E7-10491. Draft Guidances for Industry Describing Product-Specific Bioequivalence Recommendations; Availability

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Notice.

SUMMARY:

This notice announces the availability of draft guidances for industry that describe recommendations on how to design bioequivalence (BE) studies for 200 specific drug products to support abbreviated new drug applications (ANDAs). These draft guidances are being made available concurrently with the publication of a draft guidance for industry entitled “Draft Guidance for Industry—Bioequivalence Recommendations for Specific Products” (product specific BE recommendations). This draft guidance describes the new process for making available guidance on product-specific BE studies. Under the process described in the draft guidance, draft and final product-specific BE study guidance will be made available on the FDA Web site. FDA believes that making this information available on the Internet will streamline the guidance process and provide a meaningful opportunity for the public to consider and comment on product-specific BE study recommendations. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a related guidance document entitled “Draft Guidance for Industry—Bioequivalence Recommendations for Specific Products.”

DATES:

Submit written or electronic comments on the draft guidances by September 28, 2007. General comments on agency guidance documents are welcome at any time.

ADDRESSES:

Submit written requests for single copies of draft product-specific BE study guidances to the Division of Drug Information (HFD-240), Center for Drug Evaluation and Research, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Send one self-addressed adhesive label to assist that office in processing your requests. Submit written comments on the draft guidance to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.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.fda.gov/​dockets/​ecomments. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT:

Doan T. Nguyen, Center for Drug Evaluation and Research (HFD-600), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 301-827-0495.

SUPPLEMENTARY INFORMATION:

I. Background

To receive approval for an ANDA, an applicant generally must demonstrate, among other things, that its product has the same active ingredient, dosage form, strength, route of administration and conditions of use as the listed drug, and that the proposed drug product is bioequivalent to the reference listed drug (21 U.S.C. 355(j)(2)(A); 21 CFR 314.94(a)). Bioequivalent drug products show no significant difference in the rate and extent of absorption of the therapeutic ingredient (21 U.S.C. 355(j)(8); 21 CFR 320.1(e)). BE studies are undertaken in support of ANDA submissions with the goal of demonstrating BE between a proposed generic drug product and its reference listed drug. The regulations governing BE are provided at 21 CFR in part 320.

The draft guidance entitled “Bioequivalence Recommendations for Specific Products” describes the following process for making available draft and final product-specific BE recommendations:

• FDA will develop product-specific BE recommendations and post them on the Center for Drug Evaluation and Research (CDER) guidance page (http://www.fda.gov/​cder/​index.html) in draft to facilitate public consideration and comment. The recommendations can be viewed by clicking on the URL associated with the “Bioequivalence Recommendations for Specific Products” guidance on the CDER guidance page or on the Office of Generic Drugs Page (see www.fda.gov/​cder/​ogd/​index.htm). Users can also search for a specific product BE recommendation using the search tool on the CDER guidance page.
• Newly posted draft and final BE recommendations will be announced in the “Newly Added Guidance Documents” list, which is posted monthly on the CDER guidance page.
• The agency will issue a notice in the Federal Register announcing the availability on the FDA web site of new product-specific draft and final BE recommendations. The notice will identify a comment period for the recommendations.
• Comments on product-specific BE recommendations will be considered in developing final BE recommendations.
• The BE recommendations will be revised as appropriate to ensure that the most up-to-date BE information is available to the public.

FDA is making the first group of draft product-specific BE recommendations available concurrently with the issuance of the draft guidance document describing the process.

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

The FDA is making available draft recommendations for drug products containing the following active ingredients:

A

Abacavir Sulfate

Abacavir Sulfate; Lamivudine; Zidovudine

Acamprosate Calcium

Acitretin

Acyclovir

Almotriptan Malate

Alosetron HCl

Alprazolam

Amlodipine Besylate

Amlodipine Besylate; Benazepril HCl

Amoxicillin; Clavulanate Potassium

Anagrelide HCl

Anastrozole

Aprepitant

Atazanavir Sulfate

Atomoxetine HCl

Atorvastatin Calcium

B

Benzonatate

Benzphetamine HCl

Bicalutamide

Bisoprolol Fumarate

Bisoprolol Fumarate; Hydrochlorothiazide

C

Candesartan Cilexetil

Candesartan Cilexetil; Hydrochlorothiazide

Carbamazepine

Carbidopa; Entacapone; Levodopa

Carvedilol

Cefditoren Pivoxil

Celecoxib

Cetirizine HCl

Cevimeline HCl

Cilostazol

Cinacalcet HCl

Clarithromycin

Clonidine HCl

Clopidogrel

D

Danazol

Dantrolene Sodium

Darifenacin HBr

Deferasirox

Desloratadine

Dextromethorphan Polistirex

Diclofenac Sodium; Misoprostol

Dicloxacillin Sodium

Didanosine (multiple dosage forms)

