Ph. Eur. Draft on Depyrogenation of Packaging Materials
A draft of a new Ph. Eur. general chapter 5.1.12. Depyrogenation of items used in the production of parenteral preparations has been published in Pharmeuropa - Issue 30.4. The draft is open for comments until December 31, 2018.
The new general chapter covers pyrogen inactivation or removal from materials such as primary packaging systems and equipment coming into direct contact with products finally sterilized. Pyrogens in general are substances that have the ability to induce fever when infused or injected. The draft chapter defines depyrogenation "in terms of a reduction in lipopolysaccharide, the most potent and difficult-to-eliminate of pyrogenic materials".
According to the chapter depyrogenation can be carried out by dry heat treatment (for glass and other non-heat-labile materials), and other treatments, like physical and chemical procedures. Those methods may be used when heat treatment is not possible.
All processes must be validated by adding suitable endotoxin indicators (i.e. lipopolysaccharides) to the load in the positions identified as being the most difficult to depyrogenate. Depending on the material (e.g. glass, stainless steel, plastic) to be depyrogenated, a suitable endotoxin indicator is used during validation. Ready-to-use endotoxin indicators are, for example, ampoules, vials or other carriers that have been inoculated with a known amount of endotoxin. The material of the carrier must be representative of the item that is being depyrogenated. Custom-made endotoxin indicators are primary packaging materials or equipment that have been surface-inoculated with a suitable endotoxin reference standard. The endotoxin recovery rate is determined on materials that have not been depyrogenated in order to calculate the percentage recovery and to check any interference with leachables. The criterion for process validation is set as a 3.0 log10 reduction in recoverable endotoxin.