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Annual Review of Pharmacology and Toxicology

Volume 61, 2021

Use of Model-Informed Drug Development to Streamline Development of Long-Acting Products: Can These Successes Be Translated to Long-Acting Hormonal Contraceptives?

Abstract

Long-acting contraceptives are the most effective reversible contraceptive methods. Increasing patients’ access to these contraceptives may translate into fewer unintended pregnancies and lead to substantial individual and public health benefits. However, development of long-acting products can be complex and challenging. This review provides () an overview of representative development programs for long-acting antipsychotics as cases for conceptual translation to long-acting contraceptives, () several case examples on how modeling and simulation have been used to streamline the development of long-acting products, and () examples of challenges andopportunities in developing long-acting contraceptives and information on how exposure-response relationships of commonly used progestins may enable regulators and developers to rely on prior findings of effectiveness and safety from an approved contraceptive to streamline the development of long-acting contraceptives. The US Food and Drug Administration is seeking assistance from stakeholders to provide data from studies in which pharmacokinetic and pharmacodynamic or clinical outcomes of hormonal contraceptives were evaluated and not previously submitted.

Keyword(s): drug development, exposure-response, long-acting contraceptive, long-acting injectable antipsychotics, modeling and simulation
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/content/journals/10.1146/annurev-pharmtox-031120-015212
2021-01-06
2025-04-26
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Literature Cited

