2017-05246. Determination that CYANOCOBALAMIN INJECTION, 1 Milligram per Milliliter in a 10 Milliliter Vial, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness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 or Agency) has determined that CYANOCOBALAMIN INJECTION, 1 milligram per milliliter in a 10 milliliter vial, was not withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not begin procedures to withdraw approval of abbreviated new drug applications (ANDAs) that refer to this drug product, and it will allow FDA to continue to approve ANDAs that refer to the product as long as they meet relevant legal and regulatory requirements.

FOR FURTHER INFORMATION CONTACT:

Elizabeth Trentacost, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 6219, Silver Spring, MD 20993-0002, 240-402-7736.

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, dosage form, and route of administration 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approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162).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may petition the Agency to determine, or the Agency may determine on its own initiative, whether a listed drug was withdrawn from sale for reasons of safety or effectiveness.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 (21 CFR 314.161). FDA may not approve an ANDA that does not refer to a listed drug.

CYANOCOBALAMIN INJECTION, 1 milligram per milliliter in a 10 milliliter vial, is the subject of ANDA 080557, held by Fresenius Kabi USA (Fresenius), and initially approved on June 20, 1973. CYANOCOBALAMIN INJECTION is indicated for vitamin B₁₂ deficiencies due to malabsorption that may be associated with the following conditions: Addisonian (pernicious) anemia; gastrointestinal pathology, dysfunction, or surgery, including gluten enteropathy or sprue, small bowel bacterial overgrowth, and total or partial gastrectomy; fish tapeworm infestation; malignancy of pancreas or bowel; or folic acid deficiency.

In a letter dated December 21, 2016, Fresenius notified FDA that CYANOCOBALAMIN INJECTION, 1 milligram per milliliter in a 10 milliliter vial, was discontinued over 30 years ago, and Fresenius had concluded that the drug was discontinued for reasons other than safety or effectiveness. Fresenius also conveyed that they currently manufacture and market a 1 milliliter multiple dose vial of the 1 milligram per milliliter concentration.

John R. Rapoza submitted a citizen petition dated June 16, 2016 (Docket No. FDA-2016-P-1676), under 21 CFR 10.30, requesting that the Agency determine whether CYANOCOBALAMIN INJECTION, 1 milligram per milliliter in a 10 milliliter vial, was withdrawn from sale for reasons of safety or effectiveness.

After considering the citizen petition and reviewing Agency records and based on the information we have at this time, FDA has determined under § 314.161 that CYANOCOBALAMIN INJECTION, 1 milligram per milliliter in a 10 milliliter vial, was not withdrawn for reasons of safety or effectiveness. The petitioner has identified no data or other information suggesting that CYANOCOBALAMIN INJECTION, 1 milligram per milliliter in a 10 milliliter vial, was withdrawn for reasons of safety or effectiveness. We have carefully reviewed our files for records concerning the withdrawal of CYANOCOBALAMIN INJECTION, 1 milligram per milliliter in a 10 milliliter vial, from sale. We have also independently evaluated relevant literature and data for possible postmarketing adverse events. We have reviewed the available evidence and determined that this drug product was not withdrawn from sale for reasons of safety or effectiveness.

Accordingly, the Agency will list CYANOCOBALAMIN INJECTION, 1 milligram per milliliter in a 10 milliliter 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. FDA will not begin procedures to withdraw approval of approved ANDAs that refer to this drug product. Additional ANDAs for this drug product may also be approved by the Agency as long as they meet all other legal and regulatory requirements for the approval of ANDAs. If FDA determines that labeling for this drug product should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling.

Dated: March 13, 2017.

Leslie Kux,

Associate Commissioner for Policy.