By Tom Wilemon and Nate Rau, The Tennessean
Hospitals and doctors' offices are sending letters to Tennesseans notifying them of possible exposure to moldy medicine from the New England Compounding Center -- even if they never got the steroid epidurals linked to a national outbreak of fungal meningitis.
The fungus might be in injections used during heart or eye surgeries, the letters say, distributed by 74 still-unnamed Tennessee health care facilities that ordered from New England Compounding.
But who got potentially contaminated injections will be tough to sort out because of the federal government's hands-off approach to compounding pharmacies and Tennessee's lack of oversight. Neither the U.S. Food and Drug Administration nor the state requires doctors to record specific lot numbers of medicines given to each patient, making it nearly impossible to sort out who got the tainted doses.
At least one Tennessee lawmaker, Rep. Glen Casada, R-Thompson's Station, wants to talk about more state oversight, and the Tennessee Board of Pharmacy also plans to scrutinize the rules for how compounding labs operate in this state and look for ways to better protect the public.
The national fungal meningitis outbreak has sickened 61 and killed eight in Tennessee. The Tennessee Department of Heath confirmed the last two deaths Wednesday, but wouldn't say who they were or where they received contaminated medicine.
Nationwide, there are 247 patients with fungal infections and 19 related deaths, the U.S. Centers for Disease Control and Prevention said.
The new drugs doctors think might be contaminated include opthalmological injections used during surgery -- the only one doctors identified is called Avastin -- and cardioplegic drugs used to slow the heart during surgery.
In the beginning, health officials believed the crisis was limited to approximately 1,000 Tennesseans who received epidural steroid injections at three pain management clinics. With more drugs being suspected of contamination, there are possible ramifications for others who were treated with one of New England Compounding center's 1,200 types of drugs.
Doctors won't even guess the number of patients.
"I really wish I knew that," said Dr. David Reagan, chief medical officer for the Tennessee Department of Health. "That's one of the things we'll be looking to discover. That's going to take some real sorting on the part of each of the facilities."
The public will find out the names of the 74 Tennessee facilities that used the New England Compounding Center eye and heart transplant drugs after those places are reached, a health department spokesman said.
Most affected patients will be notified by letter, Reagan said, since these infection concerns do not rise to the same threat level as fungal meningitis cases.
"We have a significantly lower level of concern, but there's enough concern to make sure patients are contacted by their providers," Reagan said. "The FDA is not saying you need to go out and find people and talk on the phone or get them face to face."
It may be difficult for patients to learn where their injections were produced. Tennessee does not require clinics or hospitals to record on individual patient files lot numbers for most injections.
Neither the National Public Health Information Coalition nor the Association of State and Territorial Health Officials could say which states do require that. California, Iowa, Nebraska and several other states responded to inquiries saying they don't require it.
However, states do keep track per patient lot numbers for vaccines, which is required by federal law.
The lot numbers identify the origin of drug products and the time they were produced. The FDA specifies partial recalls of medicines or foods by lot numbers.
With rolling shortages of commonly used medicines in recent years, hospitals and clinics often order the same medicine from multiple suppliers.
Saint Thomas Outpatient Neurosurgery Center, the only Nashville center linked to the cases of fungal meningitis, has not responded to inquiries as to why it obtained a generic form of an epidural steroid medicine from New England Compounding instead of purchasing the FDA-approved, brand-name drug.
New England Compounding violated its license by manufacturing mass quantities of drugs instead of making batches per individual prescription, according to Massachusetts and federal authorities.
New England Compounding has turned over to the FDA more than 131,000 shipping invoices for materials that went to medical facilities across the U.S. from its Framingham, Mass., plant.
Compounding laboratories convert Avastin -- one of the drugs suspected in infections -- into single-dose eye injections as a cost-saving measure. It is a close chemical cousin to Lucentis, the drug approved by the FDA for macular degeneration.
Lucentis costs about $2,000 for a single-dose vial. Avastin costs about $50 a dose.
Laurale Curtsinger of Goodlettsville questioned the safety of compounded eye medicines before the fungal meningitis outbreak. She said her mother lost vision in one eye in 2009 from an infection that occurred after an injection with a compounded form of Avastin.
It's normally a cancer treatment packaged only for intravenous use, but it's also effective for wet macular degeneration, the leading cause of blindness in elderly Americans.
Curtsinger said she called the Nashville ophthalmology practice where her mother was treated and was told that her medicine came from another compounding laboratory -- not New England Compounding Center.
"What are we doing compounding these drugs in all facilities?" Curtsinger asked. "It just seems like it is open to contamination too readily. Honestly, my mind is still not completely at ease that there weren't issues."
Four patients at the Veterans Affairs hospital in Nashville developed bacterial eye infections last year after they received a compounded form of Avastin. One of them, Mason Sylvis, 78, of Inglewood never left the hospital and died in July.
Joyce McDaniel, the non-pharmacist consumer representative on the Tennessee Board of Pharmacy, said she knows changes are necessary, but she's uncertain about what route to take.
"I don't know if it's something we can regulate or if it is something that the FDA has to regulate," McDaniel said. "Obviously, there has to be some kind of oversight. I'm not sure what that is."
An FDA official was at a loss to explain how compounding laboratories are regulated in a national conference call with reporters last week. Deborah Autor, an FDA deputy commissioner, used the word "complicated" repeatedly. She said there are regulatory gray areas created by "litigation and a lack of clarity in the law."
John Smith, chief deputy general counsel for the state Department of Health, is studying Tennessee's options in advance of the Board of Pharmacy's meeting Nov. 14 and 15.
"There are two specific statutes -- one that deals with manufacturers who are more heavily regulated, and the other deals with pharmacists," Smith said. "New England Compounding Center was acting as a manufacturer although it was only licensed as a pharmacy in Tennessee.
"We're also investigating all compounding companies to ensure that they have a manufacturing license versus simply a license as a pharmacy."
Compounding pharmacies prepare customized prescriptions for patients when the medicine they need isn't commercially available or available in the form, concentration or dosage needed.
Casada, who chairs the Tennessee House Health and Human Resource Committee, said he realizes compounding laboratories play a vital role in the health care system, but there are occasions when the state should have oversight.
"First, we need to look at what went wrong," Casada said. "Of course, what went wrong in Massachusetts is the FDA did not implement their own policy and procedures. I mean, gosh, this company in Massachusetts has had several violations over six years. And the FDA has never, never implemented the disciplinary action against the compounding pharmacy."
The compounding industry is keeping a close watch as Tennessee officials mull their options. Micah Cost, director of professional affairs for the Tennessee Pharmacists Association, and John Hollis, the owner of a Nashville compounding lab, attended a meeting of the Tennessee Board of Pharmacy on Monday when it accepted the surrender of New England Compounding Center's license.
Cost warned that more regulations at the federal and state levels could add to shortages of drugs.
"Tennessee is very rural, so we would have to look at access, making sure we can maintain access for these products, for these patients," Cost said.
The Tennessee Board of Pharmacy is scheduling another meeting early next week to accept the surrender of Barry Cadden's pharmacy license.
Cadden is registered in Tennessee as the pharmacist in charge of New England Compounding Center.