  1. 1. 
    Heckman BW, Mathew AR, Carpenter MJ 2015. Treatment burden and treatment fatigue as barriers to health. Curr. Opin. Psychol. 5:31–36
     [Google Scholar]
  2. 2. 
    Fleischhacker WW, Meise U, Gunther V, Kurz M 1994. Compliance with antipsychotic drug treatment: influence of side effects. Acta Psychiatr. Scand. 89:11–15
     [Google Scholar]
  3. 3. 
    Ereshefsky L, Mascarenas CA. 2003. Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics. J. Clin. Psychiatry 64:Suppl. 1618–23
     [Google Scholar]
  4. 4. 
    Sampson MR, Troy SB, Belew Y, Arya V, Struble KA 2020. Considerations and challenges in developing novel long-acting antiretrovirals modalities for treatment and prevention of HIV-1 infection: a regulatory perspective. Curr. Opin. HIV AIDS 15:61–65
     [Google Scholar]
  5. 5. 
    Kennedy WK. 2012. When and how to use long-acting injectable antipsychotics. Curr. Psychiatry 11:840–43
     [Google Scholar]
  6. 6. 
    US Food Drug Admin. 2018. PERSERIS, NDA 210655 clinical pharmacology review Rep., US Food Drug Admin. Silver Spring, MD: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210655Orig1s000ClinPharmR.pdf
    [Google Scholar]
  7. 7. 
    US Food Drug Admin. 2015. ARISTADA, NDA 207533 clinical pharmacology review Rep., US Food Drug Admin Silver Spring, MD: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207533Orig1s000ClinPharmR.pdf
    [Google Scholar]
  8. 8. 
    US Food Drug Admin. 2012. ABILIFY MAINTENA, NDA 202971 clinical pharmacology review Rep., US Food Drug Admin Silver Spring, MD: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/202971Orig1s000ClinPharmR.pdf
    [Google Scholar]
  9. 9. 
    Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S 2011. Oral versus depot antipsychotic drugs for schizophrenia—a critical systematic review and meta-analysis of randomised long-term trials. Schizophr. Res. 127:83–92
     [Google Scholar]
  10. 10. 
    Subotnik KL, Casaus LR, Ventura J, Luo JS, Hellemann GS et al. 2015. Long-acting injectable risperidone for relapse prevention and control of breakthrough symptoms after a recent first episode of schizophrenia: a randomized clinical trial. JAMA Psychiatry 72:822–29
     [Google Scholar]
  11. 11. 
    Daniels K, Abma JC. 2018. Current contraceptive status among women aged 15–49: United States, 2015–2017 NCHS Data Brief 327, Natl. Cent. Health Stat Hyattsville, MD:
     [Google Scholar]
  12. 12. 
    U.N. Dep. Econ. Soc. Aff. 2019. Contraceptive use by method 2019 Data Bookl., U.N: https://www.un.org/en/development/desa/population/publications/pdf/family/ContraceptiveUseByMethodDataBooklet2019.pdf
    [Google Scholar]
  13. 13. 
    Junod SW, Marks L. 2002. Women's trials: the approval of the first oral contraceptive pill in the United States and Great Britain. J. Hist. Med. Allied Sci. 57:117–60
     [Google Scholar]
  14. 14. 
    Liao PV, Dollin J. 2012. Half a century of the oral contraceptive pill: historical review and view to the future. Can. Fam. Physician 58:e757–60
     [Google Scholar]
  15. 15. 
    Bitzer J, Simon JA. 2011. Current issues and available options in combined hormonal contraception. Contraception 84:342–56
     [Google Scholar]
  16. 16. 
    Molloy GJ, Graham H, McGuinness H 2012. Adherence to the oral contraceptive pill: a cross-sectional survey of modifiable behavioural determinants. BMC Public Health 12:838
     [Google Scholar]
  17. 17. 
    Trussell J. 2011. Contraceptive failure in the United States. Contraception 83:397–404
     [Google Scholar]
  18. 18. 
    Winner B, Peipert JF, Zhao Q, Buckel C, Madden T et al. 2012. Effectiveness of long-acting reversible contraception. N. Engl. J. Med. 366:1998–2007
     [Google Scholar]
  19. 19. 
    Comm. Gynecol. Pract. Long-Act. Revers. Contracept. Work. Group. 2015. Committee opinion no. 642: increasing access to contraceptive implants and intrauterine devices to reduce unintended pregnancy. Obstet. Gynecol 126:4e44–48
     [Google Scholar]
  20. 20. 
    US Food Drug Admin. 1999. Guidance for industry: applications covered by section 505(b)(2) Draft Guid., US Food Drug Admin Silver Spring, MD: https://www.fda.gov/media/72419/download
    [Google Scholar]
  21. 21. 
    Agarwal S, Qiu W, Sahajwalla C 2014. Overview of recently approved 505(b)(2) new drug applications (2010–2012): role of clinical pharmacology. J. Clin. Pharmacol. 54:1330–36
     [Google Scholar]
  22. 22. 
    Rajoli RKR, Podany AT, Moss DM, Swindells S, Flexner C et al. 2018. Modelling the long-acting administration of anti-tuberculosis agents using PBPK: a proof of concept study. Int. J. Tuberc. Lung Dis. 22:937–44
     [Google Scholar]
  23. 23. 
