Pharmaceutical Technology - May 2018

Pharmaceutical Technology eBook - Biologics and Sterile Drug Manufacturing

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32 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m in a low humidity glove box. Piercing the stopper is preferred as removing the stopper without first equilibrating the pressure may disrupt the cake and lead to product blow-out. Residual moisture testing methods The methods listed are not the only methods available, but rather the most commonly em- ployed, and consequently will be covered within the scope of this review. For each approach, it is essential to understand potential interactions and assess the benefits and risks. Test methods and key considerations are summarized here. Additional information and a compendial overview can be found online (4). Loss on drying (LOD) method. LOD is a gravimet- ric method that determines the weight loss of a sample after driving off volatile residuals. In this method, the temperature used needs to be warm enough and the time long enough to release all volatile components. Because this method deter- mines the weight loss of any volatile constituent, not only water, weight loss of other volatile com- ponents, such as an organic solvent impurity, is ref lected in the measurement. For this gravimetric method, a sample is ac- curately weighed, then placed in an oven and dried at a high enough temperature for an ap- propriate amount of time to drive off any vola- tile residues. Testing can be performed in the primary packaging container if the container can withstand the test conditions. If the sample was lyophilized in bulk, then a sample of the material should be weighed into a glass vessel or other suitable container for testing. For any sample that would sorb moisture when exposed, samples should be prepared in a controlled en- vironment to prevent moisture uptake from hu- midity in the atmosphere. LOD is a relatively simple and straight-forward method to perform, but method development is required to determine the appropriate test con- ditions of temperature, time, and sample weight. When using this method, it is important to con- sider that the sample is exposed to elevated tem- perature conditions that will drive off all volatile matter. In addition, if the material is sensitive to elevated temperatures, thermal degradation may inf luence the results. The sample weight needs to be sufficient for an adequate level of detection and resolving weight differences to accurately quantify residuals. For ex- ample, if the sample is 1 g, then the sample should be weighed to at least 0.0001 g to be able to de- tect weight changes and calculate the weight loss to suitable significant figures; in this example, to resolve to 0.1% moisture. A common temperature and condition to per- form this method are 105 °C and atmospheric pressure for one hour. Other temperatures and pressures may be appropriate, depending on the product being tested. Oven temperature control should be within ± 2° and the chamber pressure to within 2 mmHg of the intended conditions. In addition, the oven chamber should be qualified for temperature uni- formity; all locations in the chamber should be within ± 3° of the target setpoint. A vacuum oven may be required to dry the sam- ple under a reduced pressure. In this case, the oven should be fitted with multiple ports for a vacuum source, pressure gauge or instrument, and dry air or inert gas inlet to revert to atmospheric pressure at the conclusion of the test. Lyophilization

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