Tuesday 29 December 2015

Review of Lab-Related Regulatory Updates in 2015

At the beginning of 2015, the MHRA in the UK published a new guidance document on data integrity: MHRA GMP Data Integrity Definitions and Guidance for Industry. Originally released in January, it was revised in March for "Added clarifications in response to stakeholder questions". This 16 page document is primarily a set of definitions, as the title suggests, together with extra information on MHRA expectations. Although it is difficult to reach agreement on exactly what is meant by some data integrity terms, I think that the guidance does a good job of providing information on how the European GMP guidance should be interpreted with respect to data integrity.

In July, the US FDA published a new Guidance for Industry: Analytical Procedures and Methods Validation for Drugs and Biologics, July 2015. This 18 page guidance is harmonised with the ICH guidance Q2(R1), as you would expect, but provides additional detail on FDA expectations with respect to method development, content of methods, reference standards,verification of compendial methods, statistics, and method lifecycle management (including stability indicating methods, and transfer). I am a big fan of this guidance and would highly recommend a thorough read for anyone involved in managing methods. I particularly like the emphasis on method knowledge and understanding.

Also on the topic of data integrity, in September, the World Health Organization posted a new guidance on their website: Guidance on Good Data and Record Management Practices (September 2015) - Working document QAS/15.624. This 35 page document is currently a draft for comment for a restricted audience but it is readily available on the WHO website. I think that it provides a straightforward explanation of the key data integrity issues and has some good tables regarding practical implementation of ALCOA for paper and electronic records. Bearing in mind that it is a draft document I would recommend it as useful reading for anyone fairly new to the issues of data integrity to provide an understanding of the main concepts.

I haven't attempted to include pharmacopoeia updates in this blog post but there were a number of updates to both the European Pharmacopoeia and the United States Pharmacopeia. I refer you to the websites of each for more information.

 

Wednesday 11 November 2015

MTS Recommends... Using a Checklist Approach to Troubleshoot Retention Time Issues in (U)HPLC

Using a Checklist Approach to Troubleshoot Retention Time Issues in (U)HPLC
From the Chromatography Today Help Desk,
Chromatography Today, May/June 2015
ubleshoot Retention Time Issues in (U)HPLC - See more at: http://www.chromatographytoday.com/articles/hplc-uhplc/31/chromatography_today_help_desk/using_a_checklist_approach_to_troubleshoot_retention_time_issues_in_uhplc/1865/#sthash.MXY9TMlf.dpuf
Using a Checklist Approach to Troubleshoot Retention Time Issues in (U)HPLC - See more at: http://www.chromatographytoday.com/articles/hplc-uhplc/31/chromatography_today_help_desk/using_a_checklist_approach_to_troubleshoot_retention_time_issues_in_uhplc/1865/#sthash.MXY9TMlf.dpuf
Using a Checklist Approach to Troubleshoot Retention Time Issues in (U)HPLC - See more at: http://www.chromatographytoday.com/articles/hplc-uhplc/31/chromatography_today_help_desk/using_a_checklist_approach_to_troubleshoot_retention_time_issues_in_uhplc/1865/#sthash.MXY9TMlf.dpuf
Using a Checklist Approach to Troubleshoot Retention Time Issues in (U)HPLC - See more at: http://www.chromatographytoday.com/articles/hplc-uhplc/31/chromatography_today_help_desk/using_a_checklist_approach_to_troubleshoot_retention_time_issues_in_uhplc/1865/#sthash.MXY9TMlf.dpuf

Friday 16 October 2015

MTS Recommends... What’s in a Name?

What’s in a Name?
"Primary record is a term that was defined by the MHRA (Medicines and Healthcare products Regulatory Agency, the UK drug regulator) in data integrity guidance issued in 2015. In this instalment of Questions of Quality we explore what this term means in practice, and compare it with raw data in the European Union Good Manufacturing Practices (EU GMPs) and complete data in US Food and Drug Administration (FDA) GMPs. Why can’t we have harmonization of terms?"

Monday 21 September 2015

Help on: Where do the Acceptance Criteria used in Method Validation Come From?

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 know that for an assay method, typically the accuracy recoveries should be between 98 to 102% and the precision, expressed as %RSD, should be less than 2% but where do these values come from?"

Answer:
"A good place to start when you want to understand the significance of method validation acceptance criteria is to consider what the acceptance criteria actually mean. It is a way of expressing the amount of error that you are prepared to accept in the result generated by the method, or to put it another way, how far from the actual value would you still consider the result to be a reasonable estimation.

