Dear Dr Califf,
This is an open letter in follow-up to a question I have submitted to the FDA’s Center for Biologics Evaluation and Research (CBER). The question is repeated below:
Dear FDA,
My question relates to FDAs release of the Moderna booster vaccine, reported in a Fierce Pharma article dated September 21, 2022, titled:
Moderna’s new booster launch tripped up by production issues at Catalent plant: reports
This is a short excerpt:
On Tuesday night, the FDA released (PDF) a Form 483 notice it had sent to Catalent, citing 12 observations from a lengthy August inspection of its Bloomington, Indiana, site. The massive facility is among the largest in the portfolio of contract manufacturing powerhouse Catalent. Most of the observations had to do with quality control, record keeping and the failure to establish and follow procedures. The FDA noted a failure to address unexplained discrepancies in a batch of drug product (DP).
The detailed findings of highly experienced inspectors, although redacted in parts, paint a picture of deep systemic failure at the Bloomington facility. Each of the 12 observations in the 18 page report demonstrate critical non-compliance with cGMP.
Even more surprisingly, the article reveals that the Bloomington facility had received a previous Form 483 during August 27, 28, 31, September I, 2, 2020, stating:
The first sign of trouble at the Bloomington plant came in September of 2020, when the FDA cited (PDF) the company for a lack of procedures to prevent contamination.
You will no doubt appreciate that contamination of biological products is an instant ‘red flag’, given that these vaccines are ‘sterile injectables’. Contamination renders the products non-sterile, presenting serious risk to patients. Surely, this was an important ‘early warning’ that was missed by the FDA?
At the very least, one would expect the FDA to exercise its powers, such as issuance of a consent decree, to provide greater reassurance that the Form 483 inspection report observations were remediated to FDAs satisfaction. You will remember that FDA deployed a consent decree when Johnson & Johnson’s McNeil failed to remediate quality issues from 2007 – 2011, as detailed by Warren Adis, Hagan School of Business, Iona College, below:
McNeil, a Johnson & Johnson Subsidiary: FDA Case Study.
Finally, my question above ended:
I wish to better understand the decision-making process within the FDA that authorized resumption of production at the Bloomington facility, given the extensive Form 483 issues identified, such as shipping products prior to quality release.
I look forward to your urgent response to my question.
Yours sincerely,
Hedley Rees
Managing Director, PharmaFlow Ltd.