Volume 13, Issue 2 (6-2025)                   JoMMID 2025, 13(2): 78-87 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Sajjadi S, Shafizadeh F, Hallaj-Nezhadi S. A Review and Comparative Study of Preservative Efficacy Test in the United States, European, Indian, and Japanese Pharmacopeias and Implications for Asian Pharmacopeias. JoMMID 2025; 13 (2) :78-87
URL: http://jommid.pasteur.ac.ir/article-1-695-en.html
A Review and Comparative Study of Preservative Efficacy Test in the United States, European, Indian, and Japanese Pharmacopeias and Implications for Asian Pharmacopeias
Sara Sajjadi , Fatemeh Shafizadeh , Somayeh Hallaj-Nezhadi *
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract:   (122 Views)
Introduction: The preservative efficacy test (PET) is a critical tool for assessing the ability of antimicrobial preservatives to prevent microbial contamination in pharmaceutical products, ensuring their safety and stability during production and storage. This study reviews and compares PET standards across four major pharmacopeias—the United States Pharmacopeia (USP), European Pharmacopoeia (EP), Indian Pharmacopoeia (IP), and Japanese Pharmacopoeia (JP)—to identify disparities and propose harmonization strategies, with a focus on implications for Asian pharmacopeias. Methods: We systematically compared the PET protocols of the USP, EP, IP, and JP, focusing on product classification, challenge microorganisms, culture media, sample contamination methods, incubation conditions, and acceptance criteria. Data were extracted from the latest editions of each pharmacopeia and analyzed for differences in stringency and methodology. Results: Significant variations were identified across the pharmacopeias. For example, the USP requires an inoculum of 105 colony-forming units per milliliter (CFU/mL) for certain organisms, while the EP specifies 104 CFU/mL. Challenge organisms also differ, with the USP mandating Pseudomonas aeruginosa and Staphylococcus aureus, and the EP including a broader range, such as Aspergillus brasiliensis. Acceptance criteria vary, with the USP requiring a 3-log reduction in Escherichia coli within 14 days, compared to the EP's 2-log reduction over the same period. Incubation periods range from 14 days (USP and IP) to 28 days (JP), potentially affecting drug quality assessments. Conclusions: These disparities in PET standards may lead to inconsistencies in drug quality and safety across regions, particularly in Asia, where harmonization with global standards is limited. We recommend the development of a unified international framework for PET, incorporating the USP's stringent log-reduction criteria and the EP's comprehensive microbial selection, to enhance global drug safety. For Asian pharmacopeias, adopting such harmonized standards could facilitate regulatory alignment, improve product quality, and support international trade.

 
Keywords: Pharmaceutical Preservative, Pharmacopeia, Preservative efficacy test, USP, Microbial Challenge Testing, Antimicrobial Efficacy, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans
Full-Text [PDF 1012 kb]   (23 Downloads)    
Type of Study: Review article | Subject: Other
Received: 2024/11/25 | Accepted: 2025/06/11 | Published: 2025/06/11
References
1. Shitole S, Shinde S, Waghmare S, Kamble H. A review on: Preservatives used in pharmaceuticals and impacts on health. Int Res J. 2022; 5 (7): 131-40.
2. Asnaashari S, Heshmati-Afshar F, Amin-Aghdam N, Asgharian P, Hallaj-Nezhadi S. Evaluation of antimicrobial activities of different extracts from Phlomis tuberosa, Abutilon fruticosum, and Nepeta transcaucasica. Acta Microbiol Bulg. 2023: 182-8. [DOI:10.59393/amb23390211]
3. Meyer BK, Ni A, Hu B, Shi L. Antimicrobial preservative use in parenteral products: past and present. J Pharm Sci. 2007; 96 (12): 3155-67. [DOI:10.1002/jps.20976] [PMID]
4. Morris C, Leech R. Natural and physical preservative systems. In: Baird R, Bloomfield S, editors. Microbial quality assurance in Pharmaceuticals, Cosmetics, and Toiletries. Toronto, Ontario: CRC Press; 2017. p. 69-86.
5. Bhuvaneswari P, Steffi P, Thirumalaiyammal B, Mishel P. Potential uses of natural antimicrobial agents and their applications as bio-preservatives. In: Arti G, Ram P, editors. Antimicrobials in Food Science and Technology; 2024. p. 154-68. [DOI:10.1201/9781003268949-9]
6. Rashidbaigi A, Sprenkels R. Unified method for determination of preservative effectiveness in multi-dose parenteral products for global application. Int J Pharm Qual Assur. 2018; 4 (1): 1-9.
