Warning Letter January 20, 2011
Baxter Healthcare Puerto Rico
1. The Jayuya Facility (Puerto Rico)
A. CGMP Violations
2. Your firm failed to ensure your container closure system provided adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the drug product [21 C.F.R. § 211.94(b)].
For example, your firm identified 542 incidences through consumer complaints of product defects such as, leaks, bursts, and premature activation during the period of January 2008 to August 2010. These are critical defects that can impact sterility and stability of your product. Your firm identified that the probable cause was the result of defective materials used in the manufacture of the container closure system.
Your response is not adequate since the sampling plans described are not based on appropriate statistical criteria to sufficiently identify these known potential defects, especially given the history of the supplier for this container closure system.
To receive that number of complaints within a thirty one month period is disconcerting when one considers that most people do not complain. If one assumes a ten percent complaint rate, then the “true” number of complaints is almost 5,425. If one assumes a three percent complaint rate, then the “true” number is closer to 18,000. The FDA suggests that the sampling plans as described in the Warning Letter “are not based on appropriate statistical criteria”. The reader, from the FDA Warning Letter, cannot determine the AQL of the sampling plan, but must wonder, again based on the types of problems occurring if a redesign of the container closure system should be initiated and not only include the use of defective materials.