Tag Archives: herbal preparations

EMA Publishes Concept Paper on using CTD Format in Traditional Herbal Medical Products Applications

EMA Publishes Concept Paper on using CTD Format in Traditional Herbal Medical Products Applications

Full Text Here

This concept paper is concerned with the revision of the guideline on the use of the Common Technical Document (CTD) format in the preparation of a registration application for traditional herbal medicinal products (EMEA/HMPC/71049/2007).
This revision pertains to the presentation and content of the Module 3 on Quality (chemical, pharmaceutical and biological information) for traditional herbal medicinal products (THMPs) to help future applicants in their submission.

This guideline is applicable to applications for traditional use registration of THMPs for human use.
The compilation of dossiers for marketing authorisation applications for HMPs is not covered by this guideline. However, guidance provided on modules 2.3 and 3 are also applicable to HMPs applications for marketing authorisation for human and veterinary use.

In the light of experience, there is a need to update this guideline to provide further clarification on the exact location of quality data requirements in the Module 3 on Quality of the CTD and to provide further explanations on the kind of information that is required from applicants at time of application.
Minor changes in the body of the current guideline will be introduced and two annexes will be added. The first annex will be a best practice guide describing the exact location of relevant parts of the documentation and the corresponding guidelines in the CTD Module 3 sections and the second annex will be a Module 3 mock-up.

For Assistance with Registering a Herbal Product in the UK, EU or USA Click Here

Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

Avoid Expensive Mistakes, Keep On Top of New and Changing Regulations for Free!

Sign up for the most value add free newsource you can get for free. We spend a huge amount of time and effort monitoring the main drug / device regulators websites for changes in the regulatory environment, and capture between 20 and 40 new regulations, rules and initiatives each month, and summaries them in a fantastic FREE monthly Regulatory and Market Round Up. You can Un-Subscribe at any time and we don not share your details with anybody. You can’t afford to miss out on this service. Just fill in the form below.

Fill Out the Short Form Below…


  1. (required)


  2. (valid email required)

“Please note that the pages on this website are designed to provide you with general information only. We make no warranties, representations or undertakings about any of its content. This includes the completeness, accuracy and fitness for any particular purpose, or the content of any third party site referred to or accessed through it. You are personally responsible for ensuring that the information is correct and we will not be held liable or accountable for any mistakes that occur.”

EMA Publish Reflection Paper on Stability Testing for Herbal Medicinal Products

EMA Publish Reflection Paper on Stability Testing for Herbal Medicinal Products.

Full Text Here

This reflection paper addresses the need for specific requirements for establishing the stability of herbal medicinal products (HMPs). The quality, including the stability, of HMPs should be guaranteed and demonstrated in accordance with the existing requirements as set out in Annex I of Directive 2001/83/EC, as amended, Annex I of Directive 2001/82/EC, as amended and with current EU/ICH guidance on quality. The committees of the European Medicines Agency have published several quality guidelines related to stability testing, which focus mainly on chemically defined substances. In view of the complex nature of HMPs, it is considered that further guidance is needed in order to ensure that stability of these products is addressed appropriately. The purpose of this reflection paper is to consider issues relating to the application of the existing stability guidance on HMPs and to provide additional guidance where necessary.

For Assistance with Developing and Registering Herbal Products Click Here

Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

Avoid Expensive Mistakes, Keep On Top of New and Changing Regulations for Free!

Sign up for the most value add free newsource you can get for free. We spend a huge amount of time and effort monitoring the main drug / device regulators websites for changes in the regulatory environment, and capture between 20 and 40 new regulations, rules and initiatives each month, and summaries them in a fantastic FREE monthly Regulatory and Market Round Up. You can Un-Subscribe at any time and we don not share your details with anybody. You can’t afford to miss out on this service. Just fill in the form below.

Fill Out the Short Form Below…


  1. (required)


  2. (valid email required)

“Please note that the pages on this website are designed to provide you with general information only. We make no warranties, representations or undertakings about any of its content. This includes the completeness, accuracy and fitness for any particular purpose, or the content of any third party site referred to or accessed through it. You are personally responsible for ensuring that the information is correct and we will not be held liable or accountable for any mistakes that occur.”

Drug Regulators, EMA (EMEA), Publish Updated Guideline on declaration of herbal substances and herbal preparations in herbal medicinal products/ traditional herbal medicinal products

Drug Regulators, EMA (EMEA), Publish Updated Guideline on declaration of herbal substances and herbal preparations in herbal medicinal products/ traditional herbal medicinal products.

Full Text Here

The guideline EMEA/HMPC/CHMP/CVMP/287539/2005 was limited to guidance on the declaration in the SmPC. It was revised to integrate the declaration in package leaflet and labelling. The revision is in line with the “Concept paper on the declaration of herbal substances/herbal preparations in finished herbal medicinal products” (EMEA/HMPC/241953/2005). The main chapters that have been revised are the following:

Executive summary: Declaration in the package leaflet and labelling has been introduced, besides declaration in the SmPC

Definitions: Definitions for the terms “declaration” and “strength” have been added

Annex 1: This new annex has been added to the guideline, providing guidance specifically on declaration in the package leaflet and labelling.