7. Sultana T, Rana J, Chakraborty SR, Das KK, Rahman T, Noor R. Microbiological analysis of common preservatives used in food items and demonstration of their in vitro anti-bacterial activity. Asian Pac J Trop. 2014; 4 (6): 452-6. [DOI:10.1016/S2222-1808(14)60605-8]
8. Kumar M, Chopra S, Mandal UK, Bhatia A. Preservatives in pharmaceuticals: Are they really safe? Curr Drug Saf. 2023; 18 (4): 440-7. [DOI:10.2174/1574886317666220919121532] [PMID]
9. Bradley CS, Sicks LA, Pucker AD. Common ophthalmic preservatives in soft contact lens care products: benefits, complications, and a comparison to non-preserved solutions. Clin Optom. 2021; 13: 271-85. [DOI:10.2147/OPTO.S235679] [PMID] [PMCID]
10. Pinto D, Ciardiello T, Franzoni M, Pasini F, Giuliani G, Rinaldi F. Effect of commonly used cosmetic preservatives on skin resident microflora dynamics. Sci Rep. 2021; 11 (1): 8695. [DOI:10.1038/s41598-021-88072-3] [PMID] [PMCID]
11. Anger CB, Rupp D, Lo P, Takruri H. Preservation of Dispersed Systems. In: Lieberman H, Rieger M, Banker GS, editors. Pharmaceutical Dosage Forms: CRC Press; 2020. p. 377-436. [DOI:10.1201/9781003067368-9]
12. Stroppel L, Schultz-Fademrecht T, Cebulla M, Blech M, Marhöfer RJ, Selzer PM, et al. Antimicrobial preservatives for protein and peptide formulations: An overview. Pharmaceutics. 2023; 15 (2): 563. [DOI:10.3390/pharmaceutics15020563] [PMID] [PMCID]
13. Ammen EW, Al-Salihi S, Al-Salhi R. Gas chromatography-mass spectrometry combined with successive dilution for the determination of preservatives in pharmaceuticals. J Anal Chem. 2021; 76 (5): 621-9. [DOI:10.1134/S1061934821050051]
14. Alshehrei FM. Microbiological quality assessment of skin and body care cosmetics by using challenge test. Saudi J Biol Sci. 2024; 31 (4): 103965. [DOI:10.1016/j.sjbs.2024.103965] [PMID] [PMCID]
15. Xu Q, Chow PS, Xi E, Marsh R, Gupta S, Gupta KM. Evaluation of polymer-preservative interactions for preservation efficacy: molecular dynamics simulation and QSAR approaches. Nanoscale. 2024; 16 (36): 17049-63. [DOI:10.1039/D4NR02162B] [PMID]
16. Hodges N, Hanlon G. Antimicrobial preservative efficacy testing. In: Baird RM, Hodges NA, Denyer SP, editors. Handbook of microbiological quality control: Taylor & Francis; 2000. p. 188-211. [DOI:10.1201/9780203305195.ch10]
17. 〈51〉 Antimicrobial Effectiveness Testing. United States Pharmacopeia. 56th ed: United States Pharmacopeial Convention; 2024. p. 1-5.
18. Efficacy of antimicrobial preservation. European Pharmacopoeia. 10th ed: European Directorate for the Quality of Medicines & HealthCare (EDQM), Council of Europe; 2023. p. 655-8
19. Preservative effectiveness tests Japanese Pharmacopoeia. 16th ed: Ministry of Health, Labour and Welfare (MHLW), Japan; 2022. p. 2215-6.
20. Effectiveness of Antimicrobial Preservatives. Indian Pharmacopoeia: Indian Pharmacopoeia Commission (IPC), Ghaziabad; 2022. p. 195-7.
21. Sutton SV, Porter D. Development of the antimicrobial effectiveness test as USP chapter< 51>. PDA J Pharm Sci Technol. 2002; 56 (6): 300-11.
22. Omogbai B, Omoregie I. Chemical analysis and biological activity of natural preservative from beet root (Beta vulgaris) against foodborne pathogens and spoilage organisms. Afr Sci. 2016; 17 (2): 135-45.