So how much error will you allow? Obviously you want the error to be as small as possible but it will depend on what is practically achievable. In a modern analytical laboratory, error is minimised by the competent use of suitable equipment. Examples include: analytical balances to minimise error during weighing operations; volumetric glassware to minimise error in solution preparation; and instrument maintenance and calibration to minimise error in measurements.

Since these approaches are common to all laboratories, the practically achievable amount of error is fairly constant and leads to the example you quoted: "for an assay method, typically the accuracy recoveries should be between 98 to 102% and the precision, expressed as %RSD, should be less than 2%".

However, it will depend on the complexity of both the sample preparation and measurement since this may involve more sources of error being present. For example, when a sample preparation involves a difficult extraction, such as a drug extraction from a cream or ointment then it is possible that there will be a higher level of error (when compared to simply dissolving the drug) and the typical acceptance criteria may not be achievable. A way to deal with this may be to accept the error but increase the replication of samples to gain higher confidence in the result. The measurement may also be subject to higher levels of error in some assays. For example, when using UV absorbance to measure a drug molecule which has a poor chromophore, the error may be higher than that present for a drug molecule which has a strong chromophore.

In method development all sources of error should be considered and minimised where possible so that the results generated by the method are the best estimate of the true value. In method validation the practically achievable level error is compared to values which are considered to be reasonable, based on experience of using analytical practices. Some flexibility in terms of acceptance criteria is advantageous for those circumstances where it is particularly difficult to control the sources of error in a method and where more generous acceptance criteria may be felt to be satisfactory. This is why I am of the opinion that it is good not to have generic acceptance criteria in regulatory guidance documents. It is helpful to include these in in-house guidance documents but flexibility is important which allows different criteria, if scientifically justified."

On the MTS course, Validation and Transfer of Methods for Pharmaceutical Analysis, you can learn more about acceptance criteria and their justification. The topic of analytical error is covered extensively in our new MTS course, Applying Data Integrity in the Laboratory; Minimising Analytical Error, part of our Laboratory Data Integrity programme. Visit the MTS website for more information.

 

Thursday 17 September 2015

What is Meant by 'Manual Integration'?

What is meant by 'manual integration'?
As a chromatographer of many years my understanding of the term 'manual integration' is that you view an individual chromatogram using chromatography software and use the mouse to move the cursor on the screen so as to adjust the peak start and/or peak end, resulting in the integration which you feel is most suitable to quantify that particular peak. It is a contentious procedure, since it is very susceptible to falsification. Small adjustments can make the difference between a passing or failing result.

If this sounds familiar then you should be aware that this is not always what is meant when people use the terminology, particularly regulatory inspectors. It is now commonly used to describe the process of reintegrating, i.e. changing the integration parameters from the original settings and reprocessing the chromatograms. It may be used even if the same integration method and thus parameters have been applied automatically by the software, and sample and standard chromatograms are all integrated in the same way.

A distinction between the terms 'manual intervention' and manual integration' has been suggested by R McDowall in his excellent article, 'Questions of Quality: Where Can I Draw The Line?' (a previous post under MTS Recommends...). I think it would be advisable to include this distinction both in a policy on manual integration and also in the training programme for chromatographers.

MTS are offering a new course, 'How to Improve Data Integrity in the Pharma Lab', as part of our Laboratory Data Integrity programme in which the topic of chromatographic integration, including manual integration, will be explored fully. Visit the MTS website for more information.

 

Thursday 10 September 2015

MTS Recommends... How to Estimate Error in Calibrated Instrument Methods - And Why We Have Stopped Doing It!

How to Estimate Error in Calibrated Instrument Methods—And Why We Have Stopped Doing It!

By Tony Taylor in The LCGC Blog,
Aug 18, 2015

"So when was the last time you reported your results with an estimate of the error associated with the data?"

Tuesday 25 August 2015

MTS Recommends... Moving On to Implementation for Elemental Impurities Testing

Moving On to Implementation for Elemental Impurities Testing
Pharmaceutical Technology Outsourcing Resources Supplement 39 (17) 2015.

"After a long wait for the new elemental impurities guidelines, the bio/pharma industry must now look ahead to implementation and take action."

