Brand-Name and Generic: What Really Differs

A brand and its generic have the same active ingredient. The substance that actually does the work inside the tablet is the same, in kind and in amount.

The FDA requires exactly that: the same active ingredient, strength, dosage form and route.

What can differ is the excipients: binders that press powder into a tablet, disintegrants that let it break apart in water, coatings, colors, flavors.

The FDA says so plainly: a generic does not necessarily contain the same inactive ingredients as the brand.

The figure on the left holds the two products from the pharmacy, Advil and Walgreens’ own ibuprofen. Switch between them: the active-ingredient row stays put, and the excipient rows below it change.

There are more excipients than you might think. On the left is the Drug Facts label of a children’s chewable acetaminophen sold in the US. One ingredient does the work; the other ten are inactive.

That is not unusual. An analysis of every oral solid medicine approved in the United States found that 92.8% contained at least one potential allergen. Lactose was in 45%, and dyes associated with allergic reactions in 33%.

That is why the label spells them out. This one prints a warning for people with phenylketonuria because of its aspartame, and names each of its two dyes.

Press the ingredients marked in navy on the left.

But that means those substances are present, not that most people who take them react. Statements like these are written for the people who are sensitive to them.

If hives appeared after switching to a generic, the active ingredient is the same, so the excipients are the first place to look. And everything said about excipients applies to brands just as much.

If you are sensitive to a particular substance, the inactive ingredients on the Drug Facts label are a better guide than whether the box says brand or generic.

Before a generic can reach the market, it has to show in a trial that it is bioequivalent to the brand.

Healthy volunteers take each drug, and the concentration of the drug in their blood is measured as it rises and falls over time.

Not every box on the shelf went through this, though. Older painkillers such as acetaminophen and aspirin are sold under an FDA monograph, a rulebook for the ingredient rather than an approval for each product: their store brands must match its ingredient, dose and labeling, but file no bioequivalence study. The Walgreens ibuprofen in the scene is an approved generic, and had to show it.

Two values are compared: how high the concentration climbs (the peak, Cmax), and the area under the curve (AUC), which is the total amount of drug that reached the body.

Both have to be close enough to the brand’s to count as equivalent.

Then you hear what “close enough” means, and it sounds worrying: within 80–125%.

Read backwards, it sounds as if a generic working at 80% of the brand would pass.

Why a range, rather than “identical”, in the first place? Because even a brand compared with itself does not give the same value every time it is tested.

One reason is the person. Every time someone takes a drug, brand or generic, the measurement varies a little, depending on how they are that day and whether they have eaten. Press the button on the left to give the same drug again.

The other reason is the drug. Tablets are made in several runs, and each run is called a batch. Just as bread from the same recipe comes out a little different tray by tray, a new batch brings tiny differences to the tablet too.

Demand “exactly the same value” and the brand itself would fail.

So the rule applies not to one average but to the whole range. The estimated range of the ratio, error included, what the FDA calls the 90% confidence interval, has to sit entirely within 80–125%.

For a generic averaging 80%, half of that range would fall outside the line. That is not a pass. It is a fail.

Where do real generics land? When the FDA pooled the results for 2,070 generics approved over 12 years, the average difference in AUC from the brand was 3.56%.

Nearly 98% differed by less than 10%. They cluster in the middle of the range, not at its edges.

The range is not applied to every drug alike, though. For drugs such as warfarin and levothyroxine, where the dose that works and the dose that harms sit close together, a small difference can mean treatment failure or side effects.

For these, the FDA tightens the test: the limits narrow toward 90–111%, scaled to how much the brand itself varies. What matters is less the width of the range than whether the drug can tolerate it.

In the US, the story of a drug’s price is mostly a story of how many companies sell it. While a patent lasts, only one can.

When the patent ends, other companies may make the same molecule.

The first generic starts pulling the price down. By the FDA’s count, a single generic competitor can lead to price reductions of about 30%.

Each new competitor pushes further. With five generics competing, prices drop by nearly 85%.

Generic makers do not have to repeat the brand’s animal and clinical studies, and several of them usually sell the same drug. Those are the two reasons the FDA gives for the lower price.

Generics are cheap not because they work less well, but because many companies are selling the same thing.

Over the counter, the same thing plays out on a shelf. Next to the brand sits the store brand, with the same active ingredient and strength on its Drug Facts label, for less.

In 2013, 100 tablets of Bayer aspirin cost $6.29 on CVS’s website; the same pack of CVS’s own aspirin cost $1.99.

Who pays the difference? In a study of US shoppers, pharmacists chose the national brand of headache remedy only 9% of the time, against 26% for the average shopper.

The people who know these drugs best are the least willing to pay for the name.

So why does the brand still cost more? The reason most often given is the name itself. Years of recognition, advertising and distribution are priced in, and people ask for it by name, “Advil for a headache”.

A generic has to compete on price, so it is set lower. That is the market at work, and it has nothing to do with how well the drug works.