Monday, March 2, 2009


Congress and President Barack Obama should be commended for expressing a strong commitment to modernize the Food and Drug Administration.

The FDA needs funding, resources, and the support of our leaders in Washington if the agency is to get it right in confronting our most urgent health challenges - especially if they want to ensure patients receive the safest, most effective generic medications.

As a top priority, the FDA must move to modernize its standards for approving generic versions of “controlled release” drugs. Controlled release drugs are a new generation of medication. They are engineered to deliver a precise amount of a medicine, at precise intervals, over a period of hours, without losing potency or effectiveness. This controlled release mechanism helps treat patients suffering from some of the most chronic and debilitating conditions - pain, depression, Parkinson’s, Alzheimer’s or hypertension.

The good news is that more than 20 generic controlled release drug formulations are poised to be released to the market, pending FDA approval. The bad news is that the FDA is using dated generic approval standards to evaluate these modern medications. This is critical considering any deviation from how a controlled release drug is delivered to the body can lead to unbearably painful, harmful or even fatal patient consequences.

For the FDA to approve a generic drug it must, in part, be identical in strength, dosage form, and route of administration to the original, branded drug. But the FDA’s tests for controlled release generics are not measuring the very element that makes the original drugs so valuable to patients: the safe, controlled delivery of a specific amount of medication over an extended time. Measurements that don’t include time variables simply cannot assure bioequivalence for this class of drugs.

One remedy to the bioequivalence testing shortfall will only require FDA to use multiple time-based measurements of active ingredient concentration. This will allow regulators to compare the complete performance and equivalence of a generic to the original controlled release medication. This is just a small alteration in the testing standards and only requires generic controlled release applicants to submit more data.

Those who would decry this tweak of the measurements miss the bigger picture. Controlled release drugs are only one class in a whole emerging generation of medications - follow-on biologics are another example - that the FDA will need to adapt to and address if it hopes to keep patients safe. There must be no public doubt that all new classes of generic drugs are exactly bioequivalent to branded versions that have been validated by clinical trials and years of use.

By no means is this a call for the FDA to scrap its standards for bioequivalence - not at all. Rather, this is a call to make them more robust and stringent in order to honestly assess a new generation of drugs. Evidence supporting that conclusion is mounting - a host of complaints and reports from patients losing effectiveness after switching from a branded, controlled release anti-depressant to a generic led the FDA to review whether the generic was bioequivalent and therapeutically equivalent to the brand. The review board gave the generic its vote of confidence, but noted its sensitivity to the bioequivalence issue, saying:

“The question is whether the reported lack of efficacy and/or new onset side effects in these patients who switched suggests a problem with the generic product, i.e., lack of bioequivalence to the branded product, or have some other explanation.”

Simply put, the generics industry cannot flourish, innovate and compete if it does not inspire the confidence of American patients. For the FDA to continue to ignore the controlled release regulatory oversight is to invite disaster on two fronts: the complete erosion of the generic industry’s reputation in the eyes of patients, and, unthinkable, widespread patient harm caused by ineffective controlled release generics.

Many of the health and food incidents over the last few years were hard for the FDA to predict or prevent, given its resources and funding. There will be no excuse, however, if the FDA ignores the potential for harm waiting in this regulatory gap. Pretending there is no risk in changing formulations is not science-based regulation. In the real world, there are no shortcuts to patient safety.

Peter Pitts is president and co-founder of the Center for Medicine in the Public Interest and was a Food and Drug Administration associate commissioner from 2002-04. Robert Goldberg is vice president and co-founder of the Center for Medicine in the Public Interest.

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