Contamination of heparin highlighted the risks of global outsourcing and has led to increased regulatory and industry interest in modern analytical methods. This is, in turn, changing the way the US Food and Drug Administration (FDA) and other regulators approach product quality.
At an AAPS session, entitled “Mitigating Risks in Global Drug Supply Chain: Opportunities for Modern Analytics”, Lucinda Buhse, director of the division of pharmaceutical analysis at the FDA, explained how the agency is changing its methods.
Buhse said the FDA is developing gatekeeper assays to alert it to samples that need further analysis. These specific, information rich assays will be used to identify potentially contaminated products which will then be sent for more thorough analysis, for example using 2D-NMR.
Information rich assays often require high levels of operator expertise, said Buhse. To reduce operator requirements and ensure the assay is an effective first test chemometrics can be used, said William Welsh of the University of Medicine & Dentistry of New Jersey.
Chemometrics is a combination of pattern recognition and statistics, said Welsh, and can analyse information rich data along a spectrum. By removing redundant peaks while retaining unique features chemometrics simplifies information and helps to find patterns in the data, said Welsh.
Furthermore, chemometrics can build regression models to predict contaminant levels. These processes are mostly automated, said Welsh, and consequently chemometrics can help reduce operator requirements.
The cases of heparin contamination were, in part, the catalyst for increased interest in analytical methods. Buhse said the old monograph, in use at the time of the contamination cases, failed to detect oversulfated chondroitin sulphate (OSCS) in heparin at levels of up to 25 per cent.
In response the FDA, in collaboration with the US Pharmacopeia (USP), has created “one of the most comprehensive monographs” for heparin, said Ali Al-Hakim, an official at the FDA.