Pfizer's management knew last year there was "a mold issue" at the Kansas facility now slated to produce the drugmaker's urgently needed covid-19 vaccine, according to a Food and Drug Administration inspection report.

The McPherson, Kansas, facility, which FDA inspectors wrote is the nation's largest manufacturer of sterile injectable controlled substances, has a long, troubled history. Nearly a decade's worth of FDA inspection reports, recalls and reprimands reviewed by KHN show the facility as a repeat offender. FDA investigators have repeatedly noted in reports that the plant has failed to control quality and contamination or fully investigate after production failures.

The 1970s-era manufacturing site has had persistent mold concerns over the years and been the focus of at least four intense FDA inspections since Pfizer took over its operations in late 2015, when it acquired Hospira. At the end of the January 2020 inspection, FDA investigators appeared to be growing frustrated.

Pfizer's plant managers told investigators they knew they had either bacteria or mold throughout the facility at various times of the year. In a Jan. 17, 2020, establishment inspection report obtained by KHN, one of three FDA experts who visited wrote that Pfizer said it addressed problems and added "more cleaning activities in response to mold" after a 2018 inspection and "yet, there are still unexplained discrepancies."

After the January 2020 inspection report, Pfizer immediately developed and put in place a corrective action plan, company spokesperson Eamonn Nolan told KHN. Neither Pfizer nor the FDA responded to requests to provide a copy of the plan.

Nolan, in an email last week, said "significant investments have been made" in resources, equipment and the facility. He stated all improvements related to covid 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 operating in a state of good manufacturing, which means it has met a regulatory standard enforced by the FDA.

"We are confident in the McPherson site's ability to manufacture high-quality COVID-19 vaccine," he wrote.

Large clinical trials have found Pfizer's vaccine to be safe and 95% effective against covid.  

News that the plant will be a fill-and-finish site for the Pfizer-BioNTech covid vaccine means more watchful eyes focused on the facility. "That alone should be helpful," said Barbara Unger, a former pharmaceutical industry executive who now does manufacturing audits for companies.

It is unclear whether FDA investigators have returned to check on production practices in McPherson or plan to visit before vaccine production begins. The FDA did not respond to specific questions. FDA spokesperson Abigail Capobianco wrote in an email that the public "can be assured that the agency used all available tools and information to assess compliance."

Pfizer's emergency use authorization letter for its mRNA vaccine includes safeguards, such as quarterly reports to the FDA and a quality analysis from the company for each manufactured drug lot at least 48 hours before it is distributed.

The plant's manufacturing issues can be traced in FDA reports dated from 2011 to last year. Several former FDA staffers and industry experts said the ongoing challenges in McPherson highlight how agency officials must balance aggressively going after a company's manufacturing practices with the need to keep the supply of medications flowing to patients.

"I do not envy the FDA choices," Unger said, describing a balancing act. "Which has the more significant public health risk?"

The site produces a wide array of sterile, generic medications used in hospitals, and its troubles have played a role in some big health system shortages, specifically for injectable opioid analgesics, according to a 2018 FDA statement.

The FDA rejected Pfizer's biosimilar version of Amgen's anemia drug Epogen because of concerns about the fill/finish plant in 2017. The same year, John Young, who was a group president at Pfizer, told investors the company had submitted a "corrective and preventative action plan" for the facility.

That is the same language used after the January 2020 inspection, which said there were contamination concerns for the site but not in the medicines. And it was Young, now Pfizer's chief business officer, who last month told Congress that Pfizer had added production lines at the McPherson site to help meet covid-19 vaccine demands.

The facility's record of recalls and field alerts include vials of medication that contained glass and cardboard particles and, as one customer complained, a "small insect or speck of dust."

A 2017 FDA warning letter — which is a strong rebuke for the agency — said the contaminants such as cardboard and glass found in vials posed a "severe risk of harm to patients" and indicated that the facility's process for manufacturing sterile injectable products was "out of control."

