WHO published a Notice of Concern regarding a Cadila vaccine manufacturing site in Moraiya, India. This was based on the outcome of an inspection ending October 30, 2015. Deficiencies include those in the area of data integrity. The Notice of Concern (NOC) is dated January 29, 2016 but was only recently posted on the WHO website. The NOC includes the CAPAs proposed by the firm and their timeline. Deficiencies include but are not limited to:
- ‘Data Integrity issues in form of apparent fraudulent data were witnessed during the inspection’ and three examples are provided of findings of such in the microbiology laboratory. From the failures in environmental monitoring, the firm concluded that the HPEA filters in the filling and lyo areas failed filter integrity tests.
- Sterility failures were not reported, investigated or reported to investigators.
- The Annual Product Review did not include all aspects of manufacture that it should, including: manufacturing process up to the formulated bulk stage; manufacture of the diluent; use of non-validated Excel spreadsheets for trending; and reviews of Quality Agreements and CAPAs.
- The firm has no management review process.
- Change controls do not consider effectiveness verifications nor is the risk to product quality or patient safety assessed.
- Deviations are not categorized as to their potential risk.
- Vendor oversight is inadequate and audit frequency should be revised. The audit frequency should be based on a risk evaluation. The audit checklist is not a controlled document and is completed by the vendor rather than the Cadila auditors.
- Facility design and operation was not adequate to ensure adequate segregation of operations and minimize the potential for cross contamination. WHO investigators provide eleven (11) specific examples.
- Environmental monitoring is inadequate, seven (7) specific examples are provided.
- The firm has no procedure for media fill simulation or media bulk simulation (I assume that means the drug substance production of the vaccine).
- The sterilizing filtration process for the excipients human serum albumin and gelatin solutions is not validated.
In response to the inspection and its findings, Cadila Healthcare suspended manufacture of Lyssavac N – Purified Duck Embryo Rabies Vaccine and their intention to withdraw the application for prequalification of Vaxi-Rab N vaccine. In addition, they provided a list of products for which they are implementing a voluntary recall action. This included 64 final bulks / finished batches of the no-prequalified VaxiRab N vaccine and the prequalified Lyssavac N vaccines that were released for shipment.
Cadila Healthcare Limited and Cadila Pharmaceuticals received warning letters from FDA in June, 2011, February, 2015 and December, 2015. A collection of forms 483 from Cadila Healthcare are available for purchase at the FDAzilla.com STORE.