Help on: How Many Times can System Suitability Tests be Repeated?

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:

“How many times can a system suitability test for an HPLC method be repeated?”

Answer:

“If your question refers to repeating the system suitability test after a failure without making any changes to the system then the number of times this can be done is zero. The reasoning for this statement is as follows: The purpose of the test is to check that the method is performing as expected, if it fails then it indicates that there is a problem and then the source of that problem needs to be identified and corrected before the system suitability can be performed again. Admittedly, on many occasions only a probable cause can be identified and an investigation will involve making a change and then using the system suitability test to see it the problem has been corrected. Therefore, provided that there is a justifiable reason (some type of hypothesis about what has caused the failure) each time the test is carried out, I can see no reason why there should be a limit of the number of times the system suitability test is performed. The aim is to ensure that the method is completely controlled by the analyst.”

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MTS Recommends... Forced Degradation Studies in ANDA Submissions

FDA Perspectives: Scientific Considerations of Forced Degradation Studies in ANDA Submissions

Pharmaceutical Technology, May 2, 2012, By Ragine Maheswaran

The author outlines the scientific aspects of forced degradation studies that should be considered in relation to ANDA submissions.

MTS 2013 Course Calendar Now Available

The full calendar for MTS training courses in 2013 is now available. We are offering a range of courses in London, Berlin and Dublin. Topics are: validation and transfer of analytical methods; developing stability indicating methods using HPLC; an introduction to HPLC; HPLC troubleshooting; and HPLC method development. Early bird discounts apply up to 4 weeks prior to course dates. More information, including the cost, is available on the Course List page of the website.
 
Click on the image to view our new course calendar for 2013:

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MTS Recommends... Quality by Design for Analytical Methods: Implications for Method Validation and Transfer

Quality by Design for Analytical Methods: Implications for Method Validation and Transfer

Pharmaceutical Technology, Volume 36, Issue 10, pp. 74-79,Oct 2, 2012, By Phil Nethercote & Joachim Ermer

The authors describe how traditional approaches to analytical method and validation may benefit from alignment with quality-by-design concepts.

MTS Recommends... Using Reference Materials

Using Reference Materials – Commonly Encountered Errors and How to Avoid Them

The Column, 7 November 2012, Volume 8, Issue 20, Pages 10 to 15, by Jenny Button

The purity value assigned to a reference standard is something that we often take for granted but it only applies for as long as the reference material is used correctly. This article contains helpful practical advice on how to use reference materials and ensure accurate analytical results.

Validation & Method Transfer Training in London 12th to 14th Sep 2012 at Jurys Inn Heathrow

Book before 15th August for early bird savings.

These training courses from Mourne Training Services will enable you to demonstrate that your analytical methods are fit for purpose. They are suitable for anyone involved in the validation and/or transfer of methods. The 2 day validation course will give you a full understanding of validation performance characteristics to allow informed interpretation of ICH Q2(R1). The 1 day method transfer course will provided a step by step guide to achieving successful transfer of analytical methods.
Visit the MTS website for more information and the online booking form.

Tips for Successful Method Transfer

Transferring an analytical method from one laboratory to another should be straightforward but unfortunately it is a process which is often problematic. Recognition of this has resulted in a new USP chapter <1224> Transfer of Analytical Procedures, and a proposal for inclusion in an update of the EU GMP regulations.

The most common source of problems is the analytical method itself. Either the method is not robust, or it may be that it has not been well written, leading to potential misinterpretation. Prevention of these issues involves a thorough review of the method by the sending laboratory prior to any transfer attempt. The robustness of the method should be assessed by investigating the critical method factors. If lack of robustness is identified, then either further method development or implementation of control strategies will be required. Running the method at the receiving laboratory is a good way to check that the method can be followed in a consistent fashion and that the staff and facilities at the receiving laboratory are satisfactory. This analysis should NOT be considered as part of the transfer, rather it is a pre-transfer activity. These measures should help to ensure that the prospects for a successful transfer are good.

Mourne Training Services is introducing a new training course to deal with the topic of transferring analytical methods for pharmaceuticals, which will be held at locations throughout Europe in 2012. In this one day course the different approaches to transfer are explored fully and case studies are used extensively to follow the process from review of the method prior to transfer, to creating a suitable protocol with relevant acceptance criteria, and evaluating the results generated to assess whether the transfer has been successful.

Visit the MTS website for information on where and when the course will be offered, the discounts available including our early booking rate, an online booking form and a detailed course description.