Friday 14 August 2015

MTS Recommends... A Risk-Based Approach to Data Integrity

A Risk-Based Approach to Data Integrity 
By Kurt In Albon, Daniel Davis, PhD, James L. Brooks, Pharmaceutical Technology, Volume 39, Issue 7, pg 46–50, Jul 02, 2015

"Heightened regulatory scrutiny of data integrity highlights the need for comprehensive procedural reviews and strategies for managing mission-critical information."

Tuesday 4 August 2015

New Guidance for Industry from FDA: Analytical Procedures and Methods Validation for Drugs and Biologics

The FDA has issued a new guidance for Industry: Analytical Procedures and Methods Validation for Drugs and Biologics, July 2015. This guidance was previously reviewed on the MTS blog when it was first published as a draft in early 2014 and there are no major changes from the draft version.

I will be presenting a lecture on this new guidance at the upcoming conference, 'Analytical Method Development, Validation and Transfer', on the 15th September at the Maritim proArte Berlin, Germany. The overview of the presentation is as follows:

Reviewing the 2014 FDA CDER/CBER Draft Guidance: Analytical Procedures and Methods Validation for Drugs and Biologics
  • Overview of the guidance including key recommendations and impact on industry
  • Exploring recommendations for lifecycle management including revalidations and comparability studies
I'll post a summary of the lecture here on the MTS blog after the event.

 

Tuesday 23 June 2015

Update to MTS Course Calendar 2015

The MTS Course calendar for 2015 has been updated to include our new courses on Laboratory Data Integrity. Check out the new calendar for open enrolment dates in 2015 at locations in the UK, Ireland and Germany for this new event!

 

Monday 22 June 2015

New Training Course: Laboratory Data Integrity

MTS is offering a new training course on the topic of Laboratory Data Integrity. The course is made up of three days, you can attend any preferred combination of days:

1: Introduction to Laboratory Data Integrity; cGMP in the Pharma Lab
Day 1 introduces the fundamental concepts of laboratory data integrity in the context of working within a quality management system and as such this course also acts as an introduction/refresher to laboratory cGMP.

2: Applying Data Integrity in the Laboratory; Minimising Analytical Error
Day 2 deals with the effects of analytical errors on laboratory data integrity. This involves building an understanding of the nature and sources of analytical errors so that their effects can be minimised during testing, leading to high standards of data integrity and reduced numbers of OOS/OOE results due to laboratory errors.

3: How to Improve Data Integrity in the Pharma Lab
Day 3 focusses on improving laboratory data integrity and associated quality management systems by review of laboratory processes to identify data integrity risk, and implementation of appropriate solutions, paying particular attention to deficiencies that are commonly cited by regulatory authorities.

Visit the MTS website for more information and details of the open enrolment dates and locations.

 

Tuesday 16 June 2015

MTS Recommends... Questions of Quality: Where Can I Draw The Line?

Questions of Quality: Where Can I Draw The Line?

By R.D. McDowall
LCGC Europe
Volume 28, Issue 6
Jun 10, 2015

"A question that keeps raising its head when working in a regulated laboratory is can chromatographers integrate peaks manually? If they can, when can they do it? Also if they can manually integrate, when should they not do it?"

Friday 12 June 2015

'Validation & Transfer of Methods for Pharmaceutical Analysis' Approved by Royal Society of Chemistry

MTS Course approved by Royal Society of Chemistry

The MTS course,  'Validation & Transfer of Methods for Pharmaceutical Analysis' has been approved by the Royal Society of Chemistry for purposes of continuing professional development.

Approval of training courses by the Royal Society of Chemistry is a process of peer review involving members that are experts in their field. This process provides assurances to customers that an approved course has been independently verified to be of high quality and suitable for professional development.

Future training certificates for this course will include the RSC logo and the phrase, 'This course is approved by the Royal Society of Chemistry for purposes of continuing professional development.' 

 

Friday 20 March 2015

Course: Validation and Transfer of Methods for Pharmaceutical Analysis

Summary:
Course: Validation and Transfer of Methods for Pharmaceutical AnalysisThis course will provide you with the requisite scientific knowledge and understanding of analytical method validation, verification and transfer to allow informed interpretation of current regulatory guidance from EMA, FDA and ICH, e.g. Q2(R1).

The data generated using analytical test methods is essential for many of the critical decisions made in the pharmaceutical industry. To be confident in the integrity of this data it is crucial that the methods are fit for purpose. To demonstrate that a method is fit for purpose will require either a validation, verification or transfer study, depending on the source of the method in question.
This course provides a detailed explanation of how these studies are performed, 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.

