Nitrosamine Risk Assessment (Step 1)
Comprehensive evaluation for a drug product containing 1-3 APIs.
Comprehensive scope: A detailed risk assessment report for one drug product, covering up to three APIs. The report can be tailored to one specific territory upon request (e.g. inclusion of completed templates, built for compliance with specific regional guidelines). It is possible to integrate the assessment into company-specific templates or prepare formatting for a CMC Module 3 or for a specific regulatory purpose.
Early development: The service can also be offered early in development based on pilot scale processes, so that launch timings are not impacted by preparing for nitrosamine compliance.
Multi-factorial analysis: Includes a thorough assessment of APIs, excipients, and the drug product, analyzing manufacturing processes, primary packaging, and stability data. The approach is aligned with the expectations of regulators.
Expert insight: The process involves an expert chemistry assessment complemented by an extensive literature review to ensure all potential pathways are considered. The assessment is performed with scientific rigor.
Risk conclusion: Provides a clear conclusion on risk based on available information and includes strategic suggestions for NDSRI selection. The report includes recommendations for next steps if a risk is identified.
Semi-quantitative approach: Where provided inputs allow, the report includes a semi-quantitative risk assessment, including a preliminary assessment against the most conservative limit possible (e.g. CPCA-based RAIL).
Experimental boundaries: The service fee excludes experimental work and does not standardly include the design or execution of lab experiments (e.g., NAP tests, synthesizability, or stability testing in liquid/solid phases for NDSRIs). However, if such data is provided by the customer or found in literature, it will be integrated into the final assessment. It is taken into account that identifying and selecting the correct Nitrosamine Drug Substance Related Impurity (NDSRI) if applicable is a key hurdle; the assessment process can be paused if experimentation to reach said identification is needed.
Gap analysis: If the provided data is insufficient, a clear gap analysis will be provided as part of the report.
Required documentation for a maximum assessment:
For a maximum assessment, the Client needs to provide:
Bill of material of the drug product
Maximum daily dose and posology of the drug product
(Planned) market(s) or market(s) in scope of the assessment
Manufacturer provided risk assessment on API, excipients, drug product
Primary packaging information (API and drug product), including manufacturer provided risk assessment and if applicable: information on nitrocellulose usage and blister printing approach
Information on water usage at the API and drug product level
Specifications of the API and drug product (release and over shelf life); known impurities in the API and drug product; API and drug product stability data (e.g. with a focus on API dealkylation chemistry).
Drug product manufacturing processes; if possible API synthesis and purification process and information on solvent recovery or other recovery processes. Information on bulk holding approaches for the drug product and API.
Optional, if available: Formation/stability information linked to potential NDSRIs, NAP test, any preliminary experimentation to support the risk assessment, nitrites testing (Intermediates, API, DP, excipients), information on NOx measurements in manufacturing plants, and stress testing studies on API or DP.
All other information deemed relevant by the Client.
If applicable: historical risk assessments on the product, and questions from authorities linked to the nitrosamine risk for the specific product.
Logistics & Options
Lead time: 14 days for products with 1-2 APIs; 28 days for products with 3 APIs (following receipt of all customer inputs).
Urgency option: Fast-Track option of 7 days (following receipt of all customer inputs) for an additional fee of € 1,250.00, subject to confirmation of consultant availability.
On request: Broadening scope to other nitroso compounds for an additional fee.
On request: Site visit to evaluate and discuss risk for an additional fee.
On request: Collecting the necessary inputs with suppliers for an additional fee.
Package price can also be used for the assessment of herbal medicines (inputs provided by the Client to be tailored to herbal medicines).
Booking & Payment Terms
1-year validity: The Client must enable the execution of the service within one year of the date of purchase. After the 1-year validity, an extension might be applied for up to 2 additional years, provided that a price indexation adjustment is mutually agreed upon by both parties.
The pricing is based on immediate checkout via the website (full or partial prepayment). Alternatively, corporate orders can be placed via email by submitting an official Purchase Order (PO) to hello@clarbonyx.com.
Our standard Terms apply to all orders unless an alternative agreement is explicitly in place. To establish a specific framework agreement with Clarbonyx, we recommend completing our "Become a Client" form.
