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Protection of medicinal products from contamination. The terrible word contamination! State Pharmacopoeia

Herbal medicinal raw materials can be contaminated with microorganisms at all stages of their preparation (collection, drying, grinding, packaging, storage). Representatives of air microflora predominate in raw materials, spore and non-spore rods, cocci, pigment bacteria, molds, yeast are often found. Being on herbal medicinal raw materials, microbes not only mechanically pollute it, but also if stored improperly (high humidity, dustiness of the room, the presence of insects, rodents, etc.) multiply on it, using it for life. At the same time, under the action of microbial enzymes, pharmacologically important active substances are destroyed, which leads to a decrease in its medicinal value. Signs of spoilage are changes in consistency, color, odor. Fresh raw materials deteriorate especially quickly.

Sources of contamination of finished products – non-sterile air of pharmacies, equipment, raw materials, dishes, corks, water, hands of staff. The possibility of spreading microbes, especially pathogenic ones, through recipes is also becoming essential.

Microbial spoilage is subject to:

    powders (especially talc, starch), fees

    solutions, potions, infusions, decoctions, drops

    ointments, pastes, balls, candles

    sterile injectables

The largest number of microbes can be in aqueous infusions, broths, the smallest - in tinctures. Therefore, the storage of infusions and decoctions in the refrigerator should not exceed 2 days.

Being in finished medicinal preparations, microorganisms multiply in them, while destroying the active components of the preparation. The most common signs of spoilage of infusions and decoctions are the appearance of turbidity, discoloration, the formation of a film, sediment, sour odor, etc. These signs of spoilage are especially pronounced when sugar syrup is added and when stored in a warm room. Microbial contamination of finished products largely depends on the observance of the sanitary and hygienic regime in pharmacies.

To prevent microbial contamination medicines, the following rules must be observed:

    disinfect the air with germicidal lamps,

    observe the rules of personal hygiene,

    comply with the technology for the preparation of medicinal products,

    to properly store medicinal raw materials and finished dosage forms,

    use preservatives if necessary.

3.1. Determination of microbial contamination of drugs

According to the requirements of the WHO and the State Pharmacopoeia of the Republic of Belarus, there are certain standards limiting microbial contamination of drugs. Methods of microbiological analysis are used to detect microorganisms in drugs. Usually, the number of microorganisms in 1 g of dry preparation or in 1 ml of solution is determined. The methods of microbiological analysis of a specific dosage form are individual. This is due to the bactericidal and bacteriostatic action of the drugs themselves, as well as to the sensitivity or resistance of microorganisms to this drug.

The microbiological purity of medicinal products, substances and auxiliary materials for the production of medicinal products must comply with the requirements set out in Article 5.1. State Pharmacopoeia of the Republic of Belarus "General texts on sterilization" (tables 3-4).

Table 3 - Microbiological purity of medicines

Application

For parenteral administration

Ophthalmic medicines

For application to open wounds and burns

Other medicinal products subject to the requirement of "sterility"

Sterility

For topical, transdermal application

For intravaginal use

For guidance in the yxa cavity, butca

For administration into the respiratory tract (except for those medicines that must be sterile)

The total number of aerobic bacteria and fungi (in total) - no more than 10 2 in 1 g or 1 ml

Absence of bacteria families Enterobacteriaceae in 1 g or in 1 ml

Absence P... aeruginosa in 1 g or in 1 ml

Absence S. aureus in l g or in 1 ml

For oral administration or rectal administration

A. Medicinesufrom substances of synthetic origin

B. Medicinal funds from substances of natural origin (vegetable, animal, mineral), per excluding funds included in the Category 4

    The total number of aerobic bacteria is not more than 10 3 in 1 g or 1 ml

The total number of mushrooms is not more than 10 2 in 1 g or 1 ml

Absence E... withli in 1 g or 1 ml

The total number of aerobic bacteria is not more than 10 4 in 1 g or 1 ml

The total number of mushrooms is not more than 10 2 in 1 g or 1 ml

Absence E... withli b1 g or b1 ml

Absence of bacteria of the genus Salmonella in 10 g or in 10 ml

Absence P. aeruginosa in 1 g or in 1 ml

Absence S. aureus 1 g or in 1 ml

Enterobacteriaceae - no more than 10 2 in 1 g or 1 ml

V. Medicines for children

The total number of aerobic bacteria is not more than 500 per 1 g or 1 ml

The total number of mushrooms - no more than 50 in 1 g or 1 ml

Enterobacteriaceae in 1 g or in 1 ml

Absence P. aeruginosa in 1 g or in 1 ml

Absence S. aureus in 1 g or in 1 ml

Medicines consisting of one type of raw material (packaged products) or several (fees), also herbal raw materials "Angro"

A. Herbal medicinal products or medicinal raw materials "Angro", used in the form of infusions and decoctions, prepared using heat treatment

