Attachment No. 7
to the Rules of Good Manufacturing Practice
Содержимое (Table of Contents)
1. Herbal medicinal products have a complex origin and various characteristics, for this reason the control over starting raw materials, storage and processing conditions play a significant role in their manufacturing process. Starting raw materials for the manufacture of herbal medicinal products are herbal raw materials. Herbal raw materials shall be of the required quality, and the data confirming this fact shall be provided by the supplier of the starting raw materials to the manufacturer of the herbal medicinal product. To ensure the quality of herbal raw materials more detailed information on the method of their production (cultivation) may be required. Seed selection, conditions of cultivation and harvesting are important aspects for the quality of herbal raw materials and may influence the stability of the quality of a finished herbal medicinal product. For proper cultivation and collection of herbs with regard to the corresponding quality management system it is recommended to use the Guidelines on Good Agricultural and Collection Practice (GACP) for Starting Materials of Herbal Origin approved by the Committee on Herbal Medicinal Products at the European Medicines Agency <*>.
<*> For reference: Guidelines on Good Agricultural and Collection Practice (GACP) for Starting Materials of Herbal Origin are available at the following address on the Internet information and telecommunication network:
2. This Attachment shall apply to all starting materials of plant origin, including herbal raw materials.
3. Specifics of application of different rules, including these Rules to the manufacture of herbal medicinal products are presented in Table No. 1.
Table No. 1. Specifics of application of the Rules to the manufacture of herbal medicinal products <*>
<*> This table contains extended and detailed information with regard to the section concerning herbal medicinal products of Table No. 1 in Chapter IV of these Rules.
|Types of works||Good Agricultural and Collection Practices (GACP)||Chapter IV of these Rules||Chapter III of these Rules|
|Cultivation and collection of plants, algae, mushrooms and lichens, collection of exudates (secretions)|
|Cutting and drying of plants, algae, mushrooms, lichens and exudates (secretions) <*>|
|Pressing of plants and distillation <**>|
|Grinding, processing of exudates, extracting from plants, fractionating, purification, concentration or fermentation of plant substances|
|Further processing for the production of a pharmaceutical form, including the package of a medicine|
<*> Manufacturers shall guarantee that these stages are performed in accordance with the set requirements. Initial stages are covered by the standards of the Guidelines on Good Agricultural and Collection Practice (GACP) for Starting Materials of Herbal Origin. These Rules shall apply to the manufacturing stages of cutting and drying.
<**> Stages of pressing of plants and distillation (if it is necessary that these works form an integral part of the preparation operations aimed at preserving the quality of the products under approved specifications) may be performed during the preparation process, if the cultivation is carried out in accordance with the GACP. Such condition shall be deemed an exception and shall be justified in the documents of the registration dossier. It is necessary to draw up corresponding documents, ensure control and validation pursuant to the principles of these Rules for such works conducted during the preparation process.
4. (1) Herbal raw materials shall be stored in individual areas. These areas shall be protected from any intrusion of insects and animals, especially rodents. It is necessary to take effective measures to prevent expansion of any of these animals and microorganisms brought with herbal raw materials in order to stop fermentation or mould growth, as well as cross contamination. It is required to use reserved areas for the quarantine of received herbal raw materials and herbal raw materials permitted for use.
5. (2) The storage area shall be well-ventilated. The way of arrangement of packages shall not hinder free air circulation.
6. (3) Special attention shall be paid to the cleanness and proper maintenance of storage areas, especially in places gathering dust.
7. (4) If the storage of starting raw materials and herbal medicinal products requires special conditions in terms of humidity, temperature and protection from light, these conditions shall be ensured and controlled.
8. (5) In case of sampling, weighing, mixing and other process operations with herbal raw materials followed by dust formation, it is necessary to take special measures to keep the areas clean and prevent cross contamination (dust removal, allocation of special rooms).
9. (6) Equipment, filtering and other materials use in the manufacturing process shall be compatible with the solvent used for extraction to prevent any secretion or unwanted absorption of the herbal raw materials that may affect the products.
