2011-19622. Authorization of Emergency Use of Oral Formulations of Doxycycline; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the issuance of an Emergency Use Authorization (EUA) (the Authorization) for oral formulations of doxycycline for the post-exposure prophylaxis of inhalational anthrax during a public health emergency involving aerosolized Bacillus anthracis (B. anthracis). FDA is issuing this Authorization under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as requested by the Centers for Disease Control and Prevention (CDC). The Authorization contains, among other things, conditions on the emergency use of the authorized doxycycline products. The Authorization follows the determination by the Secretary of the Department of Homeland Security (DHS) that there is a significant potential for a domestic emergency involving a heightened risk of attack with a specified biological, chemical, radiological, or nuclear agent or agents—in this case, B. anthracis. On the basis of such determination, the Secretary of the Department of Health and Human Services (HHS) declared an emergency justifying the authorization of the emergency use of doxycycline hyclate tablets, accompanied by emergency use information, and later renewed that declaration. The Secretary of HHS then renewed and amended that declaration so that it applies to all doxycycline products covered by this authorization. The Authorization, which includes an explanation of the reasons for issuance, is reprinted in this document.

DATES:

The Authorization is effective as of July 21, 2011.

ADDRESSES:

Submit written requests for single copies of the EUA to the Office of Counterterrorism and Emerging Threats, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, rm. 4121, Silver Spring, MD 20993. Send one self-addressed adhesive label to assist that office in processing your request or include a fax number to which the Authorization may be sent. See the SUPPLEMENTARY INFORMATION section for electronic access to the Authorization.

FOR FURTHER INFORMATION CONTACT:

Luciana Borio, Office of Counterterrorism and Emerging Threats, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 32, rm. 4280, Silver Spring, MD 20993, 301-796-8510.

SUPPLEMENTARY INFORMATION:

I. Background

Section 564 of the FD&C Act (21 U.S.C. 360bbb-3), as amended by the Project BioShield Act of 2004 (Pub. L. 108-276), allows FDA to strengthen the public health protections against biological, chemical, nuclear, and radiological agents. Among other things, section 564 of the FD&C Act allows FDA to authorize the use of an unapproved medical product or an unapproved use of an approved medical product during a public health emergency that affects, or has a significant potential to affect, national security, and that involves biological, chemical, radiological, or nuclear agent or agents, or a specified disease or condition that may be attributable to such agent or agents. With this EUA authority, FDA can help assure that medical countermeasures may be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by such agents, when there are no adequate, approved, and available alternatives.

Section 564(b)(1) of the FD&C Act provides that, before an EUA may be issued, the Secretary must declare an emergency justifying the authorization based on one of the following grounds: “(A) A determination by the Secretary of Homeland Security that there is a domestic emergency, or a significant potential for a domestic emergency, involving a heightened risk of attack with a specified biological, chemical, radiological, or nuclear agent or agents; (B) a determination by the Secretary of Defense that there is a military emergency, or a significant potential for a military emergency, involving a heightened risk to United States military forces of attack with a specified biological, chemical, radiological, or nuclear agent or agents; or (C) a determination by the Secretary of a public health emergency under section 319 of the Public Health Service Act (PHS Act) that affects, or has a significant potential to affect, national security, and that involves a specified biological, chemical, radiological, or nuclear agent or agents, or a specified disease or condition that may be attributable to such agent or agents.”

