MTS Recommends... More Myths in Ultrahigh-Pressure Liquid Chromatography

'More Myths in Ultrahigh-Pressure Liquid Chromatography'

By Michael W. Dong, LCGC Europe, Nov 1, 2013

"This instalment describes a number of popular myths or half-truths in UHPLC and provides data that contradict or even repudiate some of these commonly held beliefs." 

6 Reasons to Join MTS in Berlin this December

We have 6 great reasons why you should join us in Berlin this December for our open enrolment training courses:

1. Choose from 3 Very Effective Training Courses

(i) Validation of Analytical Methods for Pharmaceutical Analysis,
Wed 4th & Thu 5th Dec 2013
(ii) Transfer of Analytical Methods for Pharmaceutical Analysis,
Fri 6th Dec 2013
(iii) How to Develop Stability Indicating HPLC Methods,
Mon 9th & Tue 10th Dec 2013

(Click on the course title above for: the course synopsis; a link to detailed course description; and the online booking form)

2. Festive Discount on Course Fees

We have extended our discounted early booking rate as a festive treat for our Berlin course attendees. The fees are as follows:
(i) Validation of Analytical Methods for Pharmaceutical Analysis,
only €1050 + VAT
(ii) Transfer of Analytical Methods for Pharmaceutical Analysis,
only €610 + VAT
(iii) How to Develop Stability Indicating HPLC Methods,
only €1050 + VAT

Discounts are also available for booking on more than one course, for groups and for academics. Contact us for a quotation.
(Note: VAT is charged at 19% in Germany)

3. Enhance Your Career Prospects

Our courses provide valuable technical knowledge and skills for those aspiring to develop their career in the analysis of pharmaceuticals. Not only will these new abilities allow you to attempt more advanced tasks but will also enhance your CV.
We provide a Certificate of Attendance which may, if desired, be upgraded to a Certificate of Training on successful completion of the post training assessment.

4. Lots of Useful Free Extras

At MTS we like to go that extra mile. When you attend one of our open enrolment courses you not only get comprehensive course handouts detailing the topic but we also like to give away other free extras such as a complimentary copy of our book, Validation of Analytical Methods for  Pharmaceutical Analysis, (RRP £29.90) when you attend the course of the same name. We also have an aide mémoire to assist you during method review prior to transfer to another laboratory. For HPLC users we provide a calculator containing a range of useful information, including equilibration times, mobile phase preparation and method development.

5. Get an Expert in Your Corner

All delegates on MTS training courses receive post training support. This means that if you have any questions when you go back to work and start to apply the learning from our courses, you can send them to us. 

6. Christmas Markets in Berlin are Fabulous!

Scattered throughout the city, Berlin has a huge variety of beautiful Christmas Markets selling festive treats such as traditional gifts and decorations, mulled wine, and specialty foods. Why not combine some professional development on our training courses with a visit to a Berlin Christmas market?

Joining is simple:

Just complete the online booking form for the courses you would like to attend or contact us.

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MTS Course Calendar 2014

Prices held at 2013 rates!

Our schedule for open enrolment training courses in 2014 is now available.  

We are offering courses on method validation, method transfer, developing HPLC methods (including stability indicating methods), introduction to HPLC and troubleshooting HPLC. The locations are Dublin, London and Berlin.

Click on the image for the 2014 schedule.  

Contact us for more information. Online booking forms will be available on the MTS website soon.

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MTS Recommends... Why do I have Carryover?

Why do I have Carryover?
Chromatography Today, 3rd September 2013

This is a very thorough treatment on why carryover happens and  how it can be minimised. It will be a very useful resource if you are experiencing this often infuriating problem.

Help on: When Should I Throw my HPLC Column Away?

MTS HELPDESK

Do you have any problems relating to analytical chemistry for pharmaceuticals or training? Send your questions to the MTS helpdesk using our contact form.

Question:
"If the value for the theoretical plates for an HPLC column decreases below 2000, should the column be discarded? And which parameters should be considered when deciding when to discard a column?"

Answer:
"Unfortunately the answer to your question is - it depends. Deciding when to get rid of an HPLC column is difficult and may depend on what the column is being used for and whether it is being used for a single type of method or lots of different methods and samples. The theoretical plate count (N) is a good indication of how well a column is working but it is relative, this means that you need to monitor the value over the course of the column lifetime and correlate the value with the decrease in separating power.

