State and federal authorities agreed that things got out of hand when the New England Compounding Center produced mass quantities of contaminated injectable steroids linked to more than 50 deaths among hundreds of cases of meningitis last fall.
But there are significant areas of disagreement between state and federal authorities involving the production of drugs.
As a result of the drug related meningitis outbreak, pharmacists fear that the U.S. Food and Drug Administration may try to impose manufacturing standards on pharmacies that compound, or make, certain prescription drugs.
Compounding pharmacies are playing a larger role in providing drugs - primarily generics that are less profitable for big manufacturers, which are directly overseen by the FDA.
When a pharmaceutical company’s drug loses its patent and enters the public domain, it is less profitable as a generic. “Typically, that’s when a generic manufacturer will come in and start manufacturing that compound,” Kaelan Hollon, a spokesman for Pharmaceutical Research and Manufacturers of America, which represents major drug companies, said in an e-mail.
In other cases, a pharmacist is the one who steps in.
Warren Lee is one of those. His pharmacy in Fort Smith was one of about 30 in 18 states that were inspected this year by the FDA in the wake of the meningitis outbreak.
Lee said in a written response to the warning letter issued by the federal agency after the inspection that his pharmacy does not have to comply with “current good manufacturing practices and other requirements of the Federal Food, Drug and Cosmetic Act.” The pharmacy, instead, adheres to U.S. Pharmacopoeia Standards for pharmaceutical compounding, not manufacturing.
If push comes to shove, the federal government would have the upper hand because of the Interstate Commerce Clause in the Constitution gives it jurisdictional authority, according to Reynaldo Rodriguez, director of the Dallas district of the FDA.
Short of a constitutional battle, a draft bill has been prepared in Congress.
The legislation by the Senate Committee on Health Labor and Pensions, revealed in late April, seeks to delineate authority between the states and federal government. It has the support of Tom Harkin of Iowa, a Democrat and committee chairman, and Lamar Alexander of Tennessee, the ranking Republican.
But while there is apparent bipartisan support, there are differences of perspective.
Harkin said in a prepared statement issued with the draft that “by clarifying FDA authority over high-risk compounding practices, this bill will enhance protections for patients taking compounded [drugs] … .”
Alexander said: “Our goal with this bill is to put an end to FDA inaction to make it clear who … is in charge and accountable for oversight of these pharmacies and manufacturers.”
In a May 9 meeting of the committee, Alexander said a new category of oversight would be created by the draft legislation, giving the FDA authority over what he termed “compound manufacturers” who would produce sterile drugs to be sent across state lines for hospital use.
Imposing manufacturing standards on pharmacies would be an impossibility, pharmacists argue, and could drive them out of business. That would defeat one of their major roles: filling gaps in supply from the big drug companies.
There are now 267 drugs in short supply, according to Dr. Lloyd Allen, editor-in-chief of the International Journal of Pharmaceutical Compounding.
Members of the Pharmaceutical Research and Manufacturers of America, which represents the large makers of drugs, have “stepped up the voluntary reporting of anticipated events that might lead to drug shortages, and according to the FDA, in 2011, this early notification helped prevent 195 shortages,” John Castellani, president and chief executive of the organization, said in a prepared statement.
Most shortages involve generic drugs, including older sterile injectable drugs, he said. ‘ART OF PHARMACY’
Of the 60,640 pharmacies in the United States, 23,106 are independent, according to the Alexandria, Va.-based National Community Pharmacists Association, making it the largest segment. Seventy-six percent of the independents compound medications, according to the the International Academy of Compounding Pharmacists.
All of the roughly 750 pharmacies in Arkansas do some compounding or mixing, what John Kirtley, executive director of the Arkansas State Board of Pharmacy, calls the “art of pharmacy.”
Six of the eight-member state board members are pharmacists. They are Ronnie Norris, president, of McGehee; Steve Bryant, vice president, Batesville; Justin Boyd, secretary, Fort Smith; Lenora Newsome, Smackover; Stephanie O’Neal, Wynne, and Thomas Warmack, Sheridan. Two members are not pharmacists.Larry Ross of Sherwood is a retired AT&T executive and Joyce Palla of Arkadelphia is a retired manager for Texas Instruments.
Only seven compounding pharmacies in Arkansas make sterile injectables, according to Kirtley. A particular kind of injectable, a steroid, led to the outbreak of fungal meningitis linked to the New England Compounding Center in Framingham, Mass. That led to the inspections of 30 compounders around the country this year, including one in Arkansas, which does not compound the steroid.
Carmen Catizone, executive director of the National Association of Boards of Pharmacy in Mount Prospect, Ill., said state boards can determine whether a producer is a compounder or a manufacturer. The FDA has long held that it has the authority over compounding operations, but has deferred to the states, he said.
“One thing that most people agree on is if it’s patient-specific it’s compounding,” Catizone said. But some pharmacies may be producing it for hospitals or clinics without prescription and “it’s leaning toward manufacturing.”
“The practice of pharmacy is supposed to be about patients, and that’s what the regulations are supposed to protect.
“If there is no prescription … they [compounders are] focusing on product. They’re making thousands or hundreds of thousands of doses … they’ve lost the patient. And that becomes manufacturing.”