    Rajoli RK, Back DJ, Rannard S, Freel Meyers CL, Flexner C et al. 2015. Physiologically based pharmacokinetic modelling to inform development of intramuscular long-acting nanoformulations for HIV. Clin. Pharmacokinet. 54:639–50
     [Google Scholar]
  24. 24. 
    Pani L, Pira L, Marchese G 2007. Antipsychotic efficacy: relationship to optimal D2-receptor occupancy. Eur. Psychiatry 22:267–75
     [Google Scholar]
  25. 25. 
    Laffont CM, Gomeni R, Zheng B, Heidbreder C, Fudala PJ, Nasser AF 2015. Population pharmacokinetic modeling and simulation to guide dose selection for RBP-7000, a new sustained-release formulation of risperidone. J. Clin. Pharmacol. 55:93–103
     [Google Scholar]
  26. 26. 
    INVEGA SUSTENNA® (paliperidone palmitate) [package insert] Titusville, NJ: Janssen Pharm.; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022264s029lbl.pdf
  27. 27. 
    US Food Drug Admin. 2009. INVEGA SUSTENNA, NDA 22264 clinical pharmacology review Rep., US Food Drug Admin Silver Spring, MD: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022264s000clinpharmr.pdf
    [Google Scholar]
  28. 28. 
    US Food Drug Admin. 2019. Guidance for industry: establishing effectiveness and safety for hormonal drug products intended to prevent pregnancy Draft Guid., US Food Drug Admin Silver Spring, MD: https://www.fda.gov/media/128792/download
    [Google Scholar]
  29. 29. 
    Baird DT, Glasier AF. 1993. Hormonal contraception. N. Engl. J. Med. 328:1543–49
     [Google Scholar]
  30. 30. 
    Garza-Flores J, Fatinikun T, Hernandez L, Ramos I, Cardenas M, Menjivar M 1991. A pilot study on the assessment of a progesterone/estradiol sustained release as once-a-month-injectable contraceptive. Contraception 44:45–59
     [Google Scholar]
  31. 31. 
    van der Does J, Exalto N, Dieben T, Bennink HC 1995. Ovarian activity suppression by two different low-dose triphasic oral contraceptives. Contraception 52:357–61
     [Google Scholar]
  32. 32. 
    Waellnitz K, Duijkers I, Klipping C, Rautenberg T, Rohde B, Zurth C 2016. A two-centre, open-label, randomised study of ovulation inhibition with three transdermal contraceptive patches, each containing different amounts of ethinyl estradiol and gestodene in healthy, young women. J. Obstet. Gynaecol. 36:106–13
     [Google Scholar]
  33. 33. 
    Hoogland HJ, Skouby SO. 1993. Ultrasound evaluation of ovarian activity under oral contraceptives. Contraception 47:583–90
     [Google Scholar]
  34. 34. 
    Rible RD, Taylor D, Wilson ML, Stanczyk FZ, Mishell DR Jr 2009. Follicular development in a 7-day versus 4-day hormone-free interval with an oral contraceptive containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate. Contraception 79:182–88
     [Google Scholar]
  35. 35. 
    McCann MF, Potter LS. 1994. Progestin-only oral contraception: a comprehensive review. Contraception 50:S1–195
     [Google Scholar]
  36. 36. 
    Mansour D, Korver T, Marintcheva-Petrova M, Fraser IS 2008. The effects of Implanon® on menstrual bleeding patterns. Eur. J. Contracept. Reprod. Health Care 13:Suppl. 113–28
     [Google Scholar]
  37. 37. 
    Schrager S. 2002. Abnormal uterine bleeding associated with hormonal contraception. Am. Fam. Physician 65:2073–80
     [Google Scholar]
  38. 38. 
    Gordon CM, Zemel BS, Wren TA, Leonard MB, Bachrach LK et al. 2017. The determinants of peak bone mass. J. Pediatr. 180:261–69
     [Google Scholar]
  39. 39. 
    Exton-Smith AN, Millard PH, Payne PR, Wheeler EF 1969. Pattern of development and loss of bone with age. Lancet 2:1154–57
     [Google Scholar]
  40. 40. 
    Löfman O, Larsson L, Toss G 2000. Bone mineral density in diagnosis of osteoporosis: reference population, definition of peak bone mass, and measured site determine prevalence. J. Clin. Densitom. 3:177–86
     [Google Scholar]
  41. 41. 
    Berenson AB, Rahman M, Breitkopf CR, Bi LX 2008. Effects of depot medroxyprogesterone acetate and 20-microgram oral contraceptives on bone mineral density. Obstet. Gynecol. 112:788–99
     [Google Scholar]
  42. 42. 
    DEPO-PROVERA CI (medroxyprogesterone acetate) injectable suspension [package insert] New York, NY: Pfizer 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020246s058lbl.pdf
/content/journals/10.1146/annurev-pharmtox-031120-015212
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Use of Model-Informed Drug Development to Streamline Development of Long-Acting Products: Can These Successes Be Translated to Long-Acting Hormonal Contraceptives?
Annual Review of Pharmacology and Toxicology 61, 745 (2021); https://doi.org/10.1146/annurev-pharmtox-031120-015212
/content/journals/10.1146/annurev-pharmtox-031120-015212
/content/journals/10.1146/annurev-pharmtox-031120-015212
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  • Article Type: Review Article

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