If the chromatography for a method looks good and the peaks are still separated adequately for quantitative analysis then I would not discard a column because the value of N went below 2000. However, from experience for a particular column you may know that the method does not work as well once N is below a certain value and thus this could be your indicator that the column should be discarded. It is definitely easier to use this approach if the column has only been used for one type of analysis. Once a column is used for lots of different samples then it is very difficult to predict when it will fail. 

There are a few things to be aware of if you are using plate number. The value is specific to a particular analyte and thus it will be different for each peak in your chromatogram, this can make it tricky to say a column has a particular number. Also, it is only useful if you are using isocratic elution methods, it is not meaningful for gradient methods.

Typical indicators that a column has reached the end of its life are:

Resolution – if the peaks that you are interested in are not separated adequately then the column may need to be discarded, you would expect this to build up over time. A sudden loss of resolution may have a different source. A typical value of resolution when the separation is satisfactory is Rs > 2 although a value of around 1.5 is usually considered baseline separated. Therefore a value < 1.5 indicates that the separation is not adequate.

Peak shape – peak tailing (especially on large peaks) is usually associated with the age of the column and at some stage will be too great for reasonable quantitative analysis. A typical value of an acceptable tailing factor is T < 2. Therefore when the tailing factor is above this value the column may be no longer performing at an adequate level. Peak shoulders may also appear (on all peaks) which indicate that there is a build-up on the column inlet that means the column is no longer fit for use.

Theoretical plate count, N – in the region of about 2000 is usually accepted as a limit but be careful not to throw away a column that it still working.

Pressure – The back pressure of the column will usually build up over time and may determine the lifetime of the column."

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Is Your Analytical Method Stability Indicating?

When setting up a stability programme for a pharmaceutical substance or product, analytical methods are selected to allow appropriate testing at the required time-points. A number of different types of methods may be selected but the quantitative measure of the active pharmaceutical ingredient (API) and its degradation products is probably the most important.

Since these methods are being used to interpret the effects of the stability study then it is self evident that they need to be stability indicating but how can you be sure that this is the case? The challenge is to demonstrate that each method is, in the words of ICH Q2(R1), "suitable for its intended use".

To demonstrate suitability, and therefore show that your method is stability indicating, you will need to  be able to quantify the API and its degradation products so that you can monitor the expected decrease in the amount of the API and the corresponding increase in the amount of degradation products. Therefore, samples of the degradation products will be necessary to show the method is capable. These are usually sourced by applying stress to the samples in a forced degradation study. Although the principle is straightforward, this type of investigation can be very problematic and requires a thorough understanding of the chemical properties of the API and predicted degradation products.

When carrying out an audit which involves stability testing, I will often ask the question "Is this analytical method stability indicating?" What I expect to see is a section in the validation report which details the evidence that demonstrates that the method is stability indicating.

Since the analysis of an API and its degradation products most often requires the use of HPLC, Mourne Training Services has created a training course which focuses on how to develop stability indicating HPLC methods. Strategies for generation of suitable degradation products via forced degradation is combined with a thorough step by step guide to HPLC method development.

How to Develop Stability Indicating HPLC Methods
In London (Jurys Inn Heathrow) on the 11th & 12th November and in Berlin (GLS Campus Berlin) on the 9th & 10th December 2013
Early booking rate: London - £850 + VAT; Berlin - €1050 + VAT
Late booking rate: London - £950 + VAT; Berlin - €1175 + VAT

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MTS Recommends... Learning Tool for HPLC

If you're looking for a good learning tool that explains the effect of different parameters on an HPLC separation then it might be worth taking a look at HPLC Simulator.

It is described as follows on the developer's website:

"HPLC Simulator is a web-based high-performance liquid chromatography simulation. Adjust a range of experimental parameters and see their affect on chromatographic parameters including retention time, column efficiency, and backpressure. It is intended to be used for educational purposes only."

Courses on Analytical Method Development, Validation and Transfer Coming Soon to London and Berlin

We have 3 training courses on pharmaceutical topics coming up this winter in London (Jurys Inn Heathrow) and Berlin (GLS Campus Berlin).
Click on the course titles below for more information about each course, including a course description and a link to the relevant online booking registration form.

