$260M Payout for Misbranded Cancer Drugs: Only Part of Story

Nick Mulcahy

October 06, 2017

UPDATED October 9, 2017 // At a facility located behind chain-link fencing and barbed wire in Dothan, Alabama, workers at Medical Initiatives Inc created and shipped millions of prefilled syringes containing oncology drugs between 2001 and 2014.

The drug-containing syringes were sent to oncology centers, medical practices, and physicians in all 50 states for use in the supportive care of patients with cancer undergoing chemotherapy.

The drugs, such as Procrit (epoetin alfa, Janssen), were manufactured and placed into vials elsewhere in the United States but were repackaged into plastic syringes at Medical Initiatives, which is now closed and was a subsidiary of AmerisourceBergen Specialty Group.

The process was in violation of US Food and Drug Administration (FDA) regulations on the packaging and distribution of drugs.

Last week, AmerisourceBergen Specialty Group, which is part of the US drug wholesale giant AmerisourceBergen Corp (the number 11 business in the Fortune 500), pled guilty to a single count of introducing misbranded drugs into interstate commerce, which is a federal offense, and agreed to pay $260 million to settle the criminal charge.

In federal court, a company lawyer admitted that AmerisourceBergen Specialty Group was aware of the conduct and supported it, as reported last week by the website Law360.

But the plea agreement — and its vague legal language -— does not tell the whole story of what went on at Medical Initiatives.

It does not describe the potential danger incurred by immunocompromised cancer patients who received drugs via plastic syringes that had been tainted with particulates and packaged in a Medical Initiatives "cleanroom" that, at times, contained open adhesive bandages, iPods and exposed earbuds, skin lotion, aloe gel, chewing gum, and nonsterile mops.

Nor does it describe the potential hazard of receiving medicine from the Alabama factory, which produced approximately 9 million prefilled syringes over 14 years but had only 82 syringes tested for sterility that entire time — on three occasions (2009, 2011, and 2012).

All of these details and allegations are contained in a damning 28-page "statement of information" that accompanied the plea agreement document issued by the US district court.

In effect, the statement reveals the proverbial dirty details of the case.

A press release about the $260 million plea deal from the US Department of Justice and federal cooperating agencies also hints at these troubles, which seem more alarming than the crime of "misbranded drugs."

"Injectable drugs prescribed for patients — especially vulnerable cancer patients — must be pure, sterile and produced in an FDA-compliant facility that is within the supply chain that FDA oversees," stated Mark S. McCormack, special agent in charge, FDA Office of Criminal Investigations, in the release.

Bridget M. Rohde, acting US attorney for the Eastern District of New York, where the case was tried, said the same: "Today's guilty plea demonstrates our commitment to investigating and holding accountable any pharmaceutical company that fails to ensure the health and safety of the public."

However, in a statement, AmerisourceBergen said that "neither the government nor AmerisourceBergen are aware of any adverse events [among patients] associated with the use of Medical Initiatives Inc. syringes."

Furthermore, the company said that in July 2012, the US government "seized thousands of Medical Initiatives Inc. syringes and tested some number of those. It is our understanding that testing did not reveal any quality concerns with regard to the drug product they tested."

How Bad Was It?

Medical Initiatives sold only six types of drugs as prefilled syringes for injection. The company's entire product list consisted of Aloxi (palonosetron), Anzemet (dolasetron), generic versions of granisetron injection, Kytril (granisetron), Neupogen (filgrastim), and Procrit.

The drugs on the list all had one thing in common: They were packaged by the original manufacturer in glass vials and contained an FDA-approved dose plus a "high percentage" (about 10%) of an approved amount of extra drug known as "overfill."

The overfill is provided for a variety of reasons, including to ensure that a full dose is available when drug is pulled from the glass vials in cancer clinics because some might get stuck on the glass due a drug product's viscosity.

A clever exploitation of that overfill was the profit source for Medical Initiatives and its parent AmerisourceBergen companies, and their prefilled syringe product line.

Medical Initiatives workers basically extracted the drugs — including the overfill — from the glass vials and "pooled" the drug into intravenous bags or larger containers. From those containers, which were sometimes left out overnight uncovered, the syringes would be filled. The company needed only 10 vials of drug to create 11 prefilled syringes because of the 10% overfill in each vial.

The scheme went well from a business perspective. Starting in 2001, Medical Initiatives sold hundreds of thousands of prefilled syringes per year. Following an expansion of the Alabama facility in 2006, they sold more than 1 million per year. At peak operation, Medical Initiatives generated more than $14 million in annual profit for AmerisourceBergen Corporation.

However, the prefilled syringe manufacturing process also automatically compromised the drug product.

"This process introduced significantly greater risks of contamination than had [the company] simply prepared one syringe from one vial," explains the court statement.

Many of the glass vials were single-use, meaning that the manufacturer could not guarantee the sterility of the drug product if the vials were breached. 

An expert not involved with the legal case further commented on the safety of prefilled syringes.

"There are always risks (low) — even from the original manufacturers' vials. But those risks rise significantly when that sterile product is transferred to a prefilled syringe, especially if appropriate sterile procedures and validations are not uniformly followed," said Dwight Kloth, PharmD, director of pharmacy at Fox Chase Cancer Center in Philadelphia, Pennsylvania, in email comments to Medscape Medical News

The entire process at Medical Initiatives was actually illegal; what they did to drugs and biologics (ie, altering them) requires that a company file a New Drug Application or Biologic License Application and register with the FDA. Medical Initiatives, which claimed to be a pharmacy selling drugs to individuals, did neither.

The court statement also details various shoddy manufacturing and safety processes at Medical Initiatives.

In addition to the above-stated cleanroom malpractices, company technicians wore nonsterile gowns in that supposedly cleanroom — on a routine basis. Staff wore jewelry, make-up, nail polish, and street clothing in the cleanroom.

To their credit, Medical Initiatives recorded how often foreign matter, referred to as "floaters" by employees, got into their syringes. On average, the facility had more than 100 syringes each week containing floaters; the employees would not destroy these syringes but instead filtered the floaters out. In the case of Procrit, this was in violation of FDA labeling, which calls for destruction of any such compromised product.

On the rare occasions when Medical Initiatives did allow an outside laboratory to test their prefilled syringes, some samples tested positive for bacteria in 2009 and 2011, according to the court documents. However, no follow-up testing was done to determine the source of contamination.

As part of its guilty plea, AmerisourceBergen Specialty Group has entered into an agreement with federal agencies to maintain a compliance and ethics program designed to increase accountability of individuals and corporate board members, to increase transparency, and to strengthen compliance with the FDA governance.

Dr Kloth has disclosed no relevant financial relationships.

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

For more from Medscape Oncology, follow us on Twitter: @MedscapeOnc

Editor's Note: The story has been updated to include comments from an AmerisourceBergen statement. Also, the story has been corrected; an earlier version of the story incorrectly said the company acknowledged that the 28-page statement of information was accurate.

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