Compounding

Compounding pharmacy is the long-standing process of mixing drugs by a pharmacist or physician to fit the unique needs of a patient. For example, a patient allergic to the dyes used in a pill can obtain a doctor’s prescription for the necessary medicine to be compounded without the offending dye.

History
The art of pharmaceutical compounding began with the birth of the first humans. All ancient hunter-gatherer societies had some knowledge of the medicinal properties of the animals, plants, molds, fungus and bacteria as well as inorganic minerals within their environment.

Ancient civilizations utilized pharmaceutical compounding for religion, grooming, keeping the healthy well, treating the ill and preparing the dead. These ancient compounders produced the first oils from plants and animals. They discovered poisons and the antidotes. They made ointments for a wounded patients as well as perfumes for a customer.

The earliest druggists were familiar with the various natural substances and their uses. These drug artisans compounded a variety of preparations from medications, dyes, incense, perfumes and ceremonial compounds to preservatives and cosmetics. The Bible lists many drugs that were compounded in biblical times in the Middle East.

Drug compounders seeking gold and the fountain of youth drove the Alchemy movement. Alchemy eventually contributed to the creation of modern pharmacy and the principles of pharmacy compounding.

The modern age of pharmacy and pharmacy compounding began in the nineteenth century with the isolation of various compounds from coal tar for the purpose of producing synthetic dyes. From this one natural product came the earliest antibacterial sulfa drugs, phenolic compounds made famous by Joseph Lister, and plastics.

During 1800s pharmacists specialized in the raising, preparation and compounding of crude drugs. Crude drugs, like opium, are from natural sources and usually contain multiple chemical compounds. The compounding pharmacist often extracted these crude drugs using water or alcohol to form extracts, concoctions and decoctions.

Pharmacists began isolating and identifying the active ingredients contained within these crude drugs concoctions. Using fractionation or recrystallization, the compounding pharmacist would separate the active ingredients, like morphine, and use it in place of the crude drug. During this time modern medicine began.

With the isolation of medications from the “raw materials” or crude drugs came the birth of the modern pharmaceutical company. Pharmacists were trained to compound the preparations made by the drug companies but they weren’t able to do it as efficiently on a small basis. So economies of scale, not lack of skill or knowledge, produced a market niche for the modern pharmaceutical drug companies, (Pharma).

With the turn of the twentieth century came the government involvement and subsequent regulation into the practice of medicine. In 1938 the Government of the United States imposed new regulations on the drug companies forming the Food and Drug Administration (FDA) when several people died from a poorly prepared sulfa drug that used ethylene glycol as a base. These new regulations forced the drug companies to prove any new medication they brought to market was safe.

Pharmacy compounding was still going strong in the 1930s with over 80% of the prescriptions dispensed being compounded by the compounding pharmacist. With the discovery of penicillin and the modern marketing techniques and brand promotion, the drug manufacturing industry came of age. Pharmacists continued to compound most prescriptions until the early 1950’s when the majority of dispensed drugs came directly from the large pharmaceutical companies.

From the 1950s to the 1980s pharmaceutical compounding became almost obsolete and a lost art. Pharmaceutical compounding continued losing favor as the big drug companies became larger and more powerful until they eventually dominated the practice of medicine. It was during this time that patients and physician became dissatisfied with the “one size fits all” attitude of the large Pharma companies. Physicians searching for drugs to treat their patients, lead to the reawakening of the ancient art of prescription compounding.

Today many pharmacists specialize in the ancient art of pharmaceutical compounding. In 2006 over 30 million compounded prescriptions were dispensed not counting all the admixtures and injectable drugs compounded in America’s hospitals. Pharmaceutical compounding has been responsible for the health of millions of individual patients, has given birth the modern pharmaceutical companies and continues to be a vital link in the search for new drugs and dosage forms.

Throughout history, there has always been a need for pharmacists to compound drugs for individualized dosages. When the pharmaceutical industry began mass-producing drugs and dosage forms for patients in the 1950s, compounding became less widespread. In recent years, many patients’ unique health needs have driven more business to compounding pharmacists.

Uses
Compounding is one of the pillars of new drug development. Most medications have gained widespread usage throughout the entire medical community thanks to the practice of pharmaceutical compounding and the compounding pharmacist. Every major pharmaceutical company ever in existence or currently operating started in a compounding pharmacy with a compounding pharmacist.

