Anyone that watches television, surfs the web, or flips through magazines and journals is very familiar with advertising for pharmaceuticals picturing attractive, healthy and active people. Prescriptions and over the counter medications are safely used by millions of consumers for various ailments, diseases and medical conditions everyday. While many great things have been accomplished by the development of so many medications and the marketing to millions of consumers, there are also serious side effects or other undesired results. In some cases, the U.S. Food and Drug Administration or manufacturer may recall or withdraw a specific batch or completely remove a medication from the market.

What is a drug recall?

Recalls are, with a few exceptions, voluntary on the part of the manufacturer. However, once the FDA requests a manufacturer recall a product, the pressure to do so is substantial. The negative publicity from not recalling would significantly damage a reputation, and the FDA could take the manufacturer to court where criminal penalties could be imposed. The FDA can also require recalls in certain instances with infant formulas, biological products, and devices that pose a serious health hazard. Manufacturers may of course recall drugs on their own and do so from time to time for any number of reasons.

Recall classifications

There are three drug recall classifications.

Class I

• Reasonable probability that the use of, or exposure to, a violative product will cause serious adverse health consequences or death.
• An example would include the diet aid Fen-Phen (fenfluramine/phentermine) which caused irreparable heart valve damage and pulmonary hypertension.

Class II

• Use of, or exposure to, a violative product may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote.
• An example would include a medication that is under-strength but that is not used to treat life-threatening situations.

Class III

• Use of, or exposure to, a violative product that is not likely to cause adverse health consequences.
• Examples might be a container defect (plastic material delaminating or a lid that does not seal), off-taste or incorrect color, and simple text errors such as the incorrect expiration date on the manufacturer's bottle.

How drug recalls work

When an FDA-regulated product is either defective or potentially harmful, recalling that product, removing it from the market or correcting the problem is the most effective means for protecting the public. This is a multi-step process.

Step 1: Reports of adverse effects

FDA first hears about a problem product in several ways:

• A company discovers a problem and contacts the FDA.
• The FDA inspects a manufacturing facility and determines the potential for a recall.
• The FDA receives reports of health problems through various reporting systems.
• The Centers for Disease Control and Prevention (CDC) contacts the FDA.

After receiving enough reports of adverse effects or misbranding it decides the product is a threat to the public health and it contacts the manufacturer to recommend a recall.

Step 2: Manufacturer agrees to recall

Provided the manufacturer agrees to a recall, they must establis a recall strategy with the FDA that addresses the depth of the recall, the extent of the public warnings, and a means for checking the effectiveness of the recall. The depth of the recall is identified by wholesale, retail, or consumer levels.

Step 3: Customers contacted

Once the strategy is finalized the manufacturer contacts it customers (pharmacies, wholesalers, etc.) with the following information:

• the product name, size, lot number, code or serial number, and any other important identifying information,
• reasons for the recall and the hazard involved, and
• instructions on what to do with the, beginning with ceasing distribution.

Step 4: Recall listed publicly

FDA recalls are listed in the FDA's weekly enforcement report ( http://www.fda.gov/Safety/Recalls/EnforcementReports/default.htm ), see recent recalls at http://www.fda.gov/Safety/Recalls/default.htm , and you can receive email alerts at https://public.govdelivery.com/accounts/USFDA/subscriber/new?topic_id=USFDA_48 . Many subscription services, such as Medscape and Drug Facts and Comparisons eAnswers, also include drug recall information.

Step 5: Effectiveness checks

FDA evaluates whether all reasonable efforts have been made to remove or correct a product. A recall is considered complete after all of the company’s corrective actions are reviewed by FDA and deemed appropriate. After a recall is completed, FDA makes sure that the product is destroyed or suitably reconditioned, and investigates why the product was defective in the first place.

10 worst drug recalls in the United States

To emphasize the importance of drug recalls let's look at what are commonly considered the 10 worst drug recalls in U.S. history.

Fen-Phen (fenfluramine and phentermine)

• Manufacturer: Wyeth-Ayerst Laboratories (formerly American Home Products)
• Recall date: 1997 (after 24 years on the market)
• Financial damage: Over $21 billion (awards to victims are close to $14 billion), making it one of the most costly products liability cases in history.

Fen-Phen’s was a ver popular anorectant. It is estimated that as many as 6.5 million people took it to help fight obesity. After consumers began experiencing rare heart valve deffects and pulmonary hypertension problems, the FDA set the recall in motion. American Lawyer reported that more than 50,000 Fen-Phen victims have filed suits against Fen-Phen’s maker Wyeth, and legal expenses combined with awards are believed to have exceeded $21 billion. Its 24 years in the marketplace combined with the severity of both the public reaction and the significant awards granted to its victims make its impact unprecedented.

Diethylstilbestrol (a.k.a., DES)

• Manufacturer: Multiple manufacturers (DES was never patented as it was created with British public funds)
• Recall date: 1975 (after 37 years on the market)
• Financial damage: Unknown quantity of financial reparations in the billions, but difficult to fully quantify since each manufacturer paid out legal damages correlated with its respective market share (a new way of awarding damages in these cases).