B. Medicinal herbal products or medicinal raw materials "Angro", used without heat treatment

The total number of aerobic bacteria is not more than 10 7 in 1 g or 1 ml

The total number of mushrooms is not more than 10 5 in 1 g or 1 ml

    E... withli- no more than 10 2 in 1 g

The total number of aerobic bacteria is not more than 10 in 1 g or in 1 ml

The total number of mushrooms is not more than 10 4 in 1 g or 1 ml

Absence E... withli in 1 g or in 1 ml

Absence of bacteria of the genus Salmonella in 10 g or in 10 ml

Enterobacteriaceae - no more than 10 2 in 1 g or 1 ml

Table 4 - Microbiological purity of substances and auxiliary materials for the production of medicines

Application

Substances

for production:

Sterile

medicines

Non-sterile medicines belonging to the Category 2

The total number of aerobic bacteria and fungi

(in total) no more than 10 2 in 1 g or in 1 ml

Absence of bacteria of the family Enterobacteriaceae in 1 g or in 1 ml

Category 3B non-sterile medicinal products

Absence P. aeruginosa in 1 g or in 1 ml

Absence S. aureus 1 g or 1 ml

Synthetic substances

origin for the production of non-sterile medicines

The total number of aerobic bacteria is not more than 10 2 in 1 g or in 1 ml

The total number of mushrooms is not more than 10 2 1 g or 1 ml

Absence E... withli in 1 g or in 1 ml

Natural substances

origin (vegetable, animal or mineral)

Auxiliary materials (wheat flour, starch, talc, etc.)

The total number of aerobic bacteria is not more than 10 2 in 1 g or 1 ml

The total number of mushrooms is not more than 10 per 1 g or 1 ml

Absence E... withli in 1 g or in 1 ml

Absence of bacteria of the genus Salmonella in 10 g or in 10 ml

Absence P. aeruginosa in 1 g or in 1 ml

Absence S. aureus in 1 g or in 1 ml

Enterobacteriaceae no more than 10 2 1 g or 1 ml

As you can see from the tables, sterile there should be injections, ointments, films, eye drops and all dosage forms for newborns, for the local treatment of purulent wounds, ulcers, burns.

Dosage forms for administration per os should not contain pathogenic and opportunistic microorganisms.

Allowed no more than 100 microbial cells in 1 g (ml) of the drug for dosage forms of local, intravaginal use, as well as for use in the ear and nose.

Some non-sterile medicinal products contain components and preservatives that have antimicrobial action. To avoid an incorrect assessment of the results of the test for microbiological purity, the effect of the drug in relation to the following test cultures is preliminarily determined: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis (cereus), Candida albicans... For cultivation of test cultures, appropriate media are used (table 5).

Table 5. Media for the cultivation of test cultures

Prevention of cross contamination

in production

5.18. Contamination of raw materials or products with other raw materials or products must be excluded. This risk of accidental cross-contamination arises from the uncontrolled spread of dust, gases, vapors, aerosols or microorganisms, from the handling of materials and products, due to residues on equipment and on personnel clothing. The degree of risk depends on the type of contaminant and the contaminated product. The most dangerous contaminants include highly sensitizing substances, biological drugs containing live microorganisms, certain hormones, cytotoxic drugs and other highly active substances. The most dangerous is the contamination of drugs intended for injection, as well as drugs taken in large doses and / or for a long time.

5.19. To prevent cross-contamination, appropriate technical and / or organizational measures should be provided, for example:

    production in dedicated areas (mandatory for products such as penicillins, live vaccines, medicinal products containing live bacteria, and some other biological medicinal products) or production based on production cycles (time-division campaigns) followed by appropriate purification;

    availability and organization of air locks and exhaust devices;

    minimizing the risk of contamination caused by recirculation or reintroduction of untreated or inadequately treated air;

    storing protective clothing indoors where products are processed that pose a particularly high risk of cross-contamination;

    the use of cleaning and decontamination methods with known efficacy, since ineffectively cleaned equipment is usually a source of cross-contamination;

    the use of "closed systems" of production;

    control of the presence of residues and the use of labels indicating the status of equipment cleaning.

5.20. Cross-contamination prevention measures and their effectiveness should be periodically reviewed in accordance with approved procedures.

Validation

5.21. Validation activities should support these Rules; they should be carried out in accordance with established procedures. Results and conclusions should be documented.

5.22. When a new industrial regulation or a new production method is introduced, it is necessary to prove their suitability for mass production. It must be demonstrated that this process, using the specified materials and equipment, allows the continuous production of products of the required quality.

5.23. Significant changes to the manufacturing process, including any change to equipment or raw materials and materials, which may affect product quality and / or process reproducibility, must be validated.

5.24. Processes and procedures should be periodically revalidated (revalidated) to ensure that they remain suitable for achieving specified results.