This course is ideal for anyone involved in the transfer of analytical methods. For example: Analytical chemists, laboratory managers/supervisors, quality control analysts/managers, quality assurance managers, and regulatory affairs managers.

Please note: Familiarity with the characteristics studied during analytical method validation is necessary for this course since these are used for method transfer. The MTS course, Validation of Analytical Methods for Pharmaceutical Analysis, is recommended.

MTS Recommends... Product Focus: High-Purity Laboratory Water Systems

Product Focus: High-Purity Laboratory Water Systems

By: Angelo DePalma, Ph.D - Published: 9th July 2012, Lab Manager Magazine

The water used to prepare HPLC mobile phase is a common source of contamination problems. It is critical that a suitable water purification system is selected and maintained. This article provides an interesting overview of the available laboratory options.

HPLC Training Courses in the UK

I will be delivering a series of HPLC training courses in the UK this October. The details are as follows:

How to Run HPLC Methods
London, 11th October 2012
Edinburgh, 17th October 2012

How to Troubleshoot HPLC
York, 10th October 2012
London, 12th October 2012
Warrington, 16th October 2012
Edinburgh, 18th October 2012

How to Develop HPLC Methods for Challenging Separations
Warrington, 15th October 2012

These courses are sponsored by Phenomenex. For more information: Tel 01625 501367 or email ukinfo@phenomenex.com.

Validation & Transfer of Analytical Methods 2012

In 2012, Mourne Training Services is offering two courses at locations throughout Europe on the topic of analytical methods for pharmaceuticals: a two day course on validating methods and a one day course on transferring methods.  The courses are ideal for anyone who is involved in the validation or transfer of analytical methods; for example:  analytical chemists, laboratory managers/supervisors, quality control analysts/managers, quality assurance managers, and regulatory affairs managers. 

Included in the course fees: Comprehensive course handouts containing useful reference material; Certificate of Attendance; access to training resources via e-MTS;  optional post training assessment (leading to Certificate of Training); Expert Advice from the MTS trainer on your method validation and transfer challenges, both on the day of the training and after the event; and lunch and refreshments. Delegates on the course, Validation of Analytical Methods for Pharmaceutical Analysis, will receive a copy of the MTS training book of the same name.

Validation of Analytical Methods
for Pharmaceutical Analysis

The data generated using analytical methods is essential for many of the critical decisions made in the pharmaceutical industry. To be confident in the reliability of this data it is crucial that the methods are fit for purpose. Analytical method validation is the process of demonstrating that a method is suitable for its intended use. This two day course  provides a detailed explanation of how analytical methods are validated, enabling a full understanding of method performance characteristics and associated statistics, and how they are applied to the techniques used for analysing drug related samples. This knowledge will enable informed interpretation of the regulatory guidance on validation, namely ICH Q2(R1) and guidance from FDA and EMA on bioanalytical methods.  

The approach of this course is to focus on the principles of method validation thereby enabling application to different types of samples and analytical techniques. Case studies are employed to allow consideration of real life scenarios. Examples relating to small molecule drug substances and formulated products; to physiochemical methods for biotechnological/biological products; and to bioanalysis are included. Particular attention is paid to the most common analytical techniques used for pharmaceutical analysis, e.g., High Performance Liquid Chromatography (HPLC). 

Click here for more information  

Course Schedule:

London, UK - 12th & 13th September 2012

Basel, Switzerland - 25th & 26th September 2012

Dublin, Ireland - 23rd & 24th October 2012

Manchester, UK - 13th & 14th November 2012

Berlin, Germany - 27th & 28th November 2012 

Course Fees

UK: Early bird offer : £850 + VAT per person. Additional delegates from the same company: £750 + VAT per person. Full price: £950 + VAT per person.
Other Europe: Early bird offer: €1050 + VAT per person. Additional delegates from the same company: €925 + VAT per person. Full price: €1175 + VAT per person.  

Early Bird Savings Available up to 4 Weeks Before the Course Date


Transfer of Analytical Methods
for Pharmaceutical Analysis  

Transferring an analytical method from one laboratory to another should be straightforward but unfortunately it is a process which is often problematic. Recognition of this has resulted in a new USP chapter <1224> and a proposal for inclusion in an update of the EU GMP regulations. In this one day course the different approaches to transfer are explored fully and case studies are used extensively to follow the process from review of the method prior to transfer, to creating a suitable protocol with relevant acceptance criteria, and evaluating the results generated to assess whether the transfer has been successful.  

Please note: Familiarity with the characteristics studied during analytical method validation is necessary for this course since these are used for method transfer. The MTS course, Validation of Analytical Methods for Pharmaceutical Analysis, is recommended.

