Human Medications, Human Drugs, Animal Medications, Animal Drugs, Pharmacy law, Pharmaceutical law, Compounding law, Sterile and Non Sterile Compounding 797 Compliance, Veterinary law, Veterinary Compounding Law; Health Care; Awareness of all Types of Compounding Issues; Pharmacy Benefit Managers (PBMs), Outsourcing Facilities Food and Drug Administration and Compliance Issues
Monday, November 1, 2021
FDA highlights concerns with compounding of drug products by medical offices and clinics under insanitary conditions
October 25, 2021
Background
Human drug compounding is generally a practice in which ingredients of a drug are combined, mixed, or altered to create a medication tailored to the medical needs of an individual patient. Section 503A of the Federal Food, Drug and Cosmetic Act (FD&C Act) describes the conditions under which compounded human drug products are exempt from the following three sections of the FD&C Act:
- Section 505 concerning approval prior to marketing
- Section 501(a)(2)(B) concerning current good manufacturing practice (CGMP) requirements
- Section 502(f)(1) concerning labeling with adequate directions for use
One of the conditions to qualify for these exemptions is that the drug is compounded by a licensed pharmacist in a state-licensed pharmacy or federal facility, or by a licensed physician, based on the receipt of a valid patient-specific prescription. Compounded drugs that meet the conditions of section 503A are still subject to section 501(a)(2)(A) of the FD&C Act which states a drug is considered adulterated if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health.
FDA has become increasingly aware of drug products compounded at medical offices and clinics that were prepared under insanitary conditions. FDA has also become aware of business models, such as intravenous (IV) hydration clinics, medical spas, and mobile IV infusion services, that are compounding drugs that may not meet the conditions of section 503A of the FD&C Act or comply with state regulations. Contaminated, or otherwise poor quality, compounded drug products can lead to serious patient illnesses, including death.
Case Examples and Discussion of Risk
The extent to which compounding of drug products is occurring in medical offices is not fully known as compounders seeking to compound drugs under section 503A generally do not register with FDA. Adverse events associated with drug products compounded at medical offices under insanitary conditions have been reported, but it is likely that these events are underreported. The compounding case examples below illustrate some of the risks associated with drug products prepared, packed, or held under insanitary conditions.
Cases of drug product compounding at medical offices under insanitary conditions are well documented. In 2016, a series of fungal infections were linked to an oncology medical practice where 38 patients were exposed and 17 patients were infected with Exophiala dermitides, a thermophilic black yeast. FDA communicated with state regulators and conducted an inspection of the medical office where sterile compounding was occurring. Insanitary conditions observed at the medical office during the inspection included contamination in the form of brownish soiled material inside the bottom edges of the ISO-5 classified hood used for sterile drug compounding. FDA also observed that the cleanroom design was inadequate to prevent microbiological contamination of drug products intended to be sterile as the ISO-5 classified hood was located adjacent to a refrigerator and in close proximity to a sink without any air quality control of the surrounding area. ISO-classified areas that meet standardized levels of cleanliness1 help ensure an appropriate environment for sterile drug compounding.
More recently, in July 2020, FDA was made aware of drug products intended to be sterile that were being compounded under insanitary conditions at Advanced Nutriceuticals, LLC dba The Guyer Institute of Molecular Medicine. The Guyer Institute of Molecular Medicine is a medical clinic operating under a physician's license and offering services such as platelet-rich plasma therapy, IV vitamin therapy, hormone replacement therapy, and laboratory testing. FDA worked with state regulators and conducted an inspection during which numerous deficiencies involving insanitary conditions were observed including, but not limited to:
- Personnel in street clothes with ungloved hands filling drug products intended to be sterile into syringes outside of an ISO-5 classified area. These drug products were scheduled for shipment to patients across the country.
- Personnel performing sterile drug compounding within the ISO-5 classified area failed to sanitize or change gloves after contact with non-sterile items including a face mask and trash can.
