In March independent testing centre ConsumerLab.com urged the FDA to review the performance of a generic equivalent to AstraZeneca's Toprol XL (metoprolol succinate), a drug to counter high blood pressure and the fifth most prescribed medicine in the US. This move followed numerous complaints to The People's Pharmacy consumer group by patients whose medication had been switched to generic versions of Toprol XL. In addition in December 2007 the American Epilepsy Society (AES) called on the FDA to approve a large clinical trial to establish whether taking generics as opposed to brand-name drugs increases the likelihood of "breakthrough" seizures or toxicity. A study on this scale would take several years and in the meantime the AES has stated that it will oppose any measures that limit physicians' choices when prescribing anti-seizure medicines. Generics have been broadly welcomed for providing a cheaper alternative and consequently helping to keep down costs for brand-name drugs. The market for drugs with patents ending between 2006 and 2015 is approximately $160bn and switching these to generic versions provides considerable savings for healthcare providers. However, dissenting voices have been around for some time, with The American Association of Clinical Endocrinologists, the Endocrine Society and the American Thyroid Association uniting in 2004 to warn patients with hypothyroidism that generics could harm them. Perhaps the most widely discussed case has been that of Budeprion XL 300 (bupropion HCl), Teva's generic version of GlaxoSmithKline's antidepressant Wellbutrin XL 300. There were claims that patients who switched to Budeprion XL 300 began to suffer from a range of new side effects including panic attacks, anxiety, nausea, severe depression and suicidal tendencies. This anecdotal evidence has been disputed by Teva which stated that reports about the drug were received at 0.002 per cent, a rate they consider to be consistent with other prescription drugs. Nonetheless, the anecdotal reports prompted the study by ConsumerLab.com which found that although the drugs both contained the same quantities of the active ingredient, the dissolution rates varied considerably. After two hours the brand-name drug had released 8 per cent of its bupropion HCl whereas the generic had released 34 per cent. A disparity of 25 per cent to 49 per cent was then found after four hours, with the quantities of active ingredient becoming comparable after 8 hours. Although the active ingredient in Wellbutrin XL 300 is no longer patent protected the membrane-based drug-delivery technology still is, with Budeprion XL 300 using an unrelated erodible tablet technology. Teva has not sought to dispute the findings of ConsumerLab.com but believe the methodology used renders the findings irrelevant. This viewpoint is supported by Jerome Skelly, the former director of the division of biopharmaceutics in the office of generic drugs at the FDA, who said: "Pharmacokinetic evaluations are the only method employed by the FDA for ascertaining whether or not a generic version of an innovator drug is bioequivalent." Kathleen Jaeger, president and chief executive officer of the Generic Pharmaceutical Assoication has spoken out in the past against those questioning the safety of generics. She said: "Deliberately misleading scare tactics such as this are intended to create a public perception of generic medicines as being poor-quality and unsafe substitutes for brand drugs. This could not be further from the truth." The arguments will likely carry on for years to come but given the benefits of generic drugs and the absence of any comprehensive evidence of their ineffectiveness it appears the generics market will continue to go from strength to strength.