FDA Tightens Screws on Compounders

The FDA continues to scrutinize compounding companies and took a number of enforcement actions for sterility issues uncovered.

The agency has conducted 160 inspections of compounders through May 25, and Form 483s were issued for almost all of those companies, Cynthia Schneder, director of CDER’s Office of Compliance told the DIA annual meeting June 17. Roughly 50 warning letters were later issued along with 16 letters referring findings to state pharmacy boards.

For its part, the National Institutes of Health is working quickly to correct major lapses in its drug compounding unit so officials will be able to ask the FDA to register it as a cGMP manufacturing facility subject to periodic regulatory inspections.

NIH’s 17-item 483

A May 19 to 29 FDA inspection resulted in a 17-observation Form 483 and an announcement on June 4 that NIH was suspending all operations in its Pharmaceutical Development Section and the Clinical Center Pharmacy.

Investigators found flaws in the air filtering system, deficiencies in monitoring environmental conditions and cleaning sterile processing areas, buildings not being able to facilitate proper cleaning and inadequate quality control, the Form 483 says. The facility also failed to maintain written records, ensure that protective apparel was worn, provide sufficient employee training and comply with standard operating procedures, according to the Form 483.

The PDS, which is located on NIH’s Bethesda, Md., campus, makes products for clinical research studies at NIH’s hospital and facilities.

In April, two vials of albumin were discovered to have fungal contamination, according to NIH. Vials from the same batch were administered to six patients, but it’s not known whether those or other vials were contaminated. The six patients were notified and have been followed for signs of infection, the institute adds.

Roughly 250 participants in 46 other NIH studies are potentially affected, as they receive products manufactured by the PDS. NIH says it is working to secure alternative sources for those products, and that the vast majority of patients are not in immediate need of treatment.

NIH says it will appoint a group of microbiology and sterile manufacturing experts to conduct a thorough review of the entire operation and make recommendations to Director Francis Collins on corrective actions.

NIH plans to retain a consulting firm to conduct a comprehensive evaluation of the PDS facility, its operations, procedures and processes, and quality assurance and quality control systems. Additionally, NIH has set a series of strict timelines for ongoing projects.

Dynamic airflow studies of the hoods in the pharmacy’s ISO 5 sterile areas began in July and results will be processed as soon as they are available. Similar studies will be conducted every six months.

All PDS personnel will be retrained using GMP-specific courses by Aug.14, and new standard operating procedures will be in place by Sept. 1.

Three More Compounders Warned

The FDA warned three more drug compounding pharmacies over sterility issues and other GMP shortcomings.

Florida-based Premier Pharmacy Labs and HHCS Pharmacy and Noblesville, Ind.-based Pharmakon Pharmaceuticals were cited for failing to maintain sterile rooms for manufacturing and failing to establish and follow procedures for preventing contamination.

During an April 10 to May 9, 2014, inspection of Premier facility, investigators from the FDA’s Florida district office noted the firm failed to investigate drug batches that didn’t meet specifications, regardless of whether the batches had been distributed.

Meanwhile, investigators from the FDA’s Detroit office twice inspected Pharmakon’s facility, in March and April 2014, after receiving adverse event reports of over-sedation in neonatal infants who had been given midazolam labeled with an incorrect concentration. The problem stemmed from a failure to establish that drug products met proper specifications, the warning letter says.

The FDA dinged HSSC for not monitoring employees charged with producing sterile drug products during a July 14 to 28, 2014, inspection.

Investigators from the Florida district office also noted the firm had unsealed ceiling tiles. Responding to a Form 483, the company said sealing the tiles would render HEPA filters inaccessible, but the FDA said the filters should be accessible with the tiles sealed.

None of the compounders returned a request for comment by press time.

The FDA urged the compounders to hire outside consultants with sterile drug manufacturing expertise to bring their facilities into compliance.

Since the start of the year, the FDA has warned compounders in Florida, Kentucky, New York, Kansas and Oregon over poor sterility controls.

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