Under normal circumstances, healthcare products undergo a relatively straightforward approval process in the US. A sponsor first generates data, submits that data in the form of an application to the US Food and Drug Administration (FDA), which then makes a determination as to whether the product is safe and effective for the condition for which the company is seeking approval.
Lesser known, however, is a rarely-used pathway involving emergency use authorization (EUA) by FDA. While the pathway has seen little use in recent years, the few times it has have been to confront serious public health issues, including the H7N9 influenza strain and an emerging virus known as the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). But EUAs have also been used to confront potential terror threats, and now the US Department of Health and Human Services (DHHS) is moving to continue an EUA exception first granted to the tetracycline antimicrobial product doxycycline in 2008.
FDA has recently seen its authority to issue EUAs grow substantially under the terms of a piece of legislation known as the Pandemic and All-Hazards Preparedness Reauthorization Act (PAHPRA). The legislation, passed in March 2013, is intended to bolster the government's ability to respond to health crises, and especially those of a biological nature, by permitting authorities to temporarily approve medical products based on its determination that a health emergency is likely to occur.
Prior to the legislation, FDA could only grant EUAs if a public health emergency already existed, putting the agency and the life science industry in a far more reactive posture relative to their current proactive stance.
The case of aerosolized Bacillus anthracis, a biological agent that causes anthrax, is in many ways indicative of the more reactive approach reflected in FDA's pre-PAHPRA authority. While anthrax spores were sent throughout the postal system in 2001, it wasn't until 2004 that the US Department of Homeland Security (DHS) would issue a "Material Threat Determination" that the biological agent presented a "material threat against the population of the US."
Four years later in September 2008, DHS "determined that there [was] a significant potential for a domestic emergency involving a heightened risk of attack" involving anthrax , and petitioned DHHS to issue an EUA for doxycycline hyclate tablets for post-exposure prophylactic (PEP), which it did in October 2008.
EUAs require a yearly reauthorization based on a determination of a continuing need, and DHHS reauthorized the EUA in both 2009 and 2010.
In 2011, however, it went even farther than the original EUA, granting approval to all doxycycline products to ensure that supplies would be available to public health officials to stockpile in advance of an "actual anthrax event."
The EUA specifically applies to four types of doxycycline products:
- 100 mg oral tablets
- 100 mg oral capsules
- 25 mg/5 mL suspension, supplied as dry powder
- 50 mg/5 mL syrup in a 473mL bottle
In addition, the EUA covers "any other formulation of doxycycline that has been approved by the FDA for post-exposure prophylaxis to reduce the incidence or progression of disease, including inhalational anthrax, following exposure to aerosolized B. anthracis."
The EUA does require the products to have been manufactured in accordance with current good manufacturing practices (CGMPs)-a requirement FDA may now waive under PAHPRA-and to include information to healthcare professionals indicating that it was approved under special circumstances.
Now DHHS Secretary Kathleen Sebelius has granted another year-long extension for the doxycycline EUA, declaring that "circumstances exist justifying the authorization of emergency use of all oral formulations of doxycycline accompanied by emergency use information."
While the 2008 authorization explained that "there is no current domestic emergency involving anthrax, no current heightened risk of an anthrax attack, and no credible information indicating an imminent threat of an attack involving Bacillus anthracis," Sebelius' notice comes just months after letter containing B. anthracis were sent to congressmen and President Barack Obama in April 2013. While enhanced mail security measures stopped all letter before they reached their intended targets, the episode nevertheless put into focus a threat that was before simply a one-off occurrence.
The EUA is now slated to run out on 27 June 2014.
DHHS Statement on EUA