Calif. may develop regs to control pharmacist compounding following deaths and injuries due to compounded Rxs by a pharmacy in the state
Two people have died and a dozen have been hospitalized with meningitis contracted from an injectable corticosteroid compounded by a San Francisco-area pharmacy. At least 38 patients were injected with betamethasone contaminated with Serratia marcescens, a common bacterium that should have been destroyed during compounding.
The patients were given betamethasone compounded by Doc's Pharmacy, in Walnut Creek, Calif., because the commercial equivalent was unavailable due to manufacturing problems at Schering-Plough. The drugmaker has temporarily halted production of Celestone (betamethasone) because of manufacturing deficiencies uncovered during an inspection by the Food & Drug Administration earlier this year.
At least 60 San Francisco-area physicians, hospitals, and clinics purchased betamethasone prepared by the pharmacy, according to the Contra Costa County Health Department. The department ordered a recall of all parenteral and ophthalmic products compounded by the pharmacy. The pharmacy has cooperated fully in the recall, said county health director Wendel Brunner, M.D.
"We are now sure the source of the S. marcescens contamination is Doc's Pharmacy," Brunner said. "We are continuing to investigate all aspects of these cases and have been able to rule out contamination at the health facilities" that administered the injections.
Health department technicians have cultured S. marcescens from at least 12 unopened vials of betamethasone prepared by Doc's. The common bacterium presents little or no threat unless injected. Both fatalities were caused by an epidural injection. At deadline, at least four other patients were being treated for Serratia meningitis but were expected to survive.
Area hospitals have treated several other Serratia infections at injection sites. "This is the first time in my 10 years with the board that we have seen contaminated products come out of a compounding pharmacy," said Virginia Herold, assistant executive officer of the California State Board of Pharmacy. "We're dealing with an issue that has great potential to damage public confidence in pharmacy."
Robert Horowitz, Doc's owner and chief pharmacist, did not return repeated telephone calls. According to local R.Ph.s, Doc's has developed a thriving compounding practice working with base products supplied by Professional Compounding Centers of America. PCCA supplies chemicals and other base materials to Doc's, said company president David Sparks in Houston, buying from the same bulk producers that supply Schering-Plough and other pharmaceutical manufacturers.
The betamethasone powder used by compounding pharmacies and manufacturers is not sterile, Sparks said. The final preparation is intended to be sterilized after reconstitution. Compounding pharmacies and manufacturers use filtering, autoclaving, or both, to sterilize the final solution.
According to county officials, Doc's Pharmacy prepared injectable betamethasone in 300-ml batches, then packaged the final product in vials for sale. All the reported infections have been linked to a single 300-ml batch.
County health officials suggested that a pharmacy technician may have accidentally set the autoclave incorrectly during compounding. In California, techs are allowed to compound under direct supervision of a pharmacist, but the supervising R.Ph. is responsible for the final product.
The pharmacy board and the state Department of Health Services are investigating the accident. Jon Rosenberg, M.D., head of the DHS division of communicable disease control, infection control, and healthcare epidemiology, said the two bodies would consider changes to pharmacy practice regulations governing compounding once they had identified all the factors that had contributed to the contamination and deaths.
Depending on their findings, the pharmacy, pharmacist, and technician could face a variety of administrative, civil, and criminal actions.
Sparks cautioned pharmacists who compound injectables or other products to carefully review sterile procedures. Pharmacists should also validate their sterilization procedures, he said, in order to eliminate the potential for error. "This [contamination] could have happened with any injectable product," he said. "The same technique is used in compounding and in manufacturing. Manufacturing is just a bigger scale."
Quality-control and production problems shut down Schering-Plough's commercial production of its own branded betamethasone in early 2001. Betamethasone is most often used to relieve pain due to athletic injuries and other physical strains, said company spokesman Bob Consalvo. It is also commonly used to speed lung maturation in infants at high risk for premature birth. With the product in short supply, he said, Schering-Plough restricted sales and distribution to hospital-based neonatal units.
The shortage of Schering-Plough's betamethasone, combined with an unrelated shortage of dexamethasone, a common substitute for the treatment of sports-related injuries, pushed physicians and other healthcare providers to buy betamethasone compounded by pharmacists.
Consalvo said production problems are being rectified with the addition of new equipment, new procedures, and new manufacturing guidelines. Production should resume "shortly," he said, but pharmacies can expect a delay of several weeks as product moves through the distribution chain.
Fred Gebhart. Fatal meningitis linked to compounding by Calif. pharmacy.