The US Food and Drug Administration (FDA) has published a new draft guidance intended to assist industry with developing products under the agency's so-called "Animal Rule," a regulatory pathway intended to facilitate approvals of medical countermeasures to rare, emerging or serious pathogens.
In 2002, Congress authorized and FDA passed the Animal Efficacy Rule ("Animal Rule"), a regulation which permits the approval of some products based on safety testing in humans and efficacy testing in animals.
The rule, located at 21 CFR 314.600-650 (drugs) and 601.90 (biologics), is meant to allow FDA to approve products for "serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances."
Unlike patients with more typical and common conditions, efficacy testing in these patients is either unethical or unfeasible, as it would require exposing a patient to the lethal or disabling agents, which rarely exist in the normal population. While field trials may be feasible in rare cases, such as an outbreak of Ebola or anthrax, these events are taken as the exception to the rule, and not the norm.
To date, FDA has approved just a small handful of products based on the rule, and most of them only within the last few years. For example, FDA approved the first product under the Animal Rule, J&J's Levaquin (levofloxacin, plague), in April 2012. Later that year, in December, FDA approved the first biologic product under the rule, GSK's raxibacumab (inhalation anthrax). A botulism antitoxin manufactured by Cangene was approved in March 2013.
In all cases, approval was based on FDA's findings that a product was safe for use in healthy humans, indicating that the drug was unlikely to cause harm to sick patients, and data indicating that the drug was effective in animals known to have similar disease pathways as humans. For example, raxibacumab was tested in one trial of monkeys and three trials involving rabbits.
While animal studies aren't a perfect substitute for studies involving humans, regulators have said the rule represents the best chance they have to develop medical countermeasures before they're needed.
FDA last published a draft guidance document on the Animal Rule in 2009, when the agency had not yet approved any products under the rule.
Now the agency is out with a revision to that draft, another draft guidance entitled Product Development Under the Animal Rule. As FDA explains in the document, the revision "covers a broader scope of issues for drugs developed under the Animal Rule," including new sections on study conduct, data quality, data integrity, vaccine development, the development of cellular and gene therapies, general expectations for animal studies, the types of animals used in investigations, animal care, study reports, and natural history studies.
While some of the new sections are general in nature, indicating what sponsors need to keep in mind while conducting Animal Rule-related studies, others are more specific and, at times, practical. For example, FDA includes several checklists, such as one describing "elements of an adequate and well-controlled animal efficacy study protocol." Another checklist describes recommended data elements.
But the biggest changes fall under new sections on new types of therapies. FDA gives extensive treatment to describing how vaccines can be developed under the rule, noting that bridging animal data to humans is critical, as some immune markers won't reflect a response in humans. Similarly, because some animals aren't affected by the same virulent strains as humans, diseases used to test a product in animals must be carefully selected as well.
Cellular and gene therapies are given similar treatment in the guidance, with FDA describing the various difficulties of developing CGTPs under the animal rule.
The guidance is quite long, weighing in at 53 pages—more than twice as long as most FDA guidance documents.
The guidance has not yet been announced in the Federal Register, indicating that it may be a Level 2 guidance not subject to a comment period.
Product Development Under the Animal Rule