GMP mistakes are costly

In the continual saga of companies making fundamental GMP mistakes, Gilead has recalled two lots of its coronavirus treatment drug Remdesivir because of the “presence of glass particulates.”

If only there existed international standards on visual inspection and there were a solid set of best practices on lyophilization.

Oh, wait there are.

But then Gilead has a multi-year track record in deficiencies in their testing and manufacturing processes. In all fairness, they are contracting manufacturing to Pfizer’s McPherson site…..oh wait that site got an FDA 483 in 2018 specifying significant violations of good manufacturing practices, such as an inadequate investigation into the detected presence of cardboard in vial samples.

We deserve better manufacturers. Companies need to take the quality of their products seriously. We are always improving or we are always one step away from the sort of press Gilead gets.

Critical ATMP Deficiencies

ERC The Netherlands B.V. received thirteen deficiencies from a recent inspection, one of which was classified as a critical deficiency.


These were mainly related to five main components:

  • Quality and safety of starting materials. Inspection of chemicals and consumables is insufficient.
  • The quality and safety of the final product is not guaranteed. The product is not sufficiently defined and characterized.
  • The effectiveness of a gama irradiation step, and therefore the safety of the product, is not guaranteed.
  • The change for the transition from Contractor 1 to Contractor 2 for gamma irradiation of cells has not been carried out as referred to in the GMP for ATMPs.
  • Prevention of (cross) contamination is not sufficiently guaranteed. 
  • The environmental monitoring program and personnel monitoring are inadequate.

Reviewing this together with Emergent’s 483 (and resulting actions) starts to define a set of concerns in the ATMP world.

Latest Emergent News

Today Janet Woodcock issued a statement “FDA Continues Important Steps to Ensure Quality, Safety and Effectiveness of Authorized COVID-19 Vaccines” which links to the April 2021 Form 483 of the Baltimore facility.

  • Failures to investigate deviations
  • Failures for material management
  • Failures for gowning
  • Failures of the cleaning program
  • Failures in facility design
  • All around failure for contamination control
  • Failure to have a comprehensive training program

I have requested hearings from my congressional representatives. The path where Emergent received so much money from the federal government to lead to this place is frightening.

Emergent suspends manufacturing in Baltimore

“We recognize the confusion these recent events may have caused our customers, our employees, and the public,” Emergent said in its statement. “We acknowledge that there are improvements we must make … to restore confidence in our quality systems and manufacturing processes.”

FiercePharma “FDA orders shutdown at Emergent’s troubled plant 2 weeks after handing J&J the keys” April 19, 2021

What you never want to see in the press.

Emergent needs to overcompensate to restore confidence here and hopefully are bringing in the resources on the level of consent decree mitigation.

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.

Thoughts

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.