Most (but not all) pharmacists routinely tell patients that generic drugs are identical to brand name medications. That is hardly surprising. This is what pharmacy students are told during their education process. It is also what the FDA states on its website:
“A generic drug is identical–or bioequivalent–to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. Although generic drugs are chemically identical to their branded counterparts, they are typically sold at substantial discounts from the branded price.”
What Does “Identical” Really Mean?
Now we don’t know about you, but when we see the word identical we assume that means exactly the same as. Here is how Dictionary.com defines the word identical:
1. Similar or alike in every way
2. being the very same
3. agreeing exactly
Related Words for: identical
Indistinguishable, one and the same, selfsame
Medical Dictionary
1. Exactly equal and alike
2. Of or relating to a twin or twins developed from the same fertilized ovum and having the same genetic makeup and closely similar appearance; monozygotic.
In our opinion, the FDA’s use of the word identical, when describing generic drugs, is misleading. First, the inactive ingredients (colors, binders, fillers, etc) do not have to be “alike in every way” to the brand name product. In fact, they are often quite different. These so-called inactive ingredients or “excipients” may influence how the product affects patients. For example, a patient who is allergic to a particular color may develop a rash when switched to a generic product.
Different Formulations Between Brand and Generic Drugs:
The formulation may also differ dramatically from the brand name. Many pharmacists may be unaware that the physical characteristics or release properties of a brand name drug often stay under patent even after the active ingredient becomes available generically. This is especially problematic for slow-release or long-acting medications. Generic manufacturers may have to come up with different technologies to deliver the active ingredients. This means that the products are not always “indistinguishable or one and the same.”
To see this for yourself, visit the FDA’s website and report on the antidepressant bupropion XL.
If you look at the graph the FDA provides for Budeprion XL 150 you will discover that the mean plasma concentration of the two drugs is certainly NOT identical! The generic formulation (which uses a matrix technology to release the active ingredients) produced peak blood levels in 1.5 to 2.5 hours, whereas the brand name product (using a membrane technology) produced peak blood levels around 5 hours. This kind of information for other generic formulations is not always easy to access.
What Does “Bioequivalent” Mean to the FDA?
Pharmacists have been taught that generic drugs must be bioequivalent to brand name medicines. The FDA defines that as “an equal rate and extent of drug absorbed [from] the bloodstream.” We’re back to the meaning of the word “equal” or “identical.” The FDA’s understanding of these words is quite different from most other people.
Many pharmacists do not know how the FDA actually goes about approving generic drugs. For one thing, the FDA never releases the bioequivalence curves to health professionals or the public. We have already pointed out above that the rate of absorption for a drug like Budeprion XL 150 can be quite different from the brand name Wellbutrin XL 150.
The FDA relies primarily on two measurements to determine rate and extent of drug absorption. One is the maximum concentration of drug in the bloodstream (Cmax). This occurs at one point in time over 24 to 48 hours. The other is called the area under the curve (AUC) and it represents the total amount of drug absorbed over the length of the trial (usually a day or two). If these two numbers (Cmax and AUC) are “close enough,” the FDA says the drugs are bioequivalent and the generic gets a green light.
The Problem with the FDA’s Generic Drug Approval System:
Here’s the big mistake with this approach. It does not actually compare hour-by-hour rate of absorption. Let us share an analogy. Imagine two seemingly identical 2016 Honda Civics. The difference, not detectable to the naked eye, is the engine size. One has a 158 horsepower engine (Car A). The other has a special 385 horsepower engine (Car B). The cars must travel from Washington DC to New York City. They will be judged by two metrics to determine if they are “identical” cars. The first will be the time it takes them to reach NYC. The second will be how far they traveled in actual miles (a substitute for AUC).
Both cars leave DC at 2 am and both arrive in NYC at 6 am (four hours total driving time). Their average speed is the same, ie, 63 mph. They traveled the same number of miles. But there is a tremendous difference in how they got there. Car A with the small engine drove straight to NYC, never exceeding the speed limit. Car B with the 385 HP engine went at 120 miles per hour for two hours (it had a fancy radar detector to avoid speed traps). Then car B stopped for a leisurely breakfast for 45 minutes and resumed the trip at a more modest 95 mph. Again, both cars covered the same distance and achieved the same average speed over the four-hour trip (63 mph).
Clearly the two cars traveled the distance very differently. The cars were not identical! But without seeing the data from speedometer you would never know that one traveled the speed limit and the other hit 120 mph for long periods of time. The same thing is true for generic medications. By not allowing health professionals or patients to see the actual bioeqivalence curves we cannot see the true rate of absorption on an hour-by-hour basis. This may be especially problematic for long-acting, timed-release formulations. Tis time for the FDA to allow the American public to see the data for themselves. “Trust by verify!”
Manufacturing Quality of Imported Generic Drugs Remains Worrisome:
Here is something else a pharmacist might not realize. According to the FDA, 80 percent of the active and inactive ingredients in our pharmaceuticals come from abroad. It is estimated that 40 percent of the finished pills come from abroad including countries such as India, China, Brazil and Mexico. It is also very clear that the FDA does not have the resources to inspect all or even many of the manufacturing plants producing either the raw materials or finished products millions of Americans take every day. That means that there is no verification system that the pills are exactly what they say they are.
We have seen manufacturing problems with some of the most prestigious drug companies in the U.S. (Johnson & Johnson and GSK). These problems occurred at plants where the FDA visits on a regular basis. Do we really believe that chemical companies in China that are not inspected are producing perfectly identical generic drugs at cutthroat prices?
Perhaps it is time for pharmacists to acknowledge that there are no guarantees when it comes to generic drugs. Pharmacists must be the patients’ allies and advocates. When patients experience problems with certain generic formulations, pharmacists should offer a sympathetic ear and report the problems directly to the FDA’s website (MedWatch). Perhaps if pharmacists insisted that the FDA do a better job both approving and monitoring generic drugs, patients would have more confidence in these money-saving pills. Pharmacists should also insist that the FDA make all generic bioequivalence curves available for public scrutiny. Without that data they have no way of verifying that the products they are selling are indeed “identical.”
Learn much more about generic drug problems and mistakes that health professionals make in our book, Top Screwups. You will be amazed out how serious the problems really are. But there are many things that patients and their families can do to prevent health care harm.
Revised: June 8, 2016
