ECA's Survey on RMMs has shown that many pharmaceutical companies are interested in using alternative microbial methods for non-release tests like e.g. environmental monitoring or quality control of water.
In the Q&A Sections of the EMEA Quality Working Party (QWP) website the following question was raised which relates to the topic:
What is the regulatory consequence of implementing an alternative method for rapid control of microbiological quality of WFI and Purified water?
"According to EU legislation, pharmaceutical manufacturers are required to use European Pharmacopoeial standard water in the manufacture of medicinal products.
The European Pharmacopoeia (Ph.Eur.) has recently introduced a chapter making reference to the acceptability of rapid microbial methods to replace the standard Pharmacopoeial methods provided appropriate validation has been performed.
Following discussions at QWP and the ad hoc GMP inspector's group, it is suggested that the introduction of such methods might require specific review to ensure that the appropriate validation steps have been followed and that the water continues to meet the Ph.Eur. specifications. Since, in the case of water, the validation will not be product specific, it is suggested that a company could request the Supervisory Authority to carry out a specific site inspection. The performance of such an inspection would be at the discretion of the Supervisory Authority and could involve a pharmaceutical assessor where necessary.
Since it is expected that the water will continue to meet Ph.Eur. specification, if tested, no change to dossier requirements* (variations) would be involved and therefore no regulatory impact on individual products would normally be anticipated.
*This will depend on the level of detail in the original dossiers concerned"
There are some interesting aspects in the QWP answer:
EMEA is aware of the new EP Chapter 5.1.6. That is good.
QWP proposes a "specific" site inspection by the local competent authority in the case of using an alternative method. That is additional work.
The implementation of an alternative method for water testing does not provoke a change to the dossier depending on the level of detail in the original dossiers. Once again, this statement teaches us to be very careful with the information we add to the dossier. If the level of detail is too high, modifications of these presettings are very much restricted.
The last statement is the important one. It shows a way how the industry could move forward and gain more experience with RMMs without the high costs and the long approval process of a Type II variation.
It seems that in this certain case the requirements of EMEA and the wishes of the pharmaceutical industry have a lot in common.
Nevertheless, it leaves the challenges of introducing RMMs for release testing unsolved. At this moment it remains a type II variation in Europe – with all its consequences.
Dr Ulrich Herber
on behalf of ECA