Digoxin

Dipyridamole

Divalproex Sodium

Dofetilide

Donepezil HCl

Doxazosin Mesylate

Drospirenone; Estradiol

Duloxetine HCl (multiple dosage forms)

Dutasteride

E

Efavirenz (multiple dosage forms)

Emtricitabine

Entacapone

Entecavir

Eplerenone

Erlotinib HCl

Escitalopram Oxalate

Esomeprazole Magnesium

Etidronate Disodium

Exemestane

F

Famotidine (multiple dosage forms)

Felbamate (multiple dosage forms)

Fenofibrate

Fexofenadine HCl (multiple dosage forms)

Flavoxate HCl

Fluconazole

Fluoxetine HCl; Olanzapine

Fosamprenavir Calcium

Fosinopril Sodium; Hydrochlorothiazide

G

Gabapentin (multiple dosage forms)

Galantamine HBr

Ganciclovir

Gemifloxacin Mesylate

Glimepiride

Glipizide; Metformin HCl

Glyburide; Metformin HCl

Granisetron HCl

H

Hydrochlorothiazide

Hydrochlorothiazide; Lisinopril

Hydrochlorothiazide; Losartan Potassium

Hydrochlorothiazide; Moexipril HCl

Hydrochlorothiazide; Olmesartan Medoxomil

Hydrochlorothiazide; Valsartan

I

Ibandronate Sodium

Ibuprofen; Pseudoephedrine HCl

Indinavir Sulfate

Irbesartan

Isosorbide Mononitrate

Isradipine (multiple dosage forms)

Itraconazole

L

Lamivudine

Lamivudine; Zidovudine

Lamotrigine (multiple dosage forms)

Leflunomide

Liothyronine Sodium

Losartan Potassium

M

Mefloquine HCl

Meloxicam (multiple dosage forms)

Mercaptopurine

Mesalamine

Metaxalone

Metformin HCl

Metformin HCl; Pioglitazone HCl

Miglustat

Mirtazapine

Modafinil

Moexipril HCl

Montelukast Sodium

Morphine Sulfate

Mycophenolate Mofetil

Mycophenolate Mofetil HCl

N

Nabumetone

Nateglinide

Nelfinavir Mesylate

Nevirapine

O

Olanzapine

Olmesartan Medoxomil

Olsalazine Sodium

Omeprazole (multiple dosage forms)

Omeprazole Magnesium

Ondansetron (multiple dosage forms)

Oxcarbazepine (multiple dosage forms)

P

Pantoprazole Sodium

Perindopril Erbumine

Pilocarpine HCl

Pravastatin Sodium

Q

Quetiapine Fumarate

Quinapril HCl

R

Raloxifene HCl

Ramipril

Ribavirin (multiple dosage forms)

Rifampin

Riluzole

Risedronate Sodium; Calcium Chloride

Risedronate Sodium

Risperidone

Ritonavir

Rizatriptan Benzoate

Rosiglitazone Maleate

Rosuvastatin Calcium

S

Sertraline HCl

Sibutramine HCl

Sildenafil Citrate

Simvastatin

Sirolimus

Stavudine

Sulfamethoxazole; Trimethoprim

Sumatriptan Succinate

T

Tacrolimus

Tadalafil

Tamsulosin HCl

Telithromycin

Telmisartan

Terbinafine HCl

Testosterone

Ticlopidine HCl

Tizanidine HCl

Tolterodine Tartrate

Topiramate (multiple dosage forms)

Torsemide

Tramadol HCl

Tramadol HCl; Acetaminophen

Trandolapril

Triamterene

V

Valacyclovir HCl

Valsartan

Vardenafil HCl

Venlafaxine HCl

Verapamil HCl (multiple dosage forms)

Voriconazole

Z

Zaleplon

Zidovudine (multiple dosage forms)

Ziprasidone HCl

Zolpidem Tartrate

These draft guidances are available on the CDER guidance page and may be viewed by clicking on the URL associated with the draft “Bioequivalence Recommendations for Specific Products” guidance on the CDER guidance page or on the Office of Generic Drugs Page (see www.fda.gov/​cder/​ogd/​index.htm). Users can also search for a specific product BE recommendation using the search tool on the CDER guidance page.

These draft guidances are being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidances represent the agency's current thinking on the design of product-specific bioequivalence studies to support ANDAs. Guidance does not create or confer any rights for or on any person and does 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.

III. Comments

Interested persons may submit to the Division of Dockets Management (see ADDRESSES) written or electronic comments on the draft guidance. Two copies of mailed comments are to be submitted, except that individuals may submit one copy. Comments are to be identified with the docket number found in brackets in the heading of this document. The draft guidance and received comments are available for public examination in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.

IV. Electronic Access

Persons with access to the Internet may obtain the draft product-specific BE recommendations at either http://www.fda.gov/​cder/​guidance/​index.htm or http://www.fda.gov/​ohrms/​dockets/​default.htm.

Dated: May 22, 2007.

Jeffrey Shuren,

Assistant Commissioner for Policy.