Click here for more information  

Course Schedule:

London, UK - 14th September 2012 
Basel, Switzerland - 27th September 2012 
Dublin, Ireland - 25th October 2012 
Manchester, UK - 15th November 2012

Berlin, Germany - 29th November 2012

Course Fees  
UK: Early bird offer: £495 + VAT per person. Additional delegates from the same company: £435 + VAT per person. Full price: £545 + VAT per person.  
Other Europe: Early bird offer: €610 + VAT per person. Additional delegates from the same company: €540 + VAT per person. Full price: €675 + VAT per person.

Early Bird Savings Available up to 4 Weeks Before the Course Date

Attending Both Courses?

Course Fees  UK: Early bird offer: £1225 + VAT per person. Additional delegates from the same company: £1125 + VAT per person. Full price: £1375 + VAT per person. Other Europe: Early bird offer: €1525 + VAT per person. Additional delegates from the same company: €1390 + VAT per person. Full price: €1715 + VAT per person.

Book online now to secure your place

MTS Recommends... HPLC Systems and Components Introduced at Pittcon 2012: A Brief Review

HPLC Systems and Components Introduced at Pittcon 2012: A Brief Review
By: Michael Swartz, 1st April 2012, LCGC North America
An interesting review. Includes new introductions for Supercritical Fluid Chromatography (SFC), UHPLC and Detectors.

Implementing Robustness Testing for HPLC Methods - Part 3

The third article on implementing robustness testing for HPLC methods has now been published. Mobile phase buffers this time. Click here to read the article.

Click here for Part 1
Click here for Part 2 

Help on: Robustness factorial design for GC

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 analytical method and I want to look at robustness testing by factoral design. I have never done this before and was hope you could point me in the right direction for what kind of set up I could use. It’s a GC method with a temperature ramp, fairly standard in all other aspects.”

Answer:
"The first step in any robustness study is to select the factors and levels which you are going to investigate. The most common factors investigated for GC methods are the temperatures (injector, detector and column), the flow rate of the carrier gas, and if applicable, the split ratio. Also, if it is a headspace method then some of those method variables may be important for the robustness of the method. The limits typically investigated are approx +/- 10% but really it is up to you to decide how much variation is likely to be experienced in routine use of the method. It may be unlikely that anywhere near 10% variation will be experienced.

The experimental design for the robustness testing could be simply by investigation of each parameter at two extreme levels (above and below that in the method) whilst holding everything else constant, the one factor at a time (OFAT) approach. Alternatively, you have asked about using a factorial design. In this approach the identified factors are investigated simultaneously. This does require an understanding of both how factorial design is applied and how to interpret the necessary statistics that are generated. A commonly used design for analytical methods is the Plackett-Burman design, which can be used for up to 7 factors in 8 runs.

I think that I would recommend that you invest in a suitable design of experiments software package if you decide use a factorial design approach. The training on the package, even if it is just going through the manual, should help you to understand how they are applied and also the limitations of the approach. If you feel that there are only 4 or less factors that are likely to have an effect on the robustness of the method then an OFAT approach may be easier and less time consuming, since the number of experiments will be similar and the time taken to get to grips with using factorial design won’t be necessary."

MTS Recommends... New Chromatography Columns and Accessories at Pittcon 2012

The 2012 round-up from Ron Majors on the new columns etc. at Pittcon is now available in LCGC North America.These articles provide a very useful summary of the latest developments in separation products.

Click here for part I, Apr 1, 2012
Click here for part II, May 1, 2012

Help on: Retention Time Change

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 working with TFA in my mobile phase and my analyte elutes at 13.5 minutes. In the same day the retention time has changed by 0.2 minutes. It is normal? I'm using an isocratic method.”

Answer:
"If you experience a change in retention time during a run then it indicates that something in the method conditions is changing, most likely a temperature or mobile phase pH shift. In my opinion, 0.2 minutes is a very small change for a peak at 13.5 minutes (~1.5%) and may not necessarily be a big problem. However if the shift continues, it may become an issue. I suggest that you check the following:

• Is the column temperature controlled? If not, then that is probably the source of the RT shift and if you have no way to introduce temperature control then you will experience RT shift. If you do have a column oven, then ensure that it is working correctly and that there is a suitable length of tubing to and from the column also being temperature controlled.
• Is your analyte ionisable? TFA is a very useful acid modifier for HPLC mobile phases and is successful for a range of molecules. However it is an acid modifier rather than a buffer and so some ionisable analytes may not be suitably pH controlled using only TFA.

