Lhasa Limited shared knowledge shared progress

Related pages

Related sites

Related documents



ICH M7

The ICH M7 guidelines provide a practical framework that can be applied to the identification, categorization, qualification and control of mutagenic impurities to limit potential carcinogenic risk. This framework is summarised in Figure 1 of our ICH M7 brochure, with appropriate classes summarised in Table 1.

Meaning

What do these guidelines mean for you?

The important messages to take away from these guidelines are:

  • Regulatory agencies will accept results from (Q)SAR methodologies in lieu of in vitro testing.
  • An expert review is a crucial step, allowing you to justify your case.
  • SAR methodologies can be used to support the decision making of your experts in determining mutagenic potential of impurities and thereby minimising the expense of testing.
  • Experts can make use of existing data to support decisions and submissions.

Tools

Why choose Lhasa?

Lhasa's solutions are currently used across a range of sectors but most notably pharmaceutical, cosmetic, chemical, regulators, government agencies and academia. A list of members can be viewed here.

When asked why people choose to work with Lhasa Limited, the common responses are:

  • Software is easy to use and well supported.
  • Single interface in use within Lhasa solutions, provides familiarity between products and also means your organisation has fewer systems to maintain.
  • Transparency of Lhasa systems allows trust and confidence in the science presented.

Lhasa Limited provides an integrated solution to assist in the meeting of the ICH M7 guidelines:

Derek Nexus - An Expert tool for the prediction of toxicity

  • Gives a prediction and the supporting data to aid in decision making:
    • Examples
    • Mechanisms
    • Expert opinion
    • Likelihood
  • Expert tule-based systems are considered to be the core component.
  • Conforms to the validation principles set forth by the Organisation for Economic Co-operation and Development (OECD)
    • A defined endpoint
    • An unambiguous algorithm
    • A defined domain of applicability
    • Appropriate measures of goodness-of-fit, robustness and predictivity
    • A mechanistic interpretation, if possible 

The preferred expert rule-based system for the prediction of toxicity (Dobo et al.(2012)Sutter et al. (2013))

 

 

 

 

 

Sarah Nexus - a statistical tool for the prediction of mutagenicity

  • Created with input from the Food and Drug Administration (FDA) under a Research Collaboration Agreement.
  • Conforms to the OECD validation principles.
  • Designed to address the ICH M7 guidelines.
  • Unique hierarchical model ensures results are based on data perceived to be of greatest relevance.

 

A statistical based system for the prediction of mutagenicity.

 

 

Vitic Nexus - chemical database and information management system

  • Curated by expert scientists, Vitic Nexus contains a wealth of genotoxicity records (Figures correct for Vitic Database 2013.1.0):
    • in vitro data - 146,444 records, 9,104 compounds
    • in vivo data - 10,157 records, 2,658 compounds
  • All data can be used to support expert analysis.
  • Members of our data sharing consortia can also see:
    • Aromatic amines
    • Intermediates (including the boronic acid subgroup)
    • Excipients
 

A chemical database and information management system providing the largest non-confidential dataset of mutagens for Derek Nexus and offering decision support.

 

 

Zeneth - an expert tool for  the prediction of forced chemical degradation

  • Can account for intermolecular reactions, allowing consideration of product interactions, interactions between APIs and excipients, and dimerization reactions.
  • Provides insight into relevant degradation pathways which can be used to help guide decisions on the selection of potential degradation products to be evaluated for mutagenicity studies.
  • Ability to export predicted degradants for analysis of mutagenicity in Derek Nexus and Sarah Nexus (separate licences required).
 

An expert rule-based system for the prediction of forced chemical degradation.

 

Library books

Interpretation

Lhasa Limited provides ICH M7 solutions aimed to offer guidance and support as part of a wider expert review. In fact various publications illustrate how an expert can improve performance by evaluating in silico predictions (Dobo et al.(2012),Sutter et al. (2013).

 

Expert review following in silico mutagenicity assessment has been shown to give the most accurate outcome and this is particularly important in those cases where a negative prediction is received. So what constitutes a positive or negative prediction within Lhasa Limited products and how should conflicting results be interpreted?

 

 

Positive

Negative

Derek Nexus - an expert tool for toxicity prediction

Likelihood for mutagenicity of equivocal or higher.

Inactive or likelihood for mutagenicity of doubted or lower.

Sarah Nexus - a statistical tool for mutagenicity prediction

 Positive.

 Negative.

 

 Derek Nexus and Sarah Nexus can be run from within the same Nexus interface to simplify your workflow, however it is important to remember that they are separate systems, providing completely independant predictions and reports. As such, there are times when these results will contradict each other. Vitic Nexus can also be queried from within the same Nexus interface, allowing you to pull in additional information to support your expert review.

 

In the case that results are contradicted, an expert review of all available data should be carried out to come to a logical conclusion. Expert review is very important and as such, we have worked hard to ensure that both Derek and Sarah Nexus provide the right level of information to support an expert analysis, allowing you to come to an informed decision.

 

Reports can contain a wealth of information.

Submissions

The FDA's Center for Drug Evaluation and Research accepts submissions from Derek Nexus and Sarah Nexus.

When submitting to regulators, you can make use of Lhasa Limited's reports which are in a range of formats and are customisable, allowing you to present the pertinent information to support your submission. Reports can include a wealth of supporting information and as a minimum it is recommended that you include details of the version of the software and knowledge base/database used.

Lhasa Limited releases its software updates to members at the same time as its regulatory members, allowing you to make use of up-to-date knowledge when making submissions. As regulators make use of current software versions for regulatory assessments, we recommend that you install new releases as soon as possible.

Resources

The following posters, videos, presentations and FAQs may be of interest to those people responsible for implementing ICH M7.

Papers:

Posters:

Videos:

    • FDA/CDER Current Practices for (Q)SAR Analysis under ICH M7

    • Reconciling Conflicting (Q)SAR Predictions in Impurity Evaluations

 

Presentations:

 

FAQs:

Contact Us

© 2017 Lhasa Limited | Registered office: Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK Tel: +44 (0)113 394 6020
VAT number 396 8737 77 | Lhasa Limited is registered as a charity (290866)| Company Registration Number 01765239 (England and Wales).

QuestionPro supports sample survey questions such as multiple choice, drop-down menu, likert-scale, semantic differential, matrix, constant sum, drag-and-drop, slider-scale, net-promoter scale, and many more question types.