Double Double Toil and Trouble BABEEQ -' OCTOBER 2016 individual prescriptions. MSM also provided marketing support for Ameridose. According to one report, between 2008 and 2012, Ameridose grew from 50 employees to nearly 400. I\" Tainted Steroids Late in the evening on Monday, September 24, 2012, the Tennessee Department of Health notied the Massachusetts Department of Public Health about \"a cluster of six rare fungal meningitis cases, with onset of symptoms between July 30 and September 13, 2012.\"ll All six meningitis patients had previously received an epidural injection of methylprednisolone acetate (MFA; a steroid} compounded by NECC. The next day, the Massachusetts DPH obtained documentation from NECC of all facilities in the United States that had received any portion of the three lots of methylprednisolone acetate suspected as linked to fungal infections. The following day, NECC issued a voluntary recall of the three possibly tainted lots, containing 17,646 doses of methylprednisolone acetate it had compounded.l2 According to the Massachusetts DPH, the suspected contaminated product was distributed to more than 14,000 patients in 23 states. By the time the Centers for Disease Control and Prevention stopped counting, the total number of cases with fungal infections linked to tainted steroid injections compounded by NECC totaled 751, including 64 deaths.'3 Corporate Culture Former NECC employees interviewed by media outlets conrmed that bulk, not individual, shipments were the norm by about 2009. One former employee said, \"It was usually more bulk than individual shipments . . . It was very rare that it was one bottle for one person.\" Opinions varied as to the atmosphere at NECC. While some former employees claimed that Barry, as manager, was \"good to his employees and careful about compliance," others said \"NECC did not have the same high level of quality assurance as the much larger Ameridose."'5 While NECC and Ameridose were formed as separate legal entities, they had much in common. They had common founders, directors, officers, and managers. Both companies, of course, were in the pharmaceutical business. They used the same sales and marketing company, the same public relations team, and until recently, operated out of the same complex in Framingham. They even held joint Christmas parties. I\" These and other similarities led the media, state and federal authorities, and the public to look closely at Ameridose. The result: many of the same problems experienced at NECC were also 1. When there is a criminal activity involving the corporate entity, who should be punished? Could a person be criminally responsible for regulatory violations? Is this fair? 2. What are the legal claims against NECC? 3. Who can sue in this situation other than the patients injured by the tainted injections, who can be a plaintiff? 4. When the crisis first broke out, how should NECC and its management first react? 5. What should the regulatory agencies do in relation to NECC/Ameridose problems? What kind of plan of actions should be taken in order to protect the public health?Double Double Toil and Trouble BAB269 / OCTOBER 2016 Formed in 1998, the company was located in the same Framingham, Massachusetts building family members already used for an existing successful recycling factory and for their real estate businesses. There, NECC leased about 29,000 square feet of office, processing, and warehouse space from GDC Properties Management, LLC (which was founded and managed by Gregory). Between NECC and their other business ventures, Barry, Lisa, and Gregory prospered. They bought multi-million dollar homes and vacation homes. They charged events tickets, vacations, and BMW lease payments on the corporate credit card. Business grew. Compounding Pharmacies Compounding pharmacies have been around a long time. According to the U.S. Food and Drug Administration, compounding is "combining or altering of ingredients by a licensed pharmacist, in response to a licensed practitioner's prescription for an individual patient, which produces a medication tailored to that patient's special medical needs. In its simplest form, traditional compounding may involve reformulating a drug, for example, by removing a dye or preservative in response to a patient allergy." Because each drug is prepared in accordance with the prescription, quantities are low. NECC's founders saw potential for growth and expansion in the drug compounding business. By manufacturing and distributing products in bulk (although not allowed under the terms of its state pharmacy license), NECC could ramp up production to meet strong demand for its product. Some hospitals, keen to control escalating pharmaceutical costs, were complicit in arranging to purchase compounded pharmaceuticals without first submitting a prescription. Despite a Massachusetts law requiring a patient-specific prescription from an authorized practitioner when compounding and dispensing medication, a