Nitrosamine Risk Assessment (Step 1)
Comprehensive evaluation for a drug product containing 1-3 APIs.
Comprehensive scope: A detailed risk assessment report for one drug product, covering up to three APIs. The report can be tailored to one specific territory upon request (e.g. inclusion of completed templates, built for compliance with specific regional guidelines). It is possible to integrate the assessment into company-specific templates or prepare formatting for a CMC Module 3 or for a specific regulatory purpose.
Early development: The service can also be offered early in development based on pilot scale processes, so that launch timings are not impacted by preparing for nitrosamine compliance.
Multi-factorial analysis: Includes a thorough assessment of APIs, excipients, and the drug product, analyzing manufacturing processes, primary packaging, and stability data. The approach is aligned with the expectations of regulators.
Expert insight: The process involves an expert chemistry assessment complemented by an extensive literature review to ensure all potential pathways are considered. The assessment is performed with scientific rigor.
Risk conclusion: Provides a clear conclusion on risk based on available information and includes strategic suggestions for NDSRI selection. The report includes recommendations for next steps if a risk is identified.
Semi-quantitative approach: Where provided inputs allow, the report includes a semi-quantitative risk assessment, including a preliminary assessment against the most conservative limit possible (e.g. CPCA-based RAIL).
Experimental boundaries: The service fee excludes experimental work and does not standardly include the design or execution of lab experiments (e.g., NAP tests, synthesizability, or stability testing in liquid/solid phases for NDSRIs). However, if such data is provided by the customer or found in literature, it will be integrated into the final assessment. It is taken into account that identifying and selecting the correct Nitrosamine Drug Substance Related Impurity (NDSRI) if applicable is a key hurdle; the assessment process can be paused if experimentation to reach said identification is needed.
Gap analysis: If the provided data is insufficient, a clear gap analysis will be provided as part of the report.
Required documentation for a maximum assessment:
For a maximum assessment, the Client needs to provide:
Bill of material of the drug product
Maximum daily dose and posology of the drug product
(Planned) market(s) or market(s) in scope of the assessment
Manufacturer provided risk assessment on API, excipients, drug product
Primary packaging information (API and drug product), including manufacturer provided risk assessment and if applicable: information on nitrocellulose usage and blister printing approach
Information on water usage at the API and drug product level
Specifications of the API and drug product (release and over shelf life); known impurities in the API and drug product; API and drug product stability data (e.g. with a focus on API dealkylation chemistry).
Drug product manufacturing processes; if possible API synthesis and purification process and information on solvent recovery or other recovery processes. Information on bulk holding approaches for the drug product and API.
Optional, if available: Formation/stability information linked to potential NDSRIs, NAP test, any preliminary experimentation to support the risk assessment, nitrites testing (Intermediates, API, DP, excipients), information on NOx measurements in manufacturing plants, and stress testing studies on API or DP.
All other information deemed relevant by the Client.
If applicable: historical risk assessments on the product, and questions from authorities linked to the nitrosamine risk for the specific product.
Logistics & Options
Lead time: 14 days for products with 1-2 APIs; 28 days for products with 3 APIs (following receipt of all customer inputs).
Urgency option: Fast-Track option of 7 days (following receipt of all customer inputs) for an additional fee of € 1,250.00, subject to confirmation of consultant availability.
On request: Broadening scope to other nitroso compounds for an additional fee.
On request: Site visit to evaluate and discuss risk for an additional fee.
On request: Collecting the necessary inputs with suppliers for an additional fee.
Package price can also be used for the assessment of herbal medicines (inputs provided by the Client to be tailored to herbal medicines).
Booking & Payment Terms
1-year validity: The Client must enable the execution of the service within one year of the date of purchase. After the 1-year validity, an extension might be applied for up to 2 additional years, provided that a price indexation adjustment is mutually agreed upon by both parties.
The pricing is based on immediate checkout via the website (full or partial prepayment). Alternatively, corporate orders can be placed via email by submitting an official Purchase Order (PO) to hello@clarbonyx.com.
Our standard Terms apply to all orders unless an alternative agreement is explicitly in place. To establish a specific framework agreement with Clarbonyx, we recommend completing our "Become a Client" form.