More Inspection Problems At Other Compounding Plants

More Inspection Problems At Other Compounding Plants

November 14th, 2012 // 2:28 pm @ jmpickett

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In the latest bit of evidence to raise disturbing questions about some compounding pharmacy operations and regulatory oversight, the FDA recently sent 14 investigators and three microbiologists to inspect Ameridose, which is owned by the same folks who own the New England Compounding Center, and found another remarkable series of troubling findings.

Such as? There were cracked and corroded walls where products are prepared; rodents were in the building; insects were found in sterile areas where products are packaged and stored; a bird – yes, a bird – was flying around in the same area; final drug products were not tested for potency; and 53 instances of microbiological contamination and three sterility failures were not investigated, according to the FDA.

In addition, patient complaints were not classified as adverse events or followed up and patient outcomes and interventions were not adequately investigated. These incidents involved compounded versions of such popular treatments as heparin, fenatyl and oxytocin. In some cases, complaints related to potency or ‘under-filled’ products – which refers to less drug than should have been provided – were defined as ‘non-complaints.’

It gets worse. For example, the quality control unit “failed to adequately investigate and implement permanent corrective action after 45 environmental microbiological excursions (mold and bacteria) were isolated from critical areas such as personnrl fingers inside class 100 hoods and controlled manufacturing areas during the manufacturing of sterile injectables” this year, the FDA found.

These infractions, among many others, were contained in a so-called 483 inspection report posted on the FDA web site last night as the agency grapples with the fallout from a fungal meningitis outbreak traced back to the NECC (here is the 483 report). So far, 438 cases, including 32 deaths, have been reported in nearly two dozen states (see the breakdown here).

The 483 report was released ahead of a pair of Congressional hearings that will take place this week to examine the controversy over regulatory oversight of compounders – the House Energy & Commerce Committee holds a hearing tomorrow (look here) and the Senate Health, Education, Labor & Pensions Committee holds its hearing on Thursday (see this).

Both will feature FDA commish Margaret Hamburg, who will be on the hot seat as she attempts to explain her interpretation of agency oversight and enforcement powers. The FDA has been criticized for not moving faster to regulate the NECC, especially since the agency issued a 2006 warning letter and the compounder had moved beyond traditional compounding – preparing specific medicines for individual patients – into a larger-scale manufacturing operation.

Court rulings have confused the matter, although in response to a 2002 US Supreme Court ruling, the FDA decided to defer most oversight to state board pharmacies and health officials. However, the FDA has also indicated as recently as earlier this year that it would pursue enforcement actions, such as safety concerns or the equivalent of mass production.

In recent weeks, the FDA responded to the meningitis outbreak by scrambling to investigate NECC and Ameridose, both of which are owned by Greg Conigliaro and Barry Cadden, who is also scheduled to testify at both hearings. The NECC report similarly yielded a long list of infractions, including ‘greenish-black foreign matter’ on sterilization equipment and air conditioning systems that were turned off at night (back story with report).

Both compounders have issued recalls and suspended operations as various investigations continue. Last week, for instance, Massachusetts state health officials fired state pharmacy board Jim Coffey and placed board attorney Susan Manning on leave for allegedly ignoring a complaint last July that bulk shipments of drugs were distributed to hospitals in Colorado. Coffey was to have testified at the House hearing tomorrow.

However, Massachusetts officials are also being scrutinized because Sophia Pasedis, who sits on the 11-member Massachusetts Board of Registration in Pharmacy, is also vp of regulatory affairs and compliance at Ameridose. The conflict has raised criticism and concern that state authorities may have been lenient, even though complaints had been registered against the NECC in recent years (back story).

Prior to the meningitis outbreak, the board had investigated at least twelve separate complaints concerning NECC or Cadden, issued at least four advisory letters and/or informal reprimands, and entered into a consent agreement with the company in 2006, according to a memo released by the House Energy & Commerce Committee in advance of its hearing.

One complaint cited Cadden for providing a health care practitioner with blank prescription pads referring to NECC, which violated board regulations. In June 2001, the board investigated a report submitted by the Idaho Board of Pharmacy that NECC was soliciting business for drugs that should have been discontinued by the manufacturer.

There were also indications that Cadden and Conigliaro were chafing at the regulatory attention. In one incident in September 2004, FDA and state officials conducted a joint investigation into products using Trypan blue dye. An investigator asked Cadden whether the dye was used and he denied this. But he was asked to open a drawer marked ‘Trypan Blue’ and it contained.. drum roll… 189 vials.

Cadden agreed to quarantine the products, but on their next visit, he told investigators that his attorney informed that he was not required to do so and responded “there is no regulation which states that Compounding Pharmacies cannot compound FDA non-approved drugs.” Cadden added that he intended to continue dispensing a medication containing the dye and he became “indignant [and] he said that he does not really have the time to sit with us [and] answer all those questions,” an FDA investigator wrote in a report. Cadden then told Conigliaro, who is his brother-in-law, “don’t answer any more questions!”

More than a year earlier, in February, 2003, FDA inspectors met with NECC and concluded in a report by writing that the agency emphasized “the potential for serious public health consequences if NECC’s compounding practices, in particular those relating to sterile products, are not improved.” The agency inspector, in fact, suggested that NECC be prohibited from manufacturing. However, the FDA acknowledged that “so long as a pharmacy’s operations fall within the scope of the practice of pharmacy (as outlined in FDA’s Compliance Policy Guide 460.200), FDA will generally continue to defer to state authorities for regulatory oversight” (Here is the Committee memo).