Wednesday, 20 January 2016

Upcoming Course from MTS

3rd & 4th March 2016, GLS Campus Berlin, Germany
Early booking rate (until 3rd February): €1155 + VAT (19%)
Group discounts are available on request

This course is suitable for both investigating whether an existing HPLC method is stability indicating or for developing a new stability indicating HPLC method.

You will learn:
  • Why stability indicating methods are required;
  • How HPLC method parameters, such as column and mobile phase, affect the chromatographic separation and how to find the best conditions;
  • How to perform forced degradation stress studies to obtain potential degradation products; and
  • How to investigate mass balance for analytical methods.
Visit the MTS website for more information and for the online booking form.

Other related courses from Mourne Training Services:
Validation and Transfer of Methods for Pharmaceutical Analysis
Laboratory Data Integrity

 

Friday, 15 January 2016

MTS Recommends... Out-of-Trend Identification and Removal in Stability Modelling and Regression Analysis

Out-of-Trend Identification and Removal in Stability Modelling and Regression Analysis
"This article defines the concept, justification, and method of removal of out-of-trend points in stability modelling and shelf-life prediction."
By Thomas A. Little, PhD
BioPharm International, Jan 01, 2016, Volume 29, Issue 1

Tuesday, 12 January 2016

Help on: Is 'Mass Balance' Critical?

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:
What is the 'mass balance' for an analytical method and is it critical that I investigate it as part of method development or method validation?

Answer:
When used in the context of an analytical method, the term 'mass balance' relates to its ability to analyse the degradation products of a drug molecule. A method is considered to have 'good' mass balance if:
  1. It can quantify the loss in amount of drug molecule due to degradation (which should result in a lower assay value),
  2. It can detect and quantify the degradation products formed during degradation of the drug molecule, and
  3. The amount of the drug lost is equal to the amount of degradation products formed.
A method which is used to analyse stability samples needs to have this ability so that it can provide information on the amount of degradation occurring during the time period of the stability programme. A definition of mass balance is provided in the glossary of the ICH Guideline Q1A (R2), Stability Testing of New Drug Substance and Products:

"Mass balance:
The process of adding together the assay value and levels of degradation products to see how closely these add up to 100% of the initial value, with due consideration of the margin of analytical error."

Typically a chromatographic technique is used since it is necessary to separate the degradation products from the drug molecule and each other to detect and quantify them. Reversed phase HPLC is usually preferred.

It is critical to investigate the mass balance of a method if it needs to be stability indicating. To meet the commitments of ongoing stability testing these methods are required for all products. For convenience, the same methods are often used for release and stability testing.

Whether the assessment of mass balance is performed during method development or during method validation often depends on the type of drug being manufactured. If it is a novel molecule then the stability indicating ability will usually be assessed during the method development phase which will allow modification of the conditions to optimise the analysis of the degradation products.

If however, it is a generic product and the testing methods are taken from a pharmacopoeia then the stability indicating nature of the method will still need to be considered but will typically form part of the method verification study. In this case modification of the method conditions is often not an option and if the method does not have good mass balance an alternative may need to be developed. For older products, which may not have stability indicating assay and degradation products methods, you may need to re-evaluate the methods to ensure that they comply with current regulatory expectations.

In both cases a stress study will be performed to force degradation of the drug molecule under a range of different stress conditions and thus create degradation products. The mass balance of the method can then be assessed. Although the concept is simple, the practical experiments to demonstrate mass balance can be rather complex and require careful planning. The phrase in the ICH guideline: "due consideration of the margin of analytical error" is significant. An added complication is that the preferred analytical technique, HPLC with UV detection, is not ideal since the size the degradation peak may not correspond to the actual amount present.

If you would like to know more about the detail of the experiments required for an evaluation of mass balance then you may be interested in the MTS course: How to Develop Stability Indicating HPLC Methods. This course is suitable for developing new methods or evaluating existing methods.

 

Wednesday, 6 January 2016

The MTS Contact Telephone Number has Changed

Please note that due to an office relocation the contact telephone number for Mourne Training Services has changed to:

+44 (0) 28 3083 4938

The postal address remains unchanged at present but will also be updated in the near future.

Monday, 4 January 2016

2016 MTS Course Calendar

The calendar for our 2016 open enrolment training courses is now available. Visit the Course List page on the MTS website for the dates and locations of all our courses in 2016.

There you will also find a detailed course description for each course, and links to the online booking forms where full details on the course fees can be found.