25/26 October 2022
The EMA reflection paper on markers used for quantitative and qualitative analysis of herbal medicinal products (HMPs) provides an overview on possibilities and challenges with markers. According to the Agency, markers should belong to the group of secondary plant metabolites (e.g. flavonoids, saponins, terpenes, phenols). However, in exceptional cases markers from the group of primary metabolites (e.g. carbohydrates, amino acids / proteins, fats) may be acceptable, if they allow for a specific assay.
Markers should ideally be characteristic or specific for the herbal preparation and they should also be stability-indicating (i.e. allow the quantification of the relevant degradation products).
There are two categories of markers:
The manufacturer should in general use the same marker for release and stability testing. In exceptional cases different markers can be accepted where justified on the basis of analytical data.
Reference standards are used for identity / purity testing and for the assay. They play an essential role when ensuring and demonstrating adequate and consistent quality. According to the EMA, reference standards may be
The European Pharmacopoeia (Ph. Eur.) monographs on herbal substances / preparations provide (herbal) reference standards for a dedicated purpose and they are only demonstrated to be suitable for the use indicated. Where Ph. Eur. reference standards are available they should be used as primary standards. In cases, where Ph. Eur. reference standards are not available, non-pharmacopoeial reference standards should be established following the guidance given in Ph. Eur. chapter 5.12. Reference standards. According to the agency, reference standards should be an integral part of the manufacturer’s specification.
For more information please see EMA´s Reflection paper on markers used for quantitative and qualitative analysis of herbal medicinal products and traditional herbal medicinal products and Questions & answers on quality of herbal medicinal products/traditional herbal medicinal products.