Antimicrobial Preservatives are excipients added to multi-dose containers for both sterile and nonsterile drug products. These preservatives are used to prevent growth of microbial contamination occurring during the use period. It's important to note that antimicrobial preservatives are not a substitute for good manufacturing practices.
The USP <51> Antimicrobial Effectiveness Test is a challenge test for aqueous-based products. This test demonstrates the effectiveness of antimicrobial preservatives in preventing proliferation or limiting microbial contamination. It is performed on injections, topicals, oral products, and antacids packaged in multiple-dose containers. Click here to access a table of Common Pharmaceutical Preservatives.
The challenge test adds specific microorganisms to the test product at a high-concentration to simulate contamination. Microorganisms include:
- Candida albicans
- Aspergillus niger
- Escherichia coli
- Pseudomonas aeruginosa
- Staphylococcus aureus
The product is then held for 28 days to observe change in microbial content. Acceptance criteria is specified for each drug product categories.
USP <51> Table 1. Compendial Product Categories
| Categories | Product Description |
|---|---|
| 1 | Injections; other parenterals including emulsions, otic products, sterile nasal products, and ophthalmic products made with aqueous bases or vehicles |
| 2 | Topically used products made with aqueous bases or vehicles; nonsterile nasal products and emulsions, including those applied to mucous membranes |
| 3 | Oral products other than antacids, made with aqueous bases or vehicles |
| 4 | Antacids made with an aqueous base |
USP <51> Table 3. Criteria for Tested Microorganisms
| For Category 1 Products | |
|---|---|
| Bacteria | NLT 1.0 log reduction from the initial calculated count at 7 days, NLT 3.0 log reduction from the initial count at 14 days, and no increase from the 14 days' count at 28 days |
| Yeast And Molds | No increase from the initial calculated count at 7, 14, and 28 days |
| For Category 2 Products | |
| Bacteria | NLT 2.0 log reduction from the initial count at 14 days, and no increase from the 14 days' count at 28 days |
| Yeast And Molds | No increase from the initial calculated count at 14 and 28 days |
| For Category 3 Products | |
| Bacteria | NLT 1.0 log reduction from the initial count at 14 days, and no increase from the 14 days' count at 28 days |
| Yeast And Molds | No increase from the initial calculated count at 14 and 28 days |
| For Category 4 Products | |
| Bacteria, yeast, and molds | No increase from the initial calculated count at 14 and 28 days |
For more information on USP <51> Antimicrobial Effectiveness Testing: