EU Guidelines For Quality Control Of Herbal Drugs: The European Medicines Agency’s scientific guidelines on herbal medicinal products help medicine developers prepare marketing-authorization applications for human and veterinary medicines.
Qualitative And Quantitative Particulars Of The Active Substance(S) Of A Herbal Medicinal Product
Herbal drug and herbal preparations consisting of powdered herbal substances
For powdered drugs, the grade of comminution is given For standardization, the quantity of the herbal drug is given according to the defined quantity of the constituents with known therapeutic activity.
For the quantity of the herbal drug, the content of the quantified substance(s) shall be specified in a range.
Example-Sennae folium-415-500 mg, corresponding to 12.5 mg of hydroxyanthracene glycosides calculated as sennoside B
Herbal preparations produced by steps which exceed comminution
If the herbal preparation exceeds the communication, the nature and concentration of the solvent and the physical state of the extract have to be given.
For standardized extracts: the equivalent quantity of the herbal substance shall be stated and the quantity of the genuine herbal preparation may be given as a range corresponding to a defined quantity of these constituents.
For quantified extracts: the equivalent quantity of the herbal substance shall be stated and the quantity of the genuine herbal preparation has to be given as a distinct content of the quantified substances shall be specified in a range.
For other extracts: the equivalent quantity of the herbal substance shall be stated and the quantity of the genuine herbal preparation has to be given as a distinct content.
The extraction solvent or extraction solvent mixture composition and the physical state of the extract must be indicated.
During the manufacture of the herbal preparation, any other substance is added then adjust the preparation to a defined content of constituents with a known therapeutic activity which a mentioned as an “other substance” and the genuine extract as the “active substance” or for any other purpose, the added substance must be
Description Of The Method Of Preparation Of The Herbal Medicinal Product
The manufacturing process of the herbal drug is the preparation of the herbal medicinal product from the herbal substance(s). In the case of traditional herbal medicinal products for human use while preparation, the description should include details of the process together with the controls exercised. This section should be by the ‘Note for guidance on manufacture of the finished dosage form’.
If herbal preparations are the starting material, the manufacture of the herbal preparations and their controls should not be located under this section but under the section entitled “Control of starting materials”.
Information on development pharmaceutics and process validation should also be provided by the ‘Note for guidance on development pharmaceutics, the Note for guidance: development pharmaceutics for veterinary medicinal products, and the ‘Note for guidance on process validation’.
Control Of Starting Materials
Control of herbal substances and herbal preparations
Control of herbal substances- A complete specification for each herbal substance must be submitted. The binomial scientific name of the plant (genus, species, variety, and author), chemotype (where applicable), and name of its parts have to be stated.
If a monograph is not available then referred in Annex I of Directive 2001/83/EC or 2001/82/EC. if possible, Information should be the mention from the site of collection, the time of harvesting and stage of growth, treatment during growth with pesticides, etc, and drying and storage conditions.
If the herbal substances with constituents of known therapeutic activity then assay should be done for the confirmation of the content which is mention in a range.
When herbal substances where constituents of known therapeutic activity are not known then assays of marker substances (with the test procedures) are required. Also, justify the choice of markers.
Control of herbal preparations -the comprehensive specification for the herbal substance must be followed by a description and validation of the manufacturing process for the herbal preparation. If preparations from herbal substances with constituents of known therapeutic activity are standardized then mention how much standardization is achieved.
Control of vitamins and minerals (if applicable)
If Vitamins and minerals are used products for human use then should fulfill the requirements of the Guideline on summary of requirements for active substances in the quality part of the dossier (CHMP/QWP/297/97 Rev. 1 Corr).
Control of excipients
Excipients are added during the manufacture of the herbal preparations, should be described according to the ‘Note for guidance on excipients in the dossier for application for marketing authorization of a medicinal product’ (Eudralex 3AQ 9A) or the ‘Note for guidance on excipients in the dossier for application for marketing authorization of veterinary medicinal products (EMEA/CVMP/004/98), as appropriate.
Control tests carried out at an intermediate stage of the manufacturing process of the herbal medicinal product
Details of all control tests, with details of test procedures and limits applied at any intermediate stages of the manufacturing processes, are required especially if these tests cannot be performed on the herbal medicinal product.
Control Tests On The Herbal Medicinal Product
This section should be by the ‘Note for guidance on specifications and control tests on the finished product’ (Eudralex 3AQ 11A), the ‘Guideline on specifications: test procedures and acceptance criteria for herbal substances, herbal preparations, and herbal medicinal products/traditional herbal medicinal products (EMEA/CPMP/QWP/2820/00 and EMEA/CVMP/815/00 as revised) and the analytical procedures should be validated according to the ICH/VICH guidelines Validation of analytical procedures: methodology (CPMP/ICH/281/95 and CVMP/VICH/591/98).
The control tests on the finished product should allow the qualitative and quantitative determination of the composition of the active substance Use the markers if the therapeutic activity is unknown If there is a combination of several herbal substances or preparations of several herbal substances, and it is not possible to perform a quantitative determination of each active substance, the determination may be carried out jointly for several active substances. The nee this procedure should be justified.
This section should be by the Note for guidance on stability testing of new active substances and products (CPMP/ICH/2736/99 Rev. 2 and Guideline on stability testing of new veterinary drug substances and medicinal products CVMP/VICH/899/99), the Note for guidance on stability testing of existing active substances and related finished products (CPMP/QWP/122/02 Rev. 1 and EMEA/CVMP/846/99), the ‘Note for guidance on in-use stability testing of human medicinal products (CPMP/QWP/2934/99) and the ‘Note for guidance on in-use stability testing of veterinary medicinal products (excluding immunological veterinary medicinal products) (EMEA/CVMP/424/01).
Since the herbal substance or herbal preparation in its entirety is regarded as the active substance, a mere determination of the stability of the constituents with known therapeutic activity will not suffice.
The stability of other substances present in the herbal substance or the herbal preparation, should, as far as possible, also be demonstrated, e.g., using appropriate fingerprint chromatograms. Lt should also be demonstrated that their proportional content remains comparable to the initial fingerprint.
In the case of a herbal medicinal product containing a herbal substance or herbal preparation with constituents of known therapeutic activity, the variation in content during the proposed shelf-life should not exceed±5% of the declared assay value, unless justified. In the case of a herbal medicinal product containing a herbal substance or herbal preparation where constituents with known therapeutic activity are unknown, a variation in marker content during the proposed shelf life of ±10% of the initial assay value can be accepted if justified by the applicant.
Make sure you also check our other amazing Article on : Current Good Manufacturing Practices (cGMP) For Herbal Drugs