The PharmCo Perspective on Primary Packaging and Drug Delivery. (Corrado Giovanazzo, Wyeth)
Injectable products inevitably contain very small amounts of subvisible particulate matter (i.e., synthetic polymers, starch, metal ions, insoluble degradation products, etc.) as a consequence of the low pH of the vehicles.
This process decreases solubility of component and thus increases production of particulates, and enhances the capacity to extract metal ions from contact surfaces such as vials, iv bags, rubber stopper, and the presence of metal ions (particularly zinc) that forms insoluble complexes with many active components due to charge interactions.
Guidelines to the assessment and control of such contaminants are reported in the U.S. Pharmacopoeia (USP) and in the European Pharmacopoeia (EP).
An excessive quantity of particulate matter could cause adverse drug reactions (ADRs), including phlebitis, pulmonary granulomas and dysfunctions, local tissue infarction and death, due to mechanical occlusion of small-diameter arterioles and capillaries, activation of platelets and/or neutrophils (generation of occlusive microthrombi), and indirect effects on vasomotor activity.
Therefore it is essential that stringent quality systems in place at Plant Operation are supported by process equipment, non-process equipment and primary components fully in compliance with product formulation.