The Food and Drug Administration (FDA) recently made final guidance available to government stakeholders on testing to extend the expiration date of stockpiled medical countermeasures (MCMs) used during public health emergency preparedness and response for anthrax exposure.
Stockpiles of doxycycline tablets or capsules are maintained by several government public health and emergency response stakeholders that use it for post-exposure prophylaxis (PEP) to reduce the incidence or progression of disease following anthrax exposure or during a public emergency to treat people who have inhaled anthrax.
Specifically, states asked the FDA to clarify what would be necessary to ensure stockpiled doxycycline tablets and capsules have retained their original quality — or purity and potency — beyond a manufacturer’s labeled expiration date “so the replacement of stockpiled product could be deferred,” according to the FDA’s notice in the April 25 Federal Register.
The new guidance answers that questions in numerous detailed, nonbinding recommendations.
According to the guidance, entitled Extending Expiration Dates of Doxycycline Tablets and Capsules in Strategic Stockpiles Guidance for Government Public Health and Emergency Response Stakeholders, a number of government stakeholders stockpile doxycycline tablets or capsules that are generally stored under controlled conditions for use based on national preparedness for chemical, biological, radiological, and nuclear (CBRN) emergencies, such as for anthrax exposure.
The Strategic National Stockpile (SNS), which is managed by the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response, stockpiles doxycycline and other MCMs for distribution to states, which then rapidly dispense them as PEP to impacted populations during an anthrax emergency.
Some states and local jurisdictions also stockpile doxycycline for PEP that may be utilized before SNS assets arrive from the federal government and are used as a so-called “quick strike force” to protect first responders and health care professionals, for instance, or if SNS assets aren’t provided, according to the guidance, which was prepared by the FDA’s Office of Pharmaceutical Quality in the Center for Drug Evaluation and Research.
Under section 564A(b) of the Federal Food, Drug, and Cosmetic (FD&C) Act, the FDA is authorized to extend a manufacturer-provided expiration date of an eligible FDA-approved medical product that’s stockpiled for use during CBRN emergencies if the extension is intended to help facilitate the nation’s ability to protect the public health or military preparedness and effectiveness, and if it’s ensured by an appropriate scientific evaluation conducted or accepted by the FDA, according to the guidance.
Additionally, the Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA) of 2013 contained new authorities to sustain and strengthen national preparedness for public health emergencies involving CBRN agents, including emerging infectious disease threats. Among numerous provisions, PAHPRA also permits the FDA to extend the expiration date of certain approved MCMs for emergency response purposes under the FD&C Act.
To be an eligible product under the FD&C Act, it must be an approved, cleared or licensed medical product that’s intended both for use to prevent, diagnose or treat a disease or condition involving a CBRN agent and for use during certain emergency circumstances, according to the guidance.
“For certain products that are generally known to be stable, such as doxycycline tablets and capsules, test results may be extrapolated for emergency use,” the FDA says.
However, if appropriate storage conditions of a stockpiled product have not been maintained, stability testing should be quickly performed via a testing protocol that’s outlined in the FDA’s guidance.
After such testing is completed, if government stakeholders want to request an expiration date extension for tested product lots, they would submit certain information as described in the guidance.
The FDA also recommends that stockpiles be checked routinely and tested within a reasonable time frame for lots nearing their labeled expiration date to allow government stakeholders ample time to submit requests to the FDA for an expiration date extension authorization.
“This will help to ensure that such stakeholders hold product that is authorized by FDA for use beyond its labeled expiration date during an anthrax emergency,” according to the FDA guidance.
Likewise, the FDA guidance provides a process for requesting an authorized expiration date extension and the agency said it will post a memorandum on its website for each product’s authorized extension that lists the manufacturer name, lot number, original manufacturer’s labeled expiration date, and the new expiration date.
The FDA said its April 25 guidance, which finalizes the draft guidance issued by the agency in April 2017, does not apply to commercially available doxycycline.