US Food and Drug Administration (FDA) inspectors found Warner Chilcott manufactured potentially subpotent batches of Ovcon (Norethindrone) 1mg and Ethinyl Estradiol 50mcg tablets for five years.
“We remain concerned regarding the quality problems that have gone unresolved for the last five years without you fully understanding the reason for the failures and without assurance that the product will meet its quality attributes throughout the product's shelf life”, the FDA wrote .
The FDA traces many of the problems back to when Warner Chilcott acquired Ovcon 50 and began manufacturing it at its plant in Fajardo, Puerto Rico. At the time Warner Chilcott changed the drying parameters, the FDA wrote, but two of the three validation batches failed a stability assay.
Warner Chilcott attributed the failure to the lack of robustness of the analytical method. The FDA said the decision was “without scientific justification” and Warner Chilcott should have investigated the drying process as the root cause of the stability failures.
“Instead, you continued to manufacture and release batches to the marketplace for five years by assigning the root cause of the stability failures to a problem with the analytical method. It was not until [the 2011 recall of Ovcon] your firm performed a more rigorous evaluation”, the FDA wrote.
Technology transfer technique
Warner Chilcott responded to the FDA in August but the actions were deemed insufficient to stop the Agency sending the CEO a warning letter last week. The FDA is still concerned about the failure to evaluate technical transfer data and wants Warner Chilcott to show it has changed its quality system.
“It is essential that the quality unit review relevant process design data including process knowledge and understanding obtained during technical transfer activities in order to assure an overall understanding of the process impact on the quality attributes of your drug product”, the FDA wrote.
Last year research published in the Journal of Operations Management claimed plants in Puerto Rico have a higher risk of quality failings than US mainland facilities. The authors said shortcomings in the transfer of knowledge and maintenance are the most plausible explanations for the finding.
Different products, same problems?
The Agency wants Warner Chilcott to place all lots of Ovcon 50 on stability until it can verify it has fixed the problems. Warner Chilcott should also show it can guarantee its other products meet their specifications through to their expiration dates.
“Please conduct a comprehensive retrospective review of your stability program for all approved products to ensure that your marketed products are in compliance with approved application commitments”, the FDA wrote.