Page 67

65

Compounding Pharmacy Safety Incidents Investigated by the FDA (10) Year

No. deaths

No. Injuries

Drug

Comments

Riboflavin

Contaminated sterile injection

1997

0

2

2001

3

35

Steroid

Contaminated sterile injection

2002

1

5

Methylprednisolone acetate

Contaminated sterile injection

2005

3

5

Cardioplegia solution

Contaminated sterile solution

2007

3

Colchicine

Super-potent compounding (640% of labeled strength)

2010

0

Avastin

Contamination from repackaging sterile injection product

> 12

2011

9

19

Total Parenteral Nutrition

Contamination of sterile product

2012

0

43

Ophthalmic drugs

Contaminated sterile products (29 suffered vision loss)

2012

64

753

Methylprednisolone acetate

Contaminated sterile injection

knowledge of the actual conditions at compounding pharmacies, FDA regulators could not address violations before a crisis erupted (1). The agency’s authority was limited to reacting once a problem became “obvious” (i.e., “for-cause” inspections) (1, 9).

Ambiguities in the law gave both NECC and the FDA a legal rationale. Kessler was concerned that poor and inconsistent manufacturing standards—especially for sterile drugs—would cause unnecessary patient injuries and deaths. Unfortunately, his concerns proved correct, and a steady stream of incidents, mostly related to contaminated sterile products, began appearing (see table). All of these incidents resulted from poor manufacturing procedures at compounding pharmacies that specialized in outsourcing (10).

A Compound Problem One pharmacy that took advantage of the new FDAMA provisions was the New England Compounding Center (NECC), which was founded in 1998 in Framingham, Massachusetts, by the Conigliaro family (headed by Carla and Douglas Conigliaro). NECC was run by Barry Cadden, his wife (Lisa Conigliaro Cadden), and her brother (Gregory Conigliaro). The Conigliaro family’s broader business operations included a recycling plant next door to NECC (1, 14). Barry and Lisa Cadden, who were both pharmacists, specialized in producing sterile injection solutions. From the beginning, they ran afoul of regulatory standards. In 2002, FDA

inspectors cited NECC for failing to resolve consumer complaints, address adverse drug reactions, and correct product defects (1, 15). Over the next few years, state pharmacy inspectors also visited NECC (sometimes accompanied by FDA officials) and also found safety problems at the facility. NECC negotiated a settlement with the Massachusetts pharmacy board and avoided disciplinary action (1). Because outsourcing pharmacies could legally refuse to turn over their records to the FDA, even when FDA officials received support from state inspectors, NECC resisted FDA’s requests (9, 10). Ambiguities in the law gave both NECC and the FDA a legal rationale. The 5th and 9th Circuit Courts and the US Supreme Court had responded to challenges of the FDAMA legislation by issuing separate decisions, but from state to state, the courts’ interpretations of the law were conflicting and contradictory (1, 9). FDA’s influence over large compounding pharmacies depended on where the pharmacy was located. Despite this confusion, the FDA was always able to obtain warrants and proceed with “for-cause” inspections of pharmacy records, facilities, and practices, but it was a drawn-out and tedious process (10). In addition, unlike the state pharmacy boards, the FDA lacked the authority to enforce corrective actions. In the case of NECC, publicly available correspondence suggests that NECC was less than cooperative in correcting the deficiencies cited by FDA inspectors (16). Cadden cited statues to support his position, and FDA officials rebutted those arguments by citing other regulations.

Reprinted from The Pharmacologist • June 2017

Profile for ASPET

2018 Special Compilation Issue of The Pharmacologist  

ASPET is pleased to present the second in a series of special editions of our quarterly news magazine, The Pharmacologist. This special com...

2018 Special Compilation Issue of The Pharmacologist  

ASPET is pleased to present the second in a series of special editions of our quarterly news magazine, The Pharmacologist. This special com...