Comparative evaluation of Pediatric Drug Regulation in US, Europe and India

  • Upasana Kak M.Pharm DRA
  • Sushama Talegaonkar
  • Varsha Pradhan


Profuse number of drugs are being labeled and tested for children for over a decade. This is mainly due to legislation and regulations passed globally which regulates and evaluates the area of pediatric drug development. (1) The challenges faced by the researchers were the right infrastructure for conducting pediatric trials on a global scale, whether or not the current regulations were working for children and adolescents. Successful propositions have been established to generate crucial information about pediatric drug safety and efficacy by Food and Drug Administration (US FDA) as well as European Medicines Agency (EMA). (2-4) These approaches have resulted in improved accountability and transparency of drug development for Pediatric use. It is high time and also the need of the hour for regulatory guidelines to be laid down by CDSCO, Central Drug Standard and Control Organization (India) so that drug development process and protocol can aim pediatric patient concerns as well. (4-8) This paper aims to review compare the Pediatric Drug Regulations of three different countries i.e. USA, Europe and India.

Keywords: Review, Guidelines/Legislations, ICH E11, Pediatric, Drug/Medicine, FDA, EMA, CDSCO, PIP, PSP, BPCA, PREA, Clinical Trials


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1. Casaere Spadoni. Pediatric Drug Development: Challenges and Opportunities. ELSEVIER. 2018; 90(10.1016):119-122
2. Jochen Zisowksy, Andreas Kraus, Jasper Dingemanse. Drug Development for Paediatric Population: Regulatory Aspectsg Development: Challenges and Opportunities. ELSEVIER. 2010; 2(4):364-388
3. Victor C Baum, Ralph Back, Dominique Heon, Zhimin Yang, Michiyo Sakiyama. Pediatric drug regulation: International perspective. Wiley. 2019; 29(6):572-582
4. Mette Due Theilade Thomsen. Global Pediatric Drug Development. ELSEVIER. 2019; 90:135-14
5. Jacqueline Carleer, Janina Karees. Juvenile animal studies and pediatric drug development: a European regulatory perspective. Wiley. 2011; 92(4):254-260
6. Klaus Rose. The Challenges of Pediatric Drug Development. Elsevier. 2019; 90:128-134
7. Zhaoxia Ren, Anne Zajicek. Review of BPCA and PREA: What can the obstetric community learn from Pediatric experience. Elsevier. 2015; 39(7):530-531
8. Mark A. Turner, Sabah Attar, Saski Widlt, Gilles Vassal, Laura Mangiarini, Carlo Giaquinto. Roles of Clinical Research Network in Pediatric Drug Development. Elsevier. 2017; 39(10):1939-1948
9. Sejal R. Ranmal, Anne Cram, Catherine Tuleu. Age- appropriate and acceptable paediatric dosage forms: Insights into end user perceptions, preferences and practices from Children's Acceptability of Oral Formulations (CALF) Study. Elsevier. 2016; 514(1):296-307
10. Klaus Rose, Jane M Grant-Kels. The Meanings of "Pediatric Drug Development". The Innov Regul Sci.2019; 53(6):767-774
11. Klaus Rose, David Neubauer, Jane M Grant-Kels. Rational Use of Medicine in Children- The Conflict of Interests Story. A Review. Med J. 2019;10(3)
12. ICH Harmonized Guideline. Addendum to ICH E11: Clinical Investigation of Medicinal Products in the Pediatric Population E11 (R1). Geneva, Switzerland [Internet]. ICH; 2021 [cited 2021 Jun 15]. Available from:
13. Robert M Ward, Daniel K Benjamin Jr., Jonathan M Davis, Richard L Gorman, Ralph Kauffman, Gregory L Kearns, Mary Dianne Murphy, Catherine MT Sherwin. The Need for Pediatric Drug Development. J Pediatr. 2018; 192:13-21
14. Daniel K Benjamin. Safety and transparency of pediatric clinical trials. Arch Pediatr Adolesc Med. 2009; 163:1080-1086
15. US Food and Drug Administration, Department of Health and Human Services. Best Pharmaceuticals for Children Act and Pediatric Research Equity Act. July 2016 Status Report to Congress. [Internet]. FDA; 2018 Mar 22 [cited 2021 Jun 13]. Available from:
16. Katusra Tsukamoto, Kelly A Carroll, Taku Onishi, Naoki Matsumaru, Daniel Brasseur, Hidefumi Nakamura. Improvement of Pediatric Drug Development: Regulatory and Practical Frameworks. Clin Ther. 2016; 38(3): 574–581.