Validation of Analytical Methods for Pharmaceutical Analysis
In London on 6th & 7th November and Berlin on 4th & 5th December 2013
Early booking rate: London - £850 + VAT; Berlin - €1050 + VAT
Late booking rate: London - £950 + VAT; Berlin - €1175 + VAT

Transfer of Analytical Methods for Pharmaceutical Analysis
In London on 8th November and Berlin on 6th December 2013
Early booking rate: London - £495 + VAT; Berlin - €610 + VAT
Late booking rate: London - £545 + VAT; Berlin - €675 + VAT

How to Develop Stability Indicating HPLC Methods
In London on 11th & 12th November and Berlin on 9th & 10th December 2013
Early booking rate: London - £850 + VAT; Berlin - €1050 + VAT
Late booking rate: London - £950 + VAT; Berlin - €1175 + VAT

Check the Course List page on the MTS website and book before the deadline to receive the substantial discount for early booking. We also offer group and academic discounts. Contact Us for a quote.

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Free Tool: Aide Mémoire for Analytical Method Transfer

An important step in the transfer of an analytical method to another laboratory is the review of the method prior to transfer. This assessment of the method should identify whether it is suitable for transfer and if any potential problems that may arise when the method is run in a different laboratory can be anticipated.

This review process is a major topic in the MTS course, Transfer of Analytical Methods for Pharmaceutical Analysis, and an aide mémoire to assist this review has now been developed based on the training course, which can be downloaded for free from the MTS website. The intention of the aide mémoire is to suggest common issues and problems to look out for during transfer. I've deliberately called it an 'aide mémoire' rather than a 'checklist' because I think that the term is a better description of the free tool in that it should help to anticipate common issues but is not intended as an exhaustive and complete list.

The aide mémoire is a document in progress, I will add to it from time to time based on feedback from the training courses that I deliver. If you have any ideas about what you think should be included then please send your suggestions to me using our Contact Us page.

Click on the image to the right, or click here, to access the download page for the free method transfer tool.

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Help on: Do I need Linearity, Accuracy and Precision for a Method Based on Area %?

MTS HELPDESK

Do you have any problems relating to analytical chemistry for pharmaceuticals or training? Send your questions to the MTS helpdesk using our contact form.

Question: 
“I’m currently writing a validation protocol for an optical purity method which is used for the determination of a main component and 3 known impurities. The results are expressed in % relative (area/area). Since all the results will be determined in % relative, do I need to investigate linearity, accuracy and repeatability?”

Answer:
 “It is my opinion that you will need to consider linearity, accuracy and precision for this method, even though the method is based on an area percent measurement. My reasoning is as follows:

Although the results are expressed in % relative area, it is implied that these relative areas are representative of the amounts of the main component and the impurities in the samples that you are testing and that therefore there is a correlation between % area and %w/w.

Linearity - For both the main component and the impurities, you are assuming that the relationship between the size of the peak and the concentration of the analyte is a linear one. If you are using UV detection then you probably will have a linear relationship but it is usually necessary to demonstrate that it is linear over the range of the method. Additionally, by assigning a value of 100% to the total area, and then expressing the size of each peak as a proportion of this you are actually applying a single point calibration. Therefore the equation of the line will need to pass through the origin, i.e. the value of c in the equation, y = mx + c, will need to be insignificant.

Accuracy – If you have a reference standard for your main component then I would perform an accuracy determination since this is the only way that you can show that your method does actually produce the correct result and that the area percent approach is valid. For the impurities, you will need standards of known purity to perform accuracy and you may not have these.

Note that in ICH Q2(R1), page 10, section 4.2, it says “It should be clear how the individual or total impurities are to be determined e.g., weight/weight or area percent, in all cases with respect to the major analyte.”

Precision – The result that you generate for a particular sample each time you run your method will be subject to errors and thus will be variable regardless of whether your results are expressed as %w/w or % area. These errors come from sample preparation, injection, integration, etc. An assessment of this variability is essential during validation, preferably by performing repeatability (performing the analysis 6 times on the same sample at the same time), and intermediate precision (performing the analysis on different instruments and by different analysts, etc.). The reason for this is so that you know how different the result may be when you follow the method as written.

The combination of linearity, accuracy and precision provides valuable information on the performance of an analytical method.”

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Upgrade for e-MTS, our virtual classroom area for resources, assessments and e-Learning

Our virtual environment for learning, e-MTS, will be familiar to anyone who has completed iLearn, the HPLC e-learning course, or has attempted an assessment after attendance at one of our courses. We are currently upgrading our site to the most recent version of Moodle which will allow easier navigation and extra features.
The site may be unavailable briefly during the week commencing 22nd July while the upgrade is taking place but we will endeavour to minimise disruption. Please contact us if you have any problems using our e-MTS help form.

