FDA Warns Apotex: High Tech Does Not Equal High Compliance

Apotex's Etobicoke plant near Toronto has gotten a lot of rave reviews for its automated, multi-level materials processing and tracking system. It is rightly considered a model of modern drug plant engineering (here's an article I wrote a few years back about some of its weighing and processing features; its expansion project was also given a Facility of the Year award at Interphex 2005; and here's a corporate video with some footage of the facility), but that of course does not guarantee manufacturing excellence. Apotex has been warned by FDA that it faces penalties--a freeze on NDAs or the refusal of its products into the U.S.--should the company not rectify problems at the site. Namely, FDA has cited the facility for an unusually high number of rejected batches, and a failure to adequately investigate the root causes of batch failures.


In this paragraph from FDA's June 25 letter, it's clear that training, or rather lack of it, has played a significant role in the problems, and that there has not been adequate communication between the plant floor and executive offices:

In your response, you report that the delays in submitting FARs within the required three business days was due to significant delays in reporting between the "discovery of the concern by Apotex personnel and it being reported to senior management to facilitate an investigation of the incident." You attribute these delays to the fact that training on this procedure was limited to its users. To correct this communication problem and ensure that all staff is trained and aware of these reporting requirements, you've committed to revise the SOPs covering the commercial stability complaint process, the product compliant process, and the procedure covering the final review of QC laboratory results. We acknowledge your firm's commitment to update these written procedures to ensure that requirements for reporting of initial OOS test results and submission of FARs are known to all staff. Please provide a copy of the revised and approved SOPs for our review.