former NECC salesperson told the New York Times, "it was standard practice to sell large quantities of medicine to buyers without patients' names. Buyers would later fax the names as the medicine was dispensed, and the names would be put in their file . . . Honestly, there's no way you could sell anything of quantity otherwise."'s To capitalize on the demand, Barry, Gregory, and Douglas formed a new company in 2002, Medical Sales Management Inc. ("MSM"), to advertise, market, and generate sales for NECC. MSM "promoted the compounding business at trade shows across the country, and its sales force aggressively worked the phones, cold-calling new customers and reaching out to existing ones." MSM helped NECC grow quickly and more than double the number of NECC employees to 50 between 2009 and 2012.7 In 2006, Gregory and Barry formed Ameridose, a pharmaceutical company that concentrated on "prefilling syringes and breaking down vats of liquid medications into smaller intravenous bags for individual treatments."8 Unlike NECC, Ameridose obtained a manufacturing license from the FDA, so it was permitted to produce and ship medication in bulk without first obtainingDouble Double Toil and Trouble 3.36268 -' ESTES-ER 20'5- o \"[p]ersonnel gowns, eye-protection and gloves are not sterile;\" a plant was in substandard condition (there were leaks in the clean room, walls were cracked, corroded, and covered with what was apparently adhesive in the room where sterile drugs were prepared]; 0 equipment and utensils were not cleaned, maintained, and sanitized adequately to prevent contamination; a processing rooms lacked adequate space and segregation to prevent contamination and mix-up of different products; a \"Insects were observed to be located . . . in the . . . area . . . where nished sterile product is packaged and stored;\" and a \"At least one (1) bird was observed ying in the . . . area . . . where sterile nished product is packaged and stored.\"32 By the time the media reported details of the conditions at NECC and Ameridose, patients began alleging personal injuries resulting from NECC-compounded drugs in lawsuits from Massachusetts33 to Florida\" to Tennessee.35 What aspects of law are relevant? How should the legal system respond? Should the Board of Directors of NECC and/or Ameridose consider ling for bankruptcy? Double Double Toil and Trouble SABZBEI -' OCTOBER 2'3'5-3 to protect pharmacists from inhaling substances during medication preparation, were not thoroughly cleaned. \"Tacky" mats, used to trap dirt and contaminants from shoes prior to entering clean rooms, were visibly soiled with a variety of debris. Water pooled near a leaking boiler adjacent to a clean room}? There was evidence of a systemic failure to wait the time period needed to ensure product sterility. In short, several pieces of evidence substantiated the conclusion that sterility at the facility had been compromised. The FDA reported on October 2, 2012, that, of 321 vials of methylprednisolone compounded at NECC, 83 such vials contained \"what appeared to be greenish black foreign matter" and 1? vials contained \"what appeared to be white lamentous material."23 At an inspection of NECC premises, FDA investigators observed \"greenish yellow discoloration\" lining the surface of equipment used for sterilization of components and equipment. Their report noted that the NECC facility abuts a recycling facility that handles mattresses and plastics, and that large equipment, like excavators and freight trucks, producing airborne particles were about 100 feet from NECC's rooftop HVAC system. The louvers on the HVAC return system itself was covered with \"dark particulate\" and \"white lamentous substances." Yellow residue and green residue lined equipment used to weigh materials in the formulation of sterile drug preparations.\" And the boiler was still a problem. Installed 30 feet from the entrance to the prep room, it was leaking water into puddles. The area around the boiler \"appeared to be soiled with thick white debris and thick black, granular material.\" The FDA issued a safety alert to 220,000 health professionals to notify them of fungal contamination on October 5; on October 6, NECC agreed to recall all products.30 Dr. Margaret A Hamburg, Commissioner of Food and Drugs, testied before the US. House of Representatives that \"on November 1, FDA and CDC laboratories announced that bacteria had been identied as present in three separate lots [batches] of NECC supplied, preservative-free injectable betamethasone, with each lot producing different culture results (identifying different contaminants}, and in a single lot of NECC cardioplegia solution."31 The problems at NECC led to an FDA investigation of its sister company, Ameridose. Ameridose did not fare better. FDA reports based on Ameridose inspections in October and November, 2012, yielded the following ndings: 0 inadequate testing for the identity and strength of active ingredients