17. Paolo A Tomasi, Gunter F Egger, Chrissi Pallidis, Agnes Saint-Raymond. Enabling Development of Paediatric Medicines in Europe: 10 Years of the EU Paediatric Regulation. Pediatr Drugs. 2017; 19(6): 505–513.
18. Dirk Mentzer. Progress review of the European Paediatric Regulatory Framework after six years of implementation. Int J Pharm. 2014; 469(2): 240–243.
19. Steven Hirschfeld, Agnes Saint-Raymond. Pediatric Regulatory Initiatives. Handb Exp Pharmacol. 2011; 205: 245-268
20. EMA. Better medicines for children, Amsterdam, Netherlands [Internet]. EMEA; 2015 [cited 2021 Jun 11]. Available from:
21. European Network of Pediatric Research at the EMA (Enpr-EMA). Amsterdam, Netherlands [Internet]. EnprEMA; 2021 [cited 2021 Jun 12]. Available from:
22. Paediatric medicines Regulators' Network (PmRN). Amsterdam, Netherlands [Internet]. WHO; 2021 [cited 2021 Jun 10]. Available from:
23. Klaus Rose, Philip D Walson. Do Pediatric Investigation Plans (PIPs) Advance Pediatric Healthcare? Pediatr Drugs. 2017; 19(6):515-522.
24. Carlos D Rose. Ethical Conduct of Research in Children: Pediatricians and Their IRB (Part 1 of 2) Pediatrics. 2017;139(5)
25. Haihao Sun, Jean W Temeck, Wiley Chambers, Ginger Perkins, Renan Bonnel, Dianne Murphy. Extrapolation of efficacy in pediatric drug development and evidence-based medicine: progress and lessons learned. Ther Innov Regul Sci. 2017; 2017:1–7
26. EMA. Pediatric Medicine Overview. Amsterdam, Netherlands [Internet]. EMEA; 2020 Dec [cited 2021 Jun 11]. Available from:
27. Rajeshwari Gore, Preeta K Chugh, Chakra D Tripathi, Yangshen Lhmao, Sandhya Gautam. Pediatric Off-Label and Unlicensed Drug Use and Its Implications. Curr Clin Pharmacol. 2017; 12(1):18-25
28. Mette Due Theilade Thomsen. Global Pediatric Drug Development. Curr Ther Res Clin Exp. 2019; 90:135-142
29. Christian Lenk. Off-label drug use in paediatrics: a world-wide problem. Curr Drug Targets. 2012; 13(7):878-84
30. Gallagher RM, Bird KA, Mason JR, Peak M, Williamson PR, Nunn AJ, et al. Adverse drug reactions causing admission to a paediatric hospital: a pilot study. J Clinical Pharm Ther. 2011;36:194-199.
31. Gallagher RM, Mason JR, Bird KA, Kirkham J, Peak M, Williamson PR, et al. Adverse drug reactions causing admission to a paediatric hospital. PLOS ONE. 2012;7:e50127.
32. Thiesen S, Conroy EJ, Bellis JR, Bracken LE, Mannix HL, Bird KA, et al. Incidence, characteristics and risk factors of Adverse Drug Reactions (ADRs) in hospitalised children: a prospective observational cohort study of 6601 admissions. BMC Med. 2013;11:237.
33. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.
34. Avner M, Finkelstein Y, Hackam D, Koren G. Establishing causality in pediatric adverse drug reactions: use of the Naranjo probability scale. Paediatr Drugs 2007;9:267–70.
35. Ferner RE, Aronson JK. Preventability of drug-related harms: part I – a systematic review. Drug Saf 2010; 33:985-94.
36. Hakkarainen KM, Andersson Sundell K, Petzold M, Hagg S. Methods for assessing the preventability of adverse drug events: a systematic. Drug Saf. 2012;35:105-26.
