Demonstrating equivalency between instruments

AnalMD

<p><span>In developing test methods for the Acquity, what is necessary to demonstrate equivalency between the HPLC and the UPLC method of a validated test method? Is it simple as showing reproducible results between the same samples run on an HPLC and the Acquity, or is a full validation required?</span></p>

ACQUITYEPM

Greetings A. MD,

This is a difficult question to answer. It, greatly, depends on which regulatory agencies have oversight of your work and the guidlines of your own organization. The intent of any assy is to demonstrate the identification of the compounds of interest, to the exclusion of all others in the best case, and the amount of those compounds present in each sample. I believe the current thinking, when converting methods to similar assay techniques, i.e. HPLC to UPLC, is that the basic figures of merit should be investigated, but a full blown re-validation may not be required. Relative equivalency is what is important and not, necessarily, absolute certification and re-validation. At a minimum, I would anticipate demonstrating that there is no possibility of confusion of compound identity, that the assay is linear (or can be, sensibly, calibrated) within the range of the assay, the limit of detection and the precision of the assay. Of course, the precision of the assay begs the question of whether short term precision is all that is required or must longer term robustness of the assay also be understood. Once long term precision, or robustness, is under discussion, you are well on your way to a full re-validation of the assay.

Just my thoughts,

pcb

CANHASAN

It is a good topic to discuss. I am in pharmaceutical industry. Pharmacopies have area normalization tecnique most of the time for the unknown impurities.It is quite challanging sometimes to transfer HPLC method to UPLC. It is easy if you have known impurity, resolution , p/w etc . What would be the case for the unknown impurities?

lizh

This is a difficult one and I hesitate to answer as an employee of an instrumentation supplier. However, here are a couple of older references you may find valuable.

Implementing New Technology in a Regulated Environment. M.E. Swartz and I.S. Krull, LCGC 24(8), 480-484 (2006).

System Suitability Tests in Regulatory Liquid and Gas Chromatographic Methods: Adjustments Versus Modifications, W.B. Furman, J.G. Dorsey, and L.R. Snyder, Pharm. Technol. 22(6), 58-64 (1998).

Analytical Method Equivalency: An Acceptable Analytical Practice, D. Chambers, G. Kelly, G. Limentani, A. Lister, K.R. Lung, and E. Warner, Pharm. Technol. 31(9), 64-80 (2005).

Validation, Qualification, or Verification?, M.E. Swartz and I. Krull, LCGC 23(10), 1100-1109 (2005).

But I Can't Change the Method, J.W. Dolan, LCGC 22(6), 524-528 (2004).

Also, there is a webcast presentation from Melissa Figgins from Sandoz. Within the presentation she talks about the UPLC considerations made at her company and also how they managed the change (equivalence studies and then indicated the UPLC method as an alternative method in their annual report). The link to the webcast is the following: http://www.waters.com/waters/library.htm?lid=10084046&cid=511436. At the end is the Q&A session. Melissa answers specific questions on the FDA. Today what is your company's SOPs for the methods and change management protocols. Are there any members of regulatory science groups who would like to weigh in?

Edited by: Elizabeth Hodgdon on Dec 30, 2008