A-Z Index
Image Cart
              

 Information For:

Manufacturers

Regulator

Healthcare

Consumers

Members

USP Non–US Monographs Guideline

Version 1.1, Effective March 1, 2009

Background

The United States Pharmacopeia (USP) approach for monographs for articles legally marketed outside the U.S. (Non-US Monographs) allows the creation of documentary standards (monographs) for drug products and their ingredients that have been approved in and are legally marketed in countries other than the U.S. and are intended to treat neglected diseases, as listed in the below Tables. Where appropriate, USP will provide reference materials (official USP Reference Standards) to support testing of an article against a Non-US Monograph.

Requirements

In order for a Non-US Monograph for a drug product and/or its drug substance to be developed, the Sponsor must:

  • Not have obtained final approval from the Food and Drug Administration (FDA) of the drug product in the U.S.
  • Have obtained approval for the drug product in a country with a stringent regulatory authority 1
  • Follow USP's Guideline for Submitting Requests for Revision to the USP-NF and label the Request "Non-US Monograph."
  • Inform USP if an application for approval of the drug product is filed in U.S. or if the approval status of the drug product or drug substance elsewhere changes.

Process

  • Non-US Monographs will not be published in Pharmacopeial Forum for comment, nor will they appear when final in USP–NF. Instead, a proposed monograph will be published in draft on USP's Web site, and a 90–day comment period will commence. Following the comment period and review and approval by the USP Council of Experts (including incorporation of public comments as deemed appropriate), the final monograph will be posted on USP's Web site. The Nomenclature Expert Committee will not review the title of the monograph at this time (unless the monograph also qualifies as a Pending Monograph under USP's Pending Monographs Guideline), but may review the title in the future if a USP, NF or Pending Monograph is proposed for the article.
  • When final, a Non–US Monograph will be considered authorized rather than official text because it has been approved by the USP Council of Experts but is not part of an official compendium of the U.S. (USP or NF).
  • In addition to the requirements set forth in individual Non–US Monographs, the terms and conditions set forth in the Non–US Monographs General Notices and Requirements  (113KB) shall apply to all Non–US Monographs.
  • Manufacturers of drug substances or drug products may use the designation "S–USP" on certificates of analysis or on container labels, respectively, to indicate compliance to these documentary standards for their drug products or drug substances.
1USP defines 'stringent authority' as those countries listed in Section 802 of the Federal Food, Drug and Cosmetic Act as well as those identified on The Global Fund list Http://www.theglobalfund.org/documents/psm/List_of_CountriesICH_PICS.pdf. USP will also consider this requirement to be met if a product has (i) received tentative approval from the FDA (such as tentative approval granted under the President's Emergency Plan for AIDS Relief), (ii) been prequalified by the World Health Organization, or (iii) been reviewed for safety and efficacy by another competent authority, as determined by USP.

Revision History

Version 1.1 Effective March 1, 2009

Section: Requirements
Change: Expanded the section previously requiring review by a "stringent regulatory authority" to also allow the development of monographs for articles that have been prequalified by the World Health Organization or been reviewed for safety and efficacy by another competent authority.



Section: Process
Change: Added provision referencing the General Notices and Requirements applicable to Non-US Monographs.

Section: Multiple
Change: Changed the name of this approach from SALMOUS (Standards for Articles Legally Marketed Outside the US) to Non-US Monographs.

Version 1.0 Effective January, 2007

Initial Guideline was posted.

Table 1. Neglected Diseases and HIV/AIDS

Diseases

Drug Therapy

African trypanosomiasis1

eflornithine, melarsoprol, pentamidine, suramin

Dengue

none, supportive

Hemorrhagic fever with renal syndrome (HFRS) due to Hantavirus

ribavirin, supportive

Lassa fever

ribavirin, supportive

Leishmaniasis

amphotericin B (liposomal), meglumine antimoniate, miltefosine, pentamidine, sodium stibogluconate, paromomycin

Malaria2

amodiaquine, artemether, artemether + lumefantrine, dihydroartemisinin + piperaquine (awaiting completion of phase III trials and regulatory approvals), artemisinin, artemotil, artenimol, artesunate, artesunate + amodiaquine (awaiting completion of phase III trials and regulatory approvals), artesunate + mefloquine (awaiting completion of phase III trials and regulatory approvals), chloroquine, doxycycline, halofantrine, hydroxychloroquine, mefloquine, primaquine, proguanil, pyrimethamine, quinine, sulfadoxine + pyrimethamine

Schistosomiasis

metrifonate, oxamniquine, praziquantel

Tuberculosis

amikacin, aminosalicylic acid (PAS), capreomycin, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin, levofloxacin, pyrazinamide, rifabutin, rifampin, rifapentin, streptomycin, thiacetazone, ethambutol + isoniazid, rifampin + isoniazid, rifampin + isoniazid + pyrazinamide, rifampin + isoniazid + pyrazinamide + ethambutol, gatifloxacin, moxifloxacin

