Thursday, December 6, 2012
Bugs, Birds & Ignored Complaints At A Compounder
By Ed Silverman
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).
Utah moving to fortify regulation of compounding pharmacies
By Kirsten Stewart
| The Salt Lake Tribune
First Published 4 hours ago • Updated 20 minutes ago
The Massachusetts-based pharmacy blamed for a meningitis outbreak that has killed dozens andsickened hundreds can no longer ship drugs to Utah.
New England Compounding Center (NECC) voluntarily surrendered its mail-order privileges in October, not in response to any action taken by state licensers, said David Young, chairman of the Utah Board of Pharmacy. "We’re not the only state. After losing their license in some states, I think they voluntarily surrendered them in multiple other states."
The move is mostly a formality, considering the compounding pharmacy closed in October and none of its tainted injections made it to Utah. But the scandal has highlighted regulatory weaknesses that states, including Utah, are moving to fortify. As a starting point, state inspectors are going to pharmacies statewide to determine which are compounding drugs.
It’s not that the rules or standards for compounders are too loose, Young said. The problem, he said, is that some compounders are acting more like drug manufacturers without the same oversight.
Compounders are regulated by states, whereas drugmakers are overseen by the U.S. Food & Drug Administration. But the lines between the two are blurry, Young said.
In setting compounding rules, state regulators typically defer to standards set the by the National Association of Boards of Pharmacy, Young said.
Utah law defines compounding as making a "limited quantity" drug, product or device as prescribed by a doctor, or for research, chemical analysis or teaching. Compounding does not include preparing a drug "in a dosage or form that is commonly available from a manufacturer" or preparing a drug that has been pulled from the market for safety reasons, the law states.
"What NECC was doing is making 17,000 doses of stuff and shipping it all over the place," Young said. "That’s manufacturing, not compounding."
But Young isn’t aware of any state that clearly defines when a compounder has crossed the line and should be subject to FDA oversight.
Drugmaking "is a different beast" that states aren’t equipped to handle, Young said. "If [like NECC] you’re making a steroid solution for injection into the spine, you need to be testing [drug] lots on a continuous basis and following quality control measures. The FDA has solid, tight rules on that stuff."
Congress is weighing various proposals for defining how and when the FDA should intervene. One fix could be to create a special class of compounders, Young said.
Another would be state-based rules to set compounders apart from other pharmacies.
Mark Steinegal, director of the state Division of Occupational and Professional Licensing (DOPL) estimates there are about 30 compounders in Utah.
"We do not have a complete list," because, he said, "they do not have a unique license ... [and] are lumped with other pharmacies in our databases."
To get an accurate count, DOPL is dispatching inspectors to pharmacies statewide. Results from their survey will be sent to the National Association of Boards of Pharmacy, which is reviewing its standards.
Depending on what action Congress takes, Young said Utah may also revise its compounding rules.
Utah’s compounding pharmacies
Regulators are surveying pharmacies statewide for a tally of how many compound their own drugs. To date, they know of 30:
Larry’s Smithfield Pharmacy
Edgemont Pharmacy
Roe Rx Inc.
Peterson Foodtown Inc.
South Valley
Mt. Olympus Compounding
Rock Canyon Pharmacy
Jolley’s Corner Pharmacy
Jolley’s Corner Pharmacy 3
Jolley’s Sandy Pharmacy
TMJ Inc. (Jolley’s Corner)
The Medicine Center
Skyline Pharmacy #2
Gibson’s Pharmacy
Hurricane Family Pharmacy
Dry Creek Pharmacy
The Medicine Shoppe
Taylor Drug
Mountainwest Apothecary
North View Pharmacy
Salmons Pharmacy
Stapley Pharmacy
EJV F LLC (Bulloch Drug)
Superior Care Pharmacy Inc.
Rocky Mountain Infusion Clinic
Intermountain Homecare Pharmacy @ Dixie
Infusion Innovations
CNS Pharmacy
Superior Care Pharmacy Inc.
Mountain Care Pharmacy
Coram Healthcare Corporation of Utah
Source found here
The Op-Ed: A Slew Of Off-Label Promotion Is Unlikely
By Ed Silverman // December 6th, 2012 // 12:09 pm
Earlier this week, a federal appeals court panel overturned the conviction of a former sales rep for allegedly encouraging doctors to prescribe a drug on an off-label basis, ruling that his conviction violated his First Amendment rights. The ruling may not be the final word on the issue, but a vigorous debate – including considerable speculation – has since ensued. So what happens next? Will this reach the US Supreme Court? Is all off-label promotion now protected free speech? And will consumers see a barrage of off-label advertising. Arnie Friede, a former FDA associate chief counsel and a former senior corporate counsel at Pfizer, looks at his crystal ball and finds…
The split-decision by a three judge panel of the US Second Circuit Court of Appeals in United States v. Caronia (see back story and ruling here) has pharmaceutical and First Amendment lawyers all abuzz. In fact, there has already been at least one law firm webinar on the subject a mere few days after the decision was rendered.
Just to recap, over a vigorous dissent, a two-judge majority held that, in order to avoid a First Amendment violation, the Federal Food, Drug, and Cosmetic Act should be construed as not prohibiting mere off-label promotion of an FDA-approved drug that is neither false or misleading.
In concluding that the defendant’s conviction should therefore be overturned, the majority relied to a considerable extent on the U.S. Supreme Court’s decision in Sorrell v. IMS Health (back story with ruling).
In that case, the court concluded that “(s)peech in aid of pharmaceutical marketing… is a form of expression protected by the… First Amendment” and, on First Amendment grounds, overturned a Vermont statute that prohibited the use of physician-identifiable prescribing data in detailing to doctors.
The dissent in the Caronia case by Judge Debra Ann Livingston focused to a considerable extent on the implications of the majority decision on a bedrock principle of food and drug law – “intended use” – and on the historical understanding that each intended use of a new drug must be separately approved by the FDA.
Otherwise, there would be little incentive for companies to seek approval of new drug application, supported by “substantial evidence” as that term is defined in the Food, Drug & Cosmetic Act, for an indication as yet unapproved by the agency.
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