Pfizer management knew last year that there was a “mold problem” at the Kansas plant that an inspection report from the Food and Drug Administration said is being used to manufacture the drugmaker’s much-needed Covid-19 vaccine.
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The McPherson, Kansas facility, which FDA inspectors say is the nation’s largest manufacturer of sterile injectables controlled substances, has a long, troubled history. Nearly a decade of FDA inspection reports, recalls, and referrals reviewed by KHN indicate the facility is a repeat offender. FDA investigators have repeatedly noted in reports that the facility did not control quality and contamination, or did not fully investigate after production stoppages.
The 1970s manufacturing facility has had ongoing mold problems over the years and has been the focus of at least four intense FDA inspections since Pfizer began operations in late 2015 with the acquisition of Hospira. By the end of the January 2020 inspection, FDA investigators seemed increasingly frustrated.
Pfizer plant managers told investigators that they had either bacteria or mold throughout the facility at different times of the year. In a January 17, 2020 visit inspection report received from KHN, one of three FDA experts, Pfizer wrote that following an inspection in 2018, Pfizer fixed issues and added “more cleaning activities in response to mold,” and “are still there.” unresolved discrepancies. “
Following the January 2020 inspection report, Pfizer immediately developed and implemented a corrective action plan, company spokesman Eamonn Nolan told KHN. Neither Pfizer nor the FDA responded to requests to provide a copy of the plan.
Nolan said in an email last week that “significant investments have been made in resources, equipment and facilities”. He stated that any improvements related to Coviden manufacturing would be completed before vaccine production begins. He declined to provide details on when production of the vaccine would begin, but said the site is currently in a state of good manufacturing, meaning it meets an FDA-enforced regulatory standard.
“We are confident that the McPherson site can produce high quality COVID-19 vaccines,” he wrote.
In large clinical studies, Pfizer’s vaccine has been found to be safe and 95% effective against Covid.
The news that the facility will be a fill and end-of-line location for the Pfizer BioNTech vaccine means more eyes are on the facility. “That alone should help,” said Barbara Unger, a former executive in the pharmaceutical industry who now conducts manufacturing tests for companies.
It’s unclear whether FDA investigators have returned to review manufacturing practices at McPherson or whether they are planning a visit before vaccine production begins. The FDA did not respond to certain questions. FDA spokeswoman Abigail Capobianco wrote in an email that the public “can be assured that the agency has used all the tools and information available to assess compliance”.
Pfizer’s emergency use approval letter for its mRNA vaccine includes safeguards such as quarterly reports to the FDA and a company quality analysis for each drug lot manufactured at least 48 hours prior to distribution.
The facility’s manufacturing issues can be tracked in FDA reports from 2011 through last year. Several former FDA officials and industry experts said the ongoing challenges in McPherson highlight how agency officials must aggressively balance a company’s manufacturing practices with the need to maintain patient supplies.
“I don’t envy the FDA decisions,” said Unger, describing a balancing act. “Which is the greater risk to public health?”
The site produces a wide range of sterile generics for use in hospitals, and their problems have played a role in some major health system bottlenecks, particularly opioid injectable analgesics, according to a 2018 FDA statement.
The FDA rejected Pfizer’s biosimilar version of Amgen’s anemia drug Epogen in 2017 due to bottleneck / end-line concerns. That same year, John Young, group president at Pfizer, announced to investors that the company had filed a “Corrective and Preventive Action” plan for the facility.
This is the same language used after the January 2020 inspection that found contamination concerns for the site, but not for the medicines. And it was Young, now Pfizer’s chief business officer, who told Congress last month that Pfizer had added production lines at the McPherson site to meet Covid-19 vaccine requirements.
The facility’s records of recalls and field warnings include vials of medication that contained glass and cardboard particles and, as one customer complained, a “small insect or dust speck.”
A 2017 FDA warning letter, which is a strong reprimand to the agency, stated that the contaminants contained in vials, such as cardboard and glass, pose a “serious risk of patient harm” and that the facility’s process of making sterile injectables Products “off” is control. “
FDA records show that in 2016 and 2017, several batches of vancomycin hydrochloride, a drug injected into hospital patients who have an infection that penicillin does not treat, were recalled.
