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08:00 08:55 (55 mins)

Main agenda

Conference Registration

08:55 09:00 (5 mins)

Main agenda

Chairperson's Opening Remarks

  • Rolf Schulte Oestrich - Head of Solid State Sciences, F. Hoffmann-La Roche AG, Switzerland

09:05 09:35 (30 mins)

Genotoxic Impurities

ICH Q11: Impact on Regulatory Starting Material Selection and Additional PGI Disclosure

  • Selection of Regulatory Starting Material based on EMA Reflection Paper and ICHQ11 Q&A
  • Disclosure of more Synthetic Steps and more highly reactive, Potentially Genotoxic Intermediates
  • Leveraging M7 Control Options and Purging Rationale
  • Larry Wigman - Principal Scientific Manager, Genentech

09:35 10:05 (30 mins)

Genotoxic Impurities

A Scenario of generic companies, our experience and difficulties on Guidelines from ANVISA.

  • RDC 53/15
  • Guideline 04/15
  • Degradation product qualification
  • ANVISA’s requirements regarding degradation products studies
  • Mariah de Almeida Ultramari - Degradation Products Studies Expert, Leader of the Degradation Products Laboratories, Aché Laboratories

10:05 10:35 (30 mins)

Genotoxic Impurities

Genotoxic Impurities: An Introduction and Best Regulatory Practices

  • Genotoxic Impurities and Genotoxicity
  • Guidelines on Genotoxic Impurities
  • Concern and Challenges
  • Testing Strategy
  • Puran Lal Sahu - Pr. Scientific Officer & Head - R&D, Indian Pharmacopoeia Commission

10:45 11:15 (30 mins)

Main agenda

Morning Coffee and Networking

11:15 11:45 (30 mins)

Genotoxic Impurities

In-Silico Prediction of Ames Mutagenicity: Best practice at Bayer

  • Best practice in industry
    • Mutagenicity assessment in early phases of drug discovery
    • Application of in-house tools and commercial software
    • In-house Ames mutagenicity prediction model
    • Ames mutagenicity prediction model for Aromatic Amines using quantum chemical descriptors and novel Atom-based chemical reactivity Descriptors
  • Lara Kuhnke - Medicinal Chemistry VII Computat. Chem, Bayer

11:50 12:20 (30 mins)

Genotoxic Impurities

Manual and computational methods for the evaluation of statistical predictions based on expert analysis.

The ICH M7 guideline recommends the use of two complementary (Q)SAR methodologies, one expert rule-based and one statistical-based, to assess the mutagenicity of impurities. The M7 guideline also urges the use of expert review in order to evaluate the relevance of any computational predictions, and such a manual expert evaluation can potentially overrule positive predictions. Although expert review is carried out in all circumstances it can be more challenging when the expert and the statistical system disagree. This disagreement can potentially result in over-control of non-mutagenic impurities.

Teva and Lhasa Limited are developing a more standardised approach for manual expert review using Derek and Sarah Nexus. This approach can improve the speed and accuracy of expert review and also increase the consistency of the overall outcome. This combined presentation will describe the approach, illustrated with worked examples.

  • Raphael Nudelman - Head of Chemical & Computational Toxicology, Teva Pharmaceutical Industries Ltd., Israel
  • William Nye - Account Manager, Lhasa Limited

12:25 12:55 (30 mins)

Genotoxic Impurities

The cancer TTC: a potentially useful concept compromised by a flawed derivation.

· TTC: background and origins

· Derivation of the cancer TTC based on carcinogenic potency data

·Critique of derivation: skewed dataset, false carcinogens, linear extrapolation for non-mutagenic carcinogens

· Need for re-evaluation.

  • David Snodin - Principal, Xiphora Biopharma Consulting, UK

12:55 14:10 (75 mins)

Main agenda

Lunch, Networking, Poster Presentations and Live Labs

14:10 14:40 (30 mins)

Genotoxic Impurities

The monographs of the ICH M7 addendum

  • Update on ICH M7 addendum with monographs
  • Reasonning for monographs
  • How to use monographs in less than lifetime context
  • Plans for further monographs by the ICH M7 grou
  • Lutz Mueller - Expert Toxicology Project Leader, F. Hoffmann-La Roche Ltd., Switzerland

14:45 15:15 (30 mins)

Genotoxic Impurities

Teleconference: Guilty until proven innocent?

  • This will examine the challenges faced in setting compound specific limits and the development of the ICH M7 addendum
  • What happened to the reagents left behind? (M7 addendum focuses specifically on mutagenic carcinogens)
  • Case study reflections on risks of uncertainty and impact on control strategy
  • Andrew Teasdale - Principal Scientist, Chair of Impurity Advisory Group, AstraZeneca, UK

15:20 15:50 (30 mins)

Genotoxic Impurities

Challenges of GTI assessments and best practice for following ICH M7 guideline.

  • Scientific background behind statistical and rule based in-silico approaches for ICH M7: differences, advantages, disadvantages
  • ICH M7 Konsolidator, a tool to facilitate expert reviews and regulatory submissions
  • How to resolve the conflicting, out of domain and equivocal calls: case studies
  • Roustem Saiakhov - President, MultiCASE Inc.,USA

15:50 16:20 (30 mins)

Main agenda

Afternoon Coffee

16:20 16:50 (30 mins)

Genotoxic Impurities

Challenges in Implementing ICH M7 from a Biopharmaceutical Manufacturers Perspective

Overview of the Novo Nordisk approach to the risk management of GTI

Tools and tactics used to ensure updated documentation throughout the product life-cycles

Challenges and lessons learned from applying ICH impurity guidelines on bioprocesses

  • Carsten Baun Senholt - Principal Scientist, NovoNordisk

16:55 17:25 (30 mins)

Genotoxic Impurities

Methodologies supporting practical implementation of the ICH M7 guidelines

- Databases of experimental data - relevance and importance in model building and expert review

- SAR fingerprinting for better understanding and prediction of proprietary chemical space

- Read-across and analog evaluations

  • Catrin Hasselgren - Senior Principal Scientist, Leadscope, USA

17:30 17:40 (10 mins)

Main agenda

Chairperson's Closing Remarks

  • Rolf Schulte Oestrich - Head of Solid State Sciences, F. Hoffmann-La Roche AG, Switzerland

17:40 18:25 (45 mins)

Main agenda

Closing Plenary Session: Rosetta Lander – Philae: A Long-Term Space Project to Land on a Comet

Philae is a comet Lander, part of the ESA Rosetta Mission to comet 67P/Churyumov-Gerasimenko.  After about ten years of development and a ten-year cruise through the solar system it successfully landed on the nucleus of the comet on November 12th, 2014.

Since the anchoring harpoons, which were expected to fix the lander to ground, did not work, Philae bounced in the low gravity environment, and only came to rest after a 2 hour’s “hop” in an unforeseen area on the comet surface.   Fortunately, the scientific instruments, including cameras, mass spectrometers, a magnetometer and a radar instrument could be operated, and fascinating, unprecedented scientific results have been obtained from the surface of an active comet.

Interplanetary space missions, including a long development phase and elaborated qualification tests do have similarities with pharmaceutical research, where time-spans between the concepts for a new drug until readiness for marketing can be similar.

Rosetta is an ESA mission with contributions from its member states and NASA. Rosetta's Philae Lander is provided by a consortium led by DLR, MPS, CNES and ASI with additional contributions from Hungary, UK, Finland, Ireland and Austria.

  • Stephan Ulamec - Philae Project Manager, German Aerospace Center, Germany

18:25 20:25 (120 mins)

Main agenda

Networking Drinks and Evening Social Event