Need and Recommendations for Universal Guidelines on Regulatory Status and Quality Control/Safety of Probiotic Products

Author(s): Malika Arora*, Manish Arora, Parveen Bansal, Ashish Baldi

Journal Name: Applied Clinical Research, Clinical Trials and Regulatory Affairs (Discontinued)
Continued as Applied Drug Research, Clinical Trials and Regulatory Affairs

Volume 6 , Issue 3 , 2019

Graphical Abstract:


Background: In today’s era, various health boosting products viz. probiotics, functional foods, dietary supplements and nutraceuticals are gaining great commercial interest. Although probiotics have traditional history of their use, their regulatory approval regimes across the globe are complicated and incoherent.

Objective: The present article has been compiled to give an overview of the existing approval guidelines for the probiotic products across the globe along with their associated ambiguities. Furthermore, suggestive consolidations for harmonized approval process to be implemented in future are proposed on the basis of their intended use.

Methods: The study was carried out by using secondary sources through literature survey from journals, market reports, proceedings, books and web pages of relevant regulatory authorities and a critical comparative study was conducted with respect to approval process of probiotics.

Results: As per the comparative account of the current regulatory guidelines, it has been evidenced that different countries have adopted diverse approval process for probiotics and; lack of uniformity is of great concern. But due to rapid emergence of probiotics as drugs, a harmonized approval process similar to other drugs covering all aspects of Investigational New Drug Application (INDA) and New Drug Application (NDA) has been proposed in which organisms falling under Generally Recognized As Safe (GRAS) category are exempted from INDA submission whereas non GRAS, GRAE or new organisms are not exempted. After submission of NDA and getting approval from Food and Drug Administration (FDA), product should be manufactured and marketed.

Conclusion: Regulatory bodies across the globe must ensure that probiotics based products should be regulated by lawful approval process in such a manner which will lead to maximal health benefits and minimal health risk for consumers.

Keywords: Probiotics, IND, INDA, GRAS, approval guidelines, regulatory bodies, consumers.

