ICH Q11 - A New Guideline for the Development of APIs Is Being Created

GMP News
30 April 2008

ICH Q11 - A New Guideline for the Development of APIsIs Being Created

On 11 April 2008, the International Conference on Harmonisation (ICH) publisheda concept paper with the title "Q11:Development and Manufacture of Drug Substances (chemical entities and biotechnological/biological entities)".In ICH's standardised harmonisation process, drawing up a concept paper is thefirst of five steps on the way to the finalisation of a guideline and itsacceptance by the three big industrial regions Europe, USA and Japan. Theconcept paper contains a proposal for a new guideline and explains why it isnecessary.

Which issues are meant to be harmonised and regulated throughICH Q11?

The requirements on the information about the manufacturingprocess of active pharmaceutical ingredients to be included in the dossier for amarketing authorisation differ from one region to another and confront the drugmanufacturer with the problem of having to create several versions of the CTDsections S 2.2 - S 2.6 when applying for a marketing authorisation. The answerto the question which data on API production a registration authority expects and in how much detail they should be described inthe dossier is either not clear or differs between countries. In addition, divergentrequirements on APIs manufactured by chemical synthesis and biotechnologicalmethods are the cause for further unnecessary complexity. This leads to aharmonisation gap, which is intended to be filled by means of ICH Q11.
The advantages of such a harmonisation of requirements are obvious: Saving timeand resources when first submitting a dossier and, of course, when submitting anapplication in case of post-approval changes or variations.

The description of and grounds for the development of an activeingredient and its manufacture must be oriented towards the principles of ICHQ8, Q9 and Q10. The authors of the concept paper consider the following aspectsof the development of APIs to be particularly in need of harmonisation:

  • Selection of the starting materials for API production
  • Identification of important and critical manufacturingsteps, process controls, process parameters and the correspondingexplanations; moreover, the selection of analytical methods and acceptancecriteria for completely controlling and ensuring product quality andconsistency
  • The capacity of processes to deplete or remove impuritiesand chemical compounds similar to the product
  • The assessment of process robustness
  • The proof that methods are suitable for validation on asmall scale
  • The identification and control of critical intermediates

This guideline is meant to reduce efforts not only on the partof the pharmaceutical and API industries; the harmonisation of the requirementsin connection with the authorisation process should also bring benefits to theassessors from the registration authorities.

ICH Q11 is currently in "Step 1", called the consensus-buildingphase. The intermediate steps in the harmonisation schedule of this guidelineleading to "Step 2" are as follows:

  • Approval of the guideline topic/definition of therapporteur and members of the expert working group (EWG): April 2008
  • First EWG meeting: June 2008
  • Formal confirmation that the EWG members have reached aconsensus on the guideline content by signing the "Expert Sign-off Sheets"(= finalisation of Step 1): 4th quarter 2009

It will be interesting to get to know the detailed requirementsof the guideline; however, a consensus guideline can hardly be expected beforethe beginning of 2010.

The Q11 Guideline can be found here.

Dr Gerhard Becker
On behalf of the European Compliance Academy (ECA)


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