Emergent FDA 483 from April 2020

Earlier in the week after reading the New York Times reports “U.S. Bet Big on Covid Vaccine Manufacturer Even as Problems Mounted” I commented that “This is a pretty damning report. Especially to the FDA for a failure of their inspection program if even half of it is true.”

Today John English pointed out the April 2020 FDA 483 for the Baltimore site of Emergent. And it is a doozy in six pages. Thank you FOIA.

Observation 1: Appropriate controls are not exercised over computers or related systems to assure that changes in master production and control records or other records are instituted only by authorized personnel

This one is a real bellwether to me. The failure of the quality unit to ensure a robust computer system validation program was in place, to ensure data integrity. The fact that the three parts to the observation run the gamut from infrastructure to implementation to on-going use stands out that there are significant weaknesses in data integrity as an approach.

Observation 2: Established specifications, test procedures and laboratory control mechanisms are not followed and documented at the time of performance.

Well, forget about contemporaneous. Significant data integrity and culture failure here.

Part (b) indicates a failure to manage and track lab errors.

Also some concerns on chain of custody of samples are raised.

Observation 3: The responsibilities and procedures applicable to the quality control unit are not in writing and fully followed.

This observation raises some significant questions in how they manage OOS investigations.

Observation 4: Employees are not given training in the particular operations they perform as part of their function and current good manufacturing practices

Build training plans, execute training plans, document training.

Observation 5: Separate or defined areas to prevent contamination or mix-ups are deficient regarding operations related to the holding of rejected components before disposition

It is like the FDA saw exactly what was going to happen and did nothing to stop it.


This 483 chilled me to the bones reading it. Major failures in quality here. The fact that this was in April of 2020 raises significant concerns in my mind about how Emergent got any contracts for vaccine delivery.

I have written to my congressional representatives demanding hearings. We need to know who made what decisions when. The trust in our regulatory regime requires full transparency and introspection.

Quality Bookshelf – Upton Sinclair

One of the ideas in my mind when I first started this blog almost three years ago was to explore some of the literature that asks the hard questions that reading will make us better quality thinkers. Neuroscience suggests that reading literary fiction helps people develop empathytheory of mind, and critical thinking. All critical to our success.

Unfortunately, other than a sporadic appreciation for Kafka – the source of the name of this blog – I haven’t done a great job at that. So, as an early birthday present to myself I bring you this piece written by Catherine Hamilton.

Upton Sinclair on the Working World and his Accidental Push for a Regulatory State

In 1906, socialist writer and political activist Upton Sinclair published his novel The Jungle, which became an instant bestseller and resulted in a major societal shift towards the modern regulatory environment seen in the US today.

Sinclair’s The Jungle follows the story of an immigrant family, who moved to Chicago in search of a better life, only to be met with poverty, death, and despair, in large part because of the terrible working conditions they endured, and the meagre wages they were afforded.

A novel written to illuminate the inhumane working conditions endured by the proletariat working in industries such as the meatpacking industry, Sinclair hoped that his expose of the unjust treatment of workers – those who would now be described as ‘blue collar’, an evolution of the phrase ‘white collar’ that Sinclair himself coined – would incite Americans to embrace Socialism. Indeed, when peer and fellow socialist writer Jack London received a copy of the novel, he predicted that it would turn “thousands” to socialism as it depicted “what our country really is: the home of oppression and injustice, a nightmare of misery, an inferno of suffering”.

Contrary to his objective, however, the publication of The Jungle lead to public outrage about the unsanitary conditions depicted in the meat production industry – a description that lasted only twelve pages in an over four-hundred-page novel – rather than a commentary on the injustice endured by the working class. As Sinclair himself stated in response to the outrage, “I aimed for the public’s heart, and by accident I hit it in the stomach.” This effect was perhaps understandable when we consider that Sinclair’s readers were faced with graphic images of dead meatpacking workers being ground up into the meat that they believed they were being fed; alongside these horrors, the greedy corrupt leaders – and the exploitation of their workers – that Sinclair was trying to expose, took a back seat in the public consciousness.

As such, rather than a novel – and a commentary on capitalism and the injustice of the inhumane working conditions suffered by the proletariat – the public viewed The Jungle as an expose on the meat industry, perhaps fuelled by the revelation that Sinclair spent seven weeks working undercover at one of these factories as research for the novel. As a result of this unrest, the government was pressured to enact laws to regulate the industry – the primary purpose of which was to appease the public, rather than increase the safety and sanitation around meat production – which culminated in the introduction of The Meat Inspection Act (1906) and the Pure Food and Drug Act (1906).

The former stated that the slaughter and processing of meat would be strictly regulated, and that edible meat products could not be mislabelled or misbranded. Meanwhile, the latter required the inspection of food and drug products, banned interstate and international traffic of adulterated or mislabelled food products, required active ingredients to be listed on the label of a drug’s packaging and stated that drug purity levels could not fall below the purity specified by the US Pharmacopeia/National Formulary.

These laws were the first in a series of consumer safety laws enforced by the state and lead to the founding of the Food and Drug Administration (FDA) – the US organization that regulates consumable products, including food, tobacco, supplements, pharmaceuticals, cosmetics and more, to ensure that these products aren’t harmful (or at least that their benefit outweighs the potential harm) to human (or pet) health. Thus, Sinclair’s novel became one of the most significant cogs in the foundation of the modern regulatory state.

