Risks of Compounded Drugs

Potential Risks of Pharmacy CompoundingDrugs R D.2013 Mar – free full-text PMC article

Published reports of independent testing by the FDA, state agencies, and others consistently show that compounded drugs fail to meet specifications at a considerably higher rate than FDA-approved drugs.

Pharmacy compounding involves the preparation of customized medications that are not commercially available for individual patients with specialized medical needs. Traditional pharmacy compounding is appropriate when done on a small scale by pharmacists who prepare the medication based on an individual prescription.

the regulatory oversight of pharmacy compounding is significantly less rigorous than that required for Food and Drug Administration (FDA)-approved drugs; as such, compounded drugs may pose additional risks to patients.  

Unlike FDA-approved drugs, pharmacy-compounded products are not clinically evaluated for safety or efficacy. In addition, compounded preparations do not have standard product labeling or prescribing information with instructions for safe use.

Compounding pharmacies are not required to report adverse events to the FDA, which is mandatory for manufacturers of FDA-regulated medications. Some pharmacies engage in activities that extend beyond the boundaries of traditional pharmacy compounding, such as large-scale production of compounded medications without individual patient prescriptions, compounding drugs that have not been approved for use in the US, and creating copies of FDA-approved drugs.

Compounding pharmacies are not required to report adverse events to the FDA, which is mandatory for manufacturers of FDA-regulated medications. Some pharmacies engage in activities that extend beyond the boundaries of traditional pharmacy compounding, such as large-scale production of compounded medications without individual patient prescriptions, compounding drugs that have not been approved for use in the US, and creating copies of FDA-approved drugs

Published reports of independent testing by the FDA, state agencies, and others consistently show that compounded drugs fail to meet specifications at a considerably higher rate than FDA-approved drugs.

Compounded sterile preparations pose the additional risk of microbial contamination to patients. In the last 11 years, three separate meningitis outbreaks have been traced to purportedly ‘sterile’ steroid injections contaminated with fungus or bacteria, which were made by compounding pharmacies.

In the last 11 years, three separate meningitis outbreaks have been traced to purportedly ‘sterile’ steroid injections contaminated with fungus or bacteria, which were made by compounding pharmacies.

Patients and healthcare practitioners need to be aware that compounded drugs are not the same as generic drugs, which are approved by the FDA.

The risk-benefit ratio of using traditionally compounded medicines is favorable for patients who require specialized medications that are not commercially available, as they would otherwise not have access to suitable treatment. However, if an FDA-approved drug is commercially available, the use of an unapproved compounded drug confers additional risk with no commensurate benefit.

Comparison of Compounded Drugs with FDA-Approved Drugs

One important difference is that pharmacy compounded products are not clinically tested for safety and efficacy, nor is bioequivalence testing conducted as is required for generic drugs

Compounding pharmacies often rely upon Certificates of Analysis from suppliers rather than retesting incoming bulk ingredients as pharmaceutical manufacturers are required to do

Unlike the product labeling of FDA-approved drugs, the labeling of compounded preparations is neither regulated nor standardized.

Another major difference is that compounding pharmacies are not required to report adverse events to the FDA, whereas adverse event reporting is mandatory for manufacturers of FDA-regulated medications.

Thus, adverse events associated with compounded drugs may be difficult to detect, particularly if the affected patients are widely scattered in different geographic areas.

Quality Issues with Compounded Medications

The FDA became aware of 55 product quality problems associated with compounded medicines between 1990 and 2001.

The agency therefore conducted a limited survey of 29 different compounded medicines sourced from 12 compounding pharmacies, testing 8 different drugs of various dosage types (oral, injectable, topical, etc.) against established quality standards.

Ten out of 29 samples (34%) failed quality testing, mostly for sub-standard potency ranging from 59% to 89% of the target dose.

“Shorting” an expensive drug is undoubtedly a “cost savings” measure in this industry.

By comparison, the FDA noted that the failure rate for over 3,000 FDA-approved commercial products tested from 1996 to 2001 was <2%.

Adverse Events from Use of Compounded Drugs

In September 2012, a cluster of patients in Tennessee contracted fungal meningitis several weeks after receiving an epidural injection of methylprednisolone acetate, which had been compounded by the New England Compounding Center (NECC) in Massachusetts.

The CDC estimated the steroid had been injected into roughly 14,000 patients in more than 20 states.