Originalraw materials

5.25. The purchase of raw materials is a responsible operation in which personnel who have detailed and complete information about the suppliers must be involved.

5.26. Raw materials should only be purchased from approved suppliers specified in the relevant specification and, if possible, directly from the manufacturer. It is recommended that the specifications set by the manufacturer for the feedstock are agreed with the suppliers. All aspects of raw material production and control with respect to handling, labeling, packaging, rejection procedures, and claims handling must be agreed between the manufacturer and the supplier.

5.27. In each delivery, the integrity of the packaging and seals should be checked, the compliance of the information specified in the delivery note with the supplier's labels.

5.28. If one supply of raw materials consists of different lots, then each lot should be considered as separate with respect to sampling, testing and issuance of authorization for use.

5.29. The raw materials located in the storage area must be appropriately labeled (see paragraph 5.13 of Part I of this Regulation). The labels must contain at least the following information:

    product name and, if necessary, the in-house code;

    manufacturer's batch number and / or batch number assigned upon acceptance;

    where applicable, the status of the content (for example: quarantined, on trial, allowed, rejected);

    the expiry date or, where applicable, the date after which a retest is required.

If fully computerized storage systems are used, it is not necessary to include all of this information on the label.

5.30. Adequate procedures or measures should be in place to ensure the authenticity of the contents of each raw material container. The containers from which the samples were taken must be marked (see paragraph 6.13 of Part I of this Regulation).

5.31. Use only raw materials that have been approved by the quality control department and have not expired.

5.32. Raw materials should only be dispensed by designated individuals in accordance with a written procedure to ensure that the correct raw materials are accurately weighed or weighed into clean and properly labeled containers.

5.33. Each feedstock issued and its weight or volume should be independently verified; this check should be documented.

5.34. Raw materials issued for each batch should be stored together and clearly labeled.

Technological operations:

intermediate and bulk products

5.35. Before starting any process operation, steps must be taken to ensure that the work area and equipment are clean and free of any feedstock, product, product residue or documentation not related to the planned operation.

5.36. Intermediate and bulk products should be stored under appropriate conditions.

5.37. Critical processes must be validated (see clauses 5.21 5.24 - "Validation" - part I of these Rules).

5.38. All necessary controls during production and control of the production environment must be carried out and documented.

5.39. Any significant deviation from the expected yield should be documented and investigated.

Packaging materials

5.40. The procurement, control and handling of virgin and printed packaging materials should be given the same care as the raw materials.

5.41. Particular attention should be paid to printed materials. They should be stored in adequately secure conditions, excluding access by unauthorized persons. Cut labels and other loose printed materials should be stored and transported separately in closed containers that prevent them from being mixed up. Authorization to use packaging materials should only be issued by designated persons in accordance with an approved and documented procedure.

5.42. Each shipment or batch of primary or printed packaging materials must be assigned an identification number or identification mark.

5.43. Expired or unusable printed or primary packaging materials must be destroyed and documented.

Packing operations

5.44. In planning packaging operations, special care should be taken to minimize the risk of cross-contamination, mix-ups or substitutions. It is not allowed to pack products of different types in close proximity to each other, except in cases involving physical separation.

5.45. Before starting packaging operations, steps must be taken to ensure that the work area, packaging lines, printing machines and other equipment are clean and free of any previously used drugs, materials or documents unless required for the planned operation. Line cleaning should be carried out according to the appropriate procedure.

5.46. The name and batch number of the product to be packaged must be indicated on each packing unit or line.

5.47. When products and packaging materials arrive at the packaging area, check their quantity, identity and compliance with packaging instructions.

5.48. The materials of the primary packaging must be clean before starting the filling operation. Care should be taken to prevent and eliminate any contamination such as glass shards and metal particles.

5.49. In general, labeling should be done as soon as possible after filling and sealing. If this does not happen, the necessary measures should be taken to ensure that no confusion or mislabelling occurs.

5.50. Any printing operations (e.g. batch numbers, expiration dates) performed either as a stand-alone operation or during packaging should be carefully monitored and documented for correctness. Particular attention should be paid to manual marking, which should be checked regularly.

5.51. Special precautions must be taken when using cut labels and stamps outside the packaging line. To prevent confusion in printed matter, roll labels are preferred over cut labels.

5.52. Checks should be carried out to ensure that all electronic code readers, label counters and similar devices are operating correctly.

5.53. Printing or embossing on packaging materials must be legible and resistant to fading or rubbing.

5.54. When monitoring the packaging process of products on the line, at least the following should be checked:

    general appearance of packages;

    completeness of packages;

    using the correct types of products and packaging materials;

    the correctness of applying any marking;

    correct operation of control devices on the line.

Samples taken from the packaging line should not be returned to the line.

5.55. If unforeseen circumstances have arisen during the packaging of products, it can be returned to production only after a special inspection, investigation and with the permission of a person having the appropriate authority. These actions should be drawn up in the form of a protocol, which should be kept in the prescribed manner.

