Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence Recommendations; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

The Food and Drug Administration (FDA) is announcing the availability of additional draft and revised draft product-specific bioequivalence (BE) recommendations. The recommendations provide product-specific guidance on the design of BE studies to support abbreviated new drug applications (ANDAs). In the Federal Register of May 31, 2007, FDA announced the availability of a draft guidance for industry entitled “Bioequivalence Recommendations for Specific Products” explaining the process that would be used to make product-specific BE recommendations available to the public on FDA's Web site. The BE recommendations identified in this notice were developed using the process described in that guidance. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of final product-specific BE recommendations.

DATES:

Submit written or electronic comments on the draft and revised draft product-specific BE recommendations listed in this notice by September 8, 2009.

ADDRESSES:

Submit written requests for single copies of the individual BE guidances to the Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in processing your requests. Submit written comments on the draft product-specific BE recommendations to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.regulations.gov . See the SUPPLEMENTARY INFORMATION section for electronic access to the recommendations.

FOR FURTHER INFORMATION CONTACT:

Doan T. Nguyen, Center for Drug Evaluation and Research (HFD-600), Food and Drug Administration, 7519 Standish Pl., Rockville, MD 20855, 240-276-9314.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of May 31, 2007 (72 FR 30388), FDA announced the availability of a draft guidance for industry entitled “Bioequivalence Recommendations for Specific Products” that explained the process that would be used to make product-specific BE recommendations available to the public on FDA's Web site at http://www.fda.gov/cder/guidance/bioequivalence/default.htm . As described in that draft guidance, FDA adopted this process as a means to develop and disseminate product-specific BE recommendations and provide a meaningful opportunity for the public to consider and comment on those recommendations. Under that process, draft recommendations are posted on FDA's Web site and announced periodically in the Federal Register. The public is encouraged to submit comments on those recommendations within 90 days of their announcement in the Federal Register. FDA considers any comments received and either publishes final recommendations, or publishes revised draft recommendations for comment. Recommendations were last announced in the Federal Register of September 5, 2008 (73 FR 51829). This notice announces draft product-specific recommendations, either new or revised, that have been posted on FDA's Web site in the period from May 1, 2008, through October 31, 2008. Final product-specific recommendations are being announced elsewhere in this issue of the Federal Register.

II. Drug Products for Which Draft Product-Specific BE Recommendations Are Available

FDA is announcing draft BE product-specific recommendations for drug products containing the following active ingredients:

A

Acetazolamide

Adefovir Dipivoxil

Albuterol Sulfate

Aliskiren Hemifumarate

Alprazolam

Aminosalicylic Acid

Amlodipine Besylate; Olmesartan Medoxomil

Amlodipine Besylate; Valsartan

Amprenavir

Atovaquone; Proguanil

Azacitidine

Azithromycin

B

Baclofen

Bethanechol Chloride

Bismuth Subcitrate Potassium; Metronidazole; Tetracycline HCl

Brimonidine Tartrate

Bumetanide

Busulfan

C

Calcitriol

Capecitabine

Citalopram HBr (multiple dosage forms)

Clotrimazole

Colesevelam HCl

Cyclobenzaprine HCl

D

Demeclocycline HCl

Desogestrel; Ethinyl Estradiol

Diflunisal

Disopyramide Phosphate (multiple dosage forms)

Doxercalciferol

Doxycycline

Doxycycline Hyclate

E

Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate

Enalapril Maleate

Eprosartan Mesylate

Escitalopram Oxalate

Ethinyl Estradiol; Levonorgestrel

Ethinyl Estradiol; Norethindrone Acetate (multiple reference listed drugs (RLDs))

Ethosuximide

Ezetimibe; Simvastatin

Ezetimibe

F

Famciclovir

Fenofibrate (multiple dosage forms)

Fexofenadine HCl

Frovatriptan Succinate

G

Gatifloxacin

Glipizide

Goserelin Acetate

Griseofulvin, Ultramicrocrystalline

H

Hydrochlorothiazide; Telmisartan

Hydrochlorothiazide; Triamterene

Hydralazine HCl

Hydroxyurea

I

Ibuprofen (multiple dosage forms)

Indapamide

Isoniazid

Isotretinoin

K

Ketoconazole

Ketorolac Tromethamine

L

Lansoprazole

Latanoprost

Letrozole

Leucovorin Calcium

Leuprolide Acetate

Levocetirizine Dihydrochloride

Levofloxacin

Lisdexamfetamine Dimesylate

Lithium Carbonate

Lopinavir; Ritonavir

Loratadine

M

Mebendazole

Melphalan

Metformin HCl

Methadone HCl

Midodrine HCl

Minocycline HCl

Montelukast

Montelukast Sodium

Moxifloxacin HCl

N

Nabilone

Naltrexone HCl

Naproxen Sodium (multiple RLDs)

Naratriptan HCl

Nicardipine HCl

O

Olanzapine

Olopatadine HCl

Omeprazole; Sodium Bicarbonate

P

Paroxetine HCl

Penicillamine

Phenoxybenzamine HCl

Prednisolone Sodium Phosphate

Q

Quetiapine Fumarate

R

Ramipril

Repaglinide

S

Sapropterin Dihydrochloride

Selegiline HCl

Sevelamer Carbonate

Sevelamer HCl

Simvastatin

Sitagliptin Phosphate; Metformin HCl

Sodium Iodide

Stavudine

Sulfadiazine

Sulfamethoxazole; Trimethoprim

T

Theophylline

Tiagabine HCl

Triptorelin Pamoate

Trospium Cl

U

Ursodiol

V

Valganciclovir HCl

Verapamil HCl

Vorinostat

Z

Zileuton

Ziprasidone HCl

III. Drug Products for Which Revised Draft Product-Specific BE Recommendations Are Available

FDA is announcing revised draft BE product-specific recommendations for drug products containing the following active ingredients. These recommendations were previously posted on FDA's Web site.

A

Alprazolam

C

Candesartan Cilexetil; Hydrochlorothiazide

Carbidopa; Entacapone; Levodopa

Clopidogrel Bisulfate

F

Fexofenadine HCl (multiple dosage forms)

Fosinopril Sodium; Hydrochlorothiazide

H

Hydrochlorothiazide; Valsartan

M

Minoxidil

Montelukast Sodium

Morphine Sulfate

S

Sirolimus

Z

Zolmitriptan

For a complete history of previously published Federal Register notices, please go to http://www.regulations.gov and enter docket number FDA-2007-D-0369.

These guidances are being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The guidances represent the agency's current thinking on product-specific design of BE studies to support ANDAs. They do not create or confer any rights for or on any person and do not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.

IV. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments on any of the specific BE recommendations posted on FDA's Web site. Submit a single copy of electronic comments or two paper copies of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this document. The guidance, notices, and received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

V. Electronic Access

Persons with access to the Internet may obtain the document at either http://www.fda.gov/cder/guidance/index.htm or http://www.regulations.gov .