Institut Kirchhoff Berlin GmbH supports manufacturers of medicinal products by analysing their products
In recent weeks, the contamination of plant-based medicinal products with pyrrolizidine alkaloids (PA), and measures to prevent and lower PA content in such products have come under increasing focus.
As part of the Medicinal Product Manufacturers’ Research Association’s ‘Pyrrolizidine alkaloids’ workshop on 13 April 2016 in Bonn, and the ‘BfArM in dialogue: Particular therapy approaches – Current topics’ conference on 26 April 2016 in Bonn, strategies for preventing and minimising contamination of plant-based medicinal products with pyrrolizidine alkaloids and the current state of the analysis of PA contamination in medicinal products were presented and discussed.
In March 2016, the German Federal Institute for Drugs and Medicinal Products (BfArM) announced specifications for test scenarios and limit thresholds that must be observed by the pharmaceutical industry for quality assurance purposes. As part of this process, and in relation to the scope of the tests, three categories were determined, which orientate themselves to the expected PA content in the end product. So for PA content below 0.1 µg PA/day in the end product, only sample inspections are required. Between 0.1 and 0.35 µg PA/day, continuous monitoring of sample inspections is required, and where content is between 0.35 and 1 µg PA/day, routine tests relevant for approval must be carried out. At the same time, 1 µg PA/day is defined as the upper limit. In its approval procedures, the BfArm demands the submission of product-specific documents, including among others the results of batch-specific tests.
But even before this announcement from the BfArM, the manufacturers of pharmaceutical products had taken their own independent measures for researching the causes of PA content, as well as monitoring the products and minimising PA content. These include involvement in various research projects, and especially the development of the ‘Code of Practice for Avoiding and Minimising the Contamination of Plant-Based Mecidinal Products by Pyrrolizidine Alkaloids’ by the Federal Association of Medicinal Product Manufacturers (BAH) and the Federal Association of the Pharmaceutical Industry (BPI). This states and evaluates the risks at all stages of the production chain, as well as setting out measures to tackle the risk.
For manufacturers of plant-based medicinal products, the consequence is that they must urgently determine the levels of pyrrolizidine alkaloids in raw materials and finished products; not just in the framework of the approval procedure, but also during production. We offer manufacturers of medicinal products the analysis of their raw materials and products for pyrrolizidine alkaloids. The institute analyses 28 pyrrolizidine alkaloids using LC-MS/MS, based on and expanding on the method published by the Federal Institute for Risk Assessment (BfR-PA-Tee-2.0/2014), as recommended in the BFR’s statement (no 002/2016). We have been intensively involved in the analysis of pyrrolizidine alkaloids for several years, and you can find more information about it here.