Since the end of July, the "Concept paper on the revision of the guideline on the chemistry of active substances" of the Quality Working Party (QWP) of the CHMP (Committee for Medicinal Products for Human Use) is available for public comment. The purpose of this document is to clarify and explain the need to revise and update the "Guideline on the chemistry of active substances (EMA/454576/2016)" and to outline the approach to this revision. The concept paper and the subsequent revision of the guideline were prompted by the findings and results of the "Lessons Learnt", which were prepared for retrospective consideration of the N-nitrosamine cases. The updated guideline is then intended to guide future similar cases.
The concept paper is divided into nine chapters, with six subsections in Chapter 3, "Discussion (on the problem statement)," listing and describing the underlying aspects of the guideline update sought:
"Guidance on appropriate process development in order to mitigate as much as possible the potential presence of N-nitrosamines or other CoC compounds as well as of other potent toxins (if applicable). The selected manufacturing process should be justified accordingly.
Guidance on the need to provide clear information on all the materials used in the process (including raw materials, starting materials and intermediates) in relation to their function in the corresponding manufacturing step, their applied quantities, their potential contaminants and their overall quality.
Guidance on the required discussion regarding presence or formation of N-nitrosamines or other CoC compounds as well as of other potent toxins. Clarify the new systematic approach suggested by ICH M7 on mutagenic impurities.
Guidance on the use of recycled materials.
Guidance on specific control options for N-nitrosamines or other CoC compounds as well as for other potent toxins, including possible control points and acceptance criteria.
Guidance on the need to consider formation of N-nitrosamines or other CoC compounds as well as of other potent toxins during storage."
The concept paper is open for comments until the end of October. Based on the comments received, the draft updated guideline will be prepared and again published for comment for six months.