There are only editorial changes in the guidance on declaration in the SmPC (chapter 5 and 6).

The guideline EMEA/HMPC/CHMP/CVMP/287539/2005 was limited to guidance on the declaration in the SmPC. It was revised to integrate the declaration in package  leaflet and labelling. The revision is in line with the “Concept paper on the declaration of herbal substances/herbal preparations in finished herbal medicinal products” (EMEA/HMPC/241953/2005). This revised guideline outlines the principles for uniform declaration of herbal substances/preparations in herbal medicinal products as well as in traditional herbal medicinal products. It focuses on the different types of herbal substances/preparations in relation to the quality documentation given. Examples of declaration of such active substances are provided. The main guideline describes declaration in the SmPC. Guidance on package leaflets, labelling and other herbal specific provisions, for SmPC, package leaflets and labelling, have been added in Annex 1. The guideline should be read in conjunction with current EU/(V)ICH guidelines.

Common criteria for the declaration shall ensure clear differentiation between different types of herbal substances/preparations and proper description of their qualitative and quantitative particulars. As a result, a precise and consistent description of active substances of herbal medicinal products will be guaranteed within the Community.
The complex composition of herbal substances/preparations, which is essentially determined by various factors like the production process, the extraction solvent, the genuine drug extract ratio (DER genuine), and the type/physical state of the herbal substances/preparations, needs to be stated to guarantee identification and facilitate comparison of herbal substances/preparations. However, it is not feasible to provide full characterisation in the declaration as the declaration should be kept as short
and precise as possible. The declaration is primarily intended to describe the identity and quantity of the herbal substance/preparation, being the active substance of the herbal medicinal product and should focus on those characteristics found to be useful in ensuring the safety and efficacy of the herbal substance/preparation and herbal medicinal product. Therefore, a declaration system has been established which reflects the main characteristics of herbal substances/preparations as defined in the respective specifications. For this purpose, general guidance as given in the European Pharmacopeoia (particularly the monographs “Extracts”, “Herbal Drugs”,
“Herbal Drug Preparations”, and “Herbal Teas”) as well as in the guidelines listed under References, should be followed.

Click Here for – Herbal Development Services - Click Here

Drug Regulators, EMA, Publish Reflection Paper on Ethanol Content in Herbal Medicinal Products and Tranditional Herbal Medicinal Products Used in Children

Drug Regulators, EMA, Publish Reflection Paper on Ethanol Content in Herbal Medicinal Products and Traditional Herbal Medicinal Products Used in Children

Full Text Here

Herbal medicinal products may contain significant levels of ethanol arising from its use as an extraction solvent in liquid extracts and tinctures or when added as a diluent to liquid herbal preparations. The use of ethanol is necessary for extraction of some constituents that are important for efficacy. Ethanol is metabolically active, therefore formulations without ethanol or with the lowest achievable level should be selected to avoid systemic exposure when the target population is children.

The scope of this paper is to reflect the need for safety limits for ethanol exposure by oral herbal medicinal products intended for the paediatric population. Establishing these limits is viewed as necessary to protect health and to allow safe free movement of goods within the EU. In addition, this will ensure a harmonised approach in assessment work among Member States as well as in the establishment by the HMPC of Community herbal monographs and of the list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products (respectively Article 16h (2,) and Article 16f (3) of Directive 2001/83/EC as amended).

Drug Regulators, EMEA, Publish Guidance on Herbal Medicinal Products, Test Materials for Genotoxicity

Drug Regulators, EMEA, Publish Guidance on Herbal Medicinal Products, Test Materials for Genotoxicity.

Full text click here.