5.56. If there is a significant or unusual discrepancy found during the balancing of bulk, printed packaging material and finished product units produced, an investigation should be carried out and the cause of the discrepancy established prior to issuing a release.

5.57. Upon completion of packaging operations, any remaining batch number packaging materials must be destroyed and documented. Unlabeled packaging materials are returned to the warehouse in accordance with an approved procedure.

Finished products

5.58. Before a release is issued, finished products must be kept in quarantine under the conditions established by the manufacturer.

5.59. Prior to obtaining permission to release, an assessment of the finished product and documentation must be carried out, the procedure for which is given in Chapter 6 (Quality Control) of these Rules.

5.60. After issuance of a release, finished products should be stored as marketable stock under conditions established by the manufacturer.

Rejected, reused
and returned materials and products

5.61. Rejected materials and products must be clearly labeled and stored separately in restricted areas. They must be returned to the supplier, recycled (if applicable) or destroyed. Any actions taken must be documented and approved by authorized persons.

5.62. Recycling of rejected products is allowed in exceptional cases, provided that there is no deterioration in the quality of the finished product and all requirements of the specifications are met. Processing is carried out in accordance with the approved industrial regulations after assessing the possible risk with subsequent documentation.

5.63. The reuse of an entire batch or part of a previously produced batch of appropriate quality by combining it with a batch of the same product at a certain stage of production, provided for by industrial regulations, should be authorized in advance, taking into account an assessment of the emerging risks, including any possible impact on the shelf life. Reuse activities should be documented.

5.64. The need for additional control of any finished products that have been processed, or products that have included reused products, is determined by the quality control department.

5.65 Products returned from the market, over which control by the manufacturer has been lost, should be destroyed if the conformity of their quality to the established requirements is not confirmed. The decision to resell, relabel or reuse can only be made after specific analysis by the quality control department in accordance with a written procedure. In this case, it is necessary to take into account the nature of the product, its background and condition, adherence to special storage conditions and the time elapsed since the date of production. In case of any doubts about the quality of the product, it is not allowed to be reused or re-released, but it is allowed to chemically process it in order to regenerate the active ingredients. All actions performed must be documented.

Chapter6. QUALITY CONTROL

Principle

Quality control includes sampling, testing and checking for compliance with the requirements of specifications, instructions and other documents, organization of work, documentation and issuance of release permits. The purpose of quality control is to prevent the use or sale of materials or products that do not meet specified requirements. Quality control is not limited to laboratory work, it must be involved in all decisions regarding product quality. The fundamental principle for the satisfactory operation of the quality control department is its independence from the production units (see also Chapter 1 of Part I of this Regulation).

General requirements

6.1. Each drug manufacturer must have a quality control department. This department should be independent from other departments. The head of this department must have the appropriate qualifications and experience, and must have one or more control laboratories at his disposal. The department must be provided with sufficient resources to ensure that all quality control activities are carried out efficiently and reliably.

6.2. The main responsibilities of the head of the quality control department are summarized in Chapter 2, Part I of these Rules. The quality control department as a whole may have other responsibilities as well, such as establishing, validating and implementing all quality control procedures, storing control samples of raw materials, materials and products, ensuring the correct labeling of packages with raw materials and products, monitoring product stability. , participation in the investigation of claims regarding product quality, etc. All of these responsibilities should be performed in accordance with approved procedures and documented where necessary.

6.3. When assessing the quality of the finished product, all relevant factors should be considered, including the manufacturing conditions, the results of in-process controls, review of production documentation (including packaging documentation), compliance with finished product specifications, and final packaging verification of the finished product.

6.4. Quality control personnel should have access to production areas to take samples and carry out the necessary research.

Good Laboratory Quality Control Rules

6.5. The premises and equipment of control laboratories must comply with the general and special requirements for quality control areas given in Chapter 3, Part I of these Rules.

6.6. The personnel, premises and equipment of laboratories must correspond to the type and volume of production. In some cases, the use of third-party laboratories is allowed, provided that they fulfill the requirements set out in Chapter 7 (“Activities transferred to another organization (outsourcing)”), Part I of these Rules, and make appropriate entries in the quality control documents.

Documentation

6.7. The documentation of control laboratories shall comply with the principles set out in Chapter 4 of Part I of these Regulations. An important part of this documentation relates to quality control. The following documentation should be readily available in the quality control department:

    specifications;

    sampling procedures;

    test methods and documents (including analytical operational sheets and / or laboratory journals);

    analytical reports and / or certificates;

    the results of monitoring the production environment, where required;

    test method validation reports, where applicable;

    procedures and protocols for instrument calibration and equipment maintenance.

6.8. Any quality control documentation related to records of production of batches of products must be kept for one year after the expiry date of the batch and for at least five years after the conformity assessment of the batch by an authorized person in accordance with the established procedure (clause 2.4, subparagraph c of part I of these Of the Rules).