“It’s no different than a Pfizer making thousands or millions of doses of Lipitorand sending them to pharmacies and wholesalers around the country.”
There is state and federal cooperation. Roche, for example, a large manufacturer, ran short in 2009 of Tamiflu, which is used to treat influenza symptoms. The liquid form is preferred for small children, but it was in short supply, so the FDA encouraged compounders to convert capsules of the drug into liquid form. “FDA would like to remind healthcare providers and pharmacists of the FDA-approved instructions for the emergency compounding of an oral suspension from Tamiflu … capsules,” the agency said in a release.
Shortages have increased in the past three to five years for several reasons, according to Allen. Cost increases have caused some manufacturers to shut down and when medical patents become public domain as generics, they are not as profitable, he said.
Plus, he said, 80 percent of the ingredients that go into pharmaceuticals are imported from China and India, which can pose logistical problems.
OPPOSITE OPINIONS
Compounding was the only way drugs were made until the early 20th century, Allen said, when mass production arrived. The FDA was created under President Franklin Roosevelt in 1938 “to oversee drug manufacturing at the federal level. “
“The practice of pharmacy is governed at the state level” based on each state’s laws. The FDA doesn’t have any control over compounding, Allen said.
The federal agency doesn’t see it that way.
The FDA states on its website that it has a mandate to inspect pharmacies that “have produced high-risk sterile drug products” and that the reason for the inspections carried out this year included “serious adverse event reports, historical inspection data, and reports of product quality problems.”
Inspectors for the FDA and the state Pharmacy Board saw things differently as they visited Lee Pharmacy in Fort Smith on Feb. 19.
The federal inspectors found seven areas of concern in the pharmacy. Yet state inspectors gave the pharmacy a Class A rating.
Pharmacy owner Lee said in his March 14 letter to the FDA’s Rodriguez that Lee’s business and others like it “help to fill the gaps created by the lack of manufactured drugs.” However, they are not pharmaceutical manufacturers that must comply with the Food, Drug and Cosmetic Act, Lee asserted.
The federal agency had sent a letter dated Oct. 6, 2003, to Lee Pharmacy, expressing concerns about “serious violations” of the Food, Drug and Cosmetic Act in making drugs for human and veterinary use.
While Lee Pharmacy has long since corrected those problems, it remains on the FDA radar. That episode occurred before the state Board of Pharmacy adopted U.S. Pharmacopoeia Standard 797, which sets rules for compounding of sterile medications, Kirtley said.
Lee responded to the FDA, but he said he never got further communication on the matter from the FDA. The Arkansas Democrat-Gazette has requested that the agency provide all relevant records on the matter under the federal Freedom of Information Act.
Likewise, the state Board of Pharmacy did not receive any communication from the FDA on a resolution, Kirtley said.
The 17 states where the other 29 pharmacies are have varying degrees of inspection resources, Catizone said.
Some of those states “may not even go into those pharmacies with the FDA or subsequent to an FDA visit,” Catizone said.
Kirtley sent reports of several years of inspection records of Lee Pharmacy to the Democrat-Gazette that show that the state agency “clearly understand[s] that this is a compounding pharmacy … and [conducts a] more intensive inspection process on compounding pharmacies that prepare sterile injectable products.”
The FDA opened the floodgates to compounding because of a shortage of certain manufactured drugs, Catizone said,and deferred to state boards of pharmacy to oversee the production of those medications.
“Even products that weren’t in short supply were being manufactured” by the New England Compounding Center, Catizone said. One result was that the center, which faces numerous lawsuits, has been shut down since its contaminated injectable steroid, used mainly for relief of joint pain, was linked to the deadly meningitis outbreak.
John Norton, spokesman for the National Community Pharmacists Association, said New England Compounding was “masquerading as a manufacturer.”
The U.S. Department of Health and Human Services Office of the Inspector General issued a report to FDA Commissioner Margaret Hamburg on April 10 stating that outsourced compounded sterile products are widely used inacute-care hospitals.
UAMS Medical Center does some compounding for its purposes but has to rely on outside compounders, said Mike Parr, director of the hospital pharmacy.
In fact, UAMS Medical Center had to notify some of its patients that it had gotten supplies from the New England Compounding Center, though the suspect steroid was not among them, Parr said, adding that he is not aware of any adverse reactions to any of the center’s supplies.
And while UAMS Medical Center keeps supplies of compounded drugs, it still has to provide, if asked, the names of specific individuals for whom they are designated, Parr said.
Sixty-eight percent of a representative sampling of the hospitals in the Health and Human Services report shortages of compounded sterile products. “Few hospitals … reported problems with product contamination; however as shown by the meningitis outbreak in the fall of 2012, any instance of product contamination has the potential for serious consequences.”
Not having certain drugs can have its own dire consequences, Jeffrey Turner, publicsafety commissioner for Sebastian County, said in a letter to Congress on Feb. 28. In the letter, he said his agency “is one [of] thousands of [emergency services] agencies across the [country] dealing with the nationwide shortage of emergency medications vital to treatthe injured and critically ill.
“Without the ability for Lee Pharmacy to continue to make these life saving medications for Sebastian County EMS & Rescue, lives would be lost, and emergency care could be critically hindered.”
Business, Pages 63 on 05/19/2013