The ‘Community list of herbal substances , preparations and combinations thereof for use in traditional herbal medicinal products’ is established by the European Commission based on proposals from the Committee on Herbal Medicinal Products (HMPC), in accordance with Directive 2001/83/EC as amended. The list is being developed gradually through entries of structured information relating to individual herbal substances or preparations.
Inclusion in the Community list of a herbal substance/preparation represents a significant advantage to applicants seeking registrations for traditional herbal medicinal products. This is because once a herbal substance/preparation is included in the Community list an applicant will not be required to provide evidence of the safe and traditional use of a medicinal product for which he seeks a traditional use registration if he demonstrates that the proposed product and related claims in the application comply with the information contained in the list.
Once a herbal substance/preparation is included in the Community list, competent authorities will not have the opportunity to require additional data to assess the safety and the traditional use of the product. In view of this, the HMPC has concluded that, where data on genotoxicity are inadequate or absent, it will not be possible to endorse the herbal substance/herbal preparation for inclusion in the Community list.
As a result, progress with the development of Community list is being hampered by the absence of genotoxicity data. Experience to date confirms that many well known traditional herbal substances/preparations, already widely available within the Community, will be excluded from the Community list solely as a consequence of absence of genotoxicity data and thus any potential benefits of the list to applicants will be lost.
To assist applicants, the HMPC has developed a guideline, ‘Guideline on the assessment of genotoxicity of herbal substances/preparations’ (EMEA/HMPC/107079/2007) which describes a general framework and practical approaches on how to assess or to test the potential genotoxicity of herbal substances/preparations and how to interpret the results. The stepwise approach described in the guideline sets out a pragmatic approach to address both scientific aspects of genotoxicity testing and the special needs of herbal medicinal products within the current regulatory framework applicable to these products.
Strictly speaking, genotoxicity testing should be carried out by individual applicants on their specific materials and it is recognised that this represents a major task and considerable duplication of effort particularly for applicants seeking registrations for traditional herbal medicinal products. Industry has therefore been encouraged to consider undertaking collaborative research on genotoxicity and one such study is underway within some Member States.
Community herbal monographs established by the HMPC set out the well-established and/or traditional uses for a particular plant species. The individual monographs usually cover a range of herbal preparations depending on the therapeutic uses of the particular plant. For example, the monographs for Melilot herb and Passiflora herb include a range of preparations as shown in the tables below. This guidance offers a strategy to reduce the number of test materials such that a representative range of herbal preparations is tested rather than requiring individual manufacturers to undertake their own testing on specific preparations.

Herbal Drug Regulations – EMEA Draft Guidance on Genotoxicity Testing for Traditional Herbal Medicinal Products

Drug Regulators, EMEA, Publish Draft Guidance on Genotoxicity Testing for Traditional Herbal Medicinal Products.

Inclusion in the Community list of a herbal substance/preparation represents a significant advantage to applicants seeking registrations for traditional herbal medicinal products. This is because once a herbal substance/preparation is included in the Community list an applicant will not be required to provide evidence of the safe and traditional use of a medicinal product for which he seeks a traditional use registration if he demonstrates that the proposed product and related claims in the application comply with the information contained in the list.

Progress with the development of Community list is being hampered by the absence of genotoxicity data. Experience to date confirms that many well known traditional herbal substances/preparations, already widely available within the Community, will be excluded from the Community list solely as a consequence of absence of genotoxicity data and thus any potential benefits of the list to applicants will be lost.

The stepwise approach described in the guideline sets out a pragmatic approach to address both scientific aspects of genotoxicity testing and the special needs of herbal medicinal products within the current regulatory framework applicable to these products.

Strictly speaking, genotoxicity testing should be carried out by individual applicants on their specific materials and it is recognised that this represents a major task and considerable duplication of effort particularly for applicants seeking registrations for traditional herbal medicinal products. Industry has therefore been encouraged to consider undertaking collaborative research on genotoxicity and one such study is underway within some Member States.

This guidance offers a strategy to reduce the number of test materials such that a representative range of herbal preparations is tested rather than requiring individual manufacturers to undertake their own testing on specific preparations.

Scope

This guideline addresses the selection of materials for genotoxicity testing in support of applications for traditional herbal medicinal products/ herbal medicinal products.

This guideline provides possible approaches to what types of materials should be subjected to testing for genotoxicity bearing in mind that different herbal preparations may have different toxicological profiles.

The main objective is to achieve consensus on a standard range of test materials which could be considered representative of the commonly used herbal substances/preparations with the intention of facilitating entry to the Community list.

Selection of Materials for Genotoxicty Testing

The concept of applying a reduced design approach such as ‘bracketing/ matrixing’to the selection of samples for genotoxicity testing is proposed. Using the ‘bracketing’ concept, only samples on the extremes of certain design factors would be tested. The reduced design assumes that the genotoxic potential of any intermediate preparation is represented by the test results of the extremes tested. Where a reduced testing design is proposed, evidence (usually chromatographic data) should be provided to demonstrate that the samples to be tested represent the phytochemical profile of all materials to be covered by the genotoxicity testing.

Herbal Substance Used in Herbal Medicinal Products

Where the entire herbal substance is incorporated directly into the herbal medicinal product, e.g. in capsules, tablets, the test material for genotoxicity testing, should, in theory, cover the entire spectrum of phytochemical constituents, including polar and non-polar constituents. Test materials for genotoxicity testing should therefore include extraction solvents which encompass the entire phytochemical profile. The choice of solvents should be justified. Consideration should be given to including an extract mid-range e.g. 50% water.

Fixed oils/essential oils/extracted juices etc

Where the herbal preparations include for example fixed oils, essential oils, expressed juices etc these should be addressed on a case by case basis. Some materials may need to be tested individually as part of the genotoxicity test programme. In the case of expressed juices, it may be possible to demonstrate that the material is covered by testing of, for example, an aqueous extract.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com