Application Note

RSS

Ward-Smith, R.S., Gummery, N. and Rawle, A.F.
Malvern Instruments Ltd.

With the introduction of both ISO 13320 (Particle size analysis – Laser Diffraction methods)[1] and NIST 960 – 1 (Practice Guide Particle size Characterisation)[2] the user of a laser diffraction instrument has been supplied with a wealth of useful information on theory and guidance on both dispersion and sampling. The amount of information available on how to validate the method of analysis once it has been developed is a lot more limited. The Pharmaceutical Analytical Sciences Group (PASG)[3] have attempted to lay down some guidelines, but these did not provide sufficient detail regarding the actual experiments that need to be performed. This paper sets out to define the important areas of method development and provide both guidelines and example data to suggest what experiments might be done in order to validate a method. However just because these experiments have been performed, the authors cannot guarantee that an auditing body will always approve and "rubberstamp" the method. Rather the author's are suggesting a minimal amount of work that we'd expect to be performed. Any more work will only strengthen the case of the candidate method. Lerke and Adams[4] have recently published their ideas on the subject in a useful paper. Their paper covers both method development and method validation, whereas this paper is mainly concerned with the latter.

The purpose of creating a validated method is to ascertain the robustness and integrity of a particle size method by testing all possible parameters that could cause variation in the reported size. Validation is defined by the FDA as "Establishing documentary evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specification and quality attributes".

Click here to download the complete application note in pdf format.