Privatsphäre-Einstellungen

Prüfung auf Sterilität nach international harmonisierten Vorschriften

Hanfried Seyfarth

Abteilung Biopharmazeutische Qualität und Compliance/Mikrobiologie, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Riss

Testing for Sterility According to the International Harmonised Regulations

The 6^th Supplement of Ph.Eur. 4 (Ph.Eur. 4.6) contains the harmonised text of the test for sterility. The new version contains numerous changes compared to the previous section in the Ph.Eur. 4 (2002):

• Applicability
Other methods are expressly permitted (important with a view to parametric release). The text is the official method = decision method.

• Certain of declaration
For products sterilised in the final container attention is drawn to the possibility of parametric release (in the non harmonised and non mandatory section „Guidelines for using the test for sterility“ The test for sterility must be carried out always in the case of aseptic production.

• Test conditions
Description more general. More detailed information are given in the Guidelines for using the test for sterility

• Controls
Environmental controls must be done omn a daily basis (they must be available when deciding about necessity of possible repeat tests).
Negative controls: Daily testing as they must be available when deciding about necessity of possible repeat tests.

• Duration of incubation
Generally 14 days.

• Method validation
Always for new products and by alteration of test conditions.
Reference organisms: Same organisms as before. Clarification - all organisms must be used.
Age of the reference organisms: Max. 5 passages from the original.
Inoculation of organisms: The procedure is described in great detail.
Duration of incubation: Is now fixed as 5 days.

• Individual Forms of application
Detailed description of the testing of parenteral preparations, eye preparations and other non-injectable preparations.

• Sampling number
Unchanged. In USP and JP will be this mandatory, in Ph.Eur. only recommendation. Requirements for bulk are now included.

• The amount to be tested
Has in part changed (possibly a complete new validation of the method may be required)

• Evaluation
Repeat tests are only permitted under certain conditions.
Aseptic preparations: Repeat test practically impossible.
Product sterilises in final container:
Chance in identification of organism with more sensitive tests, for example, molecular typing with RNA/DNA homology

• The procedure in the case of turbidity of nutrient media Regulation: 14 days incubation of original test and 3 days incubation of subculture.

• Nutrient media
Unchanged.

• Nutrient media controls
The possibility of a parametric release are discussed.

Key words Europäisches Arzneibuch (Ph.Eur. 4.6) • Steriltest, Anwendbarkeit, Durchführung, Methoden, Neufassung, Validierung