Preventing Alcohol Induced Dose Dumping is desired 防止酒精引起的剂量倾销是理想的.pptVIP

Preventing Alcohol Induced Dose Dumping is a Desired Product Design Feature Ajaz S. Hussain, Ph.D. Deputy Director, OPS/CDER/FDA Points to Consider and Questions Developing a regulatory decisional framework to minimize the risk of alcohol-induced dose dumping; Should this be similar to current regulatory decision criteria for food-drug or drug-drug interactions? Or, Should this leverage the “quality by design” approach to assess dose dumping potential (“rugged” vs “vulnerable”)? What should be the criteria for Distinguishing between “rugged” and “vulnerable” regulatory consequence of developing a “vulnerable” product. Preferred Approach? An in vivo pharmacokinetic study examining whether there is an alcohol-formulation interaction is not the preferred approach Pharmacokinetic studies in healthy subjects that involve co-administration of high alcohol loads (to emulate a “worst case” scenario) and a modified-release product may pose a risk, either due to the alcohol load itself and because of the potential for dose dumping in cases where the high exposure itself may be dangerous. Although, for some drugs a pharmacologic antagonist can be used to reduce risks posed by dose dumping (e.g., for opiates, a naltrexone or nalaxone block), this approach may not be feasible or provide an adequate protection for most drugs. Preferred Approach? In case of food-induced dose dumping, the FDA guidance clearly recognizes that (unless the product is well designed) food effect studies can pose a risk to study subjects - “co-administration with food can result in dose dumping, in which the complete dose may be more rapidly released from the dosage form than intended, creating a potential safety risk for the study subjects” (2). To be consistent with these FDA principles - intended to minimize risk to subjects – reliable alternate approaches to an in vivo evaluation are preferred Preferred Approach Clinical risk evaluation Evaluation of product and manufacturing process design (