in drug products before distribution; - inadequate testing to assure sterility of each batch of drug product; a failure to investigate sufciently the unexplained discrepancies in sterility testing samples or to take corrective action to correct and prevent sterility irregularities; a failure to evaluate and investigate sufciently specic patients' complaints after receiving NECC-compounded drugs; - inadequate data, procedures and controls necessary to validate and document the sterilization process and to prevent contamination; o inadequate procedures and controls to assure that drug products have the \"identity, strength, quality, and purity they purport\" BABSON Entrepreneurial Leader Collectic BAB269 / OCTOBER 2016 Double, Double, Toil and Trouble: One Compounding Pharmacy's Recipe for Steroids A Pharmaceutical, Entrepreneurial Family Barry Cadden and Lisa Conigliaro Cadden met as classmates attending the University of Rhode Island's College of Pharmacy. Barry's father was a pharmacist; Lisa's family was the entrepreneurial type. The couple graduated in 1990, got married and began building on what they knew: pharmaceuticals and entrepreneurship. Their business involvement extended to Lisa's family: her brother, Gregory Conigliaro (described as "a go-getter with an eye for niche businesses"); her brother Douglas Conigliaro, an anesthesiologist; and Douglas's wife, Carla Conigliaro. With family members, they launched several privately held businesses, one of which was New England Compounding Pharmacy, Inc. (also known as "New England Compounding Center" or "NECC"). NECC appeared to be a success story. There was broad family involvement. Barry owned a 17.5% interest in NECC. He also served as Head Pharmacist, and President. The balance of the equity was divided between Lisa (17.5%), Carla (55%) and Gregory (10%). Gregory also provided business support3 and was Treasurer, Secretary, and Vice President. All four served as Directors.Double Double Toil and Trouble erases] .- OCTOBER 2m present at Ameridose. For example, several former employees described a troubling atmosphere at Ameridose,\" including this report: \"One pharmacist said she quit because she was worried that unqualied people were helping prepare dangerous narcotics for use by hospitals. A quality control technician said he tried to stop the production line when he noticed that some labels were missing, but was overruled by management. [He was later reportedly red due to disputes over safety]. A salesman said he and his colleagues were brought into the sterile lab to help out with packaging and labeling during rush orders, something they were not trained for." 13 The former Ameridose pharmacist \"was concerned about a pilot project in which quality control workers, rather than trained pharmacists, did preliminary checks to make sure the correct drugs were present and the pumps were set correctly before lling intravenous bags.\"19 She also told the New York Times that there were some mistakes made \"because of pressure to increase output." For example, \"hydromorphone, a powerful narcotic, was made at twice the potency by a pharmacist who was working late to try to achieve production numbers for the day. The error was caught, however, before the bags left the plant."20 The red quality control technician told the New York Times, \"One of [management's] favorite phrases was, 'this line is worth more than all your lives combined, so don't stop it."' Yet another Ameridose employee said the company \"followed strict safety rules and that the quality control colleagues he worked with \"were very nice people, very qualied?\" Ameridose was a fast-paced environment. Employees were expected to work regularly on weekends or evenings. According to one report, \"the company suffered from high turnover and pressure to meet orders . . . some employees spoke little English, increasing the possibility of critical errors?\" Pressure and a quick pace naturally led to some carelessness. One former packaging worker at Ameridose said \"when sterile syringes and drugs fell to the ground . . . workers sometimes picked them up, quickly wiped them off, and shipped them anyway?\" He said he was red after complaining about safety procedures. Similar allegations were made by former employees of NECC.\" Massachusetts Department of Public Health, Massachusetts Board of Registration in Pha rmacy, and Centers for Disease Control Investigate The Massachusetts DPH conducted an onsite investigation at NECC within 48 hours of receiving the initial notication from the Tennessee Department of Health. When they arrived, Massachusetts DPH investigators discovered NECC employees cleaning sterile compounding areas. They detected signs of bleach decontamination in the compounding areas??? The report of the Massachusetts DPH's preliminary ndings\" revealed that \"visible black particulate matter" appeared in several recalled sealed vials of methylprednisolone acetate. Powder hoods, designed