Norms and regulations

The main document regulating the conditions of production of drugs in Russia is the GOST R 52249-2004, which was prepared by the Association of Engineers to control microcontaminants (ASINKOM). Important provisions of the State Standard on the premises for the production, below:

Principles

Location, design, construction, installation, equipping and maintenance of premises and equipment must correspond to the character of work performed. Office layout and design of equipment should minimize risk of errors, provide for effective cleaning and maintenance in order to prevent cross-contamination, appearance dust or dirt and, in general, eliminate any factors that worsen the quality of the product.

Key items to the production of medicines, listed below:

General provisions

3.1 The risk of contamination of materials and products produced by the environment of production facilities (buildings) should be minimized provided all protective measures.
3.2 In exploitation rooms should be carried out precautionary measures while conducting maintenance and repair should not have an adverse effect on product quality. Cleaning and disinfection must be carried in accordance with written instructions.
3.3 Lighting, temperature, humidity and ventilation must comply with the premises and is not purpose to provide direct or indirect negative impact on the operation of equipment and drugs at the time of their production and storage.
3.4 When facilities designing and operating should provide maximum protection against the penetration insects or animals.
3.5 The premises are not allowed persons who do not have access rights to them. The production, storage and quality control facilities should not be used for pass-through staff not working in them.

Industrial zone

3.6 To minimize the risk to human health due to cross contamination in the manufacture of some drugs, such as sensitizing substances ( penicillins) or biological preparations ( live microorganisms), there should be special and isolated hardware (premises, equipment, tools service, etc.). In the same premises is not permitted the production of certain types of antibiotics, certain hormones, cytotoxins, potent medicines and non-medical products. In exceptional cases, the production of such drugs is allowed in some areas in the division cycle of production over time, with special precautions and carrying out the necessary certification (validation). In buildings used for the production of drugs, poisons are not allowed to the production for industrial use (pesticides and herbicides).

3.7 Planning decisions premises as possible to meet the logical sequence of production operations and to ensure the fulfillment of the requirements for purity.

3.8 Planning decisions working areas and storage areas within the production should provide a consistent and logical placement of equipment and materials to minimize the risk of entanglement of various drugs or their components, cross-contamination and erroneous performance or omission of any operations or production control.

3.9 If the initial and primary packaging materials, intermediate or unpackaged foods are exposed to the environment, the internal surface areas (walls, floor and ceiling) should be sleek and have no open joints and cracks, not to provide the particles and must be capable of smooth and efficient cleaning and disinfection.

3.10 The design and placement of pipes, lighting, ventilation equipment, etc., should not have seats, hard to clean. If possible, their service should be done from the outside industrial premises.

3.11 Pipelines for wastewater (sewage) must have the necessary size and be equipped with devices that prevent backflow. Avoid open gutters. If necessary, they should be shallow for easy cleaning and disinfection.

3.12 In industrial zones, depending on the product, the requirements of the operations to the environment, should provide an effective ventilation system to ensure the required temperature and, if necessary, humidity and air purification.

3.13 Raw materials are weighed, usually in specially equipped premises.

3.14 If the execution of the work is accompanied by dust (eg, sampling, weighing, mixing, production operations and packaging of dry products), it is necessary to provide measures to prevent cross-contamination and cleaning.
 

3.15 The design (including the development of planning decisions) premises for the packing of medicines should include special measures against the entanglement or cross-contamination of materials and products.

3.16 Production areas should be well lit, especially at the implementation of visual controls.

3.17 in-process controls may be conducted in the area of production, if it not interfere the process.

3.18 Storage areas should be of sufficient capacity to ensure proper storage of various categories of materials and products (raw materials and packaging materials, intermediate and unprepacked finished products, products, located in quarantine authorized for issue, rejected, returned or recalled products).

3.19 In the design and organization of storage areas should provide appropriate storage conditions. storage zone should be clean, dry and have the desired temperature. If necessary, provide special storage conditions (temperature, humidity, etc.) and their control.

