Understanding Impurities and Degradants in Drugs, Packaging and Devices

AMRI’s E/L&I has comprehensive capability to perform stress testing on drug substance, drug product, associated packaging system, and medical devices.

For drug substance and drug product, including all schedules of controlled substances and potent compounds, we expose the test samples, in solution and solid state, to stress conditions which may include: acid and base hydrolysis, oxidation, heat, or light exposure (per ICH conditions).  For containers and medical devices, test samples can also be exposed to similar conditions, as well as dynamic extractions (such as sonication) to meet the needs of ISO 10993 -13, 14, & 15. Any of the stressed samples can be evaluated utilizing a variety of chromatographic capabilities (HPLC, UHPLC, GC) with various detectors available.  LC or UHPLC- high resolution MS, MS/MS or HRAM are available to provide either tentative or definitive structural identification of major degradants. A comprehensive extractable/leachable/impurity database is also available to identify potential leachates (and their degradants) that may migrate from container/closure system or drug delivery device. The resulting impurity profile can then be further evaluated by structural activity relationship assessments (knowledge based and/or statistical based) as well as through traditional toxicological risk assessments, to identify and mitigate the risk associated with potentially genotoxic degradants, as required by ICH M7 and/or ISO 10993-17. If warranted, a leachable method also can be developed and validated. In the end, a stability-indicating method may be developed to separate all degradants, appropriately validated based on the need, and carried out for risk control over the concerning shelf-life of the article in question.

Temperature and Physical Forced Degradation

Whitehouse Laboratories has the capability to employ both temperature and physical forced degradation techniques such as thermal cycling (freeze/thaw), accelerated aging as well as vibration and shock testing. These techniques are utilized to evaluate the reaction of drug product and/or combination devices and packaging to temperature excursions and mechanical forces that might be encountered during the shelf-life of the product. Whitehouse maintains a series of qualified test chambers to assist clients in evaluating and defining shelf life claims: high performance cycling chambers (-70°C to +140°C), -70°C through -90°C Cryogenic Storage, and various bench top and reach-in environmental chambers with capabilities from -70°C to +190°C for developmental studies. Whitehouse is an ISTA and ISO 17025 certified testing laboratory and provides distribution simulation services (shock and vibration) in accordance with ISO 11608 and the most current test methods from ASTM and ISTA (International Safe Transit Association).

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Forced Degradation – Controlled Substances

SSCI is uniquely positioned to provide forced degradation evaluation services for our clients.  Samples, including all schedules of controlled substances, are exposed in-house to stress conditions, including acid and base hydrolysis, oxidation, heat, and light exposure (per ICH conditions).  Samples are evaluated using a variety of chromatographic capabilities with various detectors available.  If unknown impurities arise, we can use our premier NMR and high resolution MS services for identification, and have preparative chromatography capabilities from small to medium scale to isolate impurities both at SSCI, as well as in our global AMRI analytical network to accommodate full characterization.  If interference is noted, our experienced chromatographers can develop and validate methods for your product.

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