More Than Meets the API
Various groups have questioned the efficacy and safety of generics lately. That this topic is now being widely debated serves as a reminder that a drug is more than an API.
A prominent generic currently at the center of controversy is Teva’s “Budeprion XL 300” (bupropion HCl), a generic version of GlaxoSmithKline’s “Wellbutrin XL 300” antidepressant. Some patients who switched from Wellbutrin XL 300 to Budeprion XL 300 reported having panic attacks, anxiety, nausea, depression, and suicidal tendencies.
The reports spurred the independent ConsumerLab.com to study Teva’s drug. The study showed that after two hours, Budeprion released four times as much API as did Wellbutrin.
Although bupropion HCl is no longer patent-protected, the drug-delivery technology in Wellbutrin still is. This could explain the big disparity in dissolution between Teva’s and GSK’s products.
Drug companies, doctors, and patients mostly focus on APIs as the solutions to any disease. Though it’s true the API is what relieves symptoms or cures a condition, it’s not the end of the story.
We might think, as generics companies have argued, that generic treatments deserve less scrutiny because the drugs have already been tested and approved. But this argument does not take into account excipients, stability, formulation, or drug delivery mechanism. These elements influence a drug’s safety and efficacy, and they could mean the difference between a beneficial treatment and a harmful substance.
Drug is a total package. Question has to be raised: Why did FDA approve the drug without comparatives? Teva should have also submitted comparatives. I believe the system failed as they did not check the whole package. Since the drug delivery is patent protected, cart got before the horse. The drug should not have been approved.
Is this another case of too much work and not enough money and people to check the total package?
A classic case of misdirection—the consumer laboratory checked in vitro i.e. dissolution profile. It is very common for products to display different in vitro release rates while being equivalent in-vivo. Look at the USP-many monographs contain more than one dissolution profile-see theophylline or pentoxifyline for examples. This is because the generic has demonstrated biological equivalence whilst having different in vitro performance.
This issue was resolved years ago when bioequivalemce studies were introduced for generics. It has reappeared because the innovative industry has run out of new drugs and instead of improving their way of carrying out research has decided to spend money on PR and protecting poor quality patents
I am totally in agreement with Mr. Malcolm, before taking generics to the market, Bio equivalnce studies (BE) was done and submitted to authority. We can have totally different formulation with same BE.