The full course takes place over 3 days but if preferred, it is possible to attend the first 2 days only for a method validation course or the last day only for a method transfer and verification course. In the case of attendance on the last day only it is essential that delegates are familiar with validation characteristics since these are used for method transfer and verification. Click here for Agenda & Detailed Course Description (printer friendly)

Suitable for:
Anyone who needs to understand how methods are validated, verified or transferred, either to design and carry out the investigation, or to interpret the data generated. For example: Analytical chemists, laboratory managers/supervisors, quality control analysts/managers, quality assurance managers, and regulatory affairs managers.

Included:
Comprehensive course handouts; Certificate of Attendance; access to training resources via e-MTS; optional post training assessment (leading to Certificate of Training); post training support; and a copy of the MTS training book, Validation of Analytical Methods for Pharmaceutical Analysis. Lunch and refreshments are included for open enrolment training courses.

Availability:

Open Enrolment Training
Click here for Costs & Online Booking Form.

London, UK - 22nd to 24th April 2015
Venue: Hilton Garden Inn, London Heathrow Airport (formerly Jurys Inn Heathrow)
For early bird savings, book on this course before 25th March.

Dublin, Ireland - 27th to 29th May 2015
Venue: Metro Hotel Dublin Airport
For early bird savings, book on this course before 29th April.

London, UK - 30th September to 2nd October 2015
Venue: Hilton Garden Inn, London Heathrow Airport (formerly Jurys Inn Heathrow)
For early bird savings, book on this course before 2nd September.

Berlin, Germany - 30th November to 2nd December 2015
Venue: GLS Campus Berlin
For early bird savings, book on this course before 2nd November.

On-site Training
The course may be delivered at your site; this option includes customisation to meet your specific requirements. Contact us for a quotation.

Visit the Course List page on our website for full details of all our available training courses in 2015.

 

Wednesday 18 March 2015

New 'Data Integrity Definitions' Guidance from MHRA


The MHRA has published a new set of guidance relating to data integrity: Good manufacturing practice: data integrity definitions. First published on 23rd January 2015, the guidance was revised on 13 March 2015 following stakeholder feedback.

The description provided on the MHRA website reads as follows:

"This guidance sets out our expectations for data integrity in good manufacturing practice (GMP).

It complements existing EU GMP guidance and should be read in conjunction with national medicines legislation and the GMP standards published in Eudralex volume 4."


MTS offers a range of services related to laboratory data integrity including auditing, training courses, and consultancy. Our new training course, 'Laboratory Data Integrity', is comprised of three days, you can attend any preferred combination of days: 

1: Introduction to Laboratory Data Integrity; cGMP in the Pharma Lab
Day 1 introduces the fundamental concepts of laboratory data integrity in the context of working within a quality management system and as such this course also acts as an introduction/refresher to laboratory cGMP.

2: Applying Data Integrity in the Laboratory; Minimising Analytical Error
Day 2 deals with the effects of analytical errors on laboratory data integrity. This involves building an understanding of the nature and sources of analytical errors so that their effects can be minimised during testing, leading to high standards of data integrity and reduced numbers of OOS/OOE results due to laboratory errors.

3: How to Improve Data Integrity in the Pharma Lab
Day 3 focusses on improving laboratory data integrity and associated quality management systems by review of laboratory processes to identify data integrity risk, and implementation of appropriate solutions, paying particular attention to deficiencies that are commonly cited by regulatory authorities.

Visit the MTS website for more information and details of the open enrolment dates and locations, or Contact us to find out more.

 

Monday 2 March 2015

Upcoming Courses from Mourne Training Services:

22nd to 24th April 2015 in London, UK:Upcoming Courses from Mourne Training ServicesValidation and Transfer of Methods for Pharmaceutical Analysis
Venue: Hilton Garden Inn, London Heathrow Airport

19th to 20th May in London, UK:
How to Develop Stability Indicating HPLC Methods 
Venue: Hilton Garden Inn, London Heathrow Airport
27th to 29th May 2015 in Dublin, Ireland
Validation and Transfer of Methods for Pharmaceutical Analysis
Venue: Metro Hotel Dublin Airport

Visit the Course List page on our website for more information on these courses and for full details of all our available training courses in 2015.

