Do you need support in assessing your risk of contamination by nitrosamine?
CVO-EUROPE’s knowledge of the strong regulatory constraints of the Life Sciences Industries enables us to better understand the new requirements that are gradually being imposed on manufacturers.
There is a risk of contamination by nitrosamines of drugs products, including OTC and generics:
- It concerns the chemically synthesized APIs,
- but also all raw materials, excipients, dyes, reagents, solvents and catalysts used in the manufacturing process…
Batch recalls have already occurred in France, USA, Switzerland etc…
Health authorities of different countries require all Marketing Authorization Holders (MAH) review their drug products on the possible presence of nitrosamines.
EMA asked this by September 26, 2019, for the active substance scope, with a deadline by March 26, 2020.
SwissMedic asked this by November 15, 2019, for the chemically synthesized API’s scope, with a deadline by May 15, 2020.
Nitrosamines Remediation plan & Nitrosamines CVO-EUROPE offer
CVO-EUROPE can provide support, expertise and resources for any of the following activities (non-limitative list):
Step 1a- Risk Evaluation Preparation
+ Define product prioritization Method using ICHQ9 (Quality Risk Management), ICH M7 and Risk-Mapp Master Matrix ISPE
+ Apply methods for prioritization of products in order to define the sequence they are to be evaluated
- To be considered: maximum daily dose, duration of treatment, route of administration, dosage and special groups of patients such as pregnant women and children
+ Define Questionnaire for risk evaluation, define template to support Risk analysis and mitigation
Step 1b – Risk Evaluation Execution
+ Ensure Internal risk Evaluation, preparation, execution, rapport, e.g FMEA… with the prioritization order
+ Distribute the questionnaire form to external manufacturers with the prioritization order, follow execution of the questionnaire form, collect the data from the questionnaire
+ Review the risk evaluation data (questionnaire, Risk analysis), challenge the data, manage question/answers, propose an action plan, make the decision,
+ Communicate the decision to customers, Health Authorities, archive the data
Step 2 – Confirmatory Testing
+ Require the confirmatory testing to the manufacturer, with the prioritization order
+ Define sample size: number of batches to be sampled for confirmatory testing; define specification limits
+ Ensure Nitrosamines Testing of samples: to be executed using appropriately validated and sensitive methods
+ If necessary, transfer the samples in an appropriate QC lab, or transfer the MoA to the manufacturer lab and validate it
+ Collect the data, review the data, challenge the data, propose an action plan, make the decision, communicate the decision to the customers and Health Authorities (including batch recall if applicable)
Step 3 – Change to the Market Authorization
+ Change the product specifications to be considered for batch release
+ Transfer the MoA, validate the MoA
+ Change the manufacturing process to minimize nitrosamine formation or contamination or cross-contamination; the principles described in ICH M7 guideline in relation to toxicology assessment, control strategy and changes to the manufacturing processes for active substances should be applied.
+ Validate the modified process
+ Change the manufacturers contracts
+ Change the market authorization and submit the variation to customers and Health Authorities
Learn more about Nitrosamines CVO-EUROPE offer
To contact CVO-EUROPE Business teams and experts about Nitrosamines CVO-EUROPE solution: