Ex-FDA vaccine inspectors call for better training

The former inspectors said they do not know of any instances in which Team Biologics accidentally missed a contamination of a vaccine or failed to report a manufacturing issue. However, they said they are concerned about inspectors misidentifying a problem or overlooking a serious issue if more rigorous training is not reinstated and experienced inspectors are not brought on to the team.

The FDA is already dealing with the fallout of an infant formula crisis after a Michigan manufacturing plant reported that Cronobacter bacteria had come into contact with plant equipment, contaminating the product. That exacerbated a national formula shortage. Many of the themes discussed in a recent FDA report about the baby formula crisis mirror the current problems on Team Biologics, the former inspectors said. One of the agency’s main admissions: The food division is understaffed and its inspectors lack adequate training.

Audra Harrison, a spokesperson for the FDA, said the inspectors on Team Biologics are “highly trained professionals” who produce thorough assessments of each facility during inspection.

“The FDA’s highest priority is protecting public health and, as an agency, that commitment is firm in the best of times or when facing a global pandemic,” Harrison said. “The American public can and should be confident that they remain our foremost concern.”

Two of the ex-inspectors left the agency in the last nine months and worked at the agency for more than 15 years. All were granted anonymity because they feared retribution from their former agency.

Inspections of many of the products overseen by Team Biologics require extensive understanding of how different specialized biological drug products are manufactured, packaged and stored, the former inspectors said. The team has led some of the most high-profile vaccine inspections during the pandemic, including a series of inspections at Emergent Biosolutions, the vaccine maker that accidentally botched 15 million Johnson & Johnson doses because of contamination.

However, close to half of the inspectors on the team have not received the training that they need to identify missteps or abnormalities in manufacturing when visiting facilities — a critical step in ensuring the products are safe for use once released to the market, the former inspectors said.

“The very reason Team Biologics was formed the way it was formed is because the substance is very complex and we wanted people who were hyper-specialized, and if they needed to get additional training, you would train this cadre and keep them up to speed,” said John Taylor, a former senior FDA official.

Taylor said he is aware of concerns about training among inspectors throughout the agency — not just on Team Biologics. “If training is diminishing and or the experience level of the people joining is diminishing then I can see that being a problem,” he said.

The year before Covid emerged, Team Biologics carried out, on average, about 75 inspections a year, one of the former inspectors said. When the pandemic hit, on-site inspections were significantly reduced and the backlog grew, as the team worked hard to complete in-person inspections for all the Covid-19 vaccines being produced in the United States.

But even as the urgency of the office’s work increased — with all Americans eligible for Covid-19 vaccinations — it suffered from a continued loss of veteran inspectors.

At least nine inspectors have left Team Biologics in recent years in part because the lack of training for new hires forced more veteran inspectors — inspectors who were required to pass rigorous classes when they started the job — to take on additional work, the former inspectors said. Others left because of disagreements with supervisors — almost all of whom did not have backgrounds in dealing with the procuts the inspectors on Team Biologics are required to oversee, according to the former inspectors.

Team Biologics normally has between 13 and 16 inspectors. But it has struggled to bring on new staff with prior experience working with biological drug products, the former inspectors said. Some of the newer team members joined the team after the FDA launched an internal reorganization in 2017. The reorganization paired the vaccine inspectors with those that specialized in blood and tissue products, meaning that some people who had little or no prior experience working with biological drug products started going on inspections of those manufacturing facilities.

The new hires did not receive the same kinds of intensive, in-person classroom training that inspectors hired earlier had received, focused on the biological drug products or how the products are made, the former inspectors said.

Harrison did not offer details on the number of courses or specific kind of training the FDA requires its inspectors to attend. She said inspectors who join the team “receive training on how to conduct inspections at vaccine facilities.”

Harrison acknowledged the agency’s need to build out its inspection staff and said it is pushing to expand the educational opportunities it offers its employees. The FDA is asking Congress for more than $23 million for its inspections program to help address the postponed surveillance inspections — a backlog that grew during Covid — and maintain staff.

