Regulatory Focus™ > News Articles > ICH Lays Out Roadmap for Exempting Certain Studies from Rodent Carcinogenicity Testing

ICH Lays Out Roadmap for Exempting Certain Studies from Rodent Carcinogenicity Testing

Posted 06 September 2013 | By Alexander Gaffney, RAC

The International Conference on Harmonisation (ICH), a pharmaceutical-focused regulatory harmonization group whose guidelines are widely adopted, has announced that its S1 rodent carcinogenicity guideline is moving forward well ahead of an anticipated 2017 release date.


The S1 guideline was first announced as a concept paper in May 2012 following a 2011 publication by industry group PhRMA which found that approximately a third of the results from rodent studies could be predicted using alternate and less time-consuming testing procedures.

At present, four sets of predictions can be made using predictive carcinogenic testing:

  1. When signals are absent, negative predictions can be made.
  2. When signals are present, positive signals can be made.
  3. Signals are known to affect rodent carcinogenicity, but not human carcinogenicity.
  4. Signals cannot be predicted with sufficient certainty, and are thus of little or no use.

It is this fourth category that has regulators and industry most intrigued. According to explanations published by ICH, since testing conducted for this category isn't particularly useful, if regulators could find a new approach to phase out testing in such cases, it would have the potential to reduce costs and the time-to-market for some pharmaceutical products.

"The goal of this potential change is to introduce a more comprehensive and integrated approach to address the risk of human carcinogenicity of small molecule pharmaceuticals, and to define conditions under which 2-year rodent carcinogenicity studies add value to that assessment," FDA explained in a Federal Register posting in March 2013.

The Road Ahead

But as Regulatory Focus explained earlier this year, the plan remains in the very early stages of development and myriad issues still need to be worked out.

ICH has started to work out those issues by publishing revised documents on the S1 guideline, including a concept paper, business plan and, as of September 2013, a Regulatory Notice Document giving a broad overview of ICH's proposed approach to developing the S1 guideline.

For right now, ICH is focused on generating the data necessary to validate its approaches, moving from a conceptual understanding that some testing is unnecessary to actually realizing which tests would be, and what alternative testing procedures might look like.

ICH said it is looking to evaluate two-year rat carcinogenicity data for 50 compounds from a "broad and comprehensive" array of pharmaceutical companies. Submission of this data is voluntary, but ICH explained that companies will be able to submit data to ICH without that data affecting the development program of their respective drug in any region.

For now, actual waivers will not be granted.

ICH said in an accompanying statement that the eventual adoption of the S1 guidance remains years away. The Regulatory Notice Document represents all comments received during the initial comment period opened in May 2012, and will be finalized in June 2014, when the collection of data from companies will begin.

The two-year data collection process will result in a Step 2 document being released for comment in November 2016, with final publication of the guideline in November 2017.

ICH: S1 Guideline

Tags: S1

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