Rigorous Standards for Bioequivalence

A Message from Kathleen Jaeger

Although not for the first time, and, sadly, probably not for the last, a concerted effort is under way to cast doubts about the safety and efficacy of FDA-approved generic medicines as compared with their brand counterparts. This effort is particularly prevalent at the state level, where carveout legislation is spreading like wildfire, and there has been an uptick in media stories questioning generics.

Unfortunately, these scare campaigns sometimes frighten and confuse patients. They also lead to many questions. As pharmacists, you see this firsthand when your customers come in the door with concerns about medicines you have filled. For this reason, the FDA has updated its Web site to help provide patients with sciencebased, consumer-friendly information about bioequivalence.

According to the Web site, the “FDA recently evaluated 2070 human studies conducted between 1996 and 2007. These studies compared the absorption of brand name and generic drugs into a person’s body. These studies were submitted to FDA to support approval of generics. The average difference in absorption into the body between the generic and the brand name was only 2.3%. Some generics were absorbed slightly more, some slightly less. This amount of difference would be expected and acceptable, whether for one batch of brand name drug tested against another batch of the same brand, or for a generic tested against a brand name. In fact, there have been studies in which branded drugs were compared with themselves, as well as with a generic. As a rule, the difference for the generic-to-brand comparison was about the same as the brandto- brand comparison” (www.fda.gov/ Drugs/ResourcesForYou/Consumers/ BuyingUsingMedicineSafely/Under standingGenericDrugs/ucm167991. htm).

We applaud the FDA for its strong stance demonstrating that sound science drives the drug approval process. The FDA is a valued partner in our collective efforts to ensure that patients have the most accurate information they need to make wise decisions about their health care.

The generic industry’s top priority is to ensure the safety and effectiveness of its medicines. We make sure that the products we bring to market produce the equivalent therapeutic effect of their brand counterparts.

Over the years, the FDA has confirmed that bioequivalence requirements for generics and brands are rigorous and sufficient to ensure that approved generics are therapeutically equivalent to their brand counterparts. Based on FDA analysis of hundreds of bioequivalence studies, the FDA has determined that small differences in blood levels—less than 4%—may exist in some cases between a brand and its generic equivalent. The FDA has repeatedly pointed out, however, that this minor difference is no greater than the difference that may exist between 2 separate manufactured batches of the brand drug.

A misstatement is frequently made regarding the bioequivalence of generic drugs, which asserts that blood levels of the active ingredient in generic drugs may vary from —20% to +25%, compared with the brand. This simply is not true, and any generic with a difference that dramatic would never be approved by the FDA. The 20% to 25% margin is one part of a complex statistical calculation used to help measure the bioequivalence. In no way does it represent the actual difference in the amount of active ingredient in a patient’s bloodstream, which the FDA has determined is typically <4% between generic and brand or between 2 different batches of a brand drug.

The FDA’s approval process for generic drugs is equally as stringent as the process followed to approve brand drugs. The rigorous chemistry, manufacturing, and controls phase is applicable to both new brand drugs and generic drugs. Labeling and testing requirements are also the same for both brand and generics. The same FDA field inspectors evaluate the manufacturing facilities for generics and brand products, using the same standards, to ensure compliance with good manufacturing practices.

Although no scientific evidence exists to show that problems with inequivalence exist, the agency is under increasing pressure to examine alternative approaches for demonstrating bioequivalence for certain products. Needless to say, GPhA will continue to speak out on the issue of bioequivalence and will work with the FDA to ensure that any changes to current bioequivalence standards are well-grounded in science. Our shared goal must be to ensure that patients have access to safe and effective generic medicines. â–