- Personnel in the ISO-5 classified area moved rapidly and blocked first pass (clean) air in the vicinity of open sterile units, increasing risk of product contamination.
- High efficiency particulate air (HEPA) filters located in the ISO-5 classified area and cleanroom were discolored and/or damaged.
- The ISO-5 classified cleanroom workbench where sterile drug compounding occurs was constructed of laminated wood which was peeling.
- A heating vent located below the ISO-5 classified hood was visibly dirty and had no filtering device attached.
- Hazardous drugs were handled without providing adequate containment, segregation, or cleaning of work surfaces and utensils to prevent cross-contamination.
- Stock solutions intended to be sterile were exposed to lesser quality than ISO-5 classified air after the stopper had been punctured multiple times.
- Use of expired active pharmaceutical ingredients to prepare drug products intended to be sterile.
In addition, in February 2021, FDA was made aware of a 50-year-old female patient who was hospitalized and treated for suspected septic shock with multi-organ failure after receiving an IV-vitamin infusion in her home. The patient’s blood cultures grew Pseudomonas fluorescens, a gram-negative bacterium. The IV-vitamin infusion was compounded by Age Management Institute Santa Barbara, a medical clinic providing services including IV therapies and vitamin injectables, sexual health products, hormone replacement therapy, weight loss/management products, and diagnostic laboratory assays. FDA collaborated with multiple state regulators and conducted an inspection of the firm during which several deficiencies involving insanitary conditions were observed including, but not limited to:
- Lack of a certified ISO-5 classified area for sterile compounding.
- Contamination in compounding areas including peeling paint, stained work surfaces, visibly dirty equipment, and air vents with dust and grime.
- Difficult to clean equipment and surfaces such as carpeting in the IV storage and mixing room.
- Standing water in a refrigerated storage area used to store sterile vials.
- Use of expired active pharmaceutical ingredients to prepare drug products intended to be sterile.
Furthermore, FDA has become aware of sterile compounding activities, such as adding vitamins to IV infusion bags, being performed by business entities such as IV hydration clinics, medical spas, and mobile IV infusion companies. It is unknown if drug products are prepared, packed, or held under insanitary conditions by these entities and whether a licensed practitioner is on-site to evaluate patients and write prescriptions for the drug products intended to be sterile being administered. It is also uncertain whether entities producing these sterile products are following state regulations. It is FDA’s understanding that entities such as these can be found nationwide; however, the number of these entities and the compounding practices occurring at these entities are not fully understood given that compounders seeking to compound drugs under section 503A generally do not register with FDA.
The extent to which compounding of drug products is occurring at medical offices and business entities such as IV hydration clinics is not fully known; however, compounding, packing or holding drug products intended to be sterile under insanitary conditions at any facility significantly increases the risk of serious product quality concerns, such as product contamination. Compounding drug products intended to be sterile under insanitary conditions, including employing poor aseptic practices, using dirty equipment, or working in a facility not properly designed to maintain appropriate levels of cleanliness, as noted in the examples described above, increases the risk of product contamination. Use of contaminated drug products intended to be sterile has led to serious patient illnesses, hospitalization, and death.
Conclusion
The above examples of compounding performed at medical offices highlight the crucial need for compounding to be performed in accordance with best practices and not under insanitary conditions to ensure the public has access to quality compounded drugs. Patients can be significantly harmed when drugs are compounded in a way in which sterility or quality cannot be assured. In addition, sterile compounding activities being performed by business entities such as IV hydration clinics present risk and require continued evaluation.
FDA is committed to continued evaluation of these practices and collaboration with state regulatory authorities to address identified and emerging risks to public health and promote the quality of compounded drugs. FDA urges compounders, including physicians’ offices and emerging compounding entities, to comply with all state and federal laws and regulations related to compounding and take necessary actions to protect patients who receive their compounded drug products. It is critical that any manipulation of medications, particularly those required to be sterile, occurs in accordance with conditions and practices designed to prevent contamination and other quality concerns.
