USP Non-U.S. Monograph 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-U.S. 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-U.S. Monograph.
Requirements
In order for a Non-U.S. 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 *
- Follow USP's Guideline for Submitting Requests for Revision to the USP-NF and label the Request "Non-U.S. 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- Non-U.S. Monographs will not be published in Pharmacopeial Forum for comment, nor will they appear when final in USP–NF.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 website, 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-U.S. Monographs, the terms and conditions set forth in the Non-U.S. Monographs General Notices and Requirements shall apply to all Non-U.S. 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.
*USP 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_Countries_SRA.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 trypanosomiasis (1) | 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 |
| Malaria (2) | 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 pneumonia (3) | 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 infection | 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.
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