Chagas disease (American trypanosomiasis)

benznidazole, nifurtimox

Leprosy

dapsone + rifampicin + clofazimine

Lymphatic filariasis

albendazole, diethylcarbamazine

Onchocerciasis

ivermectin

HIV/AIDS

abacavir, amprenavir, atazanavir, darunavir,delavirdine, didanosine, efavirenz, efavirenz + emtricitabine + tenofovir, emtricitabine, enfuvirtide, fosamprenavir, indinavir, lamivudine, lamivudine + stavudine, lamivudine + zidovudine, lopinavir, lopinavir + ritonavir, nelfinavir, nevirapine, ritonavir, saquinavir, stavudine, stavudine + lamivudine + efavirenz, stavudine + lamivudine + nevirapine, tenofovir, tipranavir, zalcitabine, zidovudine, zidovudine + lamivudine + nevirapine, zidovudine + lamivudine + abacavir, zidovudine + lamivudine + efavirenz



Table 2. AIDS-associated opportunistic infections

Diseases

Preferred Therapy

Pneumocystis jiroveci pneumonia (PCP)

trimethoprim-sulfamethoxazole, dapsone, dapsone + pyrimethamine + leucovorin, pentamidine, atovaquone

Toxoplasma gondii encephalitis (TE)

pyrimethamine + sulfadiazine + leucovorin, clindamycin + pyrimethamine + leucovorin, atovaquone ± pyrimethamine + leucovorin

Cryptosporidiosis

symptomatic treatment of diarrhea, and antiretrovirals

Microsporidiosis

albendazole, fumagillin

Mycobacterium tuberculosis (MTB)

isoniazid + rifampin, rifabutin + pyrazinamide + ethambutol, rifabutin (See also Table 1)

Mycobacterium avium complex disease

clarithromycin + ethambutol ± rifabutin, azithromycin + ethambutol ± rifabutin

Bacterial pneumonia3

amoxicillin (high dose), amoxicillin + clavulanate, ampicillin (high dose), ampicillin + sulbactam,cefotaxime, ceftriaxone, cefpodoxine, cefuroxime, cefepime, imipenem, meropenem, doxycycline, ciprofloxacin,gatifloxacin, levofloxacin, moxifloxacin, azithromycin, erythromycin, clarithromycin, piperacillin + tazobactam,

Salmonellosis

ciprofloxacin

Campylobacter jejuni infections

ciprofloxacin, azithromycin, aminoglycoside (e.g., gentamicin)

Shigellosis4

fluoroquinolone

Bartonella infections

macrolides (eg. erythromycin, clarithromycin, azithromycin,) doxycycline

Treponema pallidum infection (Syphilis)

benzathine penicillin, aqueous crystalline penicillin, doxycycline, ceftriaxone

Candidiasis (mucosal)

fluconazole, itraconazole, clotrimazole, nystatin, voriconazole, caspofungin

Cryptococcus neoformans meningitis

amphotericin B deoxycholate, liposomal ampnotericin B, flucytosine, fluconazole

Histoplasma capsulatum infections

amphotericin B deoxycholate, liposomal amphotericin B, itraconazole

Coccidiodomycosis

amphotericin B deoxycholate, fluconazole, itraconazole

Invasive aspergillosis

voriconazole, amphotericin B, caspofungin, itraconazole

Cytomegalovirus (CMV) disease

ganciclovir, valganciclovir, foscarnet

Herpes simplex virus (HSV) disease

famciclovir, valaciclovir, acyclovir, trifluridine

Varicella zoster virus (VZV) disease

acyclovir, valaciclovir, famciclovir, foscarnet

Human papilloma virus disease

podofilox, imiquimod

Hepatitis C virus (HCV) disease

peg-interferon alfa-2b, peg-interferon alfa-2a + ribavirin

Hepatitis B virus (HBV) disease

none recommended as preferred treatment because of lack of controlled trial data on the use of antiviral agents against HBV in HIV/HBV co-infected patients

Penicilliosis

amphotericin B + itraconazole

Leishmaniasis

pentavalent antimony, sodium stibogluconate (See also Table 1)

Paracoccidioidomycosis

amphotericin B, itraconazole

Isospora belli infection

trimethoprim + sulfamethoxazole

Chagas disease

benznidazole (See also Table 1) nifurtimox


1. For african trypanosomiasis, DB289 is a future drug in Phase III trials.
2. For artemisinin derivatives, only artemisinin-based combination therapies (ACT) should be considered for treatment of malaria to prevent drug resistance with the exception of rectal artesunate, a monotherapy for pediatric in the treatment of malaria.
3. For the drugs used in the treatment of community-acquired pneumonia in adults, see the guidelines developed by the American Thoracic Society at http://www.thoracic.org
4. Symptomatic treatment should be used unless severe, but should remember that hemolytic-uremic syndrome may follow fluroquinolone use.