Document Headings

                    Document headings vary by document type but may contain                    the following:                  
                -                       the agency or agencies that issued and signed a document                    
                -                       the number of the CFR title and the number of each part                      the document amends, proposes to amend, or is directly                      related to                    
                -                       the agency docket number / agency internal file number                    
                -                       the RIN which identifies each regulatory action listed in                      the Unified Agenda of Federal Regulatory and Deregulatory                      Actions                    

                    See the                                          Document Drafting Handbook                                        for more details.                  

###### Department of Health and Human Services

###### Food and Drug Administration

          - [Docket No. 00P-1496]

# AGENCY:

Food and Drug Administration, HHS.

# ACTION:

Notice.

# SUMMARY:

The Food and Drug Administration (FDA) has determined that metformin hydrochloride (HCl) tablets (Glucophage), 625 and 750 milligrams (mg), were not withdrawn from sale for reasons of safety or effectiveness.  This determination will allow FDA to approve abbreviated new drug applications (ANDAs) for metformin HCl 625- and 750-mg tablets.

# FOR FURTHER INFORMATION CONTACT:

Paul C. Varki, Center for Drug Evaluation and Research (HFD-7), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD  20855, 301-594-2041.

# SUPPLEMENTARY INFORMATION:

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (the 1984 amendments) (Public Law 98-417), which authorized the approval of duplicate versions of drug products approved under an ANDA procedure.  ANDA sponsors 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 under a new drug application (NDA).  Sponsors of ANDAs do not have to repeat the extensive clinical testing otherwise necessary to gain approval of an 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,” generally known as the “Orange Book.”  Under FDA regulations, drugs are withdrawn 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).  Regulations also provide that the agency must make a determination as to 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 (§ 314.161(a)(1) (21 CFR 314.161(a)(1))).  FDA may not approve an ANDA that does not refer to a listed drug.

Metformin HCl 625- and 750-mg tablets are the subject of NDA 20-357.  When first approved, the NDA provided for 500- and 850-mg tablets.  On July 8, 1998, Bristol-Myers Squibb Co. submitted a supplemental NDA to market the 625-, 750-, and 1000-mg tablets.  FDA approved this supplement on November 5, 1998.  On November 11, 1998, Bristol-Myers Squibb notified FDA that it would not market the 750-mg strength tablet.  The 625-mg strength tablet has not been marketed either.

                    On August 31, 2000, Lachman Consultant Services, Inc., submitted a citizen petition (Docket No. 00P-1496/                          ( print page 33101)                        CP1) under 21 CFR 10.30 to FDA.  The petition requested that the agency determine whether metformin HCl tablets, 625- and 750-mg were withdrawn from sale for reasons of safety or effectiveness.                

FDA has reviewed its records and, under § 314.161, has determined that Bristol-Myers Squibb’s decision not to market metformin HCl 625- and 750-mg tablets was not due to concerns about safety or effectiveness of the product.  Accordingly, the agency will maintain metformin HCl 625- and 750-mg tablets 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 metformin HCl 625- and 750-mg tablets may be approved by the agency. 

Dated: June 12, 2001.

Margaret M. Dotzel,

Associate Commissioner for Policy.

[FR Doc. 01-15442 Filed 6-19-01; 8:45 am]

BILLING CODE 4160-01-S