Differences Between a GMP and Non-GMP Lab – Part 2

Method Development

One of Velesco’s specialties is Analytical Method Development. Quite often, we receive a new compound from a client and are asked to develop a formulation and/or HPLC method to be used for analysis.  Sometimes the client will send bits of a method and other times we are able to start from scratch.  When starting from scratch, the lead scientist researches the compound to determine solubility properties and suitable detection wavelength for HPLC.  At times we are able to use the USP/NF for mobile phase, wavelength and column suggestions, however those are typically vague and only give suggestions (i.e. column code L1). Fortunately, Velesco scientists have decades of experience in HPLC, so working from past experiences, we can trial a few columns and quickly select one that gives us the desired chromatography. A fun part of method development is determining if the method will be stability-indicating. Part of testing this is to degrade the compound and analyze the chromatography to see if compound-related degradants are being accurately quantified and separated by the method. Suggested methods of degrading the compound are by light, oxidation, acid, base and heat. It’s interesting to see which methods of degradation produce which degradants. Impurity analysis is also part of method development. If impurities or degradants are co-eluting with other peaks in the chromatography, then something in the HPLC method needs to be altered to have a working method.  Temperature, mobile phase composition or gradient conditions are examples of things that can be adjusted for a change in retention time and can give greater separation of peaks.

A lot of the method development work we do is for research, so it is non-GMP.  At Velesco, we still follow GMP guidelines for documentation, even for development and research work, but we are able to exclude some of the non-essential details from our databooks, which helps to save paper and time.  We usually include the HPLC method and other applicable documentation at the beginning of the databook and then only include them later if something has been changed as part of the development.

Once we have a working method, able to accurately quantify the active ingredients and preservatives and measure degradation/impurities, we can move forward with either method validation or further experimentation with the compound or formulation, both of which will be discussed in future posts.

Leave a Reply