6.9. For some types of data (for example, analytical test results, finished product yields, parameters of the production environment, etc.), it is advisable to store records in a form that allows you to evaluate trends (trends) of changes in parameters.

6.10. In addition to the information that forms part of the batch dossier, other raw data such as laboratory journals and / or records should be retained and readily available.

Sample selection

6.11. Sampling should be carried out in accordance with approved written procedures that define:

    sampling method;

    used equipment;

    the amount of sample to be taken;

    procedures for dividing the selected sample into parts (if necessary);

    the type and condition of containers used for sampling;

    identification of containers with taken samples and containers from which samples were taken;

    any special precautions to be observed, especially when sampling sterile and harmful substances;

    storage conditions;

    procedures for cleaning and storing sampling equipment.

6.12. The selected control samples should be a representative sample of a batch of raw materials, packaging materials or finished products. Additional samples can also be taken to monitor the most important stages of the process (for example, its start or end).

6.13. The label of the container with the samples taken must indicate its contents, batch number, date of sampling, as well as the designation of the package from which these samples were taken.

6.14. Additional requirements for control and archival samples are given in Appendix 19 of these Rules.

Testing

6.15. Quality control procedures should be validated, with the exception of those established by pharmacopoeial quality standards. All tests listed in the registration dossier must be carried out in accordance with approved methods.

6.16. The test results obtained should be recorded and verified to ensure that they are consistent with each other. All calculations should be carefully checked.

6.17. The tests carried out should be recorded with at least the following information on the documents:

    the name of the raw materials, packaging materials or products and, if necessary, the dosage form;

    the batch number assigned upon acceptance and, where applicable, the manufacturer's batch number and the manufacturer's and / or supplier's name;

    test results, including observations, calculations and links to all documents containing the results of the analyzes performed;

    dates of testing;

    surnames and initials of the persons who conducted the test;

    the names and initials of the persons who reviewed the tests and the results of the calculations, where applicable;

    a clear conclusion on the issue of permission or rejection of the product (or other decision on the status of the product), date and signature of the person in charge.

6.18. All control in the production process, including that which is carried out in the production area by production personnel, must be carried out in accordance with the methods approved by the quality control department, and its results must be documented.

6.19. Particular attention should be paid to the quality of laboratory reagents, volumetric laboratory glassware and titrated solutions, standard samples and culture media. Their preparation and preparation must comply with the requirements of the instructions, approved in the prescribed manner.

6.20. Laboratory reagent solutions must be labeled with the date of preparation and signed by the contractors. The shelf life of unstable reagents and culture media and specific storage conditions must be indicated on the label. For titrated solutions, the date of the last titer determination and the corresponding correction factor should be indicated.

6.21. If necessary, the container should indicate the date of receipt of each substance used for testing (for example, reagents and reference materials), with appropriate instructions for its use and storage. In some cases, after receipt or before use of a reagent, it may be necessary to carry out an identity test and / or other test.

6.22. Animals used to control components, raw materials or products should, if necessary, be quarantined before handling them. The care and supervision of animals should be organized so as to ensure their suitability for the intended use. Animals should be marked and documented beforehand.

Document

... control quality given his medicinal forms. Manufacturing company medicinal funds - organization implementing production medicinal funds in accordance with requirements Federal ...

The emergence of a new expression or form by combining the elements of two expressions or forms that are somewhat similar. For example, the incorrect expression "play a meaning" arose as a contamination of the two expressions "play a role" and "have a meaning." In addition to compounds in one-two-way expressions or proverbs ("Don't spit in the well, if you fly out - you won't catch"), contamination is also called the connection of names and words (more precisely, roots), for example, "F. Tolstoyevsky "(Tolstoy and Dostoevsky)," tragicomic "(from tragic and comic) or "At the Academy of Poetry - in lakeside castle white marble "(Igor Severyanin).

In a broad sense, the concept of contamination is based on the following provisions:

  1. Formally, in the neoplasm, both original words are represented by at least one letter (more precisely, a phoneme)
  2. In the meaning of a neoplasm, the meanings of both original words are intertwined in a complex way.
  • Scope of Operation - Headers
  • The nature of the highlighted part:
  • common nouns, cf .: gay the swarm of our time; I was a minister fence ony; court yerzhanki; beer ner is always ready; why are you poisoning pace atelier? (see also Kaschenism)
  • proper name, cf .: At the mine of the OGPU now work knock Anovski; Boris Inca laevich on the warpath; Who was, who was Alla and etc.;
  • abbreviations, compare: The most to AiF new day of the city; AiF Oriya; Bam meekness; Causes great SORM nenie, etc.
  • pronounced "fashionableness" of the topic covered in the publication, compare: Gay nially !; WITH Internet will the human race rise up as a national?; HIV silence, etc.

