Table 1.
Comparison of Test Conditions According to Different Pharmacopoeias/Requirements (Examples)
| European Pharmacopoeia1 | United Statesa | WHO3 | Russian Pharmacopoeia6 | Chinese Pharmacopoeia7 | ||||
|---|---|---|---|---|---|---|---|---|
| Scope | General Test | Immunosera/ Vaccines | Biological Products (with exemptionsb) | Vaccines | General Test | Vaccines/ Sera | Biologics/ Vaccines | Chemicals, Traditional Medicines |
| Blank control | No | No | No | No | No | No | Blank control | No |
| Animal quantity | 5 mice | 5 mice | ≥5 mice | 5 mice | 5 mice | 5 mice | 5 mice | 5 mice |
| 2 guinea pigs | ≥2 guinea pigs | 2 guinea pigs | 2 guinea pigs | 2 guinea pigs | ||||
| Body weight (g) | 17–24 | 17–24 (m) | <22 (m) | 17–22 (m) | 19–21 | 17–20 (m) | 18–22 (m) | 17–20 |
| 250–400 (gp) | <400 (gp) | 250–350 (gp) | 250–300 (gp) | 250–350 (gp) | ||||
| Dose/ administration volume | One human dose | One human dose | ≤0.5 mL (m) | One human dose | 0.5 mL | One human dose | 0.5 mL (m) | 0.5 mL (m) |
| ≤1.0 mL | ≤1.0 mL (m) | ≤5.0 mL (gp) | ≤ 1.0 mL (m) | ≤ 1.0 mL (m) | 5.0 mL (gp) | |||
| ≤5.0 mL (gp) | ≤ 1.0 mL (gp) | ≤ 5.0 mL (gp) | ||||||
| Injection route | i.v. | i.p. | i.p.or following the approved route of product administration | i.p. | i.v. | i.p. | i.p. | Following the approved route of product administration |
| Observation time | 24 h | 7 days | 48 h | 48 h | 48 h | 7 days | 7 days | 2 days |
| Acceptance criteria | No animal dies within 24 h or within such time as specified in the individual monograph | No animal shows signs of ill health | No animal dies or exhibits any response, which is not specific for or expected from the product and may indicate a difference in its quality. No loss of body weight | No animal dies within at least 7 days or shows significant signs of toxicity | No animal dies within the specified follow-up period | No animal dies within at least 7 days, shows significant signs of toxicity, or a decrease in body weight | All animals remain healthy and survive the observation period, without any abnormal reaction, and with an increase in body weight by the end of observation period | All animals survive the observation period |
| Retest(s) number/ description | One | One | Two | No | One | One | One | One |
| If one animal dies, repeat the test | If one animal dies or shows signs of ill health, repeat the test | If the initial test/first repeat test fails, a repeat test may be conducted | If an animal dies, repeat the experiment with five mice (20 ± 0.5 g) | If an animal dies, shows clinical signs of intoxication or a decrease in body weight, repeat experiment under the same conditions | If the test fails, it may be repeated once with 10 mice/4 guinea pigs | If the test fails, it may be repeated once with 10 mice (18–19 g) | ||
a
The United States Pharmacopoeia (USP 36) refers to US Code of Federal Regulations (21 CFR, Part 610).2
b
Exemptions: therapeutic DNA plasmid products, therapeutic synthetic peptide products of 40 or fewer amino acids, monoclonal antibody products for in vivo use, or therapeutic recombinant DNA-derived products.
i.p., intraperitoneal; i.v., intravenous; m, mice; gp, guinea pigs.