Wednesday, March 16, 2011

New Changes to EMA's Review of RMM Validation Protocols!

Riccardo Luigetti, EMA, provided an overview of the EMA’s current perspectives on RMMs. Ph. Eur. chapter 5.1.6, Alternative methods for control of microbiological quality, provides the regulatory basis for the introduction of RMMs in the EU. Not only do the various EU competent authorities support RMMs, but some of the elements of the new variations regulations (implemented in January 2010) can be used to support the introduction of RMMs.

Historically, RMM validation protocols and their associated data were submitted under a Type Variation and the competent authorities reviewed all of this information as a whole.

A very recent change to the management of RMM reviews has just been introduced, which should make the validation and approval process much more predictable. The new process, which is very similar to FDA’s comparability protocol, is called the Post Approval Change Management Protocol (PACMP). In this two-step process, a testing protocol is first submitted as a Type 2 Variation, and when the protocol is approved, you perform the testing as specified in the protocol. The protocol should include the overall testing strategy, such as the planned studies, acceptance criteria and methods.

The second step of the PACMP process involves submitting the resulting data (assuming they have met the protocol’s acceptance criteria) as either a Type 1A or 1B Variation. The decision as to whether the data is submitted as a Type 1A versus a Type 1B variation is determined at the time of protocol review and approval. Because this is a new process, the EMA cannot provide examples of data submission requirements at this time; however, if the data is submitted under a Type 1A Variation, you can immediately implement the rapid method, while a Type 1B Variation requires a 30-day waiting period while the data is reviewed. In either case, as long as the data meets the protocol’s acceptance criteria, there should be no surprises during the data review once submitted.

Prior to submitting the PACMP, you can also discuss your strategies with the EMA under the Scientific Advice (SA) Procedure. This procedure was introduced in 2010 and provides an opportunity for a company to request feedback on a proposed validation and implementation plan. The procedure is short in duration (30 days), and the requesting company can be invited for a discussion meeting. The EMA’s response is in the form of an official recommendation letter, although the letter is not legally binding. Following receipt of the SA letter, the company may ask for follow up discussions.

The introduction of the PACMP is a welcomed addition to the EMA’s other recent policy changes, and will greatly simplify the validation and implementation of RMMs within the EU.


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