Moderna, a bio/pharmaceutical company developing messenger RNA (mRNA) therapeutics and vaccines, and Takeda plan to recall three lots of Moderna’s COVID-19 vaccine in Japan due to the presence of foreign particulates observed in unused vials of one lot. The particulates were determined to be stainless-steel containments from a production line of Rovi Pharma Industrial Services, a Madrid, Spain-based CDMO of the vaccine.

Moderna and Takeda, the authorized distributor and marketing authorization holder of the vaccine in Japan, issued a joint statement on September 1, 2021 to provide an update of their investigation. The companies had earlier suspended the use of three lots of the vaccine following reports from vaccination sites of a potential foreign particulate substance observed in unused vials from one lot, Lot 3004667. Following an investigation, Takeda and Moderna report that Takeda is planning to initiate the recall of the three suspended lots (Lots 3004667, 3004734, and 3004956) from the market as of September 2, 2021, in consultation with Japan’s Ministry of Health, Labor and Welfare and Osaka Prefecture. Moderna as the global marketing authorization holder said it is in full agreement with this decision.

The investigation centered on three main areas: (1) identification of the root cause of the particles and the corrective and preventive actions being taken; (2) an assessment of the nature of a particle from one vial from Lot 3004667; and (3) an associated medical safety assessment to determine if the identified particle poses a health or safety risk.

According to the root cause analysis report, conducted by Rovi, the most probable cause of the particulates identified in lot 3004667 is related to friction between two pieces of metal installed in the stoppering module of the production line due to an incorrect set-up. The two pieces are the star-wheel and the stoppers feeding device piece, which feeds stoppers into the star-wheel. It is believed that this condition occurred during the assembling of the line prior to production of batch 3004667 and was a result of improper alignment during a line changeover before starting this batch.

Based on the analysis conducted by Rovi, the manufacturing issue only impacted the lots that were included in the suspension. The following steps have been taken by Rovi to correct and prevent future defects: (1) full inspection of the manufacturing line; (2) improving standard operating procedure for changeover of the manufacturing line; and (3) setting alert inspection limits in the automatic visual inspection as an internal process control.

According to Moderna’s independent analysis, the particle from lot 3004667 is confirmed to be Grade 316 stainless steel. Grade 316 is a high grade of stainless steel commonly used in manufacturing and in food processing.

Moderna and Takeda also conducted an investigation into the deaths of two individuals in Japan who both recently received Moderna’s COVID-19 vaccine. After a health assessment conducted by Moderna and Takeda, the companies say the rare presence of stainless-steel particles in Moderna’s COVID-19 vaccine does not pose an undue risk to patient safety and it does not adversely affect the benefit/risk profile of the product.  

The companies report (as reported on September 1, 2021) that there is no evidence that the two deaths following administration of Moderna’s COVID-19 vaccine (from lot 3004734) were related to the ministration of the vaccine. “The relationship is currently considered to be coincidental,” Moderna and Takeda said in their September 1, 2021 joint statement, “It is important to conclude a formal investigation to confirm this. The investigation is being conducted with the greatest sense of urgency, transparency and integrity and is of the highest priority.”

Source: Moderna (September 1^st joint statement), Moderna (August 28^th joint statement), Takeda (September 1^st joint statement), Takeda (August 28^th joint statement), and Rovi