The presence of nitrosamine drug substance-related impurities (NDSRIs) in medications has become an urgent issue for the pharmaceutical industry.
In response, the FDA issued critical new guidance in August 2023, setting strict acceptable intake limits (AIs) for NDSRIs. While some deadlines have already lapsed, an imminent deadline looms: August 1, 2025. By this date, manufacturers must ensure that all NDSRIs in their products adhere to these newly established AI limits. Immediate action is essential to comply and avoid potential regulatory consequences.
Pharmaceutical companies must address the urgent need for a reliable nitrosamine testing partner, as neglecting this critical aspect can have severe repercussions. Inaccurate testing poses significant risks of regulatory non-compliance, which may result in substantial fines, legal challenges, and potentially costly product recalls. Such issues can hinder market access, delay drug approvals, and lead to considerable financial losses and operational disruptions. Securing a dependable testing partner is essential to mitigate these risks and ensure adherence to stringent regulatory standards.
What does this mean for the industry?
This is a call to action for pharmaceutical companies. Here’s a breakdown of the upcoming regulations:
- Risk Assessment: An NDSRI risk assessment involves identifying drug substances with a potential risk of forming nitrosamine and identifying control strategies for raw materials and excipients, processing equipment and reagents for drug substances, and packaging materials for drug substances and drug products to mitigate these risks.
- Confirmatory Testing Completion: Manufacturers of approved drugs have until August 1, 2025, to complete confirmatory testing for NDSRIs using “sensitive and appropriately validated methods.” This testing is crucial for identifying and quantifying any NDSRIs present in medications.
- Meeting AI Limits: Following confirmation of NDSRI levels, manufacturers must ensure those levels fall at or below the FDA-recommended AIs. This might involve reformulating medications, implementing stricter manufacturing controls, or exploring alternative ingredients.
Guidelines
The upcoming NDSRI regulations do not specify a single level for approved drugs after confirmatory testing by August 1, 2025. Instead, they focus on ensuring NDSRI levels fall at or below the FDA-recommended Acceptable Intake (AI) limits.
These AI limits are determined based on the predicted carcinogenic potency of the NDSRI. The FDA provides resources for these limits, including:
- Categorization based on structure using the Carcinogenic Potency Categorization Approach (CPCA)
- Specific AI values for certain NDSRIs
The Road to Compliance
Meeting the 2025 deadline requires a proactive approach from manufacturers. Here are some steps companies can take:
- Risk Assessment: If not already completed, a thorough risk assessment should be conducted to identify medications potentially susceptible to NDSRI formation.
- Proactive Testing: Don’t wait for confirmatory testing deadlines. Manufacturers can initiate testing throughout the production process to identify and address potential NDSRI formation early on.
- Communication and Collaboration: Open communication with the FDA throughout the process is essential. Additionally, collaboration with suppliers and industry partners can be invaluable in navigating these regulations.
Here’s what this means:
- Confirmatory testing identifies and quantifies the actual level of NDSRIs in a drug.
- Manufacturers need to compare this measured level to the recommended AI limit for that specific NDSRI.
If the measured NDSRI level is at or below the AI limit, the drug meets the regulations. If it exceeds the limit, manufacturers need to take steps to bring the level down, potentially through reformulation or stricter controls.
For the latest information on AI limits, you can refer to the FDA website: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/updated-information-recommended-acceptable-intake-limits-nitrosamine-drug-substance-related
This website includes tables with AI limits for various NDSRIs based on predicted carcinogenicity.
Looking Ahead
The August 2025 deadline is a significant milestone, but NDSRI control is likely to remain an ongoing focus for the industry. Continued research and development of NDSRI mitigation strategies will be crucial. As always, staying informed about the latest regulatory updates is essential for manufacturers to navigate this evolving landscape.
Why choose SK pharmteco for NDSRI testing?
SK pharmteco addresses the critical challenge of nitrosamine and NDSRI testing with unmatched expertise and a customer-focused approach. We understand the complexities and regulatory pressures you face, which is why we offer tailored solutions to meet the latest standards in nitrosamine testing. Our team is dedicated to developing advanced methods for detecting standard and compound-specific nitrosamines, as well as complex NDSRIs, in excipients, raw materials, active pharmaceutical ingredients, and drug products. By partnering with SK pharmteco, you gain a trusted ally committed to ensuring compliance and reliability, helping you navigate regulatory requirements and safeguard your products effectively.
- Rapid Turnaround Times: We deliver timely results without compromising on quality. Screening is available within 72 hours.
- Low Detection Limits: Our methods can detect nitrosamines at 1 ppb or lower.
- Specialized Analytical Capabilities: Our CGMP laboratories are equipped with state-of-the-art instrumentation including:
- LC-MS (Liquid Chromatography-Mass Spectrometry)
- GC-MS (Gas Chromatography-Mass Spectrometry)
- HR-MS (High-Resolution Mass Spectrometry)
- LC-MS/MS (Liquid Chromatography-Tandem Mass Spec capabilities including LC-QTOF and LC-QQQ)
- Seamless Collaboration: From simplified contracts to prompt project updates, our team ensures a seamless process throughout the full lifecycle. We are committed to providing exceptional service and tailored solutions that meet your needs.
- Successful Regulatory Track Record: We maintain rigorous safety and quality standards, ensuring all our facilities are compliant with global regulatory agencies. We’ve developed methods and tested drug substances and products for nitrosamines in support of NDAs and in response to Information Requests from regulatory agencies.
Partner with SK pharmteco for Expertise You Can Trust
With the impending FDA guidance, securing a dependable nitrosamine testing partner is crucial. At SK pharmteco, we provide the expertise, advanced capabilities, and dedicated support you need to navigate these regulations effectively. Contact us today to discover how our tailored solutions can address your nitrosamine testing needs and set you up for success.
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