MTS Recommends... The Top 10 HPLC and UHPLC Column Myths

The Top 10 HPLC and UHPLC Column Myths

By: Ronald E. Majors
LCGC North America, Jul 1, 2013

This article from Ron Majors does a great job of clearing up some common misconceptions about HPLC.

Auditing and Consultancy Services from MTS

Mourne Training Services has gained a reputation for high quality training solutions through our range of open enrolment training events and also in-house training programmes delivered at customer sites. We would like to draw your attention to other related services that may assist in the pharmaceutical laboratory, namely auditing and consultancy.

We can offer laboratory specific auditing which allows a detailed investigation of both compliance with the relevant regulatory standards, and whether a sound scientific approach to analytical chemistry has been applied. This may be required for an upcoming inspection or simply as an independent assessment of how your laboratory is performing. We can help you to achieve a balance between ticking all the boxes for regulatory compliance and having the understanding of the underlying science which ensures data quality.

Our auditing service may be combined with consultancy services to assist in the implementation of the audit outcomes. We will provide practical advice and assistance on how any shortcomings can be corrected. Ultimately a training solution may be identified which we will be happy to advise on, and prepare and deliver if desired.

Contact us to discuss your pharmaceutical analysis auditing, consultancy and training needs and we will provide a quality solution at a reasonable cost.

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MTS Recommends... New Chromatography Columns and Accessories at Pittcon 2013

New Chromatography Columns and Accessories at Pittcon (Part 1) &

New Chromatography Columns and Accessories at Pittcon (Part 2)

by Ronald E. Majors
LCGC Europe, May 2013

Ron's annual roundup of the new columns at Pittcon provides you with an easy way to get an overview of the latest column technologies out there.

MTS Recommends... Chromatography Modelling

Chromatography Modelling in High Performance Liquid Chromatography Method Development
by Imre Molnár, Hans-Jürgen Rieger, Institute for Applied Chromatography, Berlin, Germany
Róbert Kormány, Egis Pharmaceutical, Budapest, Hungary
Chromatography Today, March 2013

I often recommend the use of chromatography modelling in my HPLC method development courses. This article provides an overview of the history of this approach over the last 30 years and should be useful to anyone interested in the topic.

MTS Recommends... 17 Ways to Stop Pipetting Errors Ruining Your Experiments

17 Ways to Stop Pipetting Errors Ruining Your Experiments

February 01, 2008 by Nick Oswald in Lab Equipment

Many analysts just assume that micro-pipettes are dispensing perfectly every time but like any piece of analytical equipment this is only true if they are used and maintained correctly. This helpful article explains how you can ensure that pipette error is minimised.

MTS Recommends... Water Purification Guide

Water Purification Guide
This buyer's guide from SelectScience provides a straightforward overview of the different methods of water purification used to produce the water used in laboratories.
From an HPLC perspective, water is a very common mobile phase component and effective troubleshooting requires an understanding of what could be present in the water being used. I think this guide may be helpful for this purpose.

Early Booking Deadlines Coming Up Soon!

MTS offer very generous discounts for early booking on our training courses. The deadline is coming up very soon for our London courses in April and Berlin courses in May. Submit a booking form, or just contact us, to secure our early booking rate by the 22nd March for London, and by the 10th April for Berlin.

The courses are:

Validation ofAnalytical Methods for Pharmaceutical Analysis
London (@ Jurys Inn Heathrow) on 10^th & 11^th April 2013
Berlin (@ Steigenberger Hotel Berlin) on 6^th & 7^th May 2013

Transfer of Analytical Methods for PharmaceuticalAnalysis
London (@ Jurys Inn Heathrow) on 12^th April 2013
Berlin (@ Steigenberger Hotel Berlin) on 8^th May 2013

How to Develop Stability Indicating HPLC Methods
London (@ Jurys Inn Heathrow) on 15^th & 16^th April 2013

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HPLC Troubleshooting Tip: Preventing Mobile Phase Problems When Using TFA

Trifluoroacetic acid (TFA) is a very common additive in reversed phase HPLC mobile phase. It is used extensively as an ion pairing reagent for peptide analysis but also as an acid modifier in a wide range of applications. Generally, TFA provides good peak shapes and reproducible chromatography and is compatible with a range of detectors, being volatile and of low UV absorbance.  However, if you are using TFA then there are a few things to be aware of which will ensure that you get the best results.