If the problem does not escalate then it is probably fine to continue. I suggest that you monitor the retention time change. For example, does it slowly change over the course of the run or suddenly shift, or does it always change in one direction (increasing or decreasing retention time)?"

HPLC Training Courses in Dublin, June 2012

Mourne Training Services is delighted to offer 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 split into three topics:

1) an introductory programme which will demystify the parameters listed in HPLC methods;

2) a full treatment on troubleshooting HPLC systems and thus reducing downtime; and,

3) a two part method development course in which a strategic approach will enable you to develop HPLC methods quickly and efficiently. The two parts can be taken together for a complete method development course, or separately for maximum flexibility.

Book before 11th May 2012 for discounted course fees

We are offering the following discounts until 11th May 2012:

€275 per person per day, 2 days for €520 or 3 days for €740.

Academic discounts and group discounts also available up to 11th May, contact us for a quote.
After 11th May all courses are charged at full price of €350 per person per day.
Note: All prices are quoted exclusive of VAT.

Included in the Course Fees:

• Comprehensive handouts for each course containing useful reference data.
• Free tools to help you use HPLC efficiently, For example: Column equilibration calculator; Calculator for preparing mobile phase reagents; Method development calculator; Troubleshooting lookup tables; Calculator for working out how much mobile phase to prepare (for both isocratic & gradient methods).
• 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.

The Courses:

5th June 2012 How to Run HPLC Methods

If you book on this course before the 11th May, we will give you a free copy of the book, 'An Introduction to HPLC for Pharmaceutical Analysis'.

6th June 2012 How to Troubleshoot HPLC 

7th June 2012 How to Develop HPLC Methods - Part 1 

8th June 2012 How to Develop HPLC Methods - Part 2 (for Challenging Separations)

The training runs from 9:00am to 4:45pm each day. The venue is the Metro Hotel Dublin Airport, conveniently located just off Junction 4 of the M50.

Click here for a printer friendly flyer for these training courses.

MTS Recommends... Efficient HPLC Method Development and Personal Reflections

Efficient HPLC Method Development and Personal Reflections
By: Lloyd R. Snyder, 1st April 2012, LCGC North America
'A pioneer in high performance liquid chromatography reflects on his career and how "enlightened trial-and-error" can reduce the effort involved in method development.'

Implementing Robustness Testing for HPLC Methods - Part 2

The second in my series of articles on how to implement robustness testing for HPLC methods has been published by Separation Science. Click here to read the article.

Click here for Part 1
Click here for Part 3

MTS Recommends... What it Takes to Run HPLC/UHPLC

What it Takes to Run HPLC/UHPLC

By: Angelo DePalma, Ph.D - Published: 20th January 2012, Lab Manager Magazine

This article looks at running HPLC and UHPLC systems in terms of cost of ownership and provides an interesting evaluation on the cost versus benefits of adopting higher efficiency chromatography options.

MTS Recommends... RP-SPE Method Development

The Partition Coefficient (log P), Distribution Coefficient (log D) and Acid Dissociation Constant (pKa): Knowing Your Compound for Solid-Phase Extraction Method Development in Reversed-Phase Mode
By: Michael Rummel, 1st Feb 2012, The Column, Volume 8, Issue 2

HPLC Training Courses in the UK

This March I will be presenting a series of HPLC training courses in the UK. The details are as follows:

How to Develop HPLC Methods for Challenging Separations

Wednesday 21st March 2012, F.E.R.A Lakeside Conference Centre, York
Thursday 22nd March 2012, Edinburgh Conference Centre, Edinburgh
Monday 26th March 2012, Denham Grove, London

How to Validate Chromatographic Methods
Friday 23rd March 2012, Edinburgh Conference Centre, Edinburgh
Tuesday 27th March 2012, Denham Grove, London
Thursday 29th March 2012, Daresbury Park, Warrington

How to Run HPLC Methods
Wednesday 28th March 2012, Daresbury Park, Warrington

These courses are sponsored by Phenomenex. For more information: Tel 01625 501367 or email ukinfo@phenomenex.com.

Implementing Robustness Testing for HPLC Methods - Part 1

The first in a series of articles that I have written about how to implement robustness testing for HPLC methods has been published by Separation Science. Click here to read the article.

Click here for Part 2

Click here for Part 3

MTS Recommends... pKa Table

pKa information is very useful when choosing mobile phase buffers for HPLC analysis. Click here to access a table of pKa values for common functional groups.