By Terri Lewis, PhD.
On Friday, June 26, 2017, families and victims of the multi-state fungal meningitis outbreak of 2012 witnessed the sentencing of Barry Cadden, owner operator of the New England Compounding Company (NECC) in Framingham, Massachusetts. The sentencing in the Boston Federal Courthouse culminated in five years of dealing with catastrophic injury, illness, legal proceedings, financial hardships, and the deaths of loved ones who received epidural, joint, and trigger point injections using materials purchased from NECC and distributed to 13,500 persons through 75 clinics in 21 states. More than 800 individuals were sickened and 76 deaths were documented by reports to the Center for Disease Control (CDC). But this story does not end with this sentencing. In fact, this story is but a single chapter in a larger nationwide problem.
The Food and Drug Administration (FDA) regulates name brand drugs submitted to them for approval by manufacturers after presentation of evidence gather through development and clinical trials. The same is true of durable medical equipment. But some drugs escape regulation. These drugs include medications compounded for powders, potions, lotions, creams, sprays, sterile injectables, biosimilar hormones, nutraceuticals, medical foods, and medications made in quantities too small to scale up for production manufacturing conditions. Many pieces of equipment, like pumps, are approved by FDA that rely on compounded medications as the primary medicinal component. These medications are approved as a part number to equipment and not as a drug.
Compounded drugs are an important and valuable feature of our drug supply system. After the fungal meningitis outbreak of 2012, Congress passed the Drug Quality and Safety Act (DQSA), which gave FDA the authority to scrutinize compounded materials produced in large quantities by ‘outsourcing manufacturers’ and sold into interstate commerce. The Act incorporated a number of provisions which were absent – manufacturer registration, plant inspection, track and trace of materials, and labeling requirements to communicate to patient specific information – lot number, product name, components, and instructions for use.
Pressure from industry resulted in removing these provisions from the production of materials made for intrastate commerce under the theory of undue burden to small pharmacies. Instead, state Pharmacy Boards were expected to install inspection processes, procedures, and penalties into statewide distribution systems. Some states have yet to modify their state pharmacy regulations to incorporate these provisions of federal law. Many federal agency hospitals – Veterans Administration and Department of Defense – have yet to incorporate the sanitary and best practice provisions of both DQSA and USP 797 into their ongoing in house pharmacy compounding production and patient distribution programs.
On June 17, 2017, The VA Office of Inspector General (OIG) conducted a healthcare inspection in response to a confidential referral involving the sterile compounding environment and practices at the Overton Brooks VA Medical Center (facility), Shreveport, LA. The purpose of this review was to determine whether deficient conditions in the compounding pharmacy placed patients at risk. They confirmed that the facility did not comply with key elements of United States Pharmacopeia (USP) <797> (which outlines safe sterile compounding requirements and practices) as initially identified in October 2016 by the Louisiana Board of Pharmacy.
The Board’s findings included a lack of proper cleaning of the compounding rooms and incomplete air and surface testing and certification in compounding areas. During our January 2017 site visit, they found continuing noncompliance with USP <797> requirements including cleaning, environmental monitoring, employee competencies, and quality assurance activities. Non-compliance with USP <797> requirements has real potential to result in contamination of compounded sterile products and increase the number of hospitalized patient infections.
On June 22, 2017, Paul J. Elmer, 64, and Caprice R. Bearden, 62, the owner and director of Pharmakon Pharmaceuticals, Inc., a compounding pharmacy located in Noblesville, Indiana were indicted for manufacturing drugs that were either too strong or too weak based on their labels, while failing to make changes to prevent that from happening. U.S. Attorney Josh Minkler, representing federal prosecutors, also accused them of trying to cover their tracks. They were charged in a 10-count indictment alleging conspiracy to defraud the U.S., government by distributing an adulterated drug in interstate commerce and adulterating drugs while held for sale after shipment of a drug component in interstate commerce. Elmer, who was arrested and has made his initial court appearance in federal court, plead not guilty and is scheduled for Aug. 21. Bearden has filed a petition to plead guilty on all charges. The drugs in question were manufactured improperly resulting in the distribution of over (super) and under (sub potent) drug products which pose a serious risk of harm to patients.
Pharmakon was notified at least 70 times that the drugs they manufactured were weaker or stronger than the labels indicated. In each case, Pharmakon personnel failed to inform hospitals or doctors, placing patients, including infants in a neonatal unit, at extreme risk of harm. “Even after 13 infants, newborns in a neonatal care unit at an Indiana hospital, received double-strength sedative from Pharmakon, the defendants continued to ignore safety notices from the safety companies that would tell them that their drugs were too strong,” Minkler said.
Placing “greed and the reputation of their company” ahead of the health and safety of victims, Bearden received 70 potency test failures between July 2013 through February 2016. Results indicated that drugs like morphine sulfate and fentanyl were either too strong or too weak. Pharmakon’s officers are accused of lying about receipt of out-of-specification test results, and failure to correct errors, or to inform the FDA of problems with Pharmakon’s drugs.
Like NECC in Massachusetts, FDA found that Pharmakon did not comply with FDA regulations, failed to investigate what was causing the problems with its drugs, and failed to change company’s processes to address inconsistencies in product performance. Pharmakon directed that super potent and sub potent drugs be shipped to customers before receiving test results about their conformance to required standards. As a direct result, three infants in Indiana hospitals received morphine sulfate that was nearly 25 times the strength indicated on the label, resulting in the airlifting of one infant to another hospital.
These events serve as a reminder that consumers must become vigilant about the drugs they consume, their source, and the conditions under which medications are produced and purchased.
Medical care on a variety of levels is associated with estimates of 100-400,000 new patient harm events annually. We trust our physicians to keep us safe but sometimes, physicians are unaware of products sourced from unsafe locations. Roughly one quarter of these will result in life long injuries that contribute to permanent disability, chronic illness, and pain generation that will require treatment for the balance of one’s lifetime. These figures are nothing to sneeze at in the current environment of ‘opiophobia’ and health insurance uncertainty.
In keeping with the new administrations’ initiative to reduce “unneccesary regulations,” a movement is afoot to roll back safety and record keeping provisions for compounded drugs and biologics dispensed in physician offices by amending the Food Drug and Cosmetic Act and the USP to allow continued formulation and dispensation of some classes of drugs and biologics. HR 2871, the Preserving Patient Access to Compounded Medications Act of 2017 has been introduced by Representative Griffith VA-R. While some mendicants do not rely on sterility for dispensation, and patients enjoy access to natural medications or biologics, it is still important to keep an eye on potency and component tracking for understanding adverse reactions, product recall and patient safety notification purposes. What is safe for one patient may not be safe or harmless for all.
Office of Healthcare Inspections (2017, June 15). Report No. 17-01542-273 Healthcare Inspection Sterile Compounding Environment and Practices Overton Brooks VA Medical Center Shreveport, Louisiana, Washington, DC:VA Office of the Inspector General.
H.R.2871 – Preserving Patient Access to Compounded Medications Act of 2017 115th Congress (2017-2018)
FDA alerts health care professionals not to use sterile drug products from Pharmakon Pharmaceuticals Inc., Noblesville, Indiana. Retrieved from https://www.fda.gov/Drugs/DrugSafety/ucm496346.htm.
Dr. Terri Lewis is a rehabilitation educator, clinician and researcher who specializes in chronic pain and is a frequent contributor to the National Pain Report.