A manufacturer of eye drops linked to a deadly outbreak of widespread drug-resistant infections in the United States has implemented basic measures and systems to ensure sterility from brown slime in filling equipment, according to a published laboratory report. There were numerous manufacturing violations, ranging from lack of According to the Food and Drug Administration (PDF).
In February, regulators warned consumers to immediately stop using Global Pharma’s eye drops and ointments. Global Pharma’s products were marketed in the United States under the EzriCare and Delsam Pharma brands and were available through Amazon, Walmart, eBay and other retailers. Global Pharma later announced a voluntary product recall.
Health investigators linked drops to widespread drug-resistant cases Pseudomonas aeruginosa A strain never before seen in the United States. This strain is identified as VIM-GES-CRPA. It represents a carbapenem-resistant Pseudomonas aeruginosa (CRPA) associated with Verona integron-mediated metallo-β-lactamase (VIM) and Guiana extended-spectrum-β-lactamase (GES). Affected people reported using multiple brands of eye drops, but EzriCare was the most common. Additionally, tests by the Centers for Disease Control and Prevention and independent researchers have identified the outbreak strain in unsealed bottles of EzriCare artificial tears.
As of March 14, 68 people in 16 states have been infected with the strain, the Centers for Disease Control and Prevention reported. The infection killed three, left eight blind, and four had their eyes surgically removed.
Back in February, the FDA noted that Global Pharma had several manufacturing violations, but the inspection report showed the extent of the defects. This 14-page report is a summary of Global Pharma’s manufacturing facility in Tiruporur, India (just south of Chennai, Tamil Nadu), conducted between February 20th and his March 3rd. Here’s what I got from his 10-day checkup.
The inspection report specifically summarizes 11 “observations” of the failure. First, Global Pharma did not bother to verify that the eye drops it claimed to be sterile were in fact sterile. There is insufficient validation data to substantiate,” the FDA inspection report said.
fatal flaw
The facility appears to have been set up to produce contaminated products. FDA inspectors noted that Global Pharma did not ensure that the components of the solutions it purchased from its suppliers were sterile from the start. Also, areas of the facility where solutions were to be made aseptically (free from contamination) were not suitable for sterile product production. That is, walls, ceilings, and floors weren’t smooth, hard surfaces that could be easily sterilized as they should have been. Instead there were cracks, protruding nails and holes in the walls. But even if the area was cleanable, the company’s cleaning procedures were also inadequate, the report notes.
FDA inspectors noted problems with machine cleaning and maintenance that may have led to cross-contamination from other products manufactured at the facility. On his second day of inspection, the inspector also noted “black, brown, greasy deposits” on parts of the filling machine, and the equipment logbook records that it hadn’t been cleaned in nearly a month. It was done. A few days later, the manager told the inspector that there was “no cleaning procedure” for the filling machine.
Environmental monitoring for contamination within the facility was also lacking, according to the report. Also, the sterility of the primary packaging, including bottle caps, was not verified prior to use. was shipped to the United States without passing through the quality control unit.
CDC officials previously told Ars they feared the outbreak of VIM-GES-CRPA in the United States would lead to more infections and drug resistance. Pseudomonas Viruses with genes that spread resistance quickly, like VIM and GES, were rare in this country,” said Marissa Grossman, CDC’s Office of Epidemic Intelligence. Organisms don’t get more common,” she said.
In March, the FDA posted recall notices for two eye drops, Pharmadica and Apotex, due to concerns about non-sterility. Products both listed as manufactured in North America are not associated with the VIM-GES-CRPA outbreak.
