E24: A Holistic Approach to Life Cycle Management (LCM) of Nitrosamine Drug Substance Related Impurity (NDSRI) in Pharmaceutical Products: Guidance and Case Study

One-Day Course
Date to be Announced; 8:30am – 5:00pm
Dr. Partha S. Mukherjee, Amicus Therapeutics, Princeton, NJ

Several N-nitrosamines belonging to the “Cohort of Concern” are mutagenic, genotoxic, and potentially carcinogenic agents in humans, and mandate control at acceptable safe levels. NDSRIs present a far more complexity. This course will provide a comprehensive life cycle management of sequential Predictive Chemistry of formation, organic synthesis, in-silico mutagenic and carcinogenic potential risk assessment followed by method development, validation, and confirmatory testing of sensitive analytical method based on regulatory approaches for Acceptable Intake calculation of NDSRIs. A case study will be provided for a complex pair of NDSRIs prior to the approval of product.

Pharmaceutical professionals in development and commercial analytical functions, who are relatively new in the area of nitrosamines and need a robust analytical strategy for life cycle management of nitrosamines in their products. Also relevant for regulatory professionals who need to stay updated with the global regulatory outlook on nitrosamines. This is also relevant for CMC professionals who would like to gain more insight on how to implement an end-to-end CMC control strategy for standard nitrosamines and NDSRIs. This is also relevant for quality professionals who will need to gain knowledge of how nitrosamine fits in the quality control of pharmaceutical products,


  1. The impact of nitrosamines and NDSRIs
  2. Regulatory evolution of requirements of NDSRIs monitoring
  3. Typical challenges with NDSRIs from global regulatory perspective
  4. Synthesis of NDSRIs: challenges and remediation
  5. Method development of NDSRIs and challenges with method sensitivities
  6. Method validation of NDSRIs and acceptable intake limit and Limit of Quantitation settings
  7. Confirmatory testing of NDSRIs in DP and DS batches
  8. Frequency of testing for NDSRIs
  9. Future outlook for NDSRIs

Dr. Partha S. Mukherjee has extensive experience (27+ years) in Pharmaceutical CMC Development arena in Life Cycle Management from Discovery through branded, generic, and OTC product commercialization. Strong track record in Technical and Organizational Leadership, Quality (Control & Assurance), CMC, and People Management. Broad expertise in various Analytical and Bio-analytical Separation Science techniques and instrumentation for Small Molecules, Antisense Oligonucleotides, Biologics, Hemi Synthetics, Radiopharmaceuticals, and Cell and Gene Therapy (CGT) Products. High energy level, strong take-charge ability, and follow through. Demonstrated leadership skills in innovation, strategic thinking, passion for customers, developing others, collaborative working, and driving performance of the organization.  Analytical leadership in 6 of top 10 global pharmaceutical companies in all major Therapeutic Areas and covering all key dosage forms. Member of USP Small Molecule Medicines Expert Committee, BioPhorun, and WHO Technical Reviewer. Built several Analytical Centers of Excellence in major pharmas