Once the Secretary has declared an emergency justifying an authorization under section 564 of the FD&C Act, FDA may authorize the emergency use of a drug, device, or biological product if the Agency concludes that the statutory criteria are satisfied. Under section 564(h)(1) of the FD&C Act, FDA is required to publish, in the Federal Register, a notice of each authorization, and each termination or revocation of an authorization, and an explanation of the reasons for the action. Section 564 of the FD&C Act permits FDA to authorize the introduction into interstate commerce of a drug, device, or biological product intended for use in a declared emergency. Products appropriate for emergency use may include products and uses that are not approved, cleared, or licensed under sections 505, 510(k), and 515 of the FD&C Act (21 U.S.C. 355, 360(k), and 360e) or section 351 of the PHS Act (42 U.S.C. 262). FDA may issue an EUA only if, after consultation with the National Institutes of Health and CDC (to the extent feasible and appropriate given the circumstances of the emergency), FDA ^[1] concludes: (1) That an agent specified in a declaration of emergency can cause a serious or life-threatening disease or condition; (2) that, based on the totality of scientific evidence available to FDA, including data from adequate and well-controlled clinical trials, if available, it is reasonable to believe that: (A) the product may be effective in diagnosing, treating, or preventing—(1) Such disease or condition; or (2) a serious or life-threatening disease or condition caused by a product authorized under section 564, approved or cleared under the FD&C Act, or licensed under section 351 of the PHS Act, for diagnosing, treating, or preventing such a disease or condition caused by such an agent; and (B) the known and potential benefits of the product, when used to diagnose, prevent, or treat such disease or condition, outweigh the known and potential risks of the product; (3) that there is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating such disease or condition; and (4) that such other criteria as the Secretary may by regulation prescribe are satisfied.

No other criteria of issuance have been prescribed by regulation under section 564(c)(4) of the FD&C Act. Because the statute is self-executing, FDA does not require regulations or guidance to implement the EUA authority. However, in the Federal Register of July 26, 2007 (72 FR 41083), FDA announced the availability of a guidance entitled “Emergency Use Authorization of Medical Products.” The guidance provides more information for stakeholders and the public about the EUA authority and the Agency's process for the consideration of EUA requests.

II. EUA Request for Oral Formulations of Doxycycline Products

In 2004, the Secretary of DHS issued a material threat determination indicating that B. anthracis, the biological agent that causes anthrax disease, presents a material threat against the population of the United States sufficient to affect national security. On September 23, 2008, under section 564(b)(1)(A) of the FD&C Act, the Secretary of DHS determined that there is a significant potential for a domestic emergency involving a heightened risk of attack with a specified biological, chemical, radiological, or nuclear agent or agents—in this case, B. anthracis. On October 1, 2008, under section 564(b) of the FD&C Act, and on the basis of such determination, the Secretary of HHS then declared an emergency justifying the authorization of the emergency use of doxycycline hyclate tablets accompanied by emergency use information subject to the terms of any authorization issued under section 564(a) of the FD&C Act, and on October 1, 2009, and on October 1, 2010, renewed that declaration. On July 20, 2011, the Secretary of HHS renewed and amended that declaration so that it applies to all doxycycline products covered by this authorization. Notice of the determination and the declaration of the Secretary were published in the Federal Register on July 27, 2011 (76 FR 44926). On May 5, 2011, CDC requested and, on July 21, 2011, FDA issued an EUA for oral formulations of doxycycline products for the post-exposure prophylaxis of inhalational anthrax during a public health emergency involving aerosolized B. anthracis, subject to the terms and conditions of this authorization.

III. Electronic Access

An electronic version of this document and the full text of the Authorization are available on the Internet at http://www.regulations.gov.

IV. The Authorization

Having concluded that the criteria for issuance of the Authorization under section 564(c) of the FD&C Act are met, FDA has authorized the emergency use of oral formulations of doxycycline products for the post-exposure prophylaxis of inhalational anthrax during a public health emergency involving aerosolized B. anthracis subject to the terms and conditions of the authorization.

The Authorization for doxycycline products follows and provides an explanation of the reasons for its issuance, as required by section 564(h)(1) of the FD&C Act:

Dated: July 28, 2011.

Leslie Kux,

Acting Assistant Commissioner for Policy.

Footnotes

1.  The Secretary has delegated her authority to issue an EUA under section 564 of the FD&C Act to the Commissioner of Food and Drugs.