2010-13463. Determination That Cysteine Hydrochloride Injection, USP, 7.25%, Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness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(FDA) is announcing its determination that Cysteine Hydrochloride Injection, USP, 7.25% (Cysteine HCl), was not withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for Cysteine HCl if all other legal and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT:

David Joy, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6358, Silver Spring, MD 20993-0002, 301-796-3601.

SUPPLEMENTARY INFORMATION:

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (Public Law 98-417) (the 1984 amendments), which authorized the approval of duplicate versions of drug products approved 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. Sponsors of ANDAs do not have to repeat the extensive clinical testing otherwise necessary to gain approval of a new drug application (NDA). The only clinical data required in an ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug.

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approval of the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (§ 314.162 (21 CFR 314.162)). Under § 314.161(a)(1) (21 CFR 314.161(a)(1)), the agency must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness before an ANDA that refers to that listed drug may be approved. FDA may not approve an ANDA that does not refer to a listed drug.

Cysteine HCl is the subject of NDA 19-523, most recently held by Hospira, Inc. (Hospira), and initially approved on October 22, 1986. Cysteine HCl is indicated for use as an additive to amino acid solutions to meet the nutritional requirements of newborn infants requiring total parenteral nutrition (TPN) and of adult and pediatric patients with severe liver disease who may have impaired enzymatic processes and require TPN. It can also be added to amino acid solutions to provide a more complete profile of amino acids for protein synthesis. Hospira notified FDA in a letter dated May 26, 2005, that it had not commercially manufactured and marketed Cysteine HCl, and voluntarily asked that the NDA be withdrawn. The drug product was moved to the “Discontinued Drug Product List” section of the Orange Book, and FDA withdrew approval of NDA 19-523 effective June 16, 2006 (71 FR 34940). In previous instances (see, e.g., 74 FR 63404, December 3, 2009; 72 FR 9763, March 5, 2007; 61 FR 25497, May 21, 1996), the agency has determined that, for purposes of §§ 314.161 and 314.162, never marketing an approved drug product is equivalent to withdrawing the drug from sale. Regulus Pharmaceutical Consulting, Inc., submitted a citizen petition, dated April 30, 2008 (Docket No. FDA-2008-P-0278), under 21 CFR 10.30, requesting that the agency determine whether Cysteine HCl was withdrawn from sale for reasons of safety or effectiveness.

FDA has reviewed its records and, under § 314.161, has determined that Cysteine Hydrochloride Injection, USP, 7.25%, was not withdrawn for reasons of safety or effectiveness. We have also independently evaluated relevant literature and have found no information that would indicate that this product was withheld from sale for reasons of safety or effectiveness. Accordingly, the agency will continue to list Cysteine Hydrochloride Injection, USP, 7.25%, 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 Cysteine Hydrochloride Injection, USP, 7.25% may be approved by the agency if all other legal and regulatory requirements for the approval of ANDAs are met. If FDA determines that the labeling for this drug product should be revised to meet current standards, the agency will advise ANDA applicants to submit such labeling.

Dated: May 27, 2010.

Leslie Kux,

Acting Assistant Commissioner for Policy.