ST. LOUIS, Mo. — A St. Louis-area manufacturing plant, which has served as a key supplier of an antidote to sarin nerve gas for the military and civilian first responders, has suspended production due to quality-control issues.
With federal regulators spending several months to evaluate and test modifications to Meridian Medical Technologies Inc.’s manufacturing process, the nation’s stockpile of the nerve-gas antidote has shrunk. Meridian has suffered a substantial loss of business. And its parent company, Pfizer Inc., is attempting to fix these problems.
Meridian and government agencies have minimized the impact, suggesting that less than 1 percent of the millions of antidote injector units sold to the military and first responders are potentially defective — an estimate that could not be independently corroborated.
But with production temporarily suspended, supplies of the antidote have slowly dwindled — with some agencies such as the Orange County (Calif.) Fire Authority reporting that they’re unable to get orders filled.
Because of the manufacturing defect, which the company and government agencies say was uncovered this year, military stockpiles from 2010, 2011 and 2012 are being reinspected, and defective units are being discarded and replaced. Meridian is paying for this “remediation.”
“We do not have a definitive date as to when product will be available,” Christopher Loder, a Pfizer spokesman in New York, said in an email. “Pfizer takes this matter very seriously, and we are working hard to get this right and maximize output.”
Pfizer acquired Meridian as part of its purchase of King Pharmaceuticals Inc., based in Bristol, Tenn., in March 2011.
Meridian’s quality-control issues have drawn sharp criticism from at least one member of Congress, who has voiced concerns that the company — whose manufacturing and packaging plants in two St. Louis suburbs employ about 300 workers — was slow to inform its civilian customers about its defective products.
Meridian has obtained more than $200 million in business in the past decade from sole-source contracts to the Pentagon as well as state and local governments, health providers and first responders for its two-drug antidote to nerve agents — an injection of atropine and pralidoxime chloride.
This product — “Antidote Treatment Nerve Agent, Auto-Injector,” or ATNAA — is a key element in the Pentagon’s biological and chemical defense efforts. A similar product is sold to U.S. allies overseas.
Sarin is the poison gas that United Nations weapons inspectors suspect was used Aug. 21 by the Syrian military in the killing of more than 1,000 Syrian citizens, including children in a Damascus suburb. Sarin also was used in the 1995 Tokyo subway attack by terrorists who killed 12 and injured 1,500.
Meridian’s equivalent civilian product, “DuoDote,” is sold to state and local governments, health providers and emergency personnel. It is also used as an antidote for insecticide poisoning.
Since the terrorist attacks of Sept. 11, 2001, the U.S. Centers for Disease Control and Prevention, along with state and local authorities aided by the U.S. Department of Homeland Security, has stockpiled certain antidotes as a safeguard against terrorist attacks using biological and chemical warfare agents.
“Designed to meet the unique needs of patients in emergency situations, our auto-injectors allow for rapid administration of a specific dose of medications(s) under crisis conditions,” according to one of Meridian’s websites.
“From the battlefield to the backpack, Meridian auto-injectors are rugged, portable, and mechanically reliable,” Meridian states. “In extreme emergency situations, rapid administration of a vital medication can mean the difference between life and death.”
Meridian’s auto-injector — a spring-loaded hypodermic syringe — has two separate barrels for delivering the nerve gas antidotes. But company officials acknowledge that in rare instances its pre-filled syringes were not adequately filled with the antidotes and could fail to automatically “fire” their muscular injection.
Jennifer D. Elzea, a spokeswoman for the Office of the Assistant Secretary of Defense, said problems with the ATNAA product appear to have surfaced this year.
She said the Pentagon was alerted by Meridian of potential issues with its ATNAA auto-injectors on March 13.
“Our first knowledge of the issues came through Meridian,” Elzea said. “They alerted us. They were forthcoming with this information.”
She also said that FDA officials developed a remediation plan to identify and replace defective units.
According to the Defense Department, technicians have examined more than 1 million ATNAA auto-injectors and rejected improperly filled devices. Elzea said that about 2.8 million of Meridian’s stockpiled auto-injectors will be inspected. In recent years, the military has purchased about 4.4 million ATNAA units.
Under federal law, Meridian must maintain a rigorous inspection process at its manufacturing plant and also perform quality control monitoring of its finished product.
Erica Jefferson, an FDA spokeswoman, said the FDA had conducted inspections of Meridian facilities in 2010, 2011 and 2012, but no warning letters were issued. She referred questions involving quality-control issues of Meridian’s ATNAA product to the Pentagon.
