cGMP evidence summary: batch variability, inspection findings, unit-dose testing and serialization

1. cGMP was a contract requirement

The article argues that federal agreements for COVID-19 vaccines required manufacturers to follow cGMP. It points to a July 21, 2020 Pfizer technical direction letter that references 21 CFR Parts 210 and 211, a Moderna contract (No. 75A50120C00034) that lists lot consistency as a deliverable, and a BARDA contract with Protein Sciences, a Sanofi company, covering cGMP seed and virus bank lots.

2. Batch-to-batch variability

Using VAERS, the only public U.S. database that links adverse event reports to lot numbers, the author reports that rates of reported adverse events and deaths differed widely from one batch to another for Pfizer, Moderna and Janssen products. She argues that the spread is larger than would be expected for a product made under cGMP, using seasonal flu vaccines as a comparison. Related TrialSite pieces look at lot size as a possible explanation, differences across U.S. states, and mRNA integrity.

3. Inspection findings at manufacturers

The article notes that under cGMP, a non-compliance finding at a plant applies to all product made there. It cites:

• Catalent, Bloomington, Indiana, described as Moderna's fill-finish contractor. An FDA Form 483 reported visible foreign particles in some batches and a failure to thoroughly investigate unexplained discrepancies.
• Rentschler Biopharma, Laupheim, Germany, described as making mRNA drug substance for Pfizer's Comirnaty. FDA's Form 483, issued February 15, 2022, lists 9 observations, including incompletely validated equipment and systems, discoloration on cleaned equipment with no root cause identified, and a batch released after a deviation and later rejected. The form itself does not name the product involved.
• Emergent BioSolutions, reported to have received an FDA warning letter citing cross-contamination of a viral vaccine drug substance batch and failure to investigate discrepancies.
• Pfizer and the European Medicines Agency. The author says EMA raised a major objection on cGMP compliance in November 2020, by which time she estimates about 28 million doses had been made.

4. No serialization at the unit dose

Multi-dose vials are divided into individual doses by hand at the point of care. The author, drawing on supply chain specialist Hedley Rees, argues that without a barcode or serial number for each dose, individual doses cannot be traced, which leaves room for errors or tampering. She cites a reported case of 77 Iowa prisoners who were given incorrect doses.

5. No testing of each dose against the label

Pfizer's label states 225 mcg per vial and 30 mcg per dose. The author says that, based on leaked EMA manufacturing documents, vials are checked only by filled weight and visual inspection, and that no test confirms the content of each dose. She argues that batch-level testing cannot stand in for unit-dose testing.

6. Independent vial testing

According to the article, supply agreements restrict independent testing of the product. The author says she reviewed dozens of independent tests of vial contents from around the world that reported impurities. She acknowledges that no systematic, peer-reviewed study of these tests exists.

7. What the author asks for

The article calls for the reported cGMP violations to be stopped and investigated. It raises questions about manufacturers' accountability under their contracts, given liability protection under the PREP Act, and about the responsibilities of state health agencies that receive and administer these products.

Reading this evidence

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