Impurities in TFA may cause noise, high background and spiking in your chromatography. These impurities may come from using low grade reagent or old bottles of TFA. I recommend that a suitable reagent grade is used (preferably HPLC grade) and also, to prevent stability problems, use small bottles so that an opened bottle of TFA is not sitting on your laboratory shelf for a long time. Be careful that a single bottle is opened at a time, especially if there are multiple users. Depending on your requirements, you may find it more convenient to use ampoules of TFA but, as you might expect, these are more costly.

TFA is a strong acid; amounts in mobile phase are typically ~ 0.1%v/v or lower. Concentrated TFA is quite dense (1.53 g/mL). This means that the difference between %w/v and %v/v is significant and may be enough to affect your chromatography. Therefore I recommend that you specify the units rather than just write ‘0.1%’ in your analytical procedure.

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HPLC Training Courses in Dublin – May 2013

Join us in Dublin this May to learn about how to get the most out of HPLC. We are offering four HPLC training courses from our 'How to...' series which are designed to provide both theoretical and practical advice, enabling straight to lab application. Whether you are a complete beginner or are already using HPLC we can help to develop your expertise.

The courses are as follows:

How to Run HPLC Methods: Monday 20^th May 2013
Ideal for anyone new to HPLC, this course will demystify all the parameters required to run a HPLC method.

How to Troubleshoot HPLC: Tuesday 21^st May 2013
Will suit HPLC users who want to be able to keep their HPLC system up and running, by sorting out problems as they occur.

How to Develop HPLCMethods – Part 1: Wednesday 22^nd May 2013 & How to Develop HPLC Methods– Part 2: Thursday 23^rd May 2013
These two courses can be taken together or separately and will describe a strategy for selecting the best HPLC method conditions for your separation.

We are offering the following discounts until 25th April 2013:

€350 per person per day, 2 days for €650, 3 days for €950 
or 4 days for €1250

Academic discounts and group discounts also available up to 25th April, contact us for a quote.

After 25th April all courses are charged at full price of €425 per person per day.

Note: All prices are quoted exclusive of VAT

Includes:

• Comprehensive handouts for each course containing useful reference data.
• Free tools to help you use HPLC efficiently.
• A Certificate of Attendance. There is an optional post training assessment to obtain a Certificate of Training.
• Expert Advice from the MTS trainer on your HPLC problems, both on the day of the training and after the event.

Click here for a printer friendly summary of these courses.

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Help on: Validation Shows that Method is Not Linear Through Zero

MTS HELPDESK
Do you have any problems relating to analytical chemistry for pharmaceuticals or training? Send your questions to the MTS helpdesk using our contact form.

Question:
"I am currently validating an assay method as per ICH guidance. I have a problem with the linearity determination. The method has a single concentration of calibration standard and therefore I believe that I have to show that the line goes through the origin but when I run the linearity standards at the range in ICH, i.e. 80% to 120% of the assay concentration, the intercept of the resulting line is not close to zero. Can you suggest what I should do?" 

Answer: 
"If an analytical method involves the use of calibration standards which are prepared at a single concentration (more than one standard solution is commonly prepared) then the actual calibration line generated for the analysis is drawn between the calibration standard concentration response and zero. This method of calibration will only work if the line does go through zero and therefore an important part of method validation is to confirm that this is the case.

A typical assay method will be designed such that the typical response of the analyte is at a concentration level where the response is not subject to random errors, such as injection repeatability and integration in the case of an HPLC method, and therefore is significantly greater than zero.

When validating an assay method the range to be considered is usually ± 20% of the expected sample concentration, expressed as 80 to 120% in the ICH validation guidance Q2(R1). This means that it seems sensible to investigate linearity using standards prepared over this range. However, when running the method in routine analysis the linear range of the method is from 0 to 120%. To assess whether the calibration line goes through the origin involves an extrapolation of the line from 80% down to zero. With this approach it is quite likely that the line derived from the linearity study does not go through zero but the method actually is linear through zero. 

I recommend that an extra linearity standard is included in the linearity study at a concentration equivalent to 40%. This represents the actual linear range of the method and reduces the extent of the extrapolation required.”