John Avellanet, FDA compliance expert and principal at Cerulean Associates, reviewed the 2020 inspection reports. He said he feared the fixes were just “window dressing”.
“You may have solved one case, like the cardboard particles. But for some reason they never got rid of the contamination, ”Avellanet said. “Whatever quality control testing they do doesn’t seem to work because if it did they wouldn’t have those contamination problems.”
Pfizer ceased production of McPherson in December 2017, despite the FDA visiting two months earlier and improving the facility’s inspection rating. McPherson’s management ceased production and rejected batches of finished products after mold was found on equipment in a bottling area, according to an FDA inspection report. The plant was put back into operation weeks later.
When the FDA returned for inspection in late summer 2018, it found that there were no procedures to prevent microbiological contamination of drugs. A lack of staff training was also noted, staff who did not follow procedures, clogged surfaces, and internal tests that did not guarantee drugs met standards.
When CEO Albert Bourla took the helm at Pfizer in 2019, he told analysts that it would be another difficult year for US hospitals to get their hands on sterile injectables due to ongoing work at the McPherson facility.
Since then, the coronavirus pandemic has affected the FDA’s ability to inspect plants, according to a recent report from the US Government Accountability Office. In March 2020, the agency suspended non-urgent inspections at home and abroad for reasons of staff safety and has since resumed selected visits to domestic plants.
John Fuson, partner at law firm Crowell & Moring and former associate chief counsel at FDA, said the agency had sent surveys to manufacturers to help prioritize inspections. While Fuson didn’t talk directly about the Pfizer plant, the FDA lacks the resources to conduct all of the inspections.
It is unclear what oversight Pfizer’s McPherson facility had over the past year. In 2020, pharmaceutical company Gilead Sciences signed a multi-year contract with Pfizer to manufacture its remdesivir for the treatment of Coviden at its Kansas plant. Gilead spokesman Arran Attridge wrote in an email that Gilead “evaluates our manufacturing partners’ facilities” to ensure they are compliant.
According to FDA public records, FDA inspectors visited the McPherson plant annually prior to the pandemic. Depending on the inspection, the system was rated VAI (voluntary measures specified) or OAI (official measures specified). John Godshalk, a former FDA investigator who worked on vaccines, said a VAI was one of the most commonly reported inspection ratings. That means the FDA “trusts the company to correct the observations made during the inspections,” he said.
The FDA awarded Pfizer’s McPherson facility a VAI rating in January 2020 – and company executives were so pleased they reported in their third quarter financial filing that the agency had “upgraded” the facility.
Prior to January 2020, according to FDA reports, the McPherson plant appears to have been operating with the stricter OAI rating since its inspection in 2018. Former FDA investigator Godshalk said an OAI was bringing this to the company’s attention. It’s “what you don’t want as a company,” he said.
Pfizer employs around 1,500 people and contractors at the McPherson plant. Kasi Morales, general manager of McPherson Industrial Development Co., said the facility is the largest employer in the industrial city, about an hour north of Wichita, Kansas and not far from Interstate 70, a major east-west thoroughfare across the country .
The 2020 inspection report that resulted in McPherson’s “improved” rating made repeated observations where quality control procedures were not completely “contaminated” with mold and bacteria on surfaces due to moisture and cleaning practices.
No contamination was found in the drugs themselves during the inspection. However, investigators described that operators “bend over and talk about sterilized items that are being unpacked”.
In particular, the 2020 inspection report states early on that Pfizer has made “significant management changes” since the previous inspection in 2018. This final inspection lasted three weeks from December 2019 to January 2020 and the inspectors wrote, “Management was cooperative and no rejections were found. ”
Christopher Smith, Vice President of Quality Operations for Sterile Injectables for Pfizer in the United States and the European Union, was a regular at the McPherson facility during the visit. In the end, he expressed “dissatisfaction” with several of the observations made by investigators in 2020 and “repeatedly sought clarifications”.
KHN (Kaiser Health News) is a national newsroom that produces extensive journalism on health issues. Alongside Policy Analysis and Polling, KHN is one of the three most important operational programs of the KFF (Kaiser Family Foundation). KFF is a foundation that provides health information to the nation.
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