FDA records show that multiple batches of vancomycin hydrochloride, a drug injected into hospital patients who have an infection that penicillin won't treat, were recalled in 2016 and 2017.

John Avellanet, an FDA compliance expert and principal at Cerulean Associates, reviewed the 2020 inspection reports. He said he fears the fixes have been little but "window dressing."

"They may have solved it in one instance, like the cardboard particles. But for some reason, they were never able to solve the contamination," Avellanet said. "Whatever they are doing for quality control testing doesn't appear to be working, because if it was working they wouldn't continue to have these contamination problems."

Pfizer shut down McPherson's manufacturing in December 2017 even though the FDA had visited two months earlier and improved the facility's inspection rating. McPherson's management suspended production and rejected batches of finished products after finding mold on equipment in a filling area, according to an FDA inspection report. The facility returned to production weeks later.

When the FDA came back to inspect in late summer 2018, it found that procedures to prevent microbiological contamination of drugs were lacking. It also noted a lack of employee training, employees not following procedures, obstructed surfaces and in-house testing that did not guarantee drugs met standards.

In 2019, when CEO Albert Bourla took the helm at Pfizer, he told analysts it would be another hard year for U.S. hospitals to get their hands on sterile injectables because of ongoing work at the McPherson plant.

Since then, the coronavirus pandemic has taken a toll on the FDA's ability to inspect plants, according to a recent report from the U.S. Government Accountability Office. The agency halted non-urgent foreign and domestic inspections in March 2020 out of concerns for staff safety and has since resumed select visits to domestic plants.

John Fuson, a partner at the law firm Crowell & Moring and former associate chief counsel at the FDA, said the agency has sent surveys to manufacturers to help it prioritize inspections. While not speaking directly about the Pfizer plant, Fuson said the FDA lacks the resources to do all the inspections "we might like it to do."

It is unclear what oversight Pfizer's McPherson facility has had in the past year. In 2020, the pharmaceutical company Gilead Sciences signed a multiyear agreement with Pfizer to produce its covid treatment remdesivir in the Kansas plant. Gilead spokesperson Arran Attridge wrote in an email that Gilead "evaluates our manufacturing partners' facilities" to make sure they follow regulations.

FDA inspectors visited the McPherson plant annually before the pandemic, according to public FDA records. The plant was given ratings of VAI, or voluntary action indicated, or OAI, official action indicated, depending on the inspection. John Godshalk, a former FDA investigator who worked on vaccines, said a VAI is one of the most common inspection ratings given. That means the FDA is "trusting the company to fix" the observations made during the inspections, he said.

The FDA assigned 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 plant.

Before January 2020, the McPherson plant appears to have been operating with the more severe OAI rating since its 2018 inspection, according to FDA reports. Former FDA investigator Godshalk said an OAI puts the company on notice. It's "what you don't want as a company," he said.

Pfizer employs about 1,500 people at the McPherson plant, plus contractors. Kasi Morales, executive director of McPherson Industrial Development Co., said the facility is the largest employer in the industrial town 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 led to McPherson's "upgraded" rating listed repeat observations that involved quality control procedures not being fully followed and "contamination" with mold and bacteria on surfaces because of humidity and cleaning practices.

No contamination was found in the medications themselves during the inspection, but investigators described seeing operators "leaning over and talking over sterilized items being unwrapped."

Notably, the 2020 inspection report states early on that Pfizer had made "significant management changes" since the previous inspection in 2018. That latest inspection spanned three weeks from December 2019 to January 2020 and inspectors wrote "management was cooperative and no refusals were encountered."

Christopher Smith, vice president of quality operations for Pfizer's U.S. and European Union sterile injectables, was at the McPherson facility periodically during the visit. In the end, he "expressed discontent" with several of the 2020 observations made by investigators and "repeatedly sought clarifications."

This article was reprinted from khn.org with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a nonpartisan health care policy research organization unaffiliated with Kaiser Permanente.