Opportunities for Collaboration at the Interface of Pharmacovigilance and Manufacturing.

A case can be made that much common ground exists between pharmacovigilance and pharmaceutical manufacturing. Of the 8 major US statutes that shaped the pharmaceutical industry since early in the 20th Century, 7 followed fatally catastrophic events related to the use of a manufactured product, and 1 followed the discovery of a counterfeit product. To facilitate an understanding of the interplay between pharmacovigilance and manufacturing, it is convenient to divide manufacturing into 3 categories: (1) upstream sourcing of materials: pharmacovigilance plays an important role when adverse event clusters are seen during routine vigilance detection processes and the suspicion turns to possibly contaminated source material, (2) the manufacturing process itself: pharmacovigilance may be called on to conduct a health hazard evaluation if a manufacturing deviation is detected after product release (the assessment can inform the depth of a recall), and (3) downstream distribution and product use: there is only light regulation of the interval between product distribution after manufacturing release and just before administration to patients, a time during which product may be subject to an out-of-specification determination for environmental controls or subject to malfeasant activities, such as counterfeit substitution or product diversion. Recently introduced statutory remedies, including the FDA Safety and Innovation Act and the Drug Supply Chain Security Act in the United States and the Falsified Medicines Directive (directive 2011/62/EC) in the European Union, can provide capabilities to support pharmacovigilance signal management activities that have the potential to reduce the risk to patients of experiencing adverse events caused by counterfeit, diverted, or tampered product.