In September, FDA sent a warning letter to Sichuan Pharmaceutical Co., an API manufacturer in China. The letter cited the manufacturer's failure to adequately guard against potential product cross-contamination:
From September 2008 to July 2009 your firm manufactured (b)(4) API in workshop (b)(4), which is adjacent to workshops (b)(4) and (b)(4) where you manufactured (b)(4) API and (b)(4) injection, respectively. However, you failed to have adequate controls and monitoring program to prevent cross-contamination between these adjacent workshops.
In addition, your firm manufactures a (b)(4) API ((b)(4) (API) in a facility that was previously used to manufacture (b)(4) without conducting adequate decontamination, renovation, and activation of the facility. Your firm has failed to conduct adequate assessment of the cross-contamination risks.
With more API and drug production being outsourced and more facilities being designed for multiproduct operations, the cross-contamination issue looms as large as ever—as does the need for industrywide best practices to control cross-contamination risk. Simply put, there are many drug manufacturers who “do not understand the hazards of the products they are producing, especially when you look at the global marketplace,” says consultant Stephanie Wilkins, PE.
Wilkins is one of the lead authors on ISPE’s new Risk-MaPP Baseline Guide, a document that details how drug manufacturers can take a risk-based approach (as spelled out in ICH Q9) to reducing the potential for cross-contamination, and minimizing the risk of operator or patient harm.
The ISPE guide does not contain case study materials. In Pharmaceutical Manufacturing’s cover story this month, however—"Control Cross-Contamination Risk: Using a Risk-MaPP Master Matrix"—Mark O’Reilly and Aisling Horan of Alkermes (formerly Elan Drug Technologies) share details on how their Athlone, Ireland site has tackled the challenge of Risk-MaPP head on and applied its principles comprehensively. They have developed a "Master Matrix" by which to regularly monitor and assess the risks of cross-contamination from HAPIs and other products as well.
Alkermes worked closely with Wilkins on this project, and this case study is an important next step in spreading the Risk-MaPP gospel worldwide. As Wilkins has noted, “Risk-MaPP should not be hard to implement, but it really comes down to corporate culture. Companies that are agile will have no problem implementing Risk-MaPP. Other companies have difficulties with change period.”
Clearly, the Athlone site had the will and agility to handle this project. The “Master Matrix” that O’Reilly and Horan describe will serve as a model for many other facilities—worldwide—to follow.
--Paul Thomas
