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.
Continue reading here
A Compounding Fracture at the FDA
The agency has been slow to exercise control over pharmacies that mass produce drugs.
The recent deadly outbreak of meningitis caused by spinal injections of a contaminated steroid has cast a spotlight on the practice of pharmacy compounding—when pharmacists mix or adapt medicines to make a specific prescribed treatment. The House and Senate are holding oversight hearings this week on the tragedy that has sickened at least 438 people and is believed to have killed more than 30.
Congress wants to know why the Food and Drug Administration didn’t do more to prevent the production and sale of tainted steroids by the New England Compounding Center. The FDA will likely say that it doesn’t have enough authority to regulate the pharmacies that compound drugs.
But the FDA does have enough authority. And it did in 2006, when the agency sent a warning letter to the New England Compounding Center, in effect telling the NECC to stop manufacturing certain drugs or face legal action. In 2006, the warning came because the compounding pharmacy was, among other things, violating regulatory rules by producing drugs that were already commercially available from FDA-approved manufacturers. Six years later, NECC was not only still operating but also, it has become clear, selling tainted drugs. Where was the FDA? What was the problem?
The trouble didn’t come from traditional compounding, which is a legitimate part of the practice of pharmacy. Compounding pharmacies mix or alter drug ingredients to adapt a medicine based on a doctor’s prescription—for example by changing a pill into a formula, tailoring chemotherapy, or adding cherry flavoring to a child’s medicine. The practice lets physicians customize drugs to individual patients. Traditional pharmacy compounding typically is performed on a small scale and is always performed in response to a valid prescription.
The FDA normally doesn’t get involved with such practices because it isn’t tasked with regulating the legitimate practice of pharmacy. Like the practice of medicine, pharmacy is largely left to professional and state oversight. But once pharmacies begin manufacturing and shipping medicines on a mass scale, they become “drug manufacturers” and fall squarely under the FDA’s extensive authority.
There are unambiguous rules governing when a compounding pharmacy crosses the line and becomes subject to FDA supervision. The practice of compounding, for example, does not allow the manufacture of copies (or near copies) of FDA-approved drugs that are commercially available. By all accounts, the New England Compounding Center was hardly a pharmacy as generally understood; it was manufacturing unapproved duplicates of FDA-approved drugs and distributing them for a large-scale market without first receiving valid prescriptions for the individual drugs.
This all put the NECC firmly in violation of FDA rules—if the agency had chosen to enforce existing provisions. But in recent years the FDA has seldom drawn clear lines between practices that are legal and beyond its purview and ones over which it clearly has authority. The regulatory hesitation has meant that some of the shadiest compounding outfits haven’t been reined in. And it magnified risks by emboldening more pharmacies to go well beyond traditional compounding and engage in large-scale drug making—because it seemed a fairly safe bet that the FDA wouldn’t come knocking.
Meanwhile, the agency has been focused on enforcement activity that could instigate legal showdowns and set judicial precedents that would expand FDA power over the full scope of the practice of pharmacy. Part of this strategy is philosophical: Many at the agency have long believed that all of the professional practice of pharmacy belongs under the FDA’s oversight. Then there is regulatory languor: The FDA reasons that if it can assert jurisdiction over the entire profession, then it can more easily pick and choose where to focus its energies, instead of having to establish in advance which firms are crossing the line.
Take, for example, the FDA’s recent (and unsuccessful) enforcement action against the compounding firm Franck’s Pharmacy, a maker of customized veterinary drugs. Rather than allege that Franck’s had crossed the line from traditional pharmacy compounding to drug manufacturing, the FDA took the expansive position that it had the authority to regulate the practice of pharmacy in general and traditional pharmacy compounding in particular. The federal judge overseeing the Franck’s case easily rejected FDA’s power grab (although the judge didn’t dispute, and specifically noted, that the FDA has the authority to regulate drug manufacturing carried out under the guise of traditional compounding).
Ironically, the FDA is now using legal defeats like the one in the Franck’s case as the excuse for why it couldn’t be tougher on the steroid-maker NECC. This week, the FDA will ask Congress for new authorities to expand its oversight over the practice of pharmacy.
Instead, Congress should instruct the agency to issue regulations that assert the authorities that the FDA already has—drawing a bright line between the traditional practice of pharmacy (regulated by states) and the place where a compounder has crossed the line into drug manufacturing, making itself subject to federal regulation.
The FDA has failed for decades to clearly establish enforcement policies related to pharmacy compounders because the agency doesn’t want to concede that it was never supposed to have jurisdiction over the legitimate, local practices of pharmacy and medicine. In the process, the agency has undermined its own mission.
Dr. Gottlieb, a resident fellow at the American Enterprise Institute, was deputy commissioner of the FDA from 2005-07. Mr. Bradshaw was the FDA’s chief counsel from 2005-07. He was retained by Franck’s Pharmacy as an expert witness in the FDA case against the company.
A version of this article appeared November 14, 2012, on page A15 in the U.S. edition of The Wall Street Journal, with the headline: A Compounding Fracture at the FDA.
Source found here
American College of Veterinary Pharmacists Basic Veterinary Compounding Course 1/7-8/2013
Basic Veterinary Compounding Course Basic Veterinary Compounding is a 15 hour course The overall goal of this practice based course is to introduce the pharmacist and pharmacy technician to veterinary pharmacy compounding.This program provides the fundamental techniques for compounding medications for animals, as well as establishing and marketing a veterinary pharmacy practice. For Additional Information and to REGISTER ONLINE - Click Here $1095 (Non Member price) * $995 (Membe...
STATE OF WISCONSIN Board of Pharmacy
will discuss Federal Letters Requesting State Information as it Relates to Compounding Pharmacies at the next board meeting on December 12, 2012. See here
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