MTS Recommends... Analytical Procedure Lifecycle Management: Current Status and Opportunities

Analytical Procedure Lifecycle Management: Current Status and Opportunities

By Andy Rignall et al. in Pharmaceutical Technology, Volume 42, Issue 12, pg 18–23, Dec 02, 2018

Drawing on practical experience, the authors examine key questions and answers about various aspects relating to the enhanced approach for analytical procedure lifecycle management.

Click here to read the article.

Update of ICH Q2 'Validation of Analytical Procedures' Announced

At the ICH meeting in Kobe, Japan in June it was decided that the ICH guidance, 'Q2(R1): Validation of Analytical Procedures: Text and Methodology' would be revised and that an additional guidance, Q14, would be prepared on the topic of Analytical Procedure Development. Since the method validation guidance dates back to 1996, it is good news that an update is in the pipeline although it may be some time before the new version is ready. It will also be very interesting to see what the new method development guidance suggests.

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MTS Recommends... What's New In MHRA's Revised Data Integrity Guidance — A Detailed Analysis

What's New In MHRA's Revised Data Integrity Guidance — A Detailed Analysis 

A very detailed summary of all the changes in this guidance from the original GMP guidance issued in 2015, and the draft GxP version released in 2016.

By Barbara Unger
Pharmaceutical Online, March 19, 2018

Guidance on GxP Data Integrity from MHRA Finalised

The GxP Data Integrity guidance from MHRA has now been finalised.

From the MHRA Website:

"The guidance is intended to be a useful resource on the core elements of a compliant data governance system across all GxP sectors (good laboratory practice, good clinical practice, good manufacturing practice, good distribution practice and good pharmacovigilance practice).

It addresses fundamental failures identified by MHRA and international regulatory partners during GLP, GCP, GMP and GDP inspections; many of which have resulted in regulatory action."

If you need help on evaluating or improving data integrity in your laboratory then MTS can help. We offer auditing services to identify your data integrity issues, consultancy advice on how to assess data integrity risk, perform a gap analysis and implement remediation measures, and customised training courses to inform your staff about data integrity principles and problems so that they are fully engaged with your data governance systems.

Contact us to find out more about how MTS can help you with your data integrity requirements.

Read more about the new guidance on the MHRA website.
Click here for the finalised MHRA guidance.

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Data Integrity: New guidance now available on EMA’s website

The European Medicines Agency (EMA) has released new good manufacturing practice (GMP) guidance to ensure the integrity of data that are generated in the process of testing, manufacturing, packaging, distribution and monitoring of medicines.

The guidance consists of 23 questions and answers which cover a range of topics within data integrity, including aspects of the data lifecycle and associated risks, and a table which provides the link between each ALCOA principle and the existing EU GMP published in Eudralex Chapter 4 (this may be very useful for auditors new to data integrity).

MTS Recommends... WHO launches data integrity guidelines to protect patients all over the world

WHO launches data integrity guidelines to protect patients all over the world (click here to read about the guidance on the WHO website)

Annex 5 Guidance on good data and record management practices (click here for the guidance)

New Data Integrity Guidance from FDA

FDA published a new draft Guidance for Industry in April 2016 entitled, 'Data Integrity and Compliance with CGMP', the purpose of which is to clarify the role of data integrity in CGMP for drugs and the agency's current thinking on the creation and handling of data in accordance with CGMP requirements.

The document takes the form of a series of questions and answers on data integrity issues, it is assumed that these are representative of the questions commonly asked of FDA. These include several questions which were previously posted as Level 2 guidance on the FDA website (now removed) on the topics of: paper versus electronic records; shared login accounts; and use of actual samples for 'trial' injections.

I particularly like the use of the terms 'static' and 'dynamic' (previously used in the guidance: MHRA GMP Data Integrity Definitions and Guidance of Industry March 2015) to differentiate between the different types of electronic records obtained from laboratory instruments. It is a big improvement on the previous explanation of why paper printouts were not always a viable substitute for electronic records.


MTS offers a range of services related to data integrity, click here to find out more.