“FDA investigators have been critical to the nation’s response to COVID-19, ensuring FDA-regulated Covid-19 products are able to be used to save American lives,” Harrison said in a statement. “Staff turnover in public health is high and the FDA is not immune to these conditions, particularly the biologics staff who have been working on two public health emergencies while keeping the normal cadence of agency business moving forward.”

The former inspectors said the unspecified promise of additional training while blaming the pandemic for staff turnover carries a familiar echo.

“They keep promising that they will be trained, they will be trained. But it never happens,” the first former inspector, who recently left the agency, said.

The second former inspector who recently left the agency put it this way: “What our directors are doing now — they’re just like, ‘we’ll create our own training’ — which they haven’t been able to do for five years — and ‘we’ll figure it out from there.’ This is all while inspections are actively going on.”

Several of the complaints raised by former staff, including mismanagement by supervisors, were reflected in part in a 2019 whistleblower complaint first reported by Vanity Fair. The complaint detailed a scenario in which an inspector, Arie Menachem, flagged unsafe practices at a Merck manufacturing facility only to have his supervisor downplay his findings.

But the training issues described by the former inspectors are far more extensive than previously understood and have persisted, according to the former inspectors.

The former inspectors said they participated in more than a dozen training courses during their time at the agency. Some of those classes lasted weeks and required inspectors attend in-person instructional courses with industry representatives on how to inspect, manufacture and test specialized products overseen by the team.

The current inspection staff did not attend the same training courses as their veteran colleagues. The newer hires completed virtual video tutorials on basic inspection rules and procedures, the former inspectors said. Now, about half of the inspectors do not have any background in inspecting biological drug products and they are often forced to learn on the job, the former inspectors said.

“Now, they’ve just moved some of these people over, like ‘Oh, you do blood inspections, you can just come over and start doing drug [and vaccine] inspections,’ which is ridiculous,” the second of the former inspectors said. “That institutional knowledge of the manufacturing process is important.”

Executives in the pharmaceutical industry — including those that work in vaccine facilities — have begun to pick up on the lack of training, according to a person familiar with the matter who has worked with several high-profile vaccine manufacturers.

“They used to be feared in industry,” the person said of Team Biologics. “But recently it’s been clear that the training isn’t there. The inspectors make observations on what the operator does — if they move too fast or don’t sanitize their hands in the right way. It is important that the inspector is experienced and knows what to look for. The inspector who doesn’t know couldn’t catch a problem or could question a perfectly good practice.”

A serious mission

Congress founded Team Biologics in 1997 to help oversee inspections of biological drug manufacturers. The FDA at the same time created the Center for Biologics Evaluation and Research, a separate office that oversees pre-approval and pre-license investigations of the same products.

“Team Biologics … promote[s] and protect[s] the public health through coordinated, integrated assessments of the compliance status of biological drug manufacturers,” according to the FDA website.

The team began oversight of the industry manufacturing, processing and distributing of products like allergenics, vaccines, therapeutic drugs as well as in vitro diagnostic products. The team started taking on inspections of placental and umbilical cord blood products later in 2010 and gene and cell therapy several years after that.

Many of the products overseen by Team Biologics are manufactured using aseptic processing, a specific system that produces sterile injectable products.

“It is important to become thoroughly familiar with each step in the process, before attempting to evaluate the system for compliance,” a section of the FDA’s website on inspections says.

But the former inspectors say the managers of Team Biologics haven’t provided newer inspectors with rigorous training opportunities that educate them on how aseptic processing works and how to ensure everything from the equipment to the manufacturing is sound.

Harrison pushed back on that claim, saying some of the courses offered to Team Biologics inspectors focus on biological drugs, sterilization and aseptic processing. She did not provide details of how long those courses lasted or whether they were conducted in person.

When the FDA hired people onto Team Biologics during the early years after its formation, inspectors were required to go through a series of training programs, including training that educated inspectors about aseptic processing. Those programs also included sessions on the freezing of vaccine product, the fermentation process, medical device training as well as special classes on products overseen by the team.

“[Some of] the newer hires have … not even attended basic drug school,” the second former inspector said, adding that they had also not completed nearly as many hours of rigorous training as those who were hired after Team Biologics formed.

The first former inspector said they participated in one training course that lasted three weeks.