FDA encourages consumers, patients, and health care professionals to report any adverse events or quality problems experienced with the use of compounded drug products to FDA’s MedWatch Adverse Event Reporting program:
- Complete and submit the report online at www.fda.gov/medwatch/report.htm; or
- Download and complete the form, then submit it via fax at 1-800-FDA-0178.
References
- International Organization for Standardization (2015). Cleanrooms and associated controlled environments – Part 1: Classification of air cleanliness by particle concentration (ISO Standard No. 14644-1:2015).
Mobile Doctor Sentenced to Four Years for Role in Major Compounding Pharmacy Fraud Conspiracy
Department of Justice
U.S. Attorney’s Office
Northern District of Alabama
FOR IMMEDIATE RELEASE
Tuesday, October 26, 2021
Mobile Doctor Sentenced to Four Years for Role in Major Compounding Pharmacy Fraud Conspiracy
Tuscaloosa, Ala. – A Mobile-area doctor was sentenced today for her role in a major compounding pharmacy fraud scheme, announced U.S. Attorney Prim F. Escalona, Federal Bureau of Investigation Special Agent in Charge Johnnie Sharp, Jr., U.S. Department of Health and Human Services, Office of Inspector General, Special Agent in Charge Derrick L. Jackson, Defense Criminal Investigative Service Special Agent in Charge Cynthia Bruce, U.S. Postal Inspection Service Acting Inspector-in-Charge, Houston Division, Dana Carter, and IRS Criminal Investigations Atlanta Field Office Special Agent in Charge James Dorsey.
Chief U.S. District Judge L. Scott Coogler sentenced Dr. Michelle Martine Jackson, 55, of Fairhope, Alabama, to four years in prison. Jackson was also ordered to pay forfeiture of $53,000 and restitution of $3,920,584.84. Jackson pleaded guilty in June to conspiracy to commit health care fraud.
“This defendant abused the power of her prescription pad, breached the public’s trust, and cost insurers millions of dollars as a result,” U.S. Attorney Escalona said. “Her sentence is a reminder that health care fraud is a serious crime and carries serious consequences.”
Global, a pharmacy based in Haleyville, Alabama, has been the subject of a large-scale health care fraud investigation that has resulted in nearly thirty convictions to date. The Global health care fraud conspiracy involved Global managers directing Global employees to get medically unnecessary drugs for themselves, family members, and friends, changing prescriptions to add non-prescribed drugs because insurance would pay for them, automatically refilling prescriptions regardless of patient need, routinely waiving and discounting co-pays to induce patients to get and keep medically unnecessary drugs, and billing for drugs without patients’ knowledge. When prescription drug administrators attempted to police this conduct, the conspirators hid their fraud and obstructed detection efforts—including by lying to auditors and diverting their billing through affiliated pharmacies. The scheme targeted multiple health insurance plans, including the pharmacy’s Blue Cross Blue Shield of Alabama plan, as well as plans providing health insurance to the elderly, disabled, members of the military, and veterans—Medicare, TRICARE, and CHAMPVA, among others.
As part of the scheme, certain Global sales reps paid kickbacks to medical prescribers in exchange for writing prescriptions. Michelle Jackson was one of those prescribers. As part of her plea agreement, Jackson admitted that she had received cash kickbacks for writing prescriptions. She admitted that she wrote prescriptions for Global drugs that were not medically necessary, including for the sales rep’s family and friends, individuals Jackson had never treated, and family of Jackson’s staff. For example, Jackson wrote the sales rep’s pregnant daughter prescriptions for a drug that was contraindicated for pregnant women. Jackson also pre-signed blank prescription forms to enable co-conspirators to issue prescriptions under her name simply by checking boxes on the prescription forms.
