2015-22673. Determination That GLUCAGON (Glucagon Hydrochloride) for Injection, Equivalent to 1 Milligram Base/Vial and Equivalent to 10 Milligram Base/Vial, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) has determined that GLUCAGON (glucagon hydrochloride) for injection, equivalent to (EQ) 1 milligram (mg) base/vial and EQ 10 mg base/vial, was not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for glucagon hydrochloride for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, if all other legal and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT:

Daniel Orr, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6206, Silver Spring, MD 20993, 240-402-0979.

SUPPLEMENTARY INFORMATION:

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417) (the 1984 amendments), which authorized the approval of duplicate versions of drug products under an ANDA procedure. ANDA applicants must, with certain exceptions, show that the drug for which they are seeking approval contains the same active ingredient in the same strength and dosage form as the “listed drug,” which is a version of the drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing otherwise necessary to gain approval of a new drug application (NDA).

The 1984 amendments include what is now section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)), which requires FDA to publish a list of all approved drugs. FDA publishes this list as part of the “Approved Drug Products With Therapeutic Equivalence Evaluations,” which is known generally as the “Orange Book.” Under FDA regulations, drugs are removed from the list if the Agency withdraws or suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162).

A person may petition the Agency to determine, or the Agency may determine on its own initiative, whether a listed drug was withdrawn from sale for reasons of safety or effectiveness. This determination may be made at any time after the drug has been withdrawn from sale, but must be made prior to approving an ANDA that refers to the listed drug (§ 314.161 (21 CFR 314.161)). FDA may not approve an ANDA that does not refer to a listed drug.

GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, is the subject of NDA 12-122 held by Eli Lilly, and initially approved onNovember 14, 1960. GLUCAGON is indicated for treatment of severe hypoglycemia and as a diagnostic aid in the radiologic examination of the stomach, duodenum, small bowel, and colon.

Under NDA 12-122, GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, was produced from animal sources. On September 11, 1998, FDA approved Eli Lilly's NDA 20-928 for GLUCAGON (glucagon rDNA origin), 1mg/vial. Subsequently, Eli Lilly discontinued sales of animal-sourced GLUCAGON in 2002. In 2005, FDA moved animal-sourced GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, to the “Discontinued Drug Product List” section of the Orange Book.

Walter G. Jump, on behalf of Cornerstone Regulatory, submitted a citizen petition dated August 7, 2007 (Docket No. FDA-2007-P-0248), under 21 CFR 10.30, requesting that the Agency determine whether animal-sourced GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, was withdrawn from sale for reasons of safety or effectiveness.

After considering the citizen petition, reviewing Agency records, and based on the information we have at this time, FDA has determined under § 314.161 that GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, was not withdrawn for reasons of safety or effectiveness. The petitioner has identified no data or other information suggesting that GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, was withdrawn for reasons of safety or effectiveness. We have carefully reviewed our files for records concerning the withdrawal from sale of GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial. We have also independently evaluated relevant literature and data for possible postmarketing adverse events. We have reviewed the available evidence and determined that the product was not withdrawn from sale for reasons of safety or effectiveness.

Accordingly, the Agency will continue to list GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, in the “Discontinued Drug Product List” section of the Orange Book. The “Discontinued Drug Product List” delineates, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness. ANDAs that refer to GLUCAGON (glucagon hydrochloride) for injection, EQ 1 mg base/vial and EQ 10 mg base/vial, may be approved by the Agency as long as they meet all other legal and regulatory requirements for the approval of ANDAs. However, it is the Agency's view that it would be challenging for a prospective applicant to provide adequate data to meet the statutory requirements for an ANDA that relies on NDA 12-122 for GLUCAGON (glucagon hydrochloride) for injection in the absence of comparative data with the animal-sourced glucagon approved in NDA 12-122.

Dated: September 2, 2015.

Leslie Kux,

Associate Commissioner for Policy.