This was not the socialist writer’s intention, however, and Sinclair was strongly against the imposition of these laws, as the only bodies they served at the time were the big meatpacking companies. In fact, large meatpacking corporations welcomed the regulation laws, as they knew that their smaller competitors would be eliminated by the expense of adhering to the regulations. As such, these laws – which can be directly attributed to Sinclair’s novel The Jungle – acted as an agent of capitalism, the exact opposite effect that Sinclair had hoped his novel would have on US society. To add insult to injury, the implementation of these laws also resulted in the taxpayer paying $3 million to bring about their enforcement. As thoughts on health, safety and quality of consumable products has progressed, however, it is likely that the change in public thought about food quality in 1906 – and the subsequent laws enforced – has had a net positive effect on the sanitation and safety of food and drug industries.

As a writer in the progressive era – who wrote to expose corrupt leaders and institutions and to raise public awareness and sentiment towards poverty – Sinclair was considered a ‘muckraker’, seeking to expose the injustice of capitalist society through his writing. Consequently, Sinclair wrote a large body of work charged by these ambitions, though none that had such a marked (and misdirected) effect on US society as The Jungle.

Though The Jungle was Sinclair’s most notable socialist work, Sinclair penned over one hundred books in his lifetime, and many of these sought to criticize capitalism and an array of specific industries. In 1913 and 1914 for example, Sinclair visited the Colorado coal fields, which inspired his novels King Coal and The Coal War and likewise exposed the harsh working conditions suffered by coal miners. Furthermore, he ‘exposed’ the oil industry with the novel Oil! and the auto industry with The Flivver King, though none of these works became commercial successes.

 Moreover, Sinclair stepped outside the world of industry to criticize the ‘free press’ in his novel The Brass Check, highlighting the benefits of the press to the rich and the drawbacks to the poor. In this novel, Sinclair also criticizes the office, describing ‘white collar’ workers – a term Sinclair himself coined – as “the petty underlings of the business world, the poor office clerks, who are often the worst exploited of proletarians, but who, because they are allowed to wear a white collar, and to work in the office with the boss, regard themselves as members of the capitalist class”.

With this quote, Sinclair illustrates his frustration that, due to the ‘white collar’ workers’ perceived elevation of their own status, and the marginally better working conditions they enjoyed – compared to their fathers who may have worked in factories or coal mines – they allowed themselves to be exploited. Describing these workers “petty underlings” he also assigns some of the blame of the propagation of capitalism to these workers, despite his acknowledgement of their exploitation.

Another of Sinclair’s most famous quotes states that “it is difficult to get a man to understand something when his salary depends upon his not understanding it”. Though this statement pertained to discussions Sinclair had with the publishers and editors of major newspapers about publishing articles in favour of pensions and other progressive reforms, it can also be related to his feelings about ‘white collar’ workers. Namely, because these ‘white collar’ workers relied on capitalism to provide their wage – but also because the capitalist class had given them the perception of obtaining a higher class – they would not risk their comparatively comfortable position in the office to seek something more just.

Evidently, then, Sinclair harboured as much contempt for the office – and for the leaders heading these businesses – as he did for the industrial workplace, as an unjust product of capitalist society, an inadequate place of work, and a new avenue with which to oppress the proletariat.

Despite over a century having passed – much to Sinclair’s probable dismay, were he still alive – offices are still the status quo, with over 80% of Americans reported to sit all day at their place of work, the majority of whom will do this in an office or equivalent space. Providing support for Sinclair’s disapproval of the office, multiple studies have shown the harmful effects of office environments on human beings. In 2020, for example, a Perkbox study showed that that work-related office politics were the number one cause of work-related stress, while lack of interdepartmental communications came second, and concerns about others’ work performance came third, which are all stressors bred by the office environment.

Sinclair would likely philosophize that because their salaries depended on these workers not understanding the injustice of working within a capitalist system – harboring a significant proportion of the workload, and enjoying an insignificant slice of the profit – they would not consider a system in which the means of production was shared by the community, and where the rewards were, likewise, shared equally.

Jeremiah’s comments

I love Sinclair for his prose and his politics. He wrote these amazing novels that are still fun to read today. He basically drove the creation of my entire profession. He focused on a lot of the workplace aspects that form such a huge part of my practice. Whether you can agree or not with his socialism, he will greatly reward your time.

And Upton’s work so highlights the woes of unintended consequences.

OOS failures

Go and read the January 2021 FDA warning letter to Allay Pharmaceuticals and then go and read the 1993 decision in United States vs Barr Laboratories.

The Barr decision, issued 28 years ago, explains how to deal with OOS results. The FDA followed up with a guidance in 2006 “Guidance for Industry Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production.” Companies have no excuse for continued failure here, and yet as we see with Allay (and so many others) failures in investigation of out-of-specifications continues to be a major concern. Yet nothing we see is not covered in the Barr decision.

If you a pharmaceutical GMP professional these three documents should be ones you are more than ready to explain against your quality system.

Warning Letter for Aurolife demonstrates failures in process validation

The FDA commented in a Warning Letter to Aurolife Pharma that the manufacturer lacked data showing that the process was in “state of control” before batch release. The 483 pointed to the FDA’s guidance document Process Validation: General Principles and Practices, and found the company lacks a state of control of the process, which comes back to change control.

They also found major deficiencies in their OOS and cleaning programs.