In literature

Contamination is also called a combination of episodes from different works and an introduction to the story of events from another literary work.

Chemistry and biology

Pharmaceuticals

In pharmaceuticals - mixing (re-grading, leading to the wrong selection of drugs). The term is used in regulatory documents.

see also

Notes (edit)


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Synonyms:

See what "Contamination" is in other dictionaries:

    contamination- (in psychology) (from Latin contaminatio confusion) erroneous reproduction of words, which consists in combining syllables related to different words into one word (for example, instead of the words "protein" and "coil", "squirrel" is pronounced). Such permutations ... ... Big psychological encyclopedia

    - [lat. contaminatio confusion] 1) confusion, fusion of dissimilar factors into a new set; 2) lingual. the emergence of a new word or expression as a result of mixing parts of two words and expressions (eg, incorrect "play the meaning" like ... ... Dictionary of foreign words of the Russian language

    Mixing, combining, contamination Dictionary of Russian synonyms. contamination see mixing Dictionary of synonyms of the Russian language. Practical guide. M .: Russian language. Z.E. Aleksandrova. 2011 ... Synonym dictionary

    - (from Latin contaminatio contact mixing), 1) the interaction of similar in meaning or sounding linguistic units (most often words or phrases), leading to the emergence, not always natural, of new units or to the development of one ... ... Big Encyclopedic Dictionary

    Mixing magma with completely assimilated host or other izv. In the process of K., foreign material is assimilated by magma by its direct melting or by matasomatic reactions and removal of a part ... ... Geological encyclopedia

    - (from Lat. contaminatio confusion) false reproduction of information, characterized by the unification in the image or concept of parts belonging to different objects. For the manifestation of the phenomenon of contamination, semantic and phonetic is important ... ... Psychological Dictionary

    CONTAMINATION, contamination, women. (lat. contaminatio contact) (ling.). The emergence of a new form or expression or a new meaning of a word through crossing, combining elements of two homogeneous consonant forms. Incorrect expression ... ... Explanatory dictionary Ushakova

    CONTAMINATION, and, wives. 1. Mixing, uniting (book). 2. In linguistics: the emergence of a new expression, word, form by combining the elements of two expressions or forms than n. similar (eg, the wrong expression "play the meaning" of ... ... Ozhegov's Explanatory Dictionary

    Contamination of a sample or culture; in microbiol. - clogging (contamination) of a pure culture by extraneous microorganisms. (Source: "Microbiology: glossary of terms", Firsov NN, M: Bustard, 2006) ... Microbiology Dictionary

    contamination- and, w. contamination f. lat. contaminatio bringing into contact, mixing. 1.lingual. The emergence of a new word or expression through crossing, combining parts of two words or expressions; eg wrong expression to reap the lot ... Historical Dictionary of Russian Gallicisms

    CONTAMINATION- (from Lat. contaminatio desecration, infection), an uncommon term for designating the moment of infection, that is, the introduction of an infectious agent into the body (see Infection). In psychiatry, the term K. denotes an incorrect addition of words, when the beginning or end ... ... Great medical encyclopedia

Books

  • Contamination in modern English: A Fait Accompli, N. A. Lavrova. The monograph is devoted to the multifaceted study of the word-formation model of contamination in modern English language... The work examines the structural-semantic and ...

Today, quality control and safety of medicines entering the consumer market is becoming one of the main concerns. In the pharmaceutical industry, a quality assurance system for medicines is being introduced, from their creation to their sale and use by the consumer. One of the most important parameters characterizing the quality of dosage forms is its microbiological purity.

Many drugs serve as a medium for the development of microorganisms. Medicines contaminated (contaminated) with microorganisms pose a danger to the patient. In the process of evolution, the body of an adult with the help different systems adapted to protection from microflora (peeling of the epidermis, acidic environment of the stomach, lysozyme in the lacrimal fluid, etc.), but the most important organs and biological fluids (brain, heart, blood, cerebrospinal fluid) always remain sterile. The protective mechanisms of a newborn are imperfect, and in a sick person they are weakened, therefore, the risk of infection increases sharply when using non-sterile external dosage forms (ointments, oils, etc.). There is a great danger of infection of the body and with the introduction of injection solutions, in the treatment of injuries, burns, frostbite.

Microorganisms contained in the dosage form can cause decomposition of active and auxiliary substances. This leads to a loss of the therapeutic effect of the drug, a change in the appearance of the dosage form, and sometimes to the formation of toxic products. Unlike pathogenic microorganisms, many saprophytes have a wide range of enzymes and are capable of degrading a wide variety of substances, proteins, lipids, etc.

The intensity of destruction of dosage forms and substances depends on their concentration, humidity, ambient temperature, as well as the nature and degree of initial contamination. The shelf life of medicinal products is also important.