Sreeja V, Prajapati B. Probiotic formulations: Application and status as Pharmaceuticals- A review. Probiotics Anti Microb Prot 2013; 5(2): 81-91.
Mollet B, Rowland I. Functional foods: At the frontier between food and pharma. Curr Opin Biotechnol 2002; 13(5): 483-5.
Parvez S, Malik K, Kang A, et al. Probiotics and their fermented food products are beneficial for health. J Appl Microbiol 2006; 100(6): 1171-85.
Arora M, Baldi A. Regulatory categories of probiotics across the globe: A review representing existing and recommended categorization. Indian J Med Microbiol 2015; 33(5): 2-10.
Arora M, Baldi A. Selective identification and characterization of potential probiotic strains: A review on comprehensive polyphasic approach. Appl Clin Res Clin Trials and Regul Aff 2017; 4(1): 60-76.
Kumar M, Kumar R, Poovai PD, et al. Probiotics and multitude of health benefits. J Res Bio 2012; 2: 102-13.
Arora M, Sharma S, Baldi A. Comparative insight of regulatory guidelines for in USA, India and Malaysia: A critical review. Int J Biotechnol Wellness Ind 2013; 2(2): 51-64.
Snydman DR. The safety of probiotics. Clin Infect Dis 2008; 46(2): S104-11.
Ishibashi N, Yamazaki S. Probiotics and safety. Am J Clin Nutr 2001; 73(2): 465S-70S.
Salminen S, Wright A, Morelli L, et al. Demonstration of safety of probiotics- A review. Int J Food Microbiol 1998; 44: 93-106.
Sharma S, Arora M, Baldi A. Probiotics in India: Current status and future prospects. Pharm Aspire 2013; 1: 1-12.
Report of a joint FAO/WHO expert consultation on guidelines for the evaluation of probiotics in food. 2002. Accessed on 12/09/2015. Available from:].
Venugopalan V, Shriner KA, Wong-Beringer A. Regulatory oversight and safety of probiotic use. Emerg Infect Dis 2010; 16(11): 1661-5.
Amagase H. Current Market place for Probiotics: A Japanese perspective. Clin Infect Dis 2005; 46(2): S73-5.
Saxelin M. Probiotic formulations and applications, the current probiotics market, and changes in the marketplace: A European perspective. Clin Infect Dis 2008; 46(2): S76-9.
Yang Y. Scientific substantiation of functional food health claims in China. J Nutr 2008; 138(6): 1199S-205.
Guidelines for evaluation of probiotics in food. report of a joint ICMR/DBT. 2011. pdf Accessed on 20/08/2015. Available from:
Guidelines and criteria for evaluation of efficacy, safety and health claim of probiotic in food products in India. ILSI, India. Accessed on 20/08/2015 .Available from:
World Gastroenterology Organisation. Global Guidelines. Probiotics and Prebiotics. 2011. Accessed on 11/10/2015. Available from: http://www.worldgastroenterology. org/assets/export/userfiles/Probiotics_ FINAL_20110116.pdf
Republic of Philippines. Guidelines on Probiotics 2004. Accessed on 11/9/2015. Available from:
Ministero Della Slaute. Guidelines on Probiotics 2013. Accessed on 12/09/2015. Available from:
Bailey R. Functional Foods in Japan: FOSHU (Foods for Specified Health Uses) and foods with nutrient function claims. IFT Press: Oxford, United Kingdom 2008; pp. 247.
Kumar D, Arora M, Baldi A. Understanding industrial practices for pharmaceutical quality management-i, existing approaches and guidelines. Adv Res Pharm Biol 2015; 5(1): 802-11.
Burdock GA, Carabin IG, Griffiths JC. The Importance of GRAS to the functional food and nutraceutical industries. Toxicology 2006; 221: 17-27.
Kwak NS, Jukes DJ. Functional foods. Part 1: The development of a regulatory concept. Food Control 2001; 12(2): 99-107.
Patel D, Dufour Y, Domigan N. Functional food and nutraceutical registration processes in Japan and China: Similarities and diffrences. J Pharm Pharm Sci 2008; 11(4): 1-11.
Menrad K. Market and marketing of functional food in Europe. J Food Process Eng 2003; 56: 181-8.
Roberfroid MB. Global view on functional foods: European perspectives. Br J Nutr 2002; 88(2): S133-8.
Arora M, Baldi A. Good manufacturing practice regulations for probiotic based pharmaceuticals: Current scenario and suggestive recommendations. Appl Clin Res Clin Trials Regul Aff 2015; 2(3): 165-75.
Fukushima Y, Hurt E. Probiotics health claims in Japan and Europe. Caister Academic Press: Norfolk, UK 2011; pp. 253-81.
Shimizu T. Health claims on functional foods: The Japanese regulations and an international comparison. Nutr Res Rev 2003; 16(2): 241-52.
Roberfroid MB. Concepts and strategy of functional food science: The European perspective. Am J Clin Nutr 2000; 71(6): S1660-4.
Roberfroid MB. A European consensus of scientific concepts of functional foods. Nutrition 2000; 7(16): 689-91.
Wright AV. Regulating the safety of probiotics-The European approach. Curr Pharm Des 2005; 11(1): 17-23.
Kwak NS, Jukes DJ. Functional foods. Part 2: The impact on current regulatory terminology. Food Control 2001; 12(2): 109-17.
Anadón A, Martínez-Larrañaga MR, Martínez MA. Probiotics for animal nutrition in the European Union. Regulation and safety assessment. Regul Toxicol Pharmacol 2006; 45(1): 91-5.
Coppens P, Fernandes M, Pettman S. European regulations on nutraceuticals, dietary supplements and functional foods: A framework based on safety. Toxicology 2006; 221(1): 59-74.
Siro I, Kapolna E, Kapolna B, Lugasi A. Functional food: Product development, marketing and consumer acceptance - A review. Appetite 2008; 51(3): 456-67.
Sybesma W, Hugenholtz J, DeVos WM, Smid EJ. Safe use of genetically modified lactic acid bacteria in food: Bridging the gap between consumers, green groups, and industry. Electron J Biotechnol 2006; 9(4)
Degnan FH. The US food and drug administration and probiotics: Regulatory categorization. Clin Infect Dis 2008; 46(2): S133-6.
Mattia A, Merker R. Regulation of probiotic substances as ingredients in foods: Premarket approval or “generally recognized as safe” notification. Clin Infect Dis 2008; 46(2): S115-8.
U.S. FDA. Guidance for industry, early clinical trials with live bio therapeutic products: Chemistry, manufacturing, and control information 2010 pdf. Accessed on 12/09/2015. Available from:

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Article Details

Year: 2019
Published on: 13 November, 2019
Page: [231 - 249]
Pages: 19
DOI: 10.2174/2213476X06666190206120712

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