Due to findings of nitrosamines in multiple medicines since July 2018, both the FDA and the EMA published guiding documents to all Marketing Authorization Holders requiring them to evaluate their synthetic manufacturing processes for the potential presence of nitrosamines. Both agencies instructed the applicants to utilize the principles described in the ICH M7 and ICH Q9 guidelines for toxicology and risk assessments. Where the assessment identifies a risk for nitrosamine, products must be tested and the risk should be mitigated. This may include a change of the manufacturing process and/or the implementation of a respective control strategy.
These guidances also apply to synthetic peptides. While Bachem assesses both process types, Solid Phase Peptide Synthesis (SPPS) and Liquid Phase Peptide Synthesis (LPPS), this presentation will focus on the risk assessment for the more frequently applied SPPS.
General risk factors will be explained and their assessment for Bachem’s SPPS-related raw materials and processes will be presented. In preparation for potential testing, a quantification method for the nitrosamine structures of concern was developed and validated. The method is based on Head Space Gas Chromatography with MS detection. Based on the assessments we conclude that the risk for a nitrosamine contamination in SPPS peptides can be kept negligibly low.

Subject area:
Biologics

Objectives (If applicable):
NA

Target Audience (If applicable):
QA Manager
QA Staff
QC Chemist
QC Manager
R&D
Regulatory
Student