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Data Integrity Services from MTS Ltd

In recent years data integrity has become a 'buzz' term in the pharmaceutical industry due to the regularity of problems being given the label during regulatory inspections. Mourne Training Services Ltd (MTS) has significant expertise in this area since integrity of data is the primary aim of all the services we offer.

MTS offers specific Training, Auditing and Consulting services relating to data integrity.

Training 
Courses in data integrity may be required to achieve a number of different outcomes such as:

• Demonstrate commitment to data integrity in the laboratory;
• Raise awareness for all staff to understand the issues surrounding laboratory data integrity and how it affects them;
• Strengthen laboratory quality management systems to improve data integrity and remove falsification potential

MTS has worked with customers to design training that met these outcomes, which was customised to their unique requirements in terms of content and timings. We can do the same for you. We have designed 3 x 1 day courses that we offer as open-enrolment training which also provide a good starting point for selecting content in a bespoke course intended for in-house use.
The courses are:

1: Introduction to Laboratory Data Integrity; cGMP in the Pharma Lab
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
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
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.

Full course descriptions are available on the MTS website.

Auditing
MTS specialises in laboratory-based audits which are carried out by myself, Oona McPolin, an IRCA certified lead auditor with extensive experience in auditing laboratories against:

• Regulatory expectations, using standards such as the GMPs from the EU, FDA, etc.;
• Best Practice in the analytical laboratory;
• Specific objective requested by the customer, e.g., data integrity related issue such as audit trails.

MTS will provide an audit to suit your requirements which includes a detailed audit report and optional action plan. If a training need is indicated by the audit we can help to design and/or deliver a suitable training programme.

Consulting
MTS can assist with carrying out a gap analysis for data integrity or to provide any other assistance that you may require.

Contact us today to discuss your Training, Auditing and Consulting requirements and for a no obligation quotation.



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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.

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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.

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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.

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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.

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Are Your Methods Fully Compliant with Regulatory Expectations?

• Can you detect and quantify all potential degradation products during stability testing (as per ICH Q1)?
• Is your new method validated correctly (as per ICH Q2(R1))?
• Is your pharmacopoeia method verified correctly (as per EU GMP Chapter 6, FDA and USP <1226>)?
• Is your validated method transferred correctly (as per EU GMP Chapter 6, FDA and USP <1224>)?

Find out how to develop, validate, verify and transfer analytical methods by attending one (or more) of the training courses from Mourne Training Services in Dublin, London & Berlin in 2014.

Choose from: (click on the course title for more information)
Validation of Analytical Methods for Pharmaceutical Analysis
1st & 2nd October 2014, Dublin
5th & 6th November 2014, London
3rd & 4th December 2014, Berlin
Transfer of Analytical Methods for Pharmaceutical Analysis
3rd October 2014, Dublin
5th December 2014, Berlin
How to Develop Stability Indicating HPLC Methods
13th & 14th November 2014, Dublin
8th & 9th December 2014, Berlin

The cost for the 2 day courses, method validation and developing stability indicating methods, is €1050 (+VAT) or £850 (+VAT), and the cost for the 1 day transfer course is €610 (+VAT) or £495 (+VAT). Full details of discounts for multiple bookings are available on the MTS website.

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EU GMP Chapter 6 Updated - Effective from 1st October 2014

The revision of EU GMP Chapter 6 on Quality Control has now been finalised and will be effective from 1st October 2014. The reasons for change on the new document are summarised as: "Inclusion of a new section on Technical transfer of testing methods and other items such as out of specification results."

The finalised document is mostly similar (a few of the proposed changes have not made it in) to the proposed draft that I reviewed in two blog posts last year.

The new section on method transfer is summarised in the first blog:
How does the Update to Chapter 6 of the EU GMP Guidelines Affect Your Lab?

The other updates in Chapter 6 are covered in this follow-up blog post:
How Does the Update to Chapter 6 of the EU GMP Guidelines Affect You? - Part 2

Ensure that you are up to date with the method transfer expectations of EMA, FDA and USP by attending the MTS training course, 'Transfer of Analytical Methods for Pharmaceutical Analysis'. Next opportunity is on the 2nd October 2015 in London. Check out our Course List for details of other dates and locations, and other courses, or contact us for more information.

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