Developing Regulatory Strategy for Microbicides

  • Ronald NardiEmail author
  • Linda Arterburn
  • Lisa Carlton
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 383)


Ever since the discovery that a virus was responsible for AIDS, prevention of HIV infection has been a drug/vaccine development target in therapeutic research. Microbicide products are a viable, globally applicable option; however, to date, no product has been approved anywhere in the world. Development of such a product will need to account for the changing disease landscape and will need to leverage available regulatory pathways to gain approvals in the developed world and emerging markets. In countries where the regulatory pathway is not clear which is the case in several emerging markets, sponsors will need to employ a flexible approach to gather and meet local regulatory requirements and ultimately gain product approvals.


Tenofovir Disoproxil Fumarate Uninfected Partner Microbicide Product Fixed Dose Combination Product Common Technical Document 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abbas UL, Anderson RM, Mellors JW (2007) Potential impact of antiretroviral chemoprophylaxis on HIV-1 transmission in resource-limited settings. PLoS ONE 2:e875PubMedCentralPubMedCrossRefGoogle Scholar
  2. Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D (2010) Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329:1168–1174PubMedCentralPubMedCrossRefGoogle Scholar
  3. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A (2005) Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med 2:e298. doi: 10.1371/journal.pmed.0020298 PubMedCentralPubMedCrossRefGoogle Scholar
  4. Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF, Campbell RT, Ndinya-Achola JO (2007) Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 369:643–656. doi: 10.1016/S0140-6736(07)60312-2 PubMedCrossRefGoogle Scholar
  5. Birnkrant D (2010) Microbicides: Critical issues in Phase 2B and 3 Trials—Special Populations. Accessed 8 Jan 2013
  6. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR (2011) Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365:493–505. doi: 10.1056/NEJMoa1105243 PubMedCentralPubMedCrossRefGoogle Scholar
  7. European Medicines Agency (2012) Reflection paper on the non-clinical and clinical development for oral and topical HIV pre-exposure prophylaxis (PrEP). EMA.
  8. Food and Drug Administration (2003) Antiviral Drugs Advisory Committee Meeting Transcript. Accessed 8 Jan 2013
  9. Food and Drug Administration (2012a) Guidance for industry—Vaginal microbicides: development for the prevention of HIV Infection (Draft Guidance). In: FDA (ed) FDA, Federal RegisterGoogle Scholar
  10. Food and Drug Administration (2012b) Truvada for PrEP Fact Sheet: ensuring safe and proper use. U.S. Department of Health & Human Services/U.S. Food and Drug AdministrationGoogle Scholar
  11. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV (2010) Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 363:2587–2599. doi: 10.1056/NEJMoa1011205 PubMedCentralPubMedCrossRefGoogle Scholar
  12. Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ (2007) Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 369:657–666. doi: 10.1016/S0140-6736(07)60313-4 PubMedCrossRefGoogle Scholar
  13. Karim QA, Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D (2010) Effectiveness and safety of Tenofovir Gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329:1168–1174Google Scholar
  14. May MT, Ingle SM (2011) Life expectancy of HIV-positive adults: a review. Sex Health 8:526–533. doi: 10.1071/SH11046 PubMedCrossRefGoogle Scholar
  15. Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, Masse B, Eshleman SH, Hendrix C, Morrow K, Rooney JF, Soto-Torres L (2006) Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 20:543–551. doi: 10.1097/01.aids.0000210608.70762.c3 PubMedCrossRefGoogle Scholar
  16. Mills EJ, Bakanda C, Birungi J, Chan K, Ford N, Cooper CL, Nachega JB, Dybul M, Hogg RS (2011) Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: a cohort analysis from Uganda. Ann Intern Med 155:209–216. doi: 10.1059/0003-4819-155-4-201108160-00358 PubMedCrossRefGoogle Scholar
  17. Nakagawa F, May M, Phillips A (2013) Life expectancy living with HIV: recent estimates and future implications. Curr Opin Infect Dis 26:17–25. doi: 10.1097/QCO.0b013e32835ba6b1 PubMedCrossRefGoogle Scholar
  18. Peterson L, Taylor D, Roddy R, Belai G, Phillips P, Nanda K, Grant R, Clarke EE, Doh AS, Ridzon R, Jaffe HS, Cates W (2007) Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin Trials 2:e27PubMedCentralPubMedCrossRefGoogle Scholar
  19. Pinkerton SD, Abramson PR (1997) Effectiveness of condoms in preventing HIV transmission. Soc Sci Med 44:1303–1312PubMedCrossRefGoogle Scholar
  20. Polis MA (2012) Preexposure prophylaxis reduced HIV-1 spread in serodiscordant heterosexual couples. Ann Intern Med 157:JC5-3. doi: 10.7326/0003-4819-157-10-201211200-02003 Google Scholar
  21. Rosen RK, Morrow KM, Carballo-Dieguez A, Mantell JE, Hoffman S, Gai F, Maslankowski L, El-Sadr WM, Mayer KH (2008) Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial: a mixed-methods study. J Womens Health (Larchmt) 17:383–392. doi: 10.1089/jwh.2006.0325 CrossRefGoogle Scholar
  22. Stone A (2009) Regulatory issues in microbicide development. World Health Organization.
  23. Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, Henderson FL, Pathak SR, Soud FA, Chillag KL, Mutanhaurwa R, Chirwa LI, Kasonde M, Abebe D, Buliva E, Gvetadze RJ, Johnson S, Sukalac T, Thomas VT, Hart C, Johnson JA, Malotte CK, Hendrix CW, Brooks JT (2012) Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. doi: 10.1056/NEJMoa1110711 PubMedGoogle Scholar
  24. UNAIDS (2010) Global report: UNAIDS report on the global AIDS epidemic 2010.
  25. UNAIDS (2011) AIDS at 30: Nations at the crossroads.
  26. UNAIDS (2012a) AIDS Info.

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.International Partnership for MicrobicidesSilver SpringUSA

Personalised recommendations