From The Editor | September 23, 2022

FDA, CDMOs, And COVID: How To Talk About 483s


By Louis Garguilo, Chief Editor, Outsourced Pharma


As project Warp Speed and the mass production/distribution of COVID-19 vaccines was under way during the pandemic, many people around the world heard about drug contract development and manufacturing organizations – CDMOs – for the first time.

It was a surprising (Pharma doesn’t manufacture everything themselves?) and positive (We couldn’t produce the vaccines needed without these CDMOs!) first impression.

Nothing, though, proceeds perfectly, on the ground nor in the realm of public perception.

News began to circulate the FDA was halting production at a certain CDMO because of potential quality issues at the facility where it was attempting to produce one of the new vaccines.

Now, the public was reading about “483s” and FDA inspections. The FDA issued this letter of April 2021:

“During an inspection … the FDA cited a number of observations concerning whether the facility’s processes met our requirements and standards. These observations are outlined in our inspection closeout report, also known as an FDA Form 483 … The FDA’s observations are intended to identify certain conditions observed during an inspection that have the potential to lead to quality issues during the manufacturing of a product. Once we observe such conditions, we can then work with a company to help identify a path forward to remedy the issues.”

What happened next exploded onto the news networks. I covered this in the editorial, Did The U.S. Government Just Hijack A CDMO? In short, the answer was no, but the facility in question was “ordered” to stop processing the vaccine it had been contracted to produce. Suddenly, the CDMO limelight was changing hues.

Why recall these events? Because there’s news of another CDMO producing vaccine having received 483s after an FDA inspection.

Taken from another FDA letter:

“On August 31, 2022, the Agency amended the emergency use authorization (EUA) of the Moderna COVID-19 Vaccine … Due to an ongoing FDA inspection [a Catalent] facility was not included in the amended EUA. Specifically, because of the ongoing inspection, the Agency was unable to assess the adequacy of the manufacturing process at that time. FDA intends to further consider the inclusion of the Catalent facility in the Moderna COVID-19 Vaccine EUA following completion of its review of the inspectional information and any other pertinent information.”

That was followed with a communication in September by the FDA directly to Catalent.

“Based on our review of the available data and information, we have determined that the following Moderna COVID-19 Vaccine, Bivalent, batches manufactured at Catalent Indiana LLC (Catalent), Bloomington, IN, are suitable for use and meet the EUA standard, which is outlined in your Letter of Authorization … FDA intends to further consider the inclusion of the Catalent manufacturing facility following completion of its review of the inspectional information and any other pertinent information.”

So how is this latest event being portrayed to the public? To find out, I surveyed a swath of our national media coverage, and herein present a representative example from a well-known news organization for discussion.

Balanced, But …

We’ll focus on an article in the ( “inside the Beltway” absorbed) Washington Post.

While the president and implications for the Biden administration’s policies were a predictable focus, the article was well balanced. (Although as routine, the paper used unnamed sources.) The headline and sub-headline were:

FDA releasing millions of Moderna boosters as states warn of shortages; Reconfigured shots are safe but had been delayed amid inspection of Indiana packaging plant last month.”

From the article:

“[FDA] Inspectors last month began raising concerns that the facility was not sufficiently sterile and started checking whether vials packaged there might have been contaminated, as part of routine safety reviews, said people with knowledge of the inspection. FDA inspectors concluded that there were no problems with Moderna’s vaccine, and the agency is set to soon release more than 10 million doses that had been held back.”

A statement by FDA spokesperson Michael Felberbaum was included. “This authorization was based on FDA’s determination that the batches met all applicable specifications, following a careful review of information provided by Moderna about the manufacture of these batches. The agency has no concerns with the safety, effectiveness, or quality of these batches.”

The paper quoted Moderna as “working closely” with the government, and Catalent spokesperson Chris Ridley said, “We anticipate that these availability constraints will be resolved in the coming days.”

So far, so fair. But then this sentence towards the end of the article:

“The FDA inspection was another wrench in the vaccine production process, an issue that occurs with some frequency in the pharmaceutical industry.” (Italics mine.)

Which leads us back to 483s and our safety record.

Talk About 483s?

First of all, it appears we have no choice but to deal in a more public way with Form 483s and the citations listed within them.

Perhaps contrary to popular belief – I was one of those contrarians for years – we can view this rather positively.

But only if we push back on inaccurate generalizations such as above. If the Post is insinuating poor quality affecting the manufacture of our drugs, therapies and vaccines is a commonality, they are widely off base. We as an industry need to point that out.

Public opinion of the pharma industry was elevated by the efforts demonstrated during the COVID pandemic. Let’s build on that to develop ways to insert into the discussion the realities of the great difficulty of developing and manufacturing drugs, the highest standards of quality overwhelming met, and the (typically swift) measures taken when, rarely, they are not.

Bloomberg, an organization I might expect worse from, took the space to add this background to a recent article:

“Moderna tapped Catalent in June 2020 to fill and package its Covid vaccine at the Bloomington site. The companies said in April 2021 that Catalent would dedicate a new high-speed filling line at the factory to Moderna for its vaccine and any other potential products in its pipeline through June 2023. Catalent said in September 2020 it would invest $50 million to build the high-speed filling line ...”

We need to continue to talk more broadly about our manufacturing partnerships, the innovation and investments required, and yes, the spectacular quality required and achieved to produce a vaccine for a virus such as COVID.

When the FDA does its job, and feels it must issue 483s, let’s put that into context, and educate the public on the rigors of drug development and manufacturing. And support our CDMOs as well.