Thursday, 23 July 2015

Pharmeuropa 27.3 – Biological Indicators


A new edition of Pharmeuropa 27.3 (July 2015) has been issued. Pharmeuropa is a free online EDQM publication. Draft monographs are published in Pharmeuropa for public enquiry, which lasts for three months.

There is one update of importance:

Chapter 5.1.2  Biological indicators and related microbial preparations used in the manufacture of sterile products, and indicators for depyrogenation processes


Revision of the chapter was proposed because the current text was considered to be outdated and contained a number of technical shortcomings. The chapter was completely rewritten and numerous modifications were proposed and the revised chapter was published for public comment in Pharmeuropa 24.1.

A position paper on this topic was also published in Pharmeuropa Bio & Scientific Notes 2011-2.3.

The Pharmeuropa enquiry generated a large volume of comments on the proposed text and the Group of Experts with responsibility for the chapter have undertaken to redraft the chapter to address relevant comments.

The general changes are:


BIs for sterilisation processes: this section gives guidance on how BIs are selected and how
they are used to characterise sterilisation processes. A description is provided of 4 types of BIs for terminal sterilisation processes: inoculated carriers, self-contained BIs, characterised spore suspensions and custom-made BIs.

Information regarding the quality requirements for BIs and user requirement specifications are introduced.

BIs for heat sterilisation: the parameters of biological indicators for heat sterilisation are
described and how a validation cycle is established. Further information on biological validation with reduced sterilisation cycles is included.
BIs for moist heat sterilisation: it is recognised that Geobacillus stearothermophilus may not be suitable for sterilisation processes delivering an F0 between 8 and 15, therefore a different test micro-organism may be used.

BIs for dry heat sterilisation: description of the reference conditions and an example of how survivor rates of typical BIs are affected by temperature variations are given.

BIs for gas sterilisation: this section sets out that the use of gas sterilisation for disinfection is outside the scope of the chapter. There are a number of different types of gas sterilisation process and no reference cycles, therefore no criteria to which the BIs shall comply have been defined. Suitable micro-organisms for ethylene oxide sterilisation and an example are given. It is, however, the responsibility of the user to define the cycle and the suitability of any biological indicator used.

BIs for ionising radiation sterilisation: this was deleted from the previous draft (in Pharmeuropa 24.1) but has been reinstated. Although it is recognised that BIs are not considered to be necessary for defining the suitability of radiation sterilising cycles, their use may be required for the development and validation of ionising radiation sterilisation in specific cases. Information on test micro-organisms is given.

BIs for sterilisation grade filtration: information on test micro-organisms is now given for the validation of retention of micro-organisms using a membrane.

Indicators for depyrogenation processes: this section is now clearly separated from the sterilisation sections, and contains a list of characteristics of the lipopolysaccharide preparations.

Posted by Tim Sandle