Written by: John Deininger
Researched by: Nick Caleb
Edited by: Jeff Hinman, Lauren E. Trent

The city of Los Angeles is cracking down on drugs. It filed criminal charges against officials of two companies allegedly importing and distributing poisonous toothpaste. As it so happens, the poisonous chemical diethylene glycol, is better suited for cooling engines than improving dental hygiene. Finding antifreeze in toothpaste conjures images of Upton Sinclair’s The Jungle, and people falling into rendering vats. Didn’t the public outrage resulting from the book and the leadership of one of the greatest U.S. Presidents (Teddy Roosevelt) help create food and drug regulations to prevent such egregious violations of law? Yes, but there’s a lot to regulate.

The Food Drug and Cosmetics Act required manufacturers to demonstrate a product’s safety, and granted the Food and Drug Administration (FDA) broad powers to regulate food, drugs, and cosmetics. How the FDA classifies a product has important ramifications for the regulation and approval process. When it comes to FDA approval and regulation, the product’s primary use is the determining factor.

The FDA considers toothpaste a drug. That seems like an obvious and straightforward concept, but, surprisingly, ambiguity exists. Toothpaste could seemingly be either a drug or a cosmetic because it is used to protect your teeth, but also to keep them looking nice. A product is a drug if 1) drug-like effects are foreseeable in large groups of people, 2) consumers use the product predominantly for its significant pharmacological effects, or 3) manufacturers know that the product will be used for these drug-like effects. Cosmetics manufacturers, on the other hand, must simply declare their ingredients, not make any false claims on the packaging, and use safe chemicals. Since pretty teeth are more of a byproduct of the action of toothpaste’s chemicals, like fluoride, it’s out of Clinique land and into the realm of Tylenol.

While toothpaste comes in many flavors, as far as the FDA is concerned there are only two flavors of drugs: over-the-counter and prescription. Whichever category a drug falls into will determine the amount of hoops a company has to jump through to get it approved. Most toothpaste, including the one containing the coolant, is over-the-counter, but some toothpastes are only available by prescription. So where does the FDA draw the line?

Legal Street Drugs

Anyone who has ever been to a pharmacy knows that the over-the-counter drug section can span half the store. The FDA regulates 135,885 firms and deals with over 100,000 over-the-counter drugs. These drugs are treated differently than prescription drugs because they’re deemed relatively safe, and the benefits outweigh any risks.

So how does a prescription drug come within grasp of anyone but a pharmacist? A new over-the-counter drug has two routes to approval. The first is the most obvious: the manufacturer files a new drug application (an NDA to those in the industry). If the active ingredients, dosage strength, or route of administration will be new to the over-the-counter world, the manufacturer submits data to the FDA for approval. Take Claritin, for example. While Claritin was initially approved as a prescription drug in 1993, the manufacturer still had to jump through the hoops of a new drug to sell it without a prescription because its active ingredient was not already known in the over-the-counter arena.

As an interesting aside, Claritin’s manufacturer, Schering-Plough, did not propose the idea on its own. The FDA, at the urging of WellPointe HealthWorks, forced the company to make Claritin over-the-counter to make it more affordable. Canada isn’t the only place we can get cheap drugs.

The other path to over-the-counter approval is through the FDA “monographs,” a detailed study of a specific type of drug. For example, a monograph exists for toothpaste, known as anticaries within the FDA. Each monograph specifies the allowed active ingredients and their permitted quantities. Beginning in the 1970s, FDA-created panels began reviewing over-the-counter ingredients and promulgated appropriate quantities of the chemicals found in the drugs. This created a streamlined regulation process that allows thousands of over-the counter drugs to avoid review if the manufacturer complies with the monographs. If the Target brand ibuprofen has the same amount of ibuprofen and inactive chemicals as Advil, for example, then there’s little concern if the generic brand didn’t have its own study. Consumers get the benefit of an influx of manufacturers who drive down the price of the name brand product.

Prescription Drugs

Like over-the-counter drugs, prescription drugs with new active ingredient formulations require FDA approval. In the same vein, if the drug delivers its ingredients in a new manner, or it’s intended for new or additional uses, it must go through the approval process. New prescription drugs are often totally novel, and as such, go through more rigorous testing.