23. Atemnkeng MA, De Cock K, Plaizier-Vercammen J. Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use. Malar J. 2007; 6: 1-8. [DOI:10.1186/1475-2875-6-12] [PMID] [PMCID]
24. Guilfoyle DE, Roos R, Carito SL. An evaluation of preservative adsorption onto nylon membrane filters. PDA J Pharm Sci Technol. 1990; 44 (6): 314-9.
25. Russell A. Challenge testing: principles and practice. Int J Cosmet Sci. 2003; 25 (3): 147-53. [DOI:10.1046/j.1467-2494.2003.00179.x] [PMID]
26. Miao C, Ma X, Fan J, Shi L, Wei J. Methylparaben as a preservative in the development of a multi-dose HPV-2 vaccine. Hum Vaccines Immunother. 2022; 18 (5): 2067421. [DOI:10.1080/21645515.2022.2067421] [PMID] [PMCID]
27. Canavez ADPM, de Oliveira Prado Corrêa G, Isaac VLB, Schuck DC, Lorencini M. Integrated approaches to testing and assessment as a tool for the hazard assessment and risk characterization of cosmetic preservatives. J Appl Toxicol. 2021; 41 (10): 1687-99. [DOI:10.1002/jat.4156] [PMID]
28. Hodges N. Assessment of preservative activity during stability studies. In: Mazzo DJ, editor. International Stability Testing: CRC Press; 2020. p. 161-92. [DOI:10.1201/9781003076087-11]
29. Acharya T, Hare J. Sabouraud agar and other fungal growth media. Laboratory protocols in fungal biology: current methods in fungal biology: Springer; 2022. p. 69-86. [DOI:10.1007/978-3-030-83749-5_2] [PMCID]
30. Usukura J. Comparison of different temperature conditions for microbial enumeration of Aspergillus brasiliensis in the preservative efficacy test. Biocontrol Sci. 2021; 26 (2): 95-8. [DOI:10.4265/bio.26.95] [PMID]
31. Karakuş S, Insel MA, Kahyaoğlu İM, Albayrak İ, Ustun-Alkan F. Characterization, optimization, and evaluation of preservative efficacy of carboxymethyl cellulose/hydromagnesite stromatolite bio-nanocomposite. Cellulose. 2022;29(7):3871-87. [DOI:10.1007/s10570-022-04522-9] [PMID] [PMCID]
32. Streufert RK, Keller SE, Salazar JK. Relationship of growth conditions to desiccation tolerance of Salmonella enterica, Escherichia coli, and Listeria monocytogenes. J Food Prot. 2021; 84 (8): 1380-4. [DOI:10.4315/JFP-21-077] [PMID]
33. Park D, Lee HJ, Sethukali AK, Yim D-G, Park S, Jo C. Effects of temperature on the microbial growth and quality of unsealed dry pet food during storage. Food Science of Animal Resources. 2025; 45 (2): 504. [DOI:10.5851/kosfa.2024.e51] [PMID] [PMCID]
34. Hodges N, Denyer SP, Hanlon G, Reynolds J. Preservative efficacy tests in formulated nasal products: reproducibility and factors affecting preservative activity. J Pharm Pharmacol. 1996; 48 (12): 1237-42. [DOI:10.1111/j.2042-7158.1996.tb03929.x] [PMID]
35. Baird RM. Preservative efficacy testing in the pharmaceutical industries. In: Brown MRW, Gilbert P, editors. Microbiological Quality Assurance: CRC Press; 2018. p. 149-62. [DOI:10.1201/9781351074551-11] [PMCID]
36. Livingstone D, Hanlon G, Dyke S. Evaluation of an extended period of use for preserved eye drops in hospital practice. Br J Ophthalmol. 1998; 82 (5): 473-5. [DOI:10.1136/bjo.82.5.473] [PMID] [PMCID]
37. Al‐Hiti M, Gilbert P. Changes in preservative sensitivity for the USP antimicrobial agents effectiveness test micro‐organisms. J Appl Bacteriol. 1980; 49 (1): 119-26. [DOI:10.1111/j.1365-2672.1980.tb01049.x] [PMID]
38. Moser CL, Meyer BK. Comparison of compendial antimicrobial effectiveness tests: A review. Int J Pharm Compd. 2011; 15 (2): 122-9.
Add your comments about this article : Your username or Email:
CAPTCHA
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.