 

Wednesday 25 February 2015

MTS Recommends... Life Cycle Risk Assessment of HPLC Instruments


By Paul Smith, R.D. McDowall
LCGC Europe
Volume 28 Number 2
Pages 110-117
Feb 01, 2015

"What does risk assessment in the context of the life cycle of a high performance liquid chromatography (HPLC) instrument really mean? This instalment of "Questions of Quality" will look at problems with an operational liquid chromatograph to see if they can be picked up in the performance qualification (PQ) or prevented in the operational qualification (OQ). The relationship between PQ and OQ and the design qualification (DQ) phases of the life cycle are also explored."

Tuesday 10 February 2015

Course: How to Develop Stability Indicating HPLC Methods

How to Develop Stability Indicating HPLC Methods - Training Course from Mourne Training ServicesSummary:
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 measurable 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 two day training course is designed to provide a thorough understanding of how to develop HPLC methods specifically designed for stability indicating analysis of pharmaceuticals. 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.
Click here for Agenda & Detailed Course Description (printer friendly)

Suitable for:
This course is ideal for those who have some experience of using HPLC and need to ensure that they are stability indicating.

Included:
Comprehensive course handouts; Certificate of Attendance; access to training resources via e-MTS; optional post training assessment (leading to Certificate of Training); and post training support. Lunch and refreshments are included for open enrolment training courses.

Availability:

Open Enrolment Training
Click here for Costs & Online Booking Form.

London, UK - 19th & 20th May 2015
Venue: Hilton Garden Inn, London Heathrow Airport
For early bird savings, book on this course before 21st April.

Dublin, Ireland - 21st & 22nd September 2015
Venue: Metro Hotel Dublin Airport
For early bird savings, book on this course before 25th August.

Berlin, Germany - 26th & 27th November 2015
Venue: GLS Campus Berlin
For early bird savings, book on this course before 25th August.

On-site Training
The course may be delivered at your site; this option includes customisation to meet your specific requirements and may include ‘hands-on’ sessions using the instruments in your labs.
Contact us for a quotation. Visit the Course List page on our website for full details of all our available training courses in 2015.

 

Monday 5 January 2015

Help on: The Use of 'Test Injections' in Chromatography

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.
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 have noticed that in recently published FDA warning letters, the use of 'test injections' comes up as an adverse observation quite regularly. Does this mean that I shouldn't use test injections prior to HPLC analysis? I usually perform one or more injections before system suitability to make sure that the chromatography is as expected, since sometimes the first injection is not the same as those injected afterwards."

Answer:
Help on: The Use of 'Test Injections' in Chromatography"Most chromatographers would agree that it is quite legitimate to perform an injection to check if the system is ready to use and that for some methods the test injection may be different to subsequent injections. Thus 'test injections' are a common feature in many analytical laboratories.

Unfortunately, the practice was seemingly willfully misinterpreted in some laboratories to provide an opportunity to falsify data and this has resulted in intense scrutiny of the use of 'test injections' during regulatory inspections.

My main piece of advice is that it should not be necessary to use the sample solution (i.e. the test solution prepared from the material that you will generate a reportable result for) for a test injection and it is wise to avoid this. In my opinion, a test solution which was prepared for use as a standard would be appropriate as a test injection but even this approach has come under suspicion due to observed manipulation of the data from sequences of standard injections.

Therefore, an explicit procedure which details exactly how test injections will be used and also how the results will be recorded is advisable. Storing test injection raw data (e.g. chromatograms) separately to the data for the analysis (i.e. in a different file electronically) is often seen as suspicious. Obviously, knowledge of the contents of this SOP is essential for all analysts using HPLC. This information could be included in a generic HPLC SOP which details other important information, e.g., use of blank injections, system suitability, injection sequence setup, integration policy, etc.

Since the use of a test injection is usually method specific it would also be advantageous if relevant information was included in the particular analytical method."

Guidance on this topic is available from the FDA in their draft guidance on data integrity, click here.

The topic of 'test injections' is an important data integrity issue and is thoroughly examined in the MTS course, Laboratory Data Integrity. Visit the MTS website for more information.


 

Friday 2 January 2015

2015 Training Course Schedule from MTS

2015 Training Course Schedule from MTS
Our 2015 schedule is now available. You can choose from topics such as analytical method validation, method transfer and/or method development in London, Dublin or Berlin. Book early for the discounted rate!

Visit the Course List page on our website for full details.