 

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MTS Recommends... Getting it Write?

Getting It Write?

By R.D. McDowall, LCGC Europe, Volume 25, Issue 11, pp. 630-639, Nov 1, 2012 

Well written and easy to follow analytical procedures are critical in any lab but, as I often find during method transfer studies, the way a method is written can create confusion and errors. This article from Bob McDowall is a great read if you have the unenviable task of preparing procedures.

How Does the Update to Chapter 6 of the EU GMP Guidelines Affect You? - Part 2

In a previous blog post I summarised the proposed changes relating to method transfer in the public consultation document for Chapter 6 of the EU GMP Guidelines. Although the inclusion of the section on method transfer is the biggest revision to chapter 6, there are number of other proposed updates. In this blog post I will take a look at some of these.

Since the reason given for the changes is: ‘Inclusion of a new section on Technical transfer of testing methods and other items such as out of specification results’, and I have already dealt with method transfer, I will start with out of specification results. Under the section heading ‘Documentation’, there is a new requirement for: ‘a procedure for the investigation of Out Of Specification and anomalous results and Out Of Trend results’ (6.7)

The expectation that a QC laboratory will have a procedure detailing how they will deal with OOS results is long standing and most labs will already have this in place. The wording makes it clear that this procedure also needs to detail investigation of anomalous results and OOT results. These are typically investigated in the same way as OOS results.

Also under the Documentation heading, the recommendation that records are kept in a manner permitting trend evaluation has been updated to ‘should be recorded in a manner permitting trend evaluation’ with the additional sentence, ‘Any out of trend or out of specification data should be addressed and subject to investigation.’ (6.9)

Sampling is another area which has updates. In 6.11, referring to sample taking, there is an additional requirement that it ‘should be done and recorded in accordance with approved procedures.’ Therefore, if the sampling operation is not currently documented each time, it will need to be in future. In 6.12 there is an extra sentence: ‘the sampling plan used should be appropriately justified.’ It may be that the plan was devised sometime in the past and reasons which were so apparent then are no longer so clear. The requirement to justify the plan ensures that it is scientifically sound.

Under the Testing heading the paragraph regarding method validation (6.15) has been extended to include the following ‘A laboratory that is using a testing method and which did not perform the original validation (e.g. the use of a compendial method), should verify the appropriateness of the testing method.’ So even if a method is taken from a pharmacopeia its use in a particular laboratory needs to be shown to be suitable for the purpose for which it is being used. This assessment may conclude that no actual experimental work needs to be performed but some type of documentation should support this finding.

A new paragraph (6.20) has been inserted which reflects the importance of reference standards, making it clear that ‘Reference standards should be certified, qualified and verified as suitable for its intended use.’

The shelf life of analytical solutions, etc. is addressed in section 6.22. The requirement to mark with the date of preparation has been extended to opening date. Additionally: ‘Their in-use shelf life should be established/documented and scientifically justified.’

Finally, there are two new sections relating to the microbiological laboratory, these are:

‘6.21 Culture media should be prepared in accordance with the manufacturer’s requirements unless scientifically justified. The performance of all culture media should be verified prior to use.’

‘6.25 Microbiological media and strains should be decontaminated and disposed of in a manner to prevent the cross-contamination and retention of residues. The in-use shelf life of microbiological media should be established, documented and scientifically justified.’

In general, the emphasis of the updates is on scientific understanding and justification of the analytical methodology being used in the QC laboratory.

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Training Courses in London, April 2013: Analytical Method Validation & Transfer; Developing Stability Indicating HPLC Methods

In April, Mourne Training Services is offering 3 training courses in London. These are:

10th & 11th April 2013
Validation of Analytical Methods for Pharmaceutical Analysis

12th April 2013
Transfer of Analytical Methods for Pharmaceutical Analysis

15th & 16th April 2013
How to Develop Stability Indicating HPLC Methods

Click on the course titles above for more information about each course; including a course description, and a booking form containing costs and available discounts.

Submit the booking form or contact us by the 18th March to secure our early booking rate. The venue for the training is Jurys Inn Heathrow, convenient for travel by car or public transport.

If the dates don't suit you then take a look at our full course calendar for 2013. These courses are also available at our London location in November, and in Berlin (May, June & December) and Dublin (June).

