Scientific considerations for global drug development

Jennifer L Wilson¹, Kit Wun Kathy Cheung¹, Lawrence Lin¹, Elizabeth A E Green¹, Analia I Porrás², Ling Zou¹, David Mukanga³, Paul A Akpa⁴, Delese Mimi Darko⁵, Rae Yuan⁶, Sheng Ding^{7

8}, Wiltshire C N Johnson⁹, Howard A Lee^{10

11}, Emer Cooke¹², Carl C Peck^{1

13}, Steven E Kern³, Dan Hartman³, Yoshikazu Hayashi¹⁴, Peter W Marks¹⁵, Russ B Altman¹⁶, Murray M Lumpkin³, Kathleen M Giacomini¹⁷, Terrence F Blaschke¹⁸

Affiliations

¹ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
² Medicines and Health Technologies Unit, Department of Health Systems and Services, Pan American Health Organization, Regional Office of the World Health Organization, Washington, DC, USA.
³ Global Health, Bill and Melinda Gates Foundation, Seattle, WA, USA.
⁴ Department of Pharmaceutics, University of Nigeria, Nsukka, Enugu State, Nigeria.
⁵ Food and Drugs Authority, Accra, Ghana.
⁶ Sinovant Sciences Co., Shanghai, China.
⁷ School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
⁸ Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
⁹ Pharmacy Board of Sierra Leone, Freetown, Sierra Leone.
¹⁰ Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
¹¹ Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea.
¹² World Health Organization, Geneva, Switzerland.
¹³ NDA Partners LLC, San Luis Obispo, CA, USA.
¹⁴ Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.
¹⁵ Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
¹⁶ Departments of Bioengineering and Genetics, Stanford University, Stanford, CA, USA.
¹⁷ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA. kathy.giacomini@ucsf.edu.
¹⁸ Departments of Medicine and Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA, USA.

PMID: 32727913
PMCID: PMC8158457
DOI: 10.1126/scitranslmed.aax2550

Review

Scientific considerations for global drug development

Jennifer L Wilson et al. Sci Transl Med. 2020.

. 2020 Jul 29;12(554):eaax2550.

doi: 10.1126/scitranslmed.aax2550.

Authors

Affiliations

¹ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
² Medicines and Health Technologies Unit, Department of Health Systems and Services, Pan American Health Organization, Regional Office of the World Health Organization, Washington, DC, USA.
³ Global Health, Bill and Melinda Gates Foundation, Seattle, WA, USA.
⁴ Department of Pharmaceutics, University of Nigeria, Nsukka, Enugu State, Nigeria.
⁵ Food and Drugs Authority, Accra, Ghana.
⁶ Sinovant Sciences Co., Shanghai, China.
⁷ School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
⁸ Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
⁹ Pharmacy Board of Sierra Leone, Freetown, Sierra Leone.
¹⁰ Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
¹¹ Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea.
¹² World Health Organization, Geneva, Switzerland.
¹³ NDA Partners LLC, San Luis Obispo, CA, USA.
¹⁴ Pharmaceuticals and Medical Devices Agency, Tokyo, Japan.
¹⁵ Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
¹⁶ Departments of Bioengineering and Genetics, Stanford University, Stanford, CA, USA.
¹⁷ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA. kathy.giacomini@ucsf.edu.
¹⁸ Departments of Medicine and Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA, USA.

PMID: 32727913
PMCID: PMC8158457
DOI: 10.1126/scitranslmed.aax2550

Abstract

Requiring regional or in-country confirmatory clinical trials before approval of drugs already approved elsewhere delays access to medicines in low- and middle-income countries and raises drug costs. Here, we discuss the scientific and technological advances that may reduce the need for in-country or in-region clinical trials for drugs approved in other countries and limitations of these advances that could necessitate in-region clinical studies.

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Conflict of interest statement

Competing Interests: JLW, KWKC, EAEG, LL, LZ, DM, PAA, RY, HL, EC, DH, PWM, and MML have no competing interests to declare. AIP is the Unit Chief, Medicines and Health Technologies at PAHO, a BMGF grantee. SD is also the Institute Director of the Global Health Drug Discovery Institute, Beijing, China. CP teaches drug development and regulatory science, and consults for NDA Partners LLC. YH is Senior Executive Director of PMDA. RBA is a stockholder in Personalis, 23andme, and Youscript. TFB is an advisor to the UCSF-Stanford CERSI, a contractor to the Bill and Melinda Gates Foundation and a member of the Board of Directors of Durect Corporation. KMG has been a paid consultant for Gilead and Vertex Pharmaceuticals.

Figures

**Figure 1.. Allele frequencies of selected polymorphisms that affect drug ADME.**
These differences include BCRP-Q141K (rs2231142) (red), which affects rousuvastatin exposure (29). Particular HLA alleles, such as HLA-B*5701 (green) are associated with drug toxicities including Toxic Epidermal Necrolysis. CYP2C19 is a polymorphic enzyme with two common reduced function alleles, CYP2C19*2 (purple) and CYP2C19*3 (blue). This polymorphic variant is a major genetic factor for variation in response to clopidogrel, and poor CYP2C19 metabolizers are at risk for higher cardiovascular event rates.

**Figure 2.**
Percent of registered clinical trials in 2005 (upper) and 2012 (lower), classified by OECD countries (28).

See this image and copyright information in PMC

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Scientific considerations for global drug development

Affiliations

Scientific considerations for global drug development

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources