I thought I wrote enough about generic versus brand name already but then the antibiotic dug class quinolone hit my radar screen and here we go again. In talking to friends and sufferers on Facebook and elsewhere who have access to attorneys specializing in cases like this, the subject of inactive ingredients came into question as a result of two cases that went in front of court where people tried to sue a generic manufacturer but were unsuccessful. Both cases ended up at the US Supreme Court, which is odd since their job is to decide on Constitutional matters and generic drugs would not seem to be appropriate for that.
The first case referred to was handled by the US Supreme Court in 2010: Pliva, Inc., et al v. Mensing and the second case in 2012: Mutual Pharmaceuticals Co., Inc. v. Bartlett. In both cases, however, the supreme court decided on the side of the pharmaceuticals, noting that “Once a drug is approved, a manufacturer [including generic drug manufacturer] is prohibited from making any major changes to the “qualitative or quantitative formulation of the drug product, including active ingredients, or in the specifications provided in the approved application…. [including] labeling,” which also consists of all adverse side effects listed on the brand name drug’s list of adverse side effects. (emphasis added)
Thus what the Supreme Court suggested is that the generic manufacturer’s active ingredient in the generic drug must be the same as the active ingredient in the brand name and since the active ingredients in the brand name and the generic drug are the same, and the FDA approved it “as is” already, there can be no changes made. The FDA approved the brand name drug based on the safety of the active ingredients in the brand name drug. Since the brand name drug and the generic drug active ingredients are the same, this relieves the generic manufacturer from any responsibility. Whether it caused adverse side effects not listed on the box label is irrelevant since there can be no changes made once the drug was FDA approved.
Note that there is no mention anywhere in the US Supreme Court case about the inactive ingredients!
Hold it right there! If I am a generic manufacturer and my inactive ingredients modify the absorption of the active ingredient and thereby convert the good drug under the brand name into a toxic generic drug then… well what then?!
As it happens, this is the case more often than not. In the case of Cipro in particular, the active ingredient is Ciprofloxacin. One of the most important inactive ingredients is a film coating (meaning it probably absorbs in a place other than the stomach) but the generic equivalents need not contain that film coating because it is considered to be an inactive ingredient.
So if the pill absorbs elsewhere in the body in the generic than in the brand name, does it not modify the generic drug to be a different drug from the brand name? Should the generic that works so differently not require a new drug application (NDA) and an FDA approval the same way as any new drug would have to? One of the reasons why brand name drugs are so expensive is precisely because of all the work it takes to pass the NDA process and all the clinical trials that come with that.
Thus this is the main problem: inactive ingredients matter in how the drug is absorbed but they are not considered to be necessary and are not active ingredients.
Here is the example for you with Cipro brand name and one of the generic manufacturer’s Ciprofloxacin, generic for Cipro:
Cipro brand name:
Active ingredient: ciprofloxacin
cornstarch, microcrystalline cellulose, silicon dioxide, crospovidone, magnesium stearate, hypromellose, titanium dioxide, and polyethylene glycol
Active Ingredient: Ciprofloxacin
Hypromellose 2208 (15000 MPA.S), lactose monohydrate, magnesium stearate, modified corn starch (1-Octenyl succinic anhydride), sodium starch glycolate type a potato, titanium dioxide, triacetin, (cornstarch, microcrystalline cellulose, silicon dioxide, crospovidone, hypromellose, titanium dioxide, and polyethylene glycol)
Inactive ingredients that are in the generic drug but not in the brand name drug:
- Hypromellose 2208 (15000 MPA.S),
- lactose monohydrate,
- modified corn starch (1-Octenyl succinic anhydride),
- sodium starch glycolate type a potato,
Inactive ingredients that are in the brand name drug that are not in the generic drug:
- cornstarch, microcrystalline cellulose,
- silicon dioxide,
- polyethylene glycol
Inactive ingredients in both the brand name and the generic drug:
- magnesium stearate
- titanium dioxide
The differences between the inactive ingredients of the brand name and the generic drugs may explain why of the 1800 complains against this drug, in the quarter ending June 2014 in the FDA database, 1600 complaints were about generic and only 200 about the brand name drug!
The two lawsuits against the generic manufacturers were set up on the wrong legal base. Given that adverse side effects grow every day and are added to the FDA database but not to the drug’s warning–remember, once the drug is FDA approved, modifications are not possible, the list cannot be amended except in special circumstances. I now understand that fighting on the grounds of the adverse side effects not being listed cannot be done without a constitutional argument; hence these cases ended up at the US Supreme Court! A case fought on losing grounds cannot win. The attorneys should have known better!
Why did the attorneys not fight on the basis of the inactive ingredients instead? Apparently I am told some attorneys believe that the inactive ingredients must also be the same as the active ingredients (lawyers should not be believing anything until they researched the facts)! But if one reads the cases carefully, it is clear that only active ingredients matter in the eye of the law. There is room for a discussion (and a fight) on the inactive ingredients since they modify the active ingredient’s absorption, thereby creating a new drug that was not FDA approved
Do we have a case to fight generic drug makers whose inactive ingredients modify the drug to be different form the brand name? You bet! A generic drug that behaves in the body differently from its equivalent brand name drug is a different drug and needs FDA approval! It is an illegal drug that is sold without being approved by the FDA. It is that simple!
Are you an attorney? Please contact me!
Comments are welcomed!