DES was prescribed for more than thirty years to prevent miscarriages and other complications during pregnancy. It was not until 1971 before it was connected to a rare tumor that kept appearing in the daughters of women who had taken it. The FDA only banned DES prescriptions to women because no such problems have been found in men. In fact, it can still be prescribed to men to treat estrogen deficiency. Litigation over DES led to a landmark products liability award that heavily influenced how both the courts and the FDA approach oversight of drugs with multiple manufacturers.

Baycol (cerivastatin)

• Manufacturer: Bayer A.G.
• Recall date: 2001 (after four years on the market)
• Financial damage: $1.2 billion

Baycol (cerivastatin) is a synthetic member of the class of statins, used to lower cholesterol and prevent cardiovascular disease. It was withdrawn from the market in 2001 because of the high rate of serious side-effects.

Cerivastatin was marketed by the pharmaceutical company Bayer A.G. in the late 1990s as a new synthetic statin, to compete with Pfizer's highly successful Lipitor (atorvastatin).

During post-marketing surveillance, 52 deaths were reported in patients using cerivastatin, mainly from rhabdomyolysis and its resultant renal failure. Risks were higher in patients using fibrates (mainly gemfibrozil) and in patients using the high (0.8 mg/day) dose of cerivastatin. Another 385 nonfatal cases of rhabdomyolysis were reported. This put the risk of this (rare) complication at 5-10 times that of the other statins.

Vioxx (rofecoxib)

• Manufacturer: Merck
• Recall date: 2004 (after five years on the market)
• Financial damage: nearly $6 billion in litigation-related expenses alone

Bextra (valdecoxib)

• Manufacturer: Pfizer
• Recall date: 2005 (after one year on the market)
• Financial damage: over $2 billion

Rezulin (troglitazone)

• Manufacturer: Warner-Lambert
• Recall date: 2000 (after one year on the market)
• Financial damage: The manufacturer grossed $1.2 billion in sales prior to the recall.

Able Laboratories generic prescription medications

• Manufacturer: Able Laboratories
• Recall date: 2005
• Financial damage: Able Laboratories had $103 million in annual sales before recall.

Seldane (terfenadine)

• Manufacturer: Hoechst Marion Roussel (now Aventis)
• Recall date: 1997 (after 13 years on the market)
• Financial damage: Seldane was a big moneymaker for Hoechst Marion Roussel for such a long period (the year before it was pulled it sold $440 million worth of Terfenadine worldwide). In addition to its legal expenses, the loss of market share alone to drugs such as Claritin (loratadine) was steep.

Phenylpropanolamine (a.k.a., PPA)

• Manufacturer: Multiple manufacturers (widely manufactured across the industry)
• Recall date: 2000 (at least 60 years on the market)
• Financial damage: untold millions, if not billions (one manufacture alone settled for $15 million)

Phenylpropanolamine is an ingredient used in prescription and over-the-counter (OTC) drug products as a nasal decongestant to relieve stuffy nose or sinus congestion and in OTC weight control drug products to control appetite.

On May 11, 2000, FDA received results of a study conducted by scientists at Yale University School of Medicine that showed an increased risk of hemorrhagic stroke (bleeding of the brain) in people who were taking phenylpropanolamine. Phenylpropanolamine has been used for many years and a very small number of people taking the drug have had strokes. The Yale study helped show that the number of people having strokes when taking phenylpropanolamine was greater than the number of people having strokes who were not taking phenylpropanolamine. Although the risk of hemorrhagic stroke is very low, FDA has significant concerns because of the seriousness of a stroke and the inability to predict who is at risk. Because of continued reports to the FDA of hemorrhagic stroke associated with phenylpropanolamine and the results of the Yale study, the FDA now feels that the risks of using phenylpropanolamine outweighs the benefits and recommends that consumers no longer use products containing phenylpropanolamine.

Posicor (mibefradil)

• Manufacturer: Roche
• Recall date: 1998 (after one year on the market)
• Financial damage: Analysts had projected $2.9 billion in sales within 4 years.

See also

FDA: Recalls, Market Withdrawals, & Safety Alerts, http://www.fda.gov/Safety/Recalls/default.htm
Food and Drug Administration
MedWatch

References

1. FDA 101: Product Recalls From First Alert to Effectiveness Checks, http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/UCM143332.pdf
2. Wikipedia, Class I recall, https://en.wikipedia.org/wiki/Class_I_recall
3. Drug Recalls.com, America's Top 10 Recalled Drugs, Augst 2, 2011, http://www.drugrecalls.com/component/content/article/35-drugarticles/166-americas-top-10-recalled-drugs.html
4. Seamon MJ (2011). Active Pharmaceutical Ingredients and the Globalization of Pharmaceutical Manufactures: Contributors to US Drug Recalls and Shortages Pharmacy Law Column / Drug Store News Pharmacy Practice , (August), http://www.cedrugstorenews.com/userapp/August%202011%20Law%20Column.cfm
   
5. The Ten Worst Drug Recalls In The History Of The FDA - 24/7 Wall St. http://247wallst.com/2010/12/10/the-ten-worst-drug-recalls-in-the-history-of-the-fda/#ixzz1vtlDR4qu