Excipient Quality Assurance: Handling, Sampling, and Regulatory Issues

Abstract

One of the Food and Drug Administration’s (FDA) key mandates is to ensure that drug products are safe and effective, and for excipients, the pharmacologically inert ingredients that constitute most of a drug product, a key safety issue is purity. Unfortunately, there are many well-known examples of patient harm that resulted from excipient impurities. For example, in 1996, the CDC reported that 86 children in Haiti died when given a pediatric acetaminophen syrup containing glycerin contaminated with diethylene glycol (1). This glycerin was apparently manufactured in China (China would not let investigators verify this) and shipped through Europe to Haiti, using a supply chain with several participants. The product was shipped with no traceability and with insufficient controls and documentation needed to avoid or even reduce manipulation and alteration of the material. This tragic example illustrates what can happen when the components of a drug product are improperly handled. The fact that this incident happened in Haiti may lead some manufacturers to say it could not happen here in the United States, but as the excipient business becomes more global and more of a commodity business, increased care will be required to ensure that similar incidents do not happen. Section 501 [21 U.S.C. 351] of the Federal Food Drug and Cosmetic Act (FFDCA) act describes the conditions under which a drug or device may be deemed to be adulterated. One of the requirements of the act is that the drug be manufactured under current GoodManufacturing Practices (cGMP). Pursuant to this provision of the federal FFDCA act, the regulations that follow describe the intent of this provision, which is to ensure the finished drug product meets the expected safety, identity, strength, purity, and quality characteristics that it purports or is represented to possess. For finished drug products, cGMP under 21 CFR, Parts 210 and 211, refers to the finished drug products. Section 501(a)(2)(B) of the FFDCA requires that all