Over 500 cases of meningitis were confirmed, and dozens of patients died.

Several different fungal species were identified in clinical specimens from the meningitis patients. Testing by the CDC and FDA confirmed the presence of visible contamination and fungus in unopened vials of drug.

A subsequent FDA inspection stated that there was no evidence that the process NECC used to sterilize the drugs was effective, and no corrective actions were taken to locate and remove the bacteria and mold from the facility.

The 2012 meningitis outbreak was not a unique event. In 2001, five patients were infected with bacterial meningitis, and three died after receiving betamethasone injections contaminated with Serratia bacteria, which had been compounded by a pharmacy in California [53]. In 2002, four women contracted meningitis, and one died, from a steroid injection contaminated with the fungus Exophiala dermatitidis, which had been compounded by a pharmacy in South Carolina.

Implications for Clinical Practice

When there are unique medical needs that cannot be met with commercially available drugs, it may be in a patient’s best interests to receive a compounded medication. In such cases, the prescriber should discuss this with the patient, obtain their consent, and document the reason why the FDA-approved version is not appropriate

Prescribing a compounded drug may expose providers to liability if a patient has a negative outcome, especially if a suitable FDA-approved product was available.

Conclusion

Traditional pharmacy compounding provides an important therapeutic option to allow for the creation of individualized drug preparations when a patient’s unique medical needs cannot be met with a commercially available drug. Examples include making dosage forms or strengths that are not commercially available or the removal of certain allergenic ingredients

In such cases, the option of prescribing compounded drugs should remain available for physicians. In traditional compounding, if a preparation error occurs, it would only affect a limited number of patients

Conversely, when pharmacy compounding is done at a large scale in uninspected facilities, using non-validated processes and ingredients of varying quality, an error could potentially affect a large population of patients

Below is a warning issued by the FDA in 2012:

Consumer Updates > The Special Risks of Pharmacy Compounding – FDA.gov – Dec 2012

Pharmacy compounding is a practice in which a licensed pharmacist combines, mixes, or alters ingredients in response to a prescription to create a medication tailored to the medical needs of an individual patient.

It’s also a practice that is under scrutiny by the Food and Drug Administration (FDA) because of instances in which medications, primarily injectable medications that are intended to be sterile, have endangered public health.

“But consumers need to be aware that compounded medications are not FDA-approved,” Anderson says. “This means that FDA has not verified their quality, safety and effectiveness.”

A Troubling Trend

The emergence of firms with pharmacy licenses making and distributing drugs in a way that’s outside the bounds of traditional pharmacy compounding is of great concern to FDA.

Some of the adverse event reports received by the FDA associated with compounded medications have had devastating repercussions.

What You Can Do

It may sometimes be difficult to recognize if you are taking a drug made by a pharmacy compounder.  Be sure to ask your doctor and pharmacist whether the prescribed drug is compounded, why it is being compounded, where it is being compounded, and what are the possible side effects and safety concerns.

Bernstein offers these tips:

  • Ask your doctor if an FDA-approved drug is available and appropriate for your treatment.
  • Check with the pharmacist to see if he or she is familiar with compounding the product in your prescription, and whether he or she has the training, equipment, and processes in place to compound that product.
  • Get information from your doctor or pharmacist about proper use and storage of the compounded product.
  • If you receive a compounded drug, ask the pharmacist if your doctor asked for it to be compounded.
  • If you experience any problems or adverse events, contact your doctor or pharmacist immediately.
  • Report any adverse events experienced while using the product to FDA’s MedWatch program.

Below is another article exposing this problem:

Safety issues at compounding pharmacy underscore oversight problems – By Ed Silverman @Pharmalot – April 8, 2016

A tussle between a Texas compounder and the Food and Drug Administration underscores the ongoing difficulties that regulators can have overseeing this controversial portion of the medical supply chain.

The episode also illustrates how varying approaches taken by state and federal authorities to regulating compounding pharmacies can leave doctors and patients confused about the safety of medicines.

Here’s the back story: Last month, the FDA issued a health alert recommending that doctors and patients should toss sterile medicines made by IV Specialty. The agency found numerous safety issues during an inspection earlier this year, but the compounder refused an agency recommendation to halt production or issue a recall until the problems were fixed.

The FDA, which is not aware of any side effects attributed to the drugs, lacks authority to force the compounder to take these steps. Meanwhile, though, the medicines, which are injected or infused, remain available.

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