Possible differences between branded and generic drugs in pill form... why?

[Vastness]

I frequently hear reports of generic pills being somehow less effective than their branded equivalents.

Relating this to my own experience - I only have personal experience of this, in a sense, with Valium and Tramadol. I personally have only done generic Valium (which I did not find to be very effective at all, only a little sedating) however a few friends of mine who had done this drug before (I can't personally confirm the source but it is believable they were branded) claimed that the generic ones we had managed to procure were just not as good.

Regarding Tramadol - I have taken 150mg of branded Tramadol before and enjoyed it, as did a few friends. Recently we came accross some Tramadol from a different source manufactured in India. Honestly I cannot say definitively one way or the other if I noticed any difference, but again a few of my friends who have done Tramadol that was definitely branded and prescribed claimed that the generics were just not as good or effective (one friend in particular has taken quite a bit of Tramadol before and took the same dosage of prescribed, branded pills perhaps a week after taking the generics, so the apparent difference cannot be put down to tolerance).


So my question is, what exactly is the reason for this apparent difference in quality?

Honestly I was inclined to think at first that the reported difference was somehow imagined, as, in my view, if a pill contains a certain amount of active chemical, whether it be 10mg Valium, or 50mg Tramadol, that pill should be equally effective no matter how it is manufactured, and if there is a difference in the quantity of the active substance it should surely be minimal! However this is not the first time I have heard of generics being somehow lower quality and I don't feel I can completely dismiss the fact that this was reflected in my friends' experience.

Are generics actually of such low quality that they contain 50% or less of the reported quantity of drug? Are they perhaps made in a way that causes the active substance to degrade much faster? Or what?

 

[_DankOpiAmp_]

Apparently they can use all sorts of inactive ingredients in the generics whereas the brand will be consistent and this can impact absorption rates and sometimes allergies.

 

[phatass]

i have read that the inactive ingrediants in generics are produced in mass in placs like chinaa, therefore are cheaper. But the amount of the active ingrediant is exactly the same.

 

[Vastness]

Thank you both for your responses. However, that does not seem to answer my question as it does not explain at all why there would be subjective differences in the effects of branded vs generic pills.

Surely any affect that inactive ingredients might have on absorption rates, for example, wouldn't even be subjectively noticeable...

 

[Toz]

Tolerance? I've had this thought before when buying different brands of pills but in the end I think it always came down to tolerance really. I had been eating pill X for Y amount of time which lead to pill Z feeling weaker even though it had the same active ingredient listed as pill X.

 

[ThaDudeAbides]

Perhaps the inactives (if they truly are inactive) has a negative effect on the actives? For example, taking SSRI's will effect the way your brain reacts to certain drugs. When I took ant-d's, I couldn't trip very hard. Maybe they binders/inactives actually mess with the actives potency?

 

[Jimzip]

Quite a lot of the time, it's simply down to purity. For example, let's take Etizolam as an example. Here in the UK, most people purchase Etizolam from RC websites, who in turn purchase etizolam powder in bulk from India or China and press their own pills. Contrastingly, Etilaam (a branded version of Etizolam available on prescription in India) has to maintain a higher standard of purity as it's used medically.

The same is applicable for quite a few popular drugs - the other one which I've noticed tends to fluctuate in quality depending on source is Modafinil.

 

[norman$]

I'll pipe up cuz I have specialized experience in this area- I have been involved in a number of brand vs. generic patent suits (working with firms representing the generics). I have learned more about differences between brand and generic drugs than I ever wanted to, but at least I can share some of it with you all now.

(tl;dr Overall, generics are plainly equivalent to the brands they copy. But there can be real and medically important differences. Read for more. Ask your pharmacist and Dr. about it for YOUR medication.)

This really is a case-by-case thing.

In the overwhelming number of cases there is no medically or biologically relevant difference between the brand and the generic but the DO EXIST and are mostly known by your local drug experts- your pharmacist and doctor. The differences between generics and brands are most medically important where precise dosages are critical (anticonvulsants, anticoagulants) or when the time course of release is critical ... because generics need not be IDENTICAL just "bioequivalent".

Briefly, the FDA requires the generic to be "bioequivalent" with the brand. This is defined differently for different drug products. However, it generally means the generic delivers +/- 25% of drug delivered by the brand original over some (hopefully) relevant period of time. Sometimes this matters alot, sometimes not at all.

Sometimes the RATE of drug release from e.g., your tablet, may be different in important ways between the brand and the generic even if the FDA thinks the two are overall bioequivalent. Differences can arise from differences in incipients (inactive ingredients that dilute the drug, facilitate manufacture of the dosage unit, and/or control drug release), or differences in the active drug ingredients.

E.g., modafinil is essentially insoluble in anything, but it was observed to have drastically different effects depending on the batch of drug tested. It turns out that modafinil bioavailability from dosage forms (tablets/capsules/etc) is highly dependent on the rate of dissolution of the drug, which is dependent on the size of the drug particles. The best drug delivery into the blood comes from drug particles in a specific range (I think 1-20 micrometers) and drops radically as particle size goes up. In fact Cephalon (the US company that sold it) had a patent covering not the drug itself, but the drug having that particle size and used that patent to keep generic competitors off the US market. I know from both the literature and personal experience that these differences are quite real. So generics from India (Modalert (r), etc.) are generally found by users to be less potent and effective that brand name Cephalon products, and it appears that this is why- they did not control particle size well enough.

This is only one example, there are many others- like the old OxyContin 80 mg tabs were sometimes reported to be more effective than the Teva generics despite containing and releasing the same amount of drug overall... just because the time course of drug release was a bit different between the two. The two used different delayed-release technology (ingredients and manufacturing techniques) to achieve the desired slow and controlled release of narcotic, and the rates of release were just different.

And sometimes bioequivalence is more of a hand-waving, face-saving exercise ...
e.g., generic steroid nasal sprays (Flonase, Nasacort, etc.) There is no easy way to say that my generic nasal spray does or does not actually deliver the same amount of drug in the same way and to give the same effect as the brand. For these products, the amount of drug delivered is very small and the amount absorbed into the blood can be essentially undetectable.. Even when the drug is absorbed into the blood and is detectable there are wide variations in the measurements of drug concentration even with one product in one patient, so this is an unreliable measure (more accurately, a surrogate) for product efficacy.

So the generic must duplicate not the amount of drug delivered into the patient's bloodstream, but duplicate the particle size of the drug (steroids are not soluble in water) and the spray pattern that comes out of the sprayer, and then jump to the conclusion that the two will work the same. This is probably a good assumption in this instance but is not for some others.

Additional info may be found at the FDA dot GOV web site and

www(DOT)merckmanuals(DOT)com/home/drugs/trade-name_and_generic_drugs/bioequivalence_and_interchangeability_of_generic_drugs.html