Meridian has not recalled the DuoDote product for civilians, Jefferson said, “due to medical necessity and the imminent drug shortage that would result from removing product from the market.”
According to FDA records, Meridian has previously experienced quality-control issues with another product: diazepam injections, which can also be used to counteract exposure to nerve agents.
In June 2012, Meridian issued a voluntary recall for 83,701 auto-injectors of diazepam that had been shipped to customers in the United States, Italy, Singapore, Sweden and Canada. The company said that impurities had been found in its diazepam auto-injectors.
Meridian, which is headquartered in Columbia, Md., has drawn fire from a member of Congress for its delay in informing the nation’s civilian first responders about defective DuoDote units.
On Aug. 27, Tom Handel, Meridian’s senior vice president for commercial pharmaceuticals, sent a letter to wholesalers, health care providers and emergency personnel warning that, based on its review of product inventory, the auto-injector system for DuoDote had the potential for “under-dosing or failure to activate.”
The letter said that Meridian personnel found that a “small number of DuoDote auto-injectors are out of specification.”
“This could potentially prevent some of the units from activating or cause the patient to receive less of the drug than is intended,” Handel states. “Delivery of clinically inadequate drug doses is infrequent and occurs in approximately 7 units out of a thousand DuoDote auto-injectors.”
Handel’s letter, which asked customers to retain the product, said Meridian is working with the FDA to develop a “product replacement plan” and to send these replacements “as quickly as possible and based on priority of need.”
In the meantime, emergency personnel were advised to stock three auto-injectors per patient.
“If at any time after the first injection the patient experiences severe (nerve gas exposure) symptoms, two additional injections should be administered in rapid succession and definitive medical care should be sought immediately,” the letter said.
Rep Andy Harris, R-Md., an anesthesiologist who serves on the House Appropriations Committee, sent a letter on Sept. 12 asking Meridian to explain why it waited more than five months after informing the Pentagon of its problems with ATNAA auto-injectors to advise civilian first responders of DuoDote’s quality-control issues.
Harris’ remarks have drawn criticism from public interest groups due to his previous acceptance of campaign donations from Emergent BioSolutions Inc., a Rockville, Md.-based firm that is seeking additional defense contracts.
On Sept. 24, Meridian’s Handel responded to the congressman’s letter.
“The health and safety of patients and all of the customers receiving our products, particularly those responsible for protecting our national security and public safety, is our first priority,” Handel wrote. “Meridian is committed to ensuring that all of our products meet the highest standards of quality and efficacy and that this issue is resolved quickly.”
In his letter, Handel said that “Meridian personnel discovered the issue during an inspection of inventory that had not been released to any customers.” He did not say when this inspection occurred, nor answer Harris’ question as to why the company waited until late August to inform its civilian customers.
Pfizer spokesman Loder said Handel was not available for an interview.
Despite its quality-control issues, Meridian won a five-year, $60 million Project Bioshield contract in September from the Department of Health and Human Services to provide an auto-injector of midazolam to treat adult and children for seizures caused by nerve agents.
According to public documents, the FDA approved in 2006 Meridian’s DuoDote product for civilian use.
The CDC’s “Strategic National Stockpile” includes medicine and medical supplies to protect the American public if a terrorist attack, flu outbreak or natural disaster strikes. It is unclear how many doses of DuoDote are stockpiled for civilians.
Homeland Security has provided grant money to state and local health agencies and first responders to purchase DuoDote, which is available through Meridian — the exclusive U.S. manufacturer — and its distributors. The price ranges from about $39 per dosage unit to more than $81 per unit.
In 2012, the St. Louis Fire Department purchased a supply of DuoDote units. “It’s fairly expensive, but it’s one of these things you have to have in case there’s a terrorist attack,” said Fire Chief Dennis Jenkerson.
The Orange County Fire Authority began buying DuoDote in 2009. Earlier this year, it ordered 2,400 units at about $42 per unit. Meridian acknowledged the order but did not fill it.
“It didn’t go through. We never had an explanation before (the problems became) public,” said Dr. Ken Miller, the authority’s medical director.
In mid-September, the FDA extended DuoDote’s four-year shelf life for another year. Neither the FDA nor the Pentagon has declared a shortage of Meridian’s nerve-agent antidotes.
“There isn’t really a crisis,” said Miller, adding that firefighters are willing to wait until Meridian resumes full-scale production and the military’s supplies of ATNAA are bolstered.