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

###### Food and Drug Administration

          - [Docket No. FDA-2010-P-0507]

# AGENCY:

Food and Drug Administration, HHS.

# ACTION:

Notice.

# SUMMARY:

The Food and Drug Administration (FDA) has determined that Halflytely and Bisacodyl Tablets Bowel Prep Kit (polyethylene glycol (PEG) 3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution and two bisacodyl delayed release tablets, 5 milligrams (mg) (10-mg bisacodyl)) was withdrawn from sale for reasons of safety or effectiveness. The Agency will not accept or approve abbreviated new drug applications (ANDAs) for bowel prep kits containing PEG-3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution and two bisacodyl delayed release tablets, 5 mg.

# FOR FURTHER INFORMATION CONTACT:

Nikki Mueller, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6312, 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 (Pub. L. 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. ANDA applicants 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 generally known 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of the drug's NDA or ANDA for reasons of safety or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162). 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.

On September 23, 2010, FDA received a citizen petition (Docket No. FDA-2010-P-0507), submitted under § 10.30 (21 CFR 10.30), from Perrigo Company (Perrigo). The petition requests that the Agency determine whether Halflytely and Bisacodyl Tablets Bowel Prep Kit (PEG-3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution and two bisacodyl delayed release tablets, 5 mg) (Halflytely and Bisacodyl Tablets Bowel Prep Kit (10-mg bisacodyl)), manufactured by Braintree Laboratories, Inc. (Braintree), was withdrawn from sale for reasons of safety or effectiveness.

Halflytely and Bisacodyl Tablets Bowel Prep Kit (10-mg bisacodyl) (NDA 21-551) was approved on September 24, 2007. Halflytely and Bisacodyl Tablets Bowel Prep Kit (10-mg bisacodyl) was indicated for the cleansing of the colon as preparation for colonoscopy in adults. Braintree informed FDA that it ceased to manufacture and market Halflytely and Bisacodyl Tablets Bowel Prep Kit (10-mg bisacodyl) as of July 17, 2010. The drug product was then moved to the “Discontinued Drug Product List” section of the Orange Book.

                    FDA has reviewed its records concerning the withdrawal of Halflytely and Bisacodyl Tablets Bowel Prep Kit (10-mg bisacodyl). FDA has also independently evaluated relevant literature, data from clinical trials, and                           ( print page 51038)                        reports of possible postmarketing adverse events. FDA has determined, under § 314.161, that Halflytely and Bisacodyl Tablets Bowel Prep Kit (10-mg bisacodyl) was withdrawn from sale for reasons of safety or effectiveness.                

Braintree discontinued this product containing a total dose of 10 milligrams of bisacodyl from sale after receiving approval from FDA on July 16, 2010, for NDA 21-551/S-013, Halflytely and Bisacodyl Tablets Bowel Prep Kit (PEG-3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution and one bisacodyl delayed release tablet, 5 mg (5-mg bisacodyl)). The data available from a clinical study comparing the 10-mg version of Halflytely and Bisacodyl Tablets Bowel Prep Kit to a 5-mg version of the drug product showed that the Halflytley and Bisacodyl Tablets Bowl Prep Kit (5-mg bisacodyl) has comparable effectiveness to the 10-mg product and has a safety advantage over the 10-mg product because there is less abdominal fullness and cramping in the patients treated with the 5-mg product. Furthermore, the 10-mg product may be associated with ischemic colitis.

FDA has also reviewed the latest approved labeling for the 10-mg product and has determined that it would need to be updated with additional safety information if Braintree were to reintroduce the 10-mg product to the market. FDA has determined that additional clinical studies of safety and efficacy would be necessary before Halflytely and Bisacodyl Tablets Bowel Prep Kit (10-mg bisacodyl) could be considered for reintroduction to the market. Accordingly, the Agency will remove Halflytely and Bisacodyl Tablets Bowel Prep Kit (PEG-3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution and two bisacodyl delayed release tablets, 5 mg) from the list of drug products published in the Orange Book. FDA will not accept or approve ANDAs that refer to this drug product.

Dated: August 10, 2011.

Leslie Kux,

Acting Assistant Commissioner for Policy.

[FR Doc. 2011-20853 Filed 8-16-11; 8:45 am]

BILLING CODE 4160-01-P