PHARMACEUTICAL MICROBIOLOGY - V. A. Galynkin - 2015

PART I. MICROBIAL BIOLOGY

CHAPTER 4. GOOD AGRICULTURAL AND COLLECTION PRACTICE (GACP) FOR MEDICINAL PLANTS

The guidelines for the cultivation and collection of plants comprise the following sections: Introduction, General provisions, quality assurance, personnel and qualification, buildings and production areas, equipment, documentation, seeds and propagation material, cultivation, harvesting, primary Processing, packaging, storage, and distribution [22].

Adherence to these rules ensures that medicinal plant Materials are:

1) produced under hygienic conditions with minimal microbial contamination;

2) processed and stored in a manner that prevents any degradation of their quality.

Requirements for propagation material. Seeds and planting material must be derived from plants with clearly identified characteristics: genus, species, variety, cultivar, chemotype, and origin. The Use of genetically modified plants or seeds must comply with local legislative provisions.

Agricultural efficiency principles, including appropriate crop rotation, should be taken into account. Medicinal plants must not be cultivated in soil contaminated with sewage sludge, heavy metals, waste, plant protection products, or other chemicals. Growth promoters and chemical protectants should be used in minimal amounts. Irrigation Water must meet quality standards. The use of pesticides and herbicides should be avoided wherever possible. If their application is necessary, it must be carried out strictly in accordance with the manufacturer's recommendations, by qualified personnel, and using approved equipment.

Requirements for the harvesting of herbal raw materials. Harvesting must be conducted in compliance with regulatory provisions for the protection of plant species. Harvesting Methods must not damage the habitat and should provide optimal conditions for the regeneration of the collected plants.

Harvesting should be performed under optimal conditions, avoiding wet soil, dew, rain, or high air humidity. If harvesting must take place under adverse conditions, appropriate measures must be taken to prevent moisture-induced damage, and this fact must be documented. Harvesting machinery must be adjusted to minimize soil contamination. Plants should have minimal or no contact with the soil and must be promptly transported to the primary processing facility under appropriate conditions (clean and dry). During harvesting, precautions must be taken to prevent the admixture of other plants, especially toxic ones, into the medicinal plant material.

Containers used during harvesting must be thoroughly cleaned of previous harvests. Unused containers must be stored in a dry place, free from pests, rodents, farm animals, and pets. Mechanical damage and compaction (caking) of the raw material must be prevented; therefore, bags should be filled in accordance with established standards regarding the maximum allowable weight per packaging unit. Freshly harvested raw material must be delivered to the primary processing site as quickly as possible to prevent thermal degradation.

Primary plant processing may include the following stages: washing of the herbal material; Separation of the required plant part (or slicing prior to drying, e.g., in the case of roots); fumigation; freezing; distillation; and drying.

In the case of sun drying, the material should be spread in a thin layer. To ensure adequate air Circulation, drying racks must be placed at a sufficient distance from the ground. Drying directly on the ground or in direct sunlight is permitted only when it does not adversely affect the quality of the raw material. Each batch of medicinal plant material must be inspected for numerical parameters and, if necessary, sieved. Sieves must be maintained in a clean and operable condition. Designated waste containers must be provided, which are emptied and cleaned daily. Timely packaging is recommended to protect the product and reduce the risk of pest infestation.

Product packaging should be carried out under in-process control using clean, preferably new bags, sacks, or boxes. Labeling must be clear, permanent, and non-toxic.

Specifications for starting materials.

However, medicinal plants are initially not free from microorganisms; therefore, routine quality control requires consideration of several hygiene parameters, especially when the plant is intended for medical use. Driven by this fundamental requirement, the assessment of microbial contamination has increasingly become an integral part of HACCP [23]. In this context, the microbial risk inherent in medicinal plants can vary across different production stages, and this must be accounted for in a systematic quality verification strategy (Table 14). Even in dried plant products, certain microorganisms, particularly their spores, can survive extended periods of storage.

Class="center">Table 14. Assessment of microbiological contamination risk at various stages of production of herbal medicines and food products

Symbol Structure/97.html">Definitions: "-" no risk, (+) low risk, "+" medium risk, "++" high risk.

In medical and environmental research, at least Two Types of risk can be distinguished:

— Actual risk — a quantitative expression of the harm to public health associated with environmental pollution, measured in terms of additional cases of disease, mortality, etc.

— Potential risk — the possibility of an adverse human health effect, defined as the probability of this effect occurring under given conditions. It is expressed as a percentage or a fraction of a unit. When studying the probability of infectious diseases or foodborne toxicoinfections, one can speak of the potential risk of infectious diseases. Infection hazard is largely determined by the degree of product contamination (CFU/g).

One approach to ensuring the microbiological safety of herbal raw materials and phytopharmaceuticals derived from them is The Development of Microbiological Risk Analysis (MRA) [15, 17]. It serves as a novel tool for the science-based evaluation of both food-related risk factors and the measures to be taken to minimize or eliminate them.

Manufacturers of herbal medicinal products must ensure that they use only starting materials of plant origin produced in compliance with GACP. Comprehensive documentation regarding audits of herbal starting material suppliers—conducted either by the herbal medicine manufacturer or on their behalf—must be available. Audit results concerning herbal raw materials are fundamental to ensuring the quality of the starting material. The manufacturer must verify that the suppliers of the plant material/product operate in accordance with Good Agricultural and Collection Practice (GACP) guidelines.

4.1 MICROBIOLOGICAL CONTROL OF Medicinal Products

Herbal medicinal raw materials can become contaminated with microorganisms during production, with infection occurring via water, non-sterile pharmacy glassware, production facility air, and personnel handling [12].

Contamination of medicinal raw materials can occur at all stages of harvesting and storage. The moistening of plants and herbal materials promotes the active proliferation of microorganisms. Proliferated microorganisms alter the pharmacological properties of preparations derived from medicinal plants. Microorganisms may also be introduced from the ENVIRONMENT AND HUMAN handlers, contaminating medicinal products during their manufacturing process from herbal raw materials. To maintain sanitary standards in drug manufacturing, sanitary and microbiological control is performed on the environmental objects of the facility and on every batch of the finished dosage form. Medicinal products for parenteral administration (injections), eye drops, ointments, films, and others specified in regulatory and technical documentation must be sterile. Sterility testing of medicinal products is carried out by inoculation into thioglycolate medium to detect various Bacteria, including anaerobes; inoculation into Sabouraud medium detects Fungi, primarily of the genus Candida. The sterility of medicinal products with antimicrobial activity is determined using Membrane filtration: after filtering the test product, the filter is divided into parts and placed into liquid nutrient media to cultivate the retained microorganisms. If no growth is observed, the product is considered sterile. Medicinal products that do not require sterilization generally contain microorganisms and are therefore tested for microbial limit (microbial purity): Quantitative determination of viable bacteria and fungi per 1 g or 1 ml of the product is performed, along with screening for specific microorganisms (enterobacteria, Pseudomonas aeruginosa, Staphylococcus aureus) that must be absent in non-sterile medicinal products. Per 1 g or 1 ml of herbal raw material for oral administration, there must be no more than 1000 bacteria and 100 Yeasts and Molds. In cases of topical application (ear, nasal, or intravaginal use), the total microbial count must not exceed 100 microbial Cells per 1 g or 1 ml of the product. Tablet formulations must be free of pathogenic microflora, and total contamination must not exceed 10,000 microbial cells per tablet.