The FBI, HHS-OIG, DCIS, USPIS, and IRS-CI investigated the cases. Assistant U.S. Attorneys J.B. Ward, Edward Canter, and Don Long prosecuted the case. The Veteran Affairs Office of Inspector General Criminal Investigations Division aided in the investigation.
Topic(s):
Health Care Fraud
Component(s):
Thirteen Defendants Plead Guilty in $126 Million Compounding Fraud Scheme
Department of Justice
Office of Public Affairs
FOR IMMEDIATE RELEASE
Wednesday, October 27, 2021
Thirteen Defendants Plead Guilty in $126 Million Compounding Fraud Scheme
Thirteen defendants, including three compounding pharmacy owners, three physicians, two pharmacists, and three patient recruiters, pleaded guilty in the Southern District of Texas to a years-long, multi-state scheme to defraud the U.S. Department of Labor’s (DOL) Office of Workers’ Compensation Programs (OWCP) and TRICARE.
According to court documents, the defendants submitted false and fraudulent claims to the OWCP and TRICARE for prescriptions for compounded and other drugs prescribed to injured federal workers and members of the armed forces. The defendants also paid kickbacks to patient recruiters and to physicians to induce them to prescribe these drugs. The defendants chose the particular compounds and other drugs based not on the patients’ medical needs but in light of the amount of reimbursement for the drugs. The drugs were then mailed to patients, even though the patients often never requested, wanted, or needed them.
“The health care fraud and kickback scheme executed by these defendants manipulated federal health care programs for personal gain without regard for patient need or medical necessity,” said Assistant Attorney General Kenneth A. Polite Jr. of the Justice Department’s Criminal Division. “I applaud our prosecutors and law enforcement partners for their hard work on this investigation and prosecution. The Department of Justice is committed to holding accountable those whose unlawful conduct targets federal health care programs.”
“Last week’s guilty pleas are a testament to the dedication and determination of the investigative and legal teams,” said Acting Special Agent in Charge Jonathan Ulrich of the U.S. Postal Service Office of Inspector General (USPS-OIG), Southern Area Field Office. “The Postal Service spends hundreds of millions of dollars annually on health care related costs and these monies are critical to those who legitimately need medical services. As in this case, our criminal investigators will diligently pursue any individual or organization intent on defrauding the Postal Service with an eye on both federal prosecution and returning lost monies to the affected program.”
“These defendants put illegal profits above patients’ safety,” said Special Agent-in-Charge Steve Grell of the DOL Office of Inspector General (DOL-OIG), Dallas Region. “Last week’s pleas highlight our commitment to working with our law enforcement partners and OWCP to protect the integrity of DOL’s benefit programs.”
“As the investigative arm of the Department of Defense Office of Inspector General, the Defense Criminal Investigative Service (DCIS) is committed to protecting the integrity of the TRICARE program,” said Special Agent in Charge Michael C. Mentavlos of the DCIS Southwest Field Office. “The results of this case are a testament to the resolve of DCIS, our law enforcement partners, and the U.S. Attorney’s Office to hold individuals that attempt to defraud the TRICARE program accountable.”
The defendants were charged in a June 2018 indictment and pleaded guilty to wire fraud, health care fraud, and/or kickback charges. All 13 defendants are scheduled to be sentenced in February 2022 and face a statutory maximum sentence of between five and 20 years. U.S. District Judge Sim Lake of the Southern District of Texas will determine any sentence after considering the U.S. Sentencing Guidelines and other statutory factors.
The USPS-OIG, DOL-OIG, and DCIS investigated the case with assistance from the U.S. Department of Veterans Affairs, Office of Inspector General.
Trial Attorneys Catherine Wagner, Patrick Queenan, and Jay McCormack of the Criminal Division’s Fraud Section are prosecuting the case. Trial Attorneys Scott Armstrong, Sarah Edwards, John Scanlon, and Michael McCarthy of the Fraud Section previously prosecuted the case.
Topic(s):
Health Care Fraud
Component(s):
Press Release Number:
21-1056
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