10. (7) Manufacturers of herbal medicinal products shall make sure that they use only herbal raw materials produced pursuant to these Rules (subject to Table No. 1 hereof) and the registration dossier. It is necessary to have comprehensive documentation concerning the assessment of suppliers of starting materials of herbal origin carried out either by the manufacturer of the herbal medicinal product or other persons at its request. The results of the assessment of suppliers with regard to herbal raw materials are essential for the quality of starting raw materials. The manufacturer shall find out whether suppliers of herbal raw materials or products work pursuant to the Guidelines on Good Agricultural and Collection Practice (GACP) for Starting Materials of Herbal Origin.
the scientific name of the plant according to the binary system (genus, species, subspecies and (or) types, and the author (e.g. Linnaeus), if necessary, other information shall also be provided (e.g. the name of the variety, hemotypic form);
detailed data on the origin of the plant (in particular, the country or origin of growth or cultivation, time and method of preparation, probably used pesticides, possible radioactive contamination);
data on what part(s) of the plant is (are) used;
the information on the drying method, if dried plants are used;
a description of the herbal raw materials, as well as the data on its macroscopic and microscopic examination;
data on required tests for authenticity, including, if necessary, authenticity tests for ingredients with known medical potency or markers. If the herbal raw materials can be forged and (or) substituted, special differentiating tests are required. To determine authenticity an authentic sample shall be available for comparison;
the moisture content in the herbal raw materials defined in accordance with the requirements of the State Pharmacopoeia of the Russian Federation;
techniques of the quantitative measurement of components with known medical potency or, if necessary, markers, as well as methods suitable for evaluating the possible contamination by pesticides and acceptable thresholds in accordance with the requirements of the State Pharmacopoeia of the Russian Federation, or, if there are no requirements of the pharmacopoeia, an appropriate validated method, unless indicated otherwise;
techniques of testing of fungal and (or) microbial contamination, including aflatoxins, other mycotoxins and parasite invasion, as well as acceptable thresholds, if necessary;
techniques of testing for the presence of toxic metals, as well as possible contaminants and impurities, if necessary;
techniques of testing for the presence of foreign materials, if necessary;
other types of control in accordance with the requirements of the State Pharmacopoeia of the Russian Federation.
12. Any treatment performed to reduce fungal and (or) microbial contamination or any other invasion shall be documented. It is necessary to have specifications and techniques that shall include detailed data on the manufacturing process and tests, as well as thresholds of the residual contamination.
13. (9) Process instructions shall describe different operations conducted with herbal raw materials, such as cleaning, drying, grinding and sieving, as well as the data on the duration and temperature of the drying process and methods used to control the sizes of fragments of pieces or parts.
14. (10) There shall be approved instructions and records which guarantee that each package item with herbal raw materials has been checked in order to detect any falsification, substitution, presence of foreign materials (such as metal or glass fragments, animal remains or their droppings, stones, or sand) or traces of rotting.
15. (11) Process instructions shall contain methods of removal of foreign materials and appropriate techniques of cleaning and (or) selection of materials of plant origin before storing it as allowed herbal raw materials or before the manufacturing process.
16. (12) Instructions for the production of herbal medicinal products shall include detailed data on the solvent, extraction duration and temperature, information on any concentration stages and applied methods.
17. (13) As herbal raw materials are not homogeneous in themselves, samples of these materials shall be taken by staff members having special skills. Each batch shall be identified with the help of documents for this batch.
18. (14) It is required to keep control samples of herbal raw materials. In case of powder production, it is necessary to keep samples of unmilled herbal raw materials.
19. (15) The staff conducting the quality control shall be specially trained and have experience of work with herbal raw materials, intermediate products or herbal medicinal products for testing them for authenticity and presence of impurities, detection in the received raw materials of growth of fungi, infestation with storage pests, detection of heterogeneity of the raw materials.
20. (16) The authenticity and quality of herbal raw materials, intermediate products or herbal medicinal products shall be determined in accordance with the requirements of the State Pharmacopoeia of the Russian Federation, regulatory documents or a normative document.