Are generics really the same as branded drugs?

Fortune ^ | Jan 2013 | Katherine Eban

[CondoleezzaProtege]

If you’re a layperson, this is the way you probably think of generics: They’re the exact same products in different packaging...

In October the Food and Drug Administration took a highly unusual step: It declared that a generic drug it had previously approved — a version of the popular antidepressant Wellbutrin — was not in fact “bioequivalent” to the name-brand version. The FDA withdrew its approval.

...Generic drugs diverge from the originals far more than most of us believe. For starters, it’s not as if the maker of the original pharmaceutical hands over its manufacturing blueprint when its patent runs out or is challenged. The patent reveals the components, but it doesn’t explain how to make the drug. In reality, manufacturing a generic requires reverse engineering, and the result is an approximation rather than a duplicate of the original.

The FDA’s rules effectively acknowledge that. The agency’s definition of bioequivalence is surprisingly broad: A generic’s maximum concentration of active ingredient in the blood must not fall more than 20% below or 25% above that of the brand name. This means a potential range of 45%, by that measure, among generics labeled as being the same.

There are other differences. The generic must contain the same active ingredient as the original. But the additional ingredients, known as excipients, can be different and are often of lower quality. Those differences can affect what’s called bioavailability — the amount of drug that could potentially be absorbed into the bloodstream. As the American Heart Association recently noted, “Some additives traditionally thought to be inert, such as alcohol sugars, cyclodextrans, and polysorbate-80, may alter a drug’s dissolution, thereby impacting its bioavailability.”

That can result in drugs that release active ingredients into the blood far more quickly, leaving patients feeling dizzy or nauseated.

[Sans-Culotte]

generics have from 80% to 120% of the active ingredient in their offering.

My endocrinologist will not allow me to take generic Synthroid for that reason.

[Sans-Culotte]

generics have from 80% to 120% of the active ingredient in their offering.

My endocrinologist will not allow me to take generic Synthroid for that reason.

[CondoleezzaProtege]

Yes have already stated that prescription drugs and OTC items warrant different considerations. Go brand-name with the former, and be flexible with the latter.

[Phlyer]

The drug is exactly the same.

Actually, the drug substance is the same. However, differences can be introduced in the way the drug is prepared from the drug substance. As a simple example: If the drug substance is a component of a mold growth (common to many antibiotics) then the actual drug must be extracted, cleaned, dried, etc. to become a dispensable drug. Not all of these processes are identical to the original patent process (as mentioned in the article) and the 'reverse-engineering' may cause something to diverge in the active ingredient.

Excipients differ.

True, and can often be considered by the consumer. It may be significant. It may not. Your mileage may vary.

However, there is another potentially major issue. When my brother was in the army, some of his men (and their families) were having infections that were not clearing up after prescribed antibiotics. No one knew why until one of the sick kids when the hospital and they saw complete tablets in his stool discharge. The generic antibiotic (non-US manufacturer) had compressed the tablets so hard that they were not dissolving during their passage through the patient's digestive system. That's not a chemistry issue, it's a mechanical issue. It wouldn't show up on the list of ingredients. It might not show up during 'qualification' since the manufacturing process can be changed after certification as a 'generic.' But it made the generic medication ineffective.

I'm okay with generic drugs and generally use them. Sometimes we find that the 'excipients' cause stomach distress that the brand names drugs don't cause, and we take that into account. But it's not automatically 'just as good.' You (me, 'one') just need to be careful, aware of the risks, and recognize your own responsibility to make a decision. Don't just assume that Big Brother will take care of you.

[null and void]

Yeah.

From very good (hung hao 挺好) to not good (bu hao 不好), as simple as moving production to China.

[F450-V10]

My opinion drastically changed with personal experience. Always figured they were the same, because realistically, how could a miniscule amount of fillers or additives affect the response, if the active ingredient was the same? Then, in 2009, I was physically compromised for 7 months when my citalopram was changed from one brand to “Torrent”. Joint pain, malaise, weakness, corners of mouth sores. All bloodwork normal. Not until I went out of town and refilled with another generic, did the problem end almost immediately, within days. (I figured it out when a harmless side effect reappeared after the first dose...hadn’t even known it was missing for 6 months). Hard to believe it was a filler, probably insufficient dose of the active ingredient.

This happened years later with escitalopram; different symptoms but probably insufficient active ingredient. Being unable to afford brand, I always had to change generic mfgrs, which was usually easy. Later, it happened again with duloxetine and/or bupropion.
This must be mentioned: the insuffient response or bad reactions came long after I could have been conscious of any “placebo effect”. When first on a new drug, you might notice or exaggerate perceived differences. After months or years, any placebo effect is gone, you just slam them down, so it is caused by the particular make up of the drug (assuming all other conditions are equal).

Anti-depressants cause extra trouble, since a new med may take weeks or months to demonstrate effectiveness. If a new anti-depressant generic happens to be problematic, it might be attributed to the specific drug, and ruin the chances of finding the right AD for treatment.

I’m a non-practicing RN, and pharmacogenetics (reaction of drugs to a person’s genes) is becoming unbelievably accurate for many disorders. Never would have believed it even 5 years ago. Hopefully in 5 or 10 years, there won’t be as much trial & error in prescribing meds.

[plain talk]

Good article. Thanks for posting. Personally I have not noticed differences in generics which means the reverse engineering process capabilities of these companies must be pretty good.

[ifinnegan]

“Actually, the drug substance is the same”

Not sure where “actually” comes from because this is what I said.

