Analogy to "off-label" use

As a related point regarding the broad professional discretion to customize patient care, note that about 20–30% of prescription medications in the US are estimated to be "off-label," meaning the physician believes the drug to be beneficial for a patient despite it not being approved for that particular use/condition. This too is perfectly legal, subject only to state regulations on the practice of medicine, etc.

The appropriateness or the legality of prescribing approved drugs for uses not included in their official labeling is sometimes a cause of concern and confusion among physicians. This concern has been addressed by the American Society of Health-System Pharmacists in their Statement on the Use of Medications for Unlabeled Uses:^[19] Under the Federal Food, Drug and Cosmetic (FD&C) Act, a drug approved for marketing may be labeled, promoted, and advertised by the manufacturer only for those uses for which the drug's safety and effectiveness has been established and which the FDA has approved. These are commonly referred to as "approved uses." This means that adequate and well-controlled clinical trials have documented these uses, and the results of the trials have been reviewed and approved by the FDA.

The FD&C Act does not, however, limit the manner in which a physician may use an approved drug. Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in the above labeling. Such "unapproved" or more precisely, "unlabeled" uses may be appropriate and rational in certain circumstances, and, may, in fact, reflect approaches to drug therapy that have been extensively reported in medical literature.

The term "unapproved uses" is, to some extent, misleading. Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic investigations. Before such advances can be added to the approved labeling, however, data substantiating the effectiveness of a new use or regimen must be submitted by the manufacturer to the FDA for evaluation. This may take time and without the initiative of the drug manufacturer whose product is involved, may never occur. For that reason, accepted medical practice often includes drug use that is not reflected in approved drug labeling.

With respect to its role in medical practice, the package insert is informational only. The FDA tries to assure that prescription drug information in the package insert accurately and fully reflects the data on safety and effectiveness on which drug approval is based.^[19]

Drug testing and reporting of incidents

Poor practices on the part of drug compounders can result in contamination or in products that don't possess the strength, quality, and purity required. Unless a complaint is filed or a patient is harmed, drugs made by compounders are seldom tested, In Texas, one of only two states that does random testing, significant problems have been found. Random tests by the state’s pharmacy board over the last several years have found that as many as one in four compounded drugs was either too weak or too strong. In Missouri, the only other state that does testing, potency varied by as much as 300 percent.^[20]

In 2002, the FDA, concerned about the rising number of accidents related to compounded medications, identified "red flag" factors and issued a guide devoted to human pharmacy compounding, These factors include instances where pharmacists are:

• Compounding drug products that have been pulled from the market because they were found to be unsafe or ineffective.

• Compounding drugs that are essentially copies of a commercially available drug product.

• Compounding drugs in advance of receiving prescriptions, except in very limited quantities relating to the amounts of drugs previously compounded based on valid prescriptions.

• Compounding finished drugs from bulk active ingredients that aren't components of FDA-approved drugs, without an FDA-sanctioned, investigational new-drug application.

• Receiving, storing, or using drug substances without first obtaining written assurance from the supplier that each lot of the drug substance has been made in an FDA-registered facility.

• Failing to conform to applicable state law regulating the practice of pharmacy.^[14]

In recent years raw materials are increasingly obtained from foreign suppliers. Large drug companies which are FDA inspected must keep careful track of who has handled their raw materials while compounding pharmacies, some so large that they resemble commercial manufacturers, are not bound by similar guidelines. In 2011 the FDA was concerned about the suspected use of unapproved Chinese ingredients in an injectable medication used to reduce the risk of premature birth, but they were refused a sample for testing. Instead, the trade group, the International Academy of Compounding Pharmacists, suggested in an email to the compounding pharmacy that they respond to any request for samples by saying: “We do not compound or distribute ‘samples’ of any of our prescription medications to anyone.” They went on to advise that if the drug was on the premises, a pharmacist should say it was awaiting pickup by a patient. ^[20]

Unlike commercial drug manufacturers, compounding pharmacies aren't required to report adverse events associated with compounded drugs; the FDA learns of them through voluntary reporting, the media, and other sources. However, according to their records, since 1990 there have been more than 200 adverse events involving 71 compounded products, some with devastating repercussions. Three patients died of infections stemming from contaminated compounded solutions that are used to paralyze the heart during open-heart surgery. Two patients at a Washington, D.C., Veterans Affairs hospital were blinded, and several others had their eyesight damaged by a compounded product used in cataract surgery. The contaminated product had been distributed to hospitals and clinics in eight states. In March 2005, FDA issued a nationwide alert concerning a contaminated, compounded magnesium sulfate solution that caused five cases of bacterial infections in a New Jersey hospital. A South Dakota patient treated with the product developed sepsis and died. In August 2006, the FDA warned three compounding centers to stop manufacturing and distributing thousands of doses of compounded, unapproved inhalation drugs nationwide. Inhalation drugs are used to treat diseases including asthma, emphysema, bronchitis, and cystic fibrosis. An FDA spokesperson stated, "These are potentially life-threatening conditions for which numerous FDA-approved drugs are available; compounded inhalation drugs may be distributed to patients in multiple states, and patients and their doctors may not understand that they are receiving compounded products."^[14]

In 2007 Sens. Edward Kennedy (D-MA) and Pat Roberts (R-KS) introduced the Safe Drug Compounding Act of 2007 to give the FDA clear powers to regulate compounding pharmacies, with inspections and premarket approval. From 2001 to 2012, the International Academy of Compounding Pharmacists spent $1.1 million on lobbying, including efforts against this bill.^[4]