3.20 In areas of receiving and delivery materials and products should be provided to protect them from adverse weather conditions. The project area should include the acceptance of treatment packages with incoming materials before storage.

3.21 If the quarantine ensured storage in separate areas of production, these areas should be clearly marked. Access to them should be restricted to persons available to eligible. Any other system that replaces the physical separation should provide equivalent safety.

3.22 Sampling shall of raw materials usually should be done in a separate area. When sampling in the storage area should be taken against the direct or cross-contamination.

3.23 Rejected, revoked or returned materials and products should be kept in isolated areas.

3.24 Potent substances and preparations must be stored in a secure and protected areas.

3.25 There should be a safe and secure storage of printed materials because of their key role in confirming the identity of medicines.

Quality Control zones

3.26 As a general rule, the quality control laboratory should be separated from production areas. This is particularly important for biological control laboratories, microbiological agents or radioisotopes, which should also be separated from each other.

3.27 The project control laboratories must meet the requirements for running operations in them. The area of laboratories should be sufficient to prevent entanglement and cross-contamination, as well as for storage of samples and protocols.

3.28 To accommodate sensitive instruments in need of protection from electromagnetic fields, vibration, humidity or other environmental factors, may provide for separate facilities.

3.29 Special requirements for laboratories, which are carried out with samples of specific substances, for example, biological or radioactive materials. 

Supporting zones

3.30 Rest rooms and dining must be separated from production areas.
3.31 Facilities for changing and storing clothes, toilets and showers must be easily accessible, their layout and dimensions must comply with staffing levels. Not allowed out of the toilet directly to the production or storage areas.
3.32 Repair areas should be, if possible, separated from production areas. If necessary, storage of spare parts and tools in the production area shall be provided special rooms or cupboards.
3.33 Facilities for animals shall be isolated from other areas are equipped with separate systems for air, and a separate entrance.

The main points of section "Production", dedicated to the necessary conditions for production of medicines in the sphere cleaner production are given below:

General provisions

5.7 All materials and products should be stored in appropriate conditions determined by the manufacturer, in order to separate the series of production and turnover of stock.
5.8 To ensure there are no deviations within the tolerance limits should ensure that control of output of production and its quantitative comparison with the data of industrial regulation.
5.9 Not allowed simultaneous or sequential operations with a variety of products in the same room with no protection from the risk of entanglement or cross-contamination.
5.10 Production and materials should be protected from microbial and other contamination at all stages of production.
5.11 When working with dry materials and products must take special precautions to prevent the formation and propagation of dust, especially when working with a highly active and sensitizing substances.

Prevention cross-contamination in the production

5.18 There should be no possibility of contamination of raw materials or products other materials or products. During production the risk of accidental cross-contamination occurs when uncontrolled emission of dust, gases, vapors, aerosols, or microbial materials (products) and from residual contamination on equipment and clothing of people. The degree of risk depends on the type of product contamination and exposed to pollution.
The most dangerous contaminants are sensitizing agents, biological preparations containing live microorganisms, some hormones, cytotoxins, and other potent substances. Especially dangerous contamination of injectable drugs, and drugs for receiving in large doses and / or for a long time.

5.19 To prevent cross-contamination should provide the following technical and organizational measures:
a) production in selected areas (required for the penicillins, live vaccines, bacterial preparations of live microorganisms and other biological products), or the division of production cycles in time with the appropriate cleaning facilities and equipment between cycles;
b) the organization of air locks and exhaust system;
c) reduce the risk of contamination caused by recirculation or re-entering of untreated or insufficiently treated air;
d) storage protective (special) clothes within the areas of production with a high risk of cross contamination;
e) The use of highly effective methods of cleaning and processing in order to avoid inadequate treatment, are often the cause of cross-contamination;
f) Use of "closed system" of production;
d) monitoring the presence of traces of the previous product or detergent and labeling equipment with the status of purity.

5.20 Should periodically check the effectiveness of measures to prevent cross-contamination in accordance with approved instructions.

It is also an important role in regulating the production of GMP standards is a group of GOST R ISO 14644 - Cleanrooms and associated controlled environments.