Sources of microbial contamination:
indoor air. It is known that 1 liter of air in a big city contains from 1,000 to 1 million different particles, which are carriers of microflora - one microorganism per 1,000 suspended particles;
initial medicinal and auxiliary substances of animal, vegetable and synthetic origin (for example, highly contaminated - pancreatin, pepsin, glucose, talc, starch, agar, etc.);
dispersion media, including purified water, microbial contamination of which occurs during transportation, storage;
auxiliary materials (filtering - cotton wool, paper, gauze; packaging - paper, bottles, cans, boxes, corks);
human. In a calm state, a person in 1 minute emits up to 200 thousand different particles (scales, epidermal cells, etc.), while moving - up to 1 million, therefore, the presence of a significant number of visitors in the pharmacy's trading floor, the drift of dust, dirt from the outside leads to an increase microflora in the air that penetrates into production facilities;
pharmacy staff. Even in special clothing in clean rooms, employees emit into the environment up to 2 million particles ranging in size from 0.5 microns to 5 microns, 300 thousand particles measuring 5 microns and more than 160 particles containing microorganisms.
Sources of pollution are mainly mouth and nose. During a conversation, the number of particles released by a person increases;
technological process (equipment, devices, apparatus).

In recent years, the problem of microbial contamination of drugs has become the subject of discussion at international symposia, meetings of the World Federation of Pharmacists and other commissions, since numerous pharmaceutical products serve as a substrate for the reproduction of microorganisms.

Because a pharmacy is a health care institution, it must meet a high sanitary level. Therefore, measures aimed at reducing microbial contamination of the air of pharmacies, equipment, hands of personnel have great importance to reduce, and in some cases completely eliminate microbial contamination of drugs.

8.2.1 It is necessary to exclude the possibility of contamination of raw materials or products with other materials and products. The risk of accidental cross-contamination in the manufacturing process arises from the uncontrolled release of dust, gases, vapors, aerosols or
microorganisms from materials and products, as well as from residual contaminants on equipment and clothing of people.

8.2.2 The degree of risk depends on the type of contamination and the product subject to contamination. The most dangerous contaminating substances (contaminants) include sensitizing substances, biological preparations containing living microorganisms, some hormones, cytotoxins and other potent substances.

8.2.3 Contamination is especially dangerous for drugs used for injection, as well as for drugs intended to be taken in high doses, long-term use and / or long-term use.

8.2.4 To prevent cross-contamination, it is necessary to provide for such technical and organizational measures as:

Separation of production zones (mandatory for such preparations, penicillins, live vaccines, bacterial preparations from live microorganisms and some other biological preparations) or separation of their production cycles in time, with appropriate cleaning of the premises and equipment between cycles;

Organization of air locks and exhaust devices;

Reducing the risk of contamination caused by recirculation or reintroduction of untreated or inadequately treated air;

The use of highly efficient cleaning and treatment methods, due to the fact that insufficient cleaning is often the cause of cross-contamination.

Use of "closed circuits" of production;

Residue control and equipment labeling with cleanliness status.

8.2.5 The effectiveness of measures to prevent cross-contamination should be periodically reviewed in accordance with approved guidelines.

Validation (qualification)

8.3.1 Validation (qualification) studies should enhance the effectiveness of appropriate manufacturing and be carried out in accordance with approved instructions. Their results and conclusions should be recorded.

8.3.2 When approving new technological regulations or production methods, it is necessary to check the suitability of the production process, materials and equipment used for mass production. It must be shown that the specified process, the materials used and the prescribed equipment are capable of consistently producing the product of the required quality.



8.3.3 Significant changes in technology, including any changes to equipment or materials that can affect the quality of the product or the reproducibility of the process, shall be validated (qualified).

8.3.4 Manufacturing processes and procedures should be revalidated to confirm that they continue to achieve the required results.

Source materials

8.4.1 The acquisition of raw materials is a responsible operation that must be carried out by employees who have detailed and complete information about the suppliers.

8.4.2 Starting materials should be purchased from approved suppliers specified in the relevant specification and, if possible, directly from the manufacturer. Requirements for them should be specified in the specification for starting materials approved by the manufacturer of the medicinal product and agreed with the supplier. All aspects related to the production and control of raw materials, including handling, labeling, packaging, as well as procedures for filing complaints and rejection of products, must be agreed between the supplier and the manufacturer.



8.4.3 In each delivery, the integrity of containers, packaging and seals, as well as the correspondence between the data on the consignment note and the supplier's marking should be checked.

8.4.4 If a single supply of starting materials consists of several lots, then each lot should be considered as independent with respect to sampling, testing and obtaining permission to use.

8.4.5 Raw materials stored in the warehouse should be appropriately labeled. The labeling must include at least the following information:

The designation of the original product and, if necessary, the in-house code;

Batch number assigned upon acceptance;

If necessary, the status of the content (for example, in quarantine, on testing, permission received, marriage);

If necessary, the expiration date or the date after which it is necessary to re-check.

