Wednesday, October 27, 2010

Regulatory RMM Perspectives at the PDA Global Microbiology Conference: The Australian TGA

Yesterday, I reported on the Compendial RMM session where we heard from the chairs of the USP, Ph. Eur. and the JP. Today, global regulators representing FDA, the Japanese PMDA and the Australian TGA provided their current perspectives on rapid microbiological methods.

Vivian Christ, Australian TGA first reviewed some of the policies and guidance that they follow with regard to RMMs. The TGA utilizes relevant sections in the Ph. Eur. and BP in that these compendia allow for the validation alternate methods. They also rely on the validation guidance from USP 1223, Ph. Eur. 5.1.6, PDA TR #33, and ISO 17025 (validation of non-standard methods), to name a few. From the legislative perspective, the TGA turns to the TGA GMPs, which allows for other acceptable methods as long as they are shown to be equivalent to those in the GMP guide, as well as Annex 11 (computer validation) and Annex 15 (IQ, OQ, PQ). However, unlike other regulatory agencies, such as the FDA, the TGA only “quietly” embraces new technologies but they have not come out with a formal statement or policy.

The TGA views RMMs to be used in a wide range of applications, including finished product testing and in-process testing. Validation expectations include a DQ, IQ and OQ performed by the vendor, and the PQ (jointly performed by the vendor and user) and verification of the method using actual product. Testing on potential interfering substances should be performed, and for users intending to develop a matrix testing strategy (i.e., grouping products together), a justification for doing so should be provided. Furthermore, there is the expectation that equivalence or superiority to classical method is demonstrated, as well as the computer validation of software. For a qualitative method, the validation should address specificity, sensitivity, ruggedness, robustness, and equivalence. For quantitative tests, the user should demonstrate accuracy, precision, ruggedness, robustness, equivalence sensitivity, linearity, and specificity.

Many companies have discussed implementing RMMs with the TGA but very few have actually taken the plunge and have moved forward. The TGA doesn’t really understand the reason for this. However, when companies do come in to discuss their intentions, the TGA encourages them.

TGA does have some regulatory concerns. For example, what happens if a company obtains a positive result by a RMM but not the referee test (what does this mean?). Next, do specifications need to be changed, and how will the company use the results from RMM testing, such as batch release? All of these points must be considered. From an administrative perspective, the local inspectors are starting to see RMMs but primarily for in-process testing, where there is no requirement for a formal regulatory change submission. Additionally, there is no published policy on the testing requirements for RMMs. From an economic standpoint, the TGA is considering cutting the costs associated with formal change submissions and RMMs, such as lumping many products together for a single RMM. Hopefully, we will hear more about this in the near future. In summary, the TGA hopes that more companies will move forward, validate and implement RMMs.


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