FDA is focusing on companies “that pose the greatest risk”—those that
compound sterile injectable products such as steroids and have a history of
problems linked to patient illnesses or death, Howard Sklamberg, Director of
Compliance for FDA's Center for Drug Evaluation and Research, told the
Post.
Compounding pharmacies have been in the spotlight since a fungal meningitis
outbreak was identified in October 2012. As of March 4, the outbreak had caused
the deaths of 48 people and sickened 672 others, according to CDC. The outbreak
was traced to contaminated injectable steroids manufactured in unsanitary
conditions at New England Compounding Center in Framingham, Massachusetts. “The
company got greedy and overextended, and we got sloppy," Joe Connolly,
a
lab technician at the center, told
60 Minutes in an investigation
that aired on March 10. “Quantities of drugs increased by a factor of 1,000. …
We became a manufacturer overnight," Connolly said.
Wide
variety of problems found
Inspectors found 13 deficiencies at PharMEDium Services in Cleveland, MS; 12
at AnazaoHealth in Tampa, FL; 7 at Central Admixture
Pharmacy
Services (CAPS) in Chicago; and 7 at Lee Pharmacy in Fort Smith, AR. The report
listed numerous problems related to drug sterilization and testing;
environmental and building conditions; equipment, containers, and closures;
employee apparel; and production and process control procedures.
Inadequate procedures and testing to ensure sterilization, potency,
stability, and appropriate beyond-use dates of sterile injectable drug products
occurred at all four facilities. PharMEDium, for example, did not perform
endotoxin testing on all finished sterile injectable drug products and assigned
a 90-day expiration date for a drug without using “meaningful and specific test
methods” to ensure stability, according to the report.
At AnazaoHealth, CAPS, and Lee Pharmacy, procedures designed to prevent
contamination did not include validation of the sterilization process. CAPS did
not test an adequate number of batches of each drug to determine appropriate
beyond-use dates. Lee Pharmacy’s sterilization processes for suspensions and
solutions were not designed to follow a scientific rationale and thus had no
adequate controls to prevent failures.
Inspectors noted deficient
environmental monitoring of aseptic processing areas,
inappropriate
air
filtration systems, inadequate procedures for cleaning and disinfecting
rooms and equipment, and improper storage and handling of equipment at all four
facilities. At PharMEDium, inspectors also cited poor building maintenance,
including a “rust-colored build-up of material behind the
HEPA filter screen,” as well as
quarter-inch holes in the walls and an “off-white colored residue” in the clean
room. A PharMEDium employee was seen “dragging a full trash bag across the clean
room floor,” and AnazaoHealth employees used a disinfectant spray on packages of
components, containers, closures, and utensils before transferring them to clean
rooms but “then wiped them off with a dirty rag,” the report states. At CAPS, a
bag of citric acid in the warehouse had a hole, exposing the product to ambient
air. Lee Pharmacy did not monitor “viable and nonviable particles during
aseptic filling of sterile drug products,” FDA said.
Three of the facilities were cited for employee use of nonsterile or
inappropriate clothing and incorrect gloving procedures. In the
clean room of the CAPS
facility, employees did not use hoods or goggles, and they wore nonsterile
hairnets, beard covers, face masks, and clothing that exposed areas of the skin.
At AnazaoHealth, employees “performing aseptic operations in ISO 5 hoods reused
sterile cloth gowns throughout a production day,” and large open packages of
gloves “were dated when opened but had no controls to prevent their use in
aseptic operations once sterility is compromised,” the inspectors noted. Lee
Pharmacy had no written procedures for changing or sanitizing sterile gloves
during set-up and filling operations.
Inspectors also found unclean, nonsterile, and leaking drug product
containers, bags, and closures, including many items not tested to ensure
suitability for their intended use. At PharMEDium, for example, container
closure systems “did not provide adequate protection against external factors”
such as light, which could cause drug deterioration or contamination, the report
states. At AnazaoHealth, nondepyrogenated glass vials and rubber stoppers were
used in endotoxin testing of all sterile injectable drugs. The CAPS facility had
not taken appropriate action to investigate and correct recurring leaks in
sterile injectable total parenteral nutrition bags.
The complete inspection reports can be accessed on
the
FDA website.
Facilities
serve a need
Compounding pharmacies serve a crucial need. Many hospitals outsource sterile
compounding to avoid the costs of building, staffing, and maintaining their own
clean rooms, which must comply with
United States Pharmacopeia
(
USP)
<797> standards. In New York, after the state
pharmacy board issued a temporary ban on PharMEDium’s products for which there
is no patient-specific prescription, some hospitals were left scrambling to
prepare large volumes of compounded
Continue reading
here