Interesting example of small molecule drug being isolated from a mold, for example.

I’d guess that is rare now. I’d wonder if it falls under BLA now?

[be-baw]

Thanks for the advice. I will take your suggestions under serious considerations, including trying different kinds of acetaminophen .

Almost 3 years ago, I was in Georgia with unbearable neck and back pain. I went to a chiropractor, got a terrific massage and adjustments on my back and neck.

She put one hand on the top of my head, the other on my jaw and SNAP. It reminded me how people have their necks broken by people on tv or in the movies.

But It worked. My neck pain was gone for a few months. She didn’t help much with back pain...I got at most an hour of relief.

But now my neck pain is much worse than my back pain. When I turn my head my neck sounds like a bag of Orville in the microwave. I don’t know if that adjustment messed me up, but it makes me leery to go back to the chiropractor.

I went to a pain clinic and they inject you periodically with cardiocosteroids. I don’t want those until I’m sure other problems have been resolved.

NSAIDs work, but I’m a bleeder. Can’t take them.

Tramadol works. I took it as needed for about 3 years and had no ill effects when I stopped. It’s not an opioid and my experience with it was very good.

I was a recreational toker when I was in college in the early to mid 70’s. It might have been a gateway to other drugs for me in a sense because I ended up taking LSD and mushrooms 2 or 3 times each. I would not recommend either.

I need to be able to eat before I can eat properly. Right now I’m not able to. I’m on the verge of desperation here, and I’ll take a quick fix, until I get closer to normal.

Thanks for your feedback. I very much appreciate it.

[Albion Wilde]

Speaking from experience, I’d say I wasted ten years of my life struggling along with the generic for the condition I have. Paying extra for the original has been worth it. But I think that companies advertising these fakes as the same thing should pay a penalty. How hard is it to test for absorbtion? Studies need to be done so that the dosage they claim is the dosage you get.

[Do_Tar]

There have been at least 2 recent recalls for American made Rx drugs, Losartan and Diovan because of tainted ingredients supplied from China.

[CondoleezzaProtege]

Wow again, more proof it’s better to err on side of brand-name for Prescription-items

But with Over the Counter-items: I’ve benefited from drugstore brand alternatives when the brand-name stuff doesn’t offer dye-free versions of tablets for example.

And for other minor instances. “Benadryl” brand cream on mosquito bites...burned my skin AND made me super drowsy. (Didn’t know a cream could be absorbed so quickly!)

But the Target-store version with the same active ingredient (Diphenhydramine/Zinc) doesn’t do either and works fine. Their inactive ingredients are the same too except one variation:

Benadryl has: Polyethylene Glycol Monostearate 1000.
Up & Up has: Peg-2 Stearate, Peg-20 Stearate.

#FirstWorld consumer issues.

[metmom]

My daughter took some forensics courses that included studying drugs and how they are absorbed into the body>

For some people, generics actually work better.

It all depends on a person’s body chemistry.

[Phlyer]

"Drug Substance" and "Drug" are not the same in FDA usage. One is the underlying molecule, and the other is a prepared form of it, which has an approved name.

The patent owner has the approval for the named drug. Another producer can't use the name.

So, Motrin and Advil are both drug names for ibuprofen.

When the drug becomes 'generic' it often has the drug substance name, but that doesn't mean the drug substance has been prepared the same way, even aside from the other, supposedly inert components added to the drug as sold.

[Jewbacca]

“You’re Scottish?”

No, but oddly enough my great-great grandfather invented copper wire when he and a Scotsman found the same penny.

[Jewbacca]

“Not sure where in the states you are located, but international supermarkets are likely to carry it, both pre-made (and without additives) or the necessary ingredients. Asian markets...as well as Latin, etc...”

I know it is widely available.

People just don’t eat it like they used to eat it. There is a strong preference toward muscle meat in modern diets, which is leaving out key amino acids.

You can go buy a several pound bag (or jug) of kosher beef gelatin powder for less than a couple of dollars at any store with a kosher section (which most have).

[ifinnegan]

Yes, but given the entire sentence of drug being the same and excipients different in context the meaning is understood.

[ml/nj]

Generic drugs diverge from the originals far more than most of us believe. For starters, it’s not as if the maker of the original pharmaceutical hands over its manufacturing blueprint when its patent runs out or is challenged. The patent reveals the components, but it doesn’t explain how to make the drug. In reality, manufacturing a generic requires reverse engineering, and the result is an approximation rather than a duplicate of the original.

And might be superior, given lessons learned during the passage of time. (Think of all those "new and improved" products!)

ML/NJ

[CondoleezzaProtege]

It all depends on a person’s body chemistry.

Your daughter must have studied in a good place. So many med-school establishments are stuck in 'one size fits all' thinking.

[TexasTransplant]

I quit taking ALL of them and I feel much better

I wish I could have my Veterinarian be my Dr (she has declined) but she always asks the right questions when I bring in my Dog and he gets Healthy

My Dr just lectures me and Prescribes poison

Again... I quit taking ALL of my scripts and am doing very well... just changed my diet.

My friends still believing that Drugs are going to fix what ails them are now candidates for Dialysis and Insulin Injections... and are 60lbs heavier (we started at about the same weight)... they can still eat Potatoes, Rice and Bread and only have to worry about insulin injections (that don’t FIX anything, they just lower sugar in your blood until you jack it up again)
People are So Dumb
(Waiting for the Crispy Creme Diet Guy, big tree, red, dumb)