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New Course: How to Develop Stability Indicating HPLC Methods

Pharmaceuticals need to be assessed for stability to support the assigned shelf life. Therefore, when analysing stability samples obtained from these studies analytical methods are required which are stability indicating, i.e. there is a measureable response which correlates with degradation, if present. HPLC is a popular technique for monitoring the decrease in drug and corresponding increase in degradation products due to its separating abilities. However, the HPLC method must be developed carefully to ensure that degradation products are both separated and detected appropriately. 

This year MTS is introducing a new 2-day course which will enable you to develop a suitable method. The course will describe strategies for performing forced degradation studies and selecting optimal HPLC method parameters to ensure that all relevant degradation products are separated.

The course dates and locations are as follows:

15^th & 16^th April 2013: Jurys Inn Heathrow, London, UK
17^th & 18^th June 2013: Steigenberger Hotel Berlin , Germany
11^th & 12^th November 2013: Jurys Inn Heathrow, London, UK
9^th & 10^th December 2013: GLS Campus Hotel Berlin , Germany

Contact us if you have any questions about the course, the full costs are detailed on the booking form, click here.

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How does the Update to Chapter 6 of the EU GMP Guidelines Affect Your Lab?

The European Commission has launched the public consultation of several revised GMP guidelines including Chapter 6: Quality Control (click here to view the document). The reason for change given is: "Inclusion of a new section on Technical transfer of testing methods and other items such as out of specification results." Since we specialise in method transfer at MTS (and offer a training course on the topic), we have put together a summary of the proposed updates. 

Although up to now the GMP guidelines did not explicitly refer to method transfer activities, for some time it has been an expectation that method transfer activities will both be performed and documented.  The updated guidance provides detail regarding the regulatory expectations for these activities. The new method transfer section is at the end of chapter 6 under the heading ‘Technical transfer of testing methods’.

The first part defines the expected pre-transfer activities: “Prior to transferring a test method, the transferring site should verify that the test method(s) comply with those as described in the Marketing Authorisation or the relevant technical dossier.” - It makes sense to check the method against the one submitted in the MA/technical dossier prior to transfer since you want to be sure that you are working on the right method version from the beginning.

It goes on: “The original validation of the test method(s) should be reviewed to ensure compliance with current ICH/VICH requirements.  A gap analysis should be performed and documented to identify any supplementary validation that should be performed, prior to commencing the technical transfer process.” - The original validation data should demonstrate that the method is fit for purpose, a key requirement before you start using it in another laboratory. The data will also provide information on the method capability, essential for evaluation of the success of the method transfer. My interpretation of the second sentence is that the gap analysis and identification of supplementary validation work is performed prior to the technical transfer process, which leaves open the possibility of using a co-validation approach for the actual transfer. 

The next part confirms that a written protocol is required for transfer (fairly standard in most laboratories) and provides guidance on what should be included: 

“The transfer of test methodology from one laboratory (transferring laboratory) to another laboratory (receiving laboratory) should be described in a written protocol. 

The protocol should include, but not be limited to, the following parameters: 

• identification of the relevant test method(s) undergoing transfer 
• identification of the additional training requirements 
• identification of standards and samples to be tested by both laboratories 
• identification of any special transport and storage conditions of test items 
• identification of the testing to be performed 
• the acceptance criteria which should be based upon the current validation study of the methodology and with respect to ICH/VICH requirements” 

These protocol requirements are straightforward. Points to note are: 

1. The requirement for documentation of the training requirements is formalised. 
2. Attention is drawn to transport and storage of samples, the purpose is to ensure that the same materials is analysed at both laboratories. This implies a comparative testing approach. 
3. The acceptance criteria should be based on the validation data. Whatever acceptance criteria were felt to be acceptable during validation may also be applied during transfer. My advice is to look at the actual data obtained when setting the transfer acceptance criteria, rather than just using the same values. This is particularly important when criteria are defined in a generic procedure.

The actual transfer is mentioned in terms of dealing with deviations and the requirements for the report are defined: “Deviations from the protocol should be investigated prior to closure of the technical transfer process. The technical transfer report should document the comparative outcome of the process and should identify areas requiring further test method revalidation, if applicable.”

Finally, it is recognised that some methods do not conform to the validation approach outlined in ICH, the particular example of NIR is quoted: “Where appropriate, specific requirements described in others European Guidelines, should be addressed for the transfer of particular testing methods (e.g. Near Infrared Spectroscopy)."

The other updates in Chapter 6 will be summarised in an additional blog very soon.

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