These new drugs face years of development in order to seek FDA approval. Before the drug even gets to the FDA, a manufacturer files an investigational new drug (IND) application that becomes effective within a month. The IND specifies how the drug will be studied and discusses the current data obtained from preclinical studies. Clinical trials are then broken into three phases. Phase I, using a very small number of participants, determines how the drug is metabolized and the optimal dose. Phase II involves a slightly larger sampling of people and tests the drug’s safety. Finally, Phase III involves thousands of people from across the country and looks at the drug’s long-term effects.

The Ailments of the Approval System

In theory it sounds highly structured and reliable, but a mixture of questionable testing and deregulation have chipped away at the reliability of the process. First of all, pharmaceutical companies fund most new drug trials, and private coordinators monitor the studies without everyday FDA oversight. This raises questions of biased data. There are also concerns that the FDA is not an independent agency acting in the best interest of the public, since industry dollars provided $382 million dollars of their budget in 2006.

Finally, the FDA’s policies have swung from an extremely slow drug approval process to one that is very quick — possibly too quick. During the height of the AIDS panic in the late 1980s, the FDA came under incredible pressure to speed up the approval process. AIDS patients began protesting the non-partisan FDA because it was taking thirty months to approve new drugs. This was the first time since its creation that the FDA had seen protestors at their doorstep. During those thirty months, too many AIDS patients were becoming AIDS victims. Additionally, pharmaceutical companies began threatening to move overseas. In 1992, Congress stepped in and passed the Prescription Drug Users Fee Act.

Following the Act, the drug approval time decreased from thirty months to twelve months, and important drugs were approved in a mere six. Important lifesaving drugs should be approved as quickly as possible, but it is drugs like Viagra (which is certainly not a priority drug that provides a new treatment or represents a significant improvement over existing treatments) that are benefiting from the fast track. An unexpected consequence of this faster approval period appears to be an increased workload for reviewers, a lower retention rate for reviewers compared to other federal agencies, and reviewers not receiving the training the FDA finds necessary. While life-saving drugs certainly deserve as speedy an approval process as possible, Senator Bob Dole’s little blue pill shouldn’t also add to that increased FDA workload.

I Fought the Law and the Law Won

The FDA does have several tools at its disposal to enforce pharmaceutical laws. If the Food, Drug and Cosmetics Act is violated, the FDA can press criminal charges, as the City Attorney is attempting to do with the toothpaste importer and distributor. Intentionally misleading or defrauding the FDA is a felony, and the United States Department of Justice can bring down a world of hurt for violations. Misdemeanor charges resulting from strict liability can bring a penalty of $1,000, or one year in jail.

However, the FDA rarely brings criminal charges because it has several ways to force compliance. Recalls are an extremely common avenue for fixing problems. For instance, the June 11th edition of the FDA’s weekly enforcement report shows recalls ranging from turnip pickles to red blood cells. The recalls can be voluntary or ordered by the FDA, and product seizures can even occur without a court order. Additionally, the threat of bad press will often be enough to force a company to comply. Just this week the FDA sent a warning letter to Cardinal Health, causing the stock to drop. Finally, the FDA may bring civil suits against companies that do not comply, as it did against California hearing device manufacturer Advanced Bionics, LLC.

Since the toothpaste importer and distributor voluntarily chose to recall the tainted toothpaste, and the FDA destroyed the product, we are all safe to brush our teeth anti-freeze free. However, the charges may not be so easily beat. Without having seen the court documents, the charges and potential penalties sound like a violation of California law–as a drug composed of a poisonous substance. The law imposes a penalty for violating the law, and makes no exception for “we didn’t mean to.” In short, these guys have some serious legal hurdles.

Ultimately, the FDA is a powerful bureaucracy tasked with the huge undertaking of regulating, approving, and watching over the United States’ pharmaceutical industry. When the FDA functions properly, millions of Americans’ benefit through treatment of their ailments–from minor tartar build-up to full-blown cancer. Unfortunately, when the FDA fails in its mission, the consequences can be deadly.