37. Fortnum H, Lee AJ, Rupnik B, Avery A, Collaboration YCS. Survey to assess public awareness of patient reporting of adverse drug reactions in Great Britain. J Clin Pharm Ther. 2011;37:161–165.
38. Lorimer S, Cox A, Langford NJ. A patient’s perspective: the impact of adverse drug reactions on patients and their views on reporting.J Clin Pharm Ther. 2012;37:148-52.
39. Arnott J, Hesselgreaves H, Nunn AJ, Peak M, Pirmohamed M, Smyth RL, et al. Enhancing communication about paediatric medicines: lessons from a qualitative study of parents’ experiences of their child’s suspected adverse drug reaction. PLOS ONE 2012;7:e46022.
40. Bellis JR, Kirkham JJ, Nunn AJ, Pirmohamed M. Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to apaediatric hospital. Br J Clin Pharmacol. 2013;77:545–53.
41. McKenzie MW, Marchall GL, Netzloff ML, Cluff LE. Adverse drug reactions leading to hospitalization in children. J Pediatr. 1976;89:487-90.
42. Mitchell AA , Lacouture PG , Sheehan JE , Kauffman RE, Shapiro S. Adverse drug reactions in children leading to hospital admission. Pediatrics. 1988;82:24-29.
43. Impicciatore P, Choonara I, Clarkson A, Provasi D, Pandolfini C, Bonati M. Incidence of adverse drug reactions in paediatric in/out-patients: a systematic review and meta-analysis of prospective studies. Br J Clin Pharmacol. 2001;52:77–83.
44. Clavenna A, Bonati M. Adverse drug reactions in childhood: a review of prospective studies and safety alerts. Arch Dis Child 2009;94:724-728.
45. Le J, Nguyen T, Law AV, Hodding J. Adverse drug reactions among children over a 10-year period. Pediatrics. 2006;118:555-62. 10.1542/peds.2005-2429.
46. Jonville-Bera AP, Giraudeau B, Blanc P, Beau-Salinas F, Autret-Leca E. Frequency of adverse drug reactions in children: a prospective study. Br J Clin Pharmacol. 2002;53:207-10.
47. Hawcutt DB, Mainie P, Riordan A, Smyth RL, Pirmohamed M. Reported paediatric adverse drug reactions in the UK 2000–2009. Br J Clin Pharmacol 2012;73:437-46.
48. Easton KL, Parsons BJ, Starr M, Brien JE. The incidence of drug-related problems as a cause of hospital admissions in children. Med J Aust. 1998;169:356-9.
49. Martinez-Mir I , Garcia-Lopez M , Palop V , Ferrer JM , Estan L, Rubio E , et al. A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital. Br J Clin Pharmacol. 1996;42:319–24.
50. Yosselson-Superstine S, Weiss T. Drug-related hospitalization in paediatric patients. J Clin Hosp Pharm. 1982;7:195-203.
51. Buajordet I, Wesenberg F, Brors O, Langslet A. Adverse drug events in children during hospitalization and after discharge in a Norwegian university hospital. Acta Paediatr. 2002;91:88–94.
52. Lamabadusuriya SP, Sathiadas G. Adverse drug reactions in children requiring hospital admission. Ceylon Med J. 2003;48:86–7.
53. World Health Organization (WHO). Safety of Medicines. A Guide to Detecting and Reporting Adverse Drug Reactions. Geneva, Switzerland. [Internet]. WHO; 2002 [cited 2021 Jun 12]. Available from:
54. Emilie Bouquet 1, Kristina Star 2, Annie Pierre Jonville-Bera 1, Genevieve Durrieu. Pharmacovigilance in paediatrics. 2018;73(2):171-180.
55. Kshirsagar, Seyberth H, A.N. Promoting safety of medicines for children.
56. World Health Organization (WHO). Safety of Medicines. A Guide to Detecting and Reporting Adverse Drug Reactions. Geneva, Switzerland [Internet]. WHO; 2002 [cited 2021 Jun 16]. Available from:
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How to Cite
Kak, U., S. Talegaonkar, and V. Pradhan. “Comparative Evaluation of Pediatric Drug Regulation in US, Europe and India”. International Journal of Drug Regulatory Affairs, Vol. 9, no. 3, Sept. 2021, pp. 42-46, doi:10.22270/ijdra.v9i3.485.