If the warehouses are completely computerized, then it is not necessary to indicate all this information on the label.

8.4.6 Instructions and procedures should be developed and approved to ensure that the contents of each package are identical with the starting materials. Bulk finished product packages from which samples have been taken must be appropriately labeled.

8.4.7 In the manufacture of medicinal products, only those raw materials that are approved by the quality control department and the shelf life of which have not expired can be used.

8.4.8 Raw materials should only be dispensed by designated individuals in accordance with written instructions ensuring that the required materials are accurately weighed and weighed into clean and properly labeled containers.

8.4.9 An independent verification of each substance dispensed, its mass and volume should be carried out. The results of the audit should be documented.

8.4.10 Materials issued for each batch should be kept together and clearly marked.

8.5 Technological operations: intermediate and bulk finished products

8.5.1 Before starting any technological operation, it is necessary to take measures to ensure that the production area and equipment are clean and do not contain remnants of raw materials, products, product residues or documentation not related to this process.

8.5.2 Intermediate and bulk finished goods should be stored under appropriate conditions.

8.5.3 Critical processes shall be validated in accordance with subsection 8.3 "Validation (qualification)" of this standard.

8.5.4 All necessary internal control and monitoring activities should be documented. environment in production.

8.5.5 Any material deviations from the expected yield should be recorded and investigated.

Packaging materials

8.6.1 The acquisition, storage and control of virgin and labeled packaging material should be given the same care as for the raw material.

8.6.2 Particular attention should be paid to the quality of the labeled materials:

They must be stored in a secure environment, excluding access by unauthorized persons;

Cut labels and other scattered materials should be stored and transported separately in a closed container that prevents them from being mixed up;

8.6.3 Authorization for the use of packaging materials should only be given by specially designated persons, in accordance with an approved written instruction.

8.6.4 Each delivery or batch of labeled or primary packaging material must be assigned a number or distinguishing mark.

8.6.5 Expired or unusable labeled or primary packaging materials should be destroyed with a record.

Packing operations

8.7.1 Packaging procedures should be designed to minimize the risk of cross-contamination, mix-up or substitution. Packaging of various types of products in the immediate vicinity is not allowed if there is no physical separation of the packaging areas.

8.7.2 Before starting packing operations, ensure that the work area, packaging lines, marking machines and other equipment are clean and free of materials, products or documentation related to prior work unless they are used in the current process. Preparation (cleaning) of the product packaging line must be carried out in accordance with the instructions.

8.7.3 The name and batch number of the product to be packaged must be indicated on each line or installation.

8.7.4 Upon receipt of products and packaging materials in the packaging workshop, their quantity, authenticity and compliance with packaging instructions should be checked.

8.7.5 The primary filling packaging must be clean before starting the operation. Particular attention should be paid to avoid the presence of glass and metal particles.

8.7.6 Marking should be done as soon as possible, immediately after filling and sealing the product. If this is not possible for any reason, then the necessary measures should be taken against product mix-up or false labeling.

8.7.7 The correctness of any markings (eg, coding or expiry date) carried out both during and outside the packaging process should be carefully controlled and documented. Particular attention should be paid to manual marking, which should be monitored at regular intervals.

8.7.8 Special precautions should be taken when using cut labels and when marking outside the packaging line. To prevent confusion, it is recommended to use roll labels instead of cut labels.

8.7.9 The correct operation of electronic code readers, label counters and similar devices should be monitored.

8.7.10 Information on packaging materials, which is applied by printing or embossing, must be distinct, resistant to light (fading) and abrasion.

8.7.11 When carrying out control on the line during the packaging of products, at least the following should be checked:

General view of the packaging;

Completeness of packaging;

Use of proper products and packaging materials;

Correctness of printing inscriptions;

Correct operation of control devices on the line.

Product samples taken from the packaging line must not be returned.

8.7.12 Products, the packaging of which unforeseen circumstances have arisen, may be returned to production again only after a special check, investigation and with the permission of the Authorized Person. In such cases, detailed records should be drawn up and kept.

8.7.13 If there is a significant and unusual discrepancy between the number of bulk finished products, marking packaging materials and the number of units of finished products received, then an investigation should be carried out and a satisfactory explanation for this fact should be found in order to obtain permission to sell the product.

8.7.14 Upon completion of the packaging operations, any remaining batch number-bearing packaging materials must be destroyed and the destruction documented with an appropriate protocol. The return to the warehouse of packaging materials that do not bear a batch number is carried out in accordance with the approved instructions.

Finished products

8.8.1 Finished products must be kept under quarantine until a permit for their sale is issued under the conditions established by the manufacturer.

8.8.2 The procedure for assessing the quality of the finished product and the requirements for the documentation required to obtain permission to sell are given in Section 9 of this standard "Quality Control".

8.8.3 After the issuance of the marketing authorization, the finished product is stored in the finished product warehouse under the conditions established by the manufacturer.