AMRI’s Global Analytical Services has launched a new forced degradation service to meet the industry demand for supporting drug substance, product including medical devices, and associated packaging system development and commercialization.

“We are excited to introduce this service to help our customers navigate the lack of specific regulatory recommendations in available guidance documents on how to conduct forced degradation studies,” said Pamela Smith, vice president, global analytical services, AMRI. “This service is made possible by the union of industry leading analytical capabilities from AMRI, SSCI and Whitehouse Laboratories with the aim to provide essential knowledge to overcome one of the most often cited deficiencies in the chemistry, manufacturing, and controls (CMC) section of new drug and abbreviated new drug applications.”

Stability chambers 25 °C/60%RH, 2-8°C, 30°C/65% RH, 40°C /75% RH, low (-20°C to -10°C) and ultra-low freezer conditions (-70°C) and photostability are available at AMRI to achieve commonly used accelerated conditions prescribed by the International Conference of Harmonization (ICH). However, in a purposeful forced degradation strategy more severe conditions than these are often needed to establish the impurity profile for the product, provide knowledge about the possible chemical and physical degradation pathways, and guide the selection of excipients for drug product formulations and the design suitable packaging configurations.

For drug substance and drug product, stress is applied to test samples in solution and/or in the solid-state to evaluate acid and base hydrolysis, extreme temperatures, photolytic and oxidation conditions, and may also include freeze–thaw cycles. Stability-indicating methods are developed and validated to accurately measure the changes in active ingredients’ concentration with time, without interference from other degradation products, impurities and excipients. AMRI’s Global Analytical Services offers a variety of advanced chromatographic techniques with various detectors to provide the sensitivity necessary to detect impurities at or below the ICH threshold limits. Preparative chromatography capabilities allow impurities at small to medium scale to be isolated. Identification and characterization of degradation product are performed based on formal stability results in accordance with ICH requirements. When required, nuclear magnetic resonance (NMR) spectroscopy is used along with high resolution mass spectrometry (MS) techniques to elucidate the structures of unidentified impurities.

While forced degradation studies are often focused solely on chemical degradation, stress testing of the drug substance must also evaluate the potential physiochemical changes of the targeted polymorphic form to avoid unintended changes in properties outlined in ICH Q6A that can impact drug product performance.