“It was intense. And you had to pass things by 90 percent or so. If you didn’t, you had to retake,” the former inspector said. “Then every year thereafter we had to go to headquarters where we were retrained on whatever is new. But that has not happened for more than 10 years.”

Harrison did not answer questions about exactly how many inspectors who have joined Team Biologics since 2020 have prior experience inspecting facilities that produce drug products. She also did not answer questions about how many people had experience inspecting vaccine facilities before joining the team.

A Merger

Team Biologics merged with another team— one that focused on unlicensed blood and tissue products — after the FDA moved in 2017 to reorganize parts of the agency, the inspectors said. The reorganization came to be known internally as “program alignment.” The move attempted to streamline processes, including inspections, within the FDA. But former inspectors said it complicated the work because their new supervisors did not have experience working in complex biological drug inspections.

In the years that followed, a new set of inspectors — both from the previous unlicensed blood and tissue product investigative team as well as new hires — did not have the experience necessary for inspecting biological drug products, the former inspectors said.

“Blood, along with the other biologics — they are life-sustaining products. It requires complex manufacturing. The risk profile of not doing it well is profound,” Taylor, the former FDA official, said. “You want people who are really well versed in the science and issue spotting so they can identify these issues quickly … and steps can be taken to address the problem.”

The newer staff were also never enrolled in the same training programs as their veteran colleagues had completed, making it difficult for them to actively participate in inspections outside of completing basic, administrative tasks, one of the former inspectors said.

One of the former inspectors said the current inspectors plunge into the job having only watched online instructional videos, most of which focused on how to wear proper inspection gear and how to clean manufacturing areas. Some of the videos also included details on how to conduct visual inspections of facilities. The current inspectors learn primarily on the job, the former inspector said.

“Not only were we supposed to cover and do the inspections, we were supposed to train them [ourselves],” the second former inspector said of needing to help educate newer inspectors.

The former inspectors who spoke to POLITICO also shadowed their colleagues on the job when they first started. The one main difference: They were required to pass through intensive training programs — mostly in person — that gave them specific knowledge of the products they were required to oversee. Some of those trainings were held in conjunction with CBER, the former inspectors said.

Over the last several years, particularly since the pandemic began, the newer hires on Team Biologics have, on average, issued fewer Form 483s — documents that lay out specific findings during inspections such as instances where manufacturing staff improperly handled drug substances or a facility having unsanitary equipment, the former inspectors said.

The number of inspections that occurred during the pandemic dropped off — a fact that could explain the lower rates of issuing 483s. But the former inspectors said the lower rates are also reflective of a far more serious and systematic issue on the team — that the inspectors may not know what to look for while on inspections. Harrison did not answer questions about how many 483s have been filed by the newer hires on Team Biologics.

The FDA realignment in 2017 also paired inspectors who had been accustomed to working on inspections of manufacturers who used extremely technical, often difficult-to-master production concepts for products like vaccines, with supervisors who have never worked on biological drug inspections, the former inspectors said.

Harrison did not answer questions about whether the supervisors of Team Biologics have experience inspecting facilities that produce the products the team is responsible for overseeing.

“[They] … have a scientific educational background coupled with experience in inspectional techniques,” Harrison said.

In his whistleblower report, former inspector Menachem called out his managers who decided to issue a less serious finding than he had suggested following his inspection at Merck in 2018 where he found the company was destroying evidence of possible violations, according to his whistleblower letter obtained by POLITICO. In the letter, he also said his managers declined his request for additional staff to help him with the inspection.

U.S. Special Counsel Henry Kerner wrote about Menachem’s whistleblower complaint in a letter to President Joe Biden in March 2021, confirming that the downgrading of the finding compromised “compliance and safety efforts,” according to the letter.

Menachem left the FDA in 2019. Since then, others have left Team Biologics, some to join the private sector where salaries are significantly higher than those offered at the FDA. In recent weeks, one of the supervisors on Team Biologics announced their departure.

The FDA regularly publishes stats on its inspection backlog and has made progress this year, in part because in some instances, inspectors are conducting remote assessments and because many of the restrictions on in-person inspections imposed during the pandemic have been lifted.