Generic Drug Development
When a company decides to develop a generic version of a trade-name drug, the company's experts in drug formulation figure out how to design it. They must ensure that the generic version is bioequivalent (within a few percentage points) to the original drug, that appropriate inactive ingredients are used, and that the generic version differs from its trade-name counterpart in size, color, and shape--a legal requirement. The company must then seek the FDA's approval of the generic version.
Bioequivalence Studies: The company must conduct studies to determine whether the generic version is bioequivalent to the original drug--that is, whether the two drugs have virtually the same effect in humans. Bioequivalence testing involves determining whether the generic version releases its active ingredient (the drug) into the bloodstream at virtually the same speed and in virtually the same amounts as the original drug and whether the generic version produces virtually the same levels of drug in the blood over time. For bioequivalence testing, a relatively small number (24 to 36) of healthy volunteers can be used. In contrast, studies of new drugs are more complex and require a large number of participants (and thus are much more expensive), because these studies must prove that the drugs are safe and effective (see Section 2, Chapter 10).
Inactive Ingredients: A generic version is likely to have some inactive ingredients that are different from those of the original drug. Inactive ingredients are added for specific reasons--for example, to provide bulk so that a tablet is large enough to handle, to keep a tablet from crumbling between the time it is manufactured and the time it is used, to help a tablet dissolve in the stomach or intestine, or to provide a pleasant taste and color. Usually, inactive ingredients are harmless substances that do not affect the body. However, because inactive ingredients can cause unusual and sometimes severe allergic reactions in a few people, one version, or brand, of a drug may be preferable to another. For example, bisulfites (such as sodium metabisulfite), which are used as preservatives in many products, cause asthmatic allergic reactions in many people. Consequently, drug products containing bisulfites are now prominently labeled as such.
Evaluation and Approval Procedures: The FDA evaluates every generic version of a drug. The FDA approves a generic drug if studies indicate that the original trade-name drug and the generic version are essentially bioequivalent. The FDA also makes sure that a new generic drug contains the appropriate amount of the active (drug) ingredient and that it is manufactured according to federal standards (Good Manufacturing Practices).
 See the table When Generic Substitution May Not Be Appropriate.
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