Validating Chromatographic Methods - A practical guide
David M. Bliesner
John Wiley & Sons ISBN 97880471741473 2006 ( 291 pages ) ~US$100
The path to Hell is paved with good intentions. New Zealand was the first country to legislate GLP, and GLP has now developed into a cGxP Hydra that frequently obstructs, rather than assists, those analysts beating a path to the underworld of regulatory approval of analytical data.
This book is another paving stone on that path, with the author intending to " bring order and cGMP to the often chaotic process of chromatographic method validation ". Sadly, the order is in the form of copious pages of little boxes in extensive flowcharts, many of which are specific to organisation structure, rather than helpful assistance for technical actions.
1. Preface ( 2 pages )
There is need for a good guide, and the author solicits feedback. Mine would be to forget the detail of the road structure, and focus on ensuring the minimum energy pathway is followed to the correct destination.
The author notes the book uses an HPLC example throughout, because it is a common technique, so I expected that critical column parameters, such as particle size, would not be subject to typos.
2. Body of book ( seven sections, 56 pages )
At least half the pages are flowcharts and tables. Not a good read, as the format is a few pages at the start of each section, followed by pages of tables - often filled with processes that are related to organisational structure trivia, eg
Step - 1.10
Description - Team leader schedules planning meeting with team members.
Estimated Duration - 0.5 day
Explanation - The team leader should make an attempt to dovetail this meeting with the team members' existing schedules.
Hullo, anybody home?. Step 1.8 ( 0.5 day ) was to select the team, step 1.9 ( 0.5 day ) was to compile and distribute documentation package. Any rational manager would organise the meeting via email or at the time of document distribution. If the manager takes a further half day to organise a meeting, questions should be raised about their performance.
There is no doubt that much of what the author says is valuable, such as in section 1.4 " Additional points to consider when validating chromatographic methods". The sub-sections are titled..
- Do not underestimate the Value of Planning and Organisation
- Make it simple, keep it simple and remember your end users
- QA is your friend
- Don't underestimate the value of experience
- Common sense is an uncommon virtue
- Mistakes are made under pressure
- Realise the impact of your successes and your failures.
For me, those two pages should have been the basis of the book, but sadly the nauseously-detailed flowcharts dominated instead. It also unfortunate that the author chose to use the generic Quantitation Limit and Limit of Quantitation, rather than Lower Limit of Quantitation ( which immediately indicates that there will also be an upper limit - even if it's not determined in most methods ).
He also notes that organisations tend to not allow enough time for such method validations, and highly recomends a trial run at the validation. I think this is where my world and his collide. Confirmation that the method is suitable for validation should have been determined much earlier, and the prelimiary part of an evaluation should have been ensuring that the method really was fit for purpose and would emerge with only trivial changes, as validations usually cost a lot of money. Method changes during validation are red-flags that reviewers will focus on.
I would have preferred to see a little more definition on the issues of instrument qualification and electronic raw data storage and integrity ( which isn't discussed ). The example assumes raw data is in hardcopy format.
I'm also not sure that many HPLC instruments are particularly good at performing a transition of 49% mobile phase B back to 0% over one minute. Admittedly, mobile phase A contains aqueous buffer, and there is a subsequent stabilisation time, but I prefer methods to have a less steep slope, and possibly a slightly shorter stabilisation time, as some instruments and software I've used have only been capable and qualified for maximum rate of change of 40%/min.
3. Appendices ( 227 pages )
Copiously-detailed templates describing validation in detail. Given that the HPLC column would be a critical component, it's disappointing that proof reading didn't capture obvious errors, such as using mm instead of Âµm for the only two mentions of column particles sizes that I encountered. However it should be noted that the MS Word templates on the accompanying CD correctly used Âµm.
4. References ( 1 page - 8 refs )
Such books can become obsolete quickly as pharmaceutical publishers seek to maximise revenues by increasing the frequency of updates, and this book, apparently completed about Dec 2005, missed the merging of the two ICH (Q2A, Q2B) references in Nov 2005. Two of the other references ( USP <621>, <1225> ) are in an annual publication, so readers would need to check the current edition.
If you have been asked to perform a method validation for the first time, this book would enable you to perform that task, probably to the satisfaction of the regulators and any managers who like to organise meetings. It enables you to ensure that most of required processes will be considered and enacted. However, whilst it's strong on role descriptions, it's morbidly-obese with regard to tables and flowcharts, but anorexic with regard to technical considerations.
It could be a good supplement to help interpret what the objective of a validation should be, and is undoubtably much cheaper than a consultant. However, if your organisation intends to routinely validate methods, your QA department should have the skills to advise on method validation, and help define what is required. If they can't, the organisation should hire an appropriate consultant, and perhaps sack some of the QA staff to pay for the consultants.
It was an interesting read, but much of the information is intended for the manager who will review the documents, rather than the analyst. Now I have purchased the book, I'll use it, but it wouldn't be in my top ten list for any chromatographer, other than those whose organisations are about to embark, for the first time, on method validation for submission to the FDA.
For analysts without organisational support or experience, they could severely prune and modify the Word templates to build a suitable framework for a validation that they could then submit to QA.
My opinions only, yours will differ.