Without the practice of pharmaceutical compounding and compounding pharmacists none of the drugs we have today would have been discovered. This facet of pharmacy has been the greatest developer of drugs and the most positive influence within the entire allopathic, osteopathic, naturopathic and homeopathic, medical communities. Pharmaceutical compounding is a branch of pharmacy that continues to play the crucial role of new drug research and development.

Physicians often prescribe compounded medicines for patients with unique health needs, because they are able to tailor a prescription to each individual. Compounding preparations are especially prevalent for:


 * Patients requiring limited dosage strengths and dosage forms (i.e., infants)
 * Those with allergies to certain ingredients in manufactured drugs
 * Veterinary medicine
 * Pediatrics (i.e., making a medicine more palatable to children with flavor additives)
 * Home health care
 * Hospice patients
 * Bioidentical hormone replacement therapy, specifically the Wiley Protocol
 * Patients who need drugs that have been discontinued by pharmaceutical manufacturers because of low profitability

Regulation
Compounding pharmacies are licensed and regulated by state Boards of Pharmacy in the 50 states and the District of Columbia. Additionally, pharmacies follow guidelines from U.S. Pharmacopeia.

Compounding pharmacists must work within the jurisdiction of the FDA, they are simply exempt from many FDA requirements so long as they are state-compliant and compound pursuant to a valid prescription. However, the FDA registers and inspects the facilities that supply manufacturers with active pharmaceutical ingredients.

The Pharmacy Compounding Accreditation Board was created in 2006 as a voluntary accreditation body by pharmacy organizations to establish high quality standards for compounding pharmacies.

Controversies
There is currently a controversy over who should regulate compounding pharmacies. The FDA is concerned that many compounders are acting as large-scale manufacturers of new drugs, and are subject to the numerous rules that apply to drug makers. The FDA has repeatedly asserted that all compounded drugs are new drugs and are thus illegal, but it will exercise its “enforcement discretion.” The Agency has issued numerous warning letters to compounding pharmacies, threatening actions including, but "not limited to, seizure of your products or injunction against you or your firm." The International Academy of Compounding Pharmacists states that "Congress, the U.S. Supreme Court, and each of the 50 state boards of pharmacy that regulate compounding have long recognized the value of pharmacy compounding, yet the FDA has contended for nearly 20 years that compounded medications are illegal. Compounded medications are not new, unapproved drugs and pharmacies dispensing them act only under a doctor’s prescription.  To the extent that there are patient safety issues, state boards of pharmacy are well-equipped to deal with them.”  Recent court rulings, such as Medical Center Pharmacy v. Gonzales (2006) support the position taken by IACP.

Compounding pharmacy has been caught up in the recent controversy over hormone replacement therapy. Synthetic hormones, manufactured by large drug companies such as Wyeth Pharmaceuticals, were found to lead to increased rates of heart disease, breast cancer and stroke in the Women’s Health Initiative study, halted in 2002. As an alternative to synthetics, many physicians prescribe bioidentical hormones for patients suffering from menopausal symptoms. These hormones are mixed in a compounding pharmacy. Groups such as the North American Menopause Society have raised concerns about the marketing of these drugs. The compounding pharmacy profession purports to make no claims about the safety and efficacy of bioidentical hormones, and believes it should be up to a patient and her doctor to decide on the best course of treatment for menopausal symptoms.

The stance of the FDA has been that each time a drug is compounded it creates a “new drug”. Since that “new drug” has not received FDA approval, the FDA then claims the compound is adulterated and therefore illegal. The illogic of such a position is clarified when one considers the actual practice of medicine in the United States, which uses multiple medications simultaneously (polypharmacy).

While many people take two or more medications daily, very few prescription drugs are studied when combined together. This polypharmacy is impossible to study because of the difficulty and the cost of conducting a full-scale study of each drug combination. For example say there are three hundred drugs available for a doctor to choose from. If a patient is taking an average of six prescription drugs daily, there would be over 10^14 possible drug combinations that individual patient could take. It would be impossible to study that many drug combinations.

Yet the polypharmacy is practiced universally and the FDA accepts it. Using the FDA’s own logic, combining various medications together is illegal if the patient swallows all the drugs after they have been compounded into one capsule… but let that same patient individually take the same multiple prescription drugs and swallow them one at a time… then the FDA has no problem with it.

IJPC papers on compounding

 * White Paper - Did you know without compounding...?
 * White Paper - What do you know about compounding?
 * White Paper - Reasons why the FDA should not be involved in Pharmacy Compounding
 * White Paper - Recent advances in pharmacy compounding quality