The qualification process is limited to animal models used for product approval under the Animal Rule. A qualified model may be used for efficacy testing in development programs for multiple investigational drugs for the same targeted disease or condition. Such animal models are considered to be product-independent (i.e., not linked to a specific drug). A model developed for use in the development program of a single investigational drug is not eligible for qualification.
The Animal Rule states that FDA can rely on the evidence from animal studies to provide substantial evidence of the effectiveness of a drug only when all of the following four criteria, quoted below, are met:
(1) There is a reasonably well-understood pathophysiological mechanism of the toxicity of the substance and its prevention or substantial reduction by the product;
(2) The effect is demonstrated in more than one animal species expected to react with a response predictive for humans, unless the effect is demonstrated in a single animal species that represents a sufficiently well-characterized animal model for predicting the response in humans;
(3) The animal study endpoint is clearly related to the desired benefit in humans, generally the enhancement of survival or prevention of major morbidity; and
(4) The data or information on the kinetics and pharmacodynamics of the product or other relevant data or information, in animals and humans, allows selection of an effective dose in humans.
Animal Models for Qualification
Qualification of an animal model implies that FDA has accepted that a specific animal species given a specific challenge agent by a specific route, produces a disease process or condition that in multiple important aspects corresponds to the human disease or condition of interest. FDA will make this determination based on the adequacy of the data from the human disease or condition and the corresponding data from the animal model natural history studies. Once an animal model is qualified, FDA does not have to reevaluate this conclusion each time this model is used within the bounds of its stated context of use (see Context of Use section below for more information). An animal model that can be used for efficacy testing in development programs for multiple investigational drugs for the same targeted disease or condition will greatly support medical countermeasure development, due to increased economies of time, animals, and resources.
Context of Use
Animal models are evaluated and qualified for a specific context of use (COU). The COU is a complete and precise statement that describes the appropriate use and application of the qualified animal model in drug development and regulatory review. It also specifies the details necessary to replicate the model. These details include, but are not limited to:
- Characterization of the animals to be used
- Characterization and preparation of the challenge agent
- Procedural information for the challenge agent exposure
- Identification of the primary and secondary endpoints
- Triggers for intervention
- Ranges of values of key parameters of the disease or condition that will be used as measures of quality control and quality assurance when the model is replicated
The submission of additional data may support the expansion of the COU of a qualified animal model. Expansion of a COU may include, but are not limited to, additional clinical indications, use of a different challenge agent, or different route of exposure.
Use of Qualified Animal Models
Before using a qualified animal model in an efficacy study of an investigational drug, sponsors should demonstrate that the animal model is a suitable test system for their drug with regard to the drug’s mechanism of action, related host factors, and the ability to select a dose and regimen in humans. Similarly, since animal models are qualified without reference to a specific drug, the use of a qualified animal model does not ensure that the model will be found acceptable as “a single animal species that represents a sufficiently well-characterized animal model for predicting the response in humans” as stated in the second criterion for drug approval under the Animal Rule. FDA may not accept evidence of effectiveness from a single animal model (even if it is qualified) for an investigational drug, unless the Agency concludes there is sufficient evidence that the results generated in this model adequately predict the response to the drug in humans. The regulatory decision to allow approval of a drug based on the use of an animal model in a single species will be made by the review division on a case-by-case basis.
Qualification does not imply that data obtained from adequate and well-controlled efficacy studies using a qualified animal model are sufficient for approval of products under the Animal Rule without review or without supporting data. Qualification also does not imply that the model will be acceptable under the second criterion of the Animal Rule.
Since qualification is a regulatory conclusion, FDA recommends the use of Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies to the extent practicable, for the model-defining natural history studies submitted to support the qualification of an animal model, to facilitate study conduct in a manner that ensures data quality and integrity. Submitters will be expected to submit a plan to ensure data integrity for studies not performed in accordance with GLP regulations. The model-defining natural history studies submitted for qualification, regardless of the data quality and integrity assurance plan used, will be subject to inspection by FDA to verify the quality and integrity of the data.
Submitters should contact the Animal Model Qualification program (AnimalModelQualification@fda.hhs.gov) for further discussions regarding study conduct practices.
Key Guidances for Animal Model Qualification
Product-independent animal models can be evaluated and qualified as part of the qualification program outlined for Drug Development Tools (DDTs) (see Qualification Process for Drug Development Tools – Guidance for Industry and FDA Staff). Animal models proposed for qualification should address the principles outlined in the draft Guidance for Industry Product Development Under the Animal Rule (PDF - 2MB)
 An animal model is defined as a specific combination of an animal species, challenge agent (refer to footnote 4 for a definition), and route of exposure that produces a disease process or pathological condition that in multiple important aspects corresponds to the human disease or condition of interest.
 In the context of animal model qualification, the model-defining natural history studies are the animal studies that establish the ranges of values of key parameters of the disease or condition that will be specified in the context of use for the qualified model and that will be used as measures of quality control and quality assurance when the model is replicated.