Decree of the Ministry of Health No. 1 / 1998 Coll.
Decree of the Ministry of Health laying down quality requirements, procedure for the preparation, testing, storage and dosing of medicinal products (Czech Pharmacopoeia 1997)
Valid
Effective from 01.02.1998
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1
DECLARATION
Ministry of Health
of 9 December 1997
laying down the quality requirements, the procedure for the preparation, testing, storage and dosage of medicinal products (Czech Pharmacopoeia 1997)
The Ministry of Health, after consulting the Ministry of Agriculture and the Ministry of Industry and Trade pursuant to § 75 (4) of Act No. 79 / 1997 Coll. on Medicines and on amendments and additions to certain related laws:
The Czech Pharmacopoeia 1997 is published in an annex to this decree. It is used in the preparation, manufacture and control of medicines.
Repeal
The Decree of the Ministry of Health of the Czech Socialist Republic No. 10 / 1987 Coll., on the binding of Czechoslovak Pharmacopoeia - fourth edition in the Czech Socialist Republic, as amended by Decree No. 62 / 1990 Coll. and Decree No. 376 / 1991 Coll.
This Decree shall take effect on 1 February 1998.
Minister:
PhDr.
Annex to Decree No 1 / 1998 Coll.
_
1.1. Preliminary provisions
The Czech Pharmacopoeia (hereinafter referred to as "Pharmacopoeia") contains in particular the provisions of the European Pharmacopoeia (hereinafter referred to as Ph. Eur.), the Czech terminology convention for a number of professional names which did not have the corresponding Czech terms (immunology and drug technology). In cases where the introduction of Czech terminology had no solution, English names were accepted in the Czech transcription.
The basic terms used in the Pharmacopoeia are taken from the Act No. 79 / 1997 Coll. on Medicines and on amendments and additions to certain related laws.
The pharmacopoeia covers individual articles of the active substance, the excipients, medicinal products, medical supplies and packaging.
The product or product used in the pharmacopoeia shall be understood as the subject matter of the pharmacopoeia articles in general.
Authorised authority in the field of medicinal products for human use means, in particular, the State Institute for Drug Control and the Ministry of Health of the Czech Republic, the Department of State Control of Veterinary Bioprafts and Medicines and the Ministry of Agriculture of the Czech Republic, in the field of emergency situations (emergency state, state of danger and war).
1. General principles
General provisions
Czech Pharmacopoeia is based on the translation of European Pharmacopoeia, 3rd edition, and some texts already from its Supplement 1998. Only some states and articles have been added to adapt their text to the Czech conditions. Completed texts representing "Czech specificity 'do not contradict the provisions of the European Pharmacopoeia.
The general principles concern all stables and articles of the Czech Pharmacopoeia 1997. The word "pharmacopoeia" means "Czech Pharmacopoeia."
The use of a reference to the name of a pharmacopoeia general state or article means that the method, active substance, additive, medicinal product, medical material or packaging complies with the requirements of the relevant state or article. Such references to articles and statuses shall be in italics. In the case of general operations, the references are usually given by a simplified number, which is also shown in the brackets in italics.
The medicinal product satisfies the requirements of the Pharmacopoeia throughout its shelf life. The subject matter of any other article shall be as good as possible throughout its application. The period of application and the date from which that period is calculated shall be approved by the authorised authority on the basis of the results of the stability studies.
The provisions of the Articles shall be binding unless otherwise specified in the General Principles or Articles. The General Statutes shall become binding when they are referred to in the Article and where such a reference is not made in a manner which indicates that the relevant text referred to is not binding, but is rather quoted for information or guidance.
The active substances, the excipients, the medicinal products, the medical material and the packaging described in the Articles are intended for human and veterinary use (unless one of these purposes is precisely defined) and, if they do not comply with any of the requirements set out in the Article, are not of pharmaceutical quality. However, this does not mean that carrying out all the tests described in any article is a necessary condition for the manufacturer to determine whether the substance complies with the pharmacopoeia prior to release into use. The manufacturer may obtain assurance as to whether a product is of pharmaceutical quality, based on data obtained, for example, from validation studies of the production process and on ongoing operational checks. Therefore, the need to comply with the requirements of the Pharmacopoeia does not preclude the possibility of resorting to parametric release of products in certain situations considered appropriate by the competent authority.
The purity tests and the determination of the content or efficacy described in the pharmacopoeia are the official methods on which the pharmacopoeia standards are based. Alternative analytical methods may be used for control purposes, subject to compliance with official methods. In case of doubt or dispute, only official methods of analysis are decisive. Certain substances which are the subject of a pharmacopoeia article may exist in different classes suitable for different purposes. Unless otherwise specified in the Article, the requirements shall apply to all qualities of the substance. In certain articles, in particular those concerning excipients, a list of critical properties relevant to their use may be attached for information and advice. Test methods for the determination of one or more of these critical properties may also be provided for information.
The general provisions on pharmaceutical forms shall apply to all preparations of a defined species and may not be exhaustive for the medicinal product in question. For the medicinal product concerned, the authorised authority may lay down additional requirements to those provided for in the general article of the pharmaceutical form.
Conventional terms. The term "authorised authority 'means, in general, a national, transnational or international body or organisation which is entitled to decide the relevant problems. It may be, for example, a national pharmaceutical authority, licensing authority or official control laboratory. In the Czech Republic, see Introductory provision (1.1).
The term "unless otherwise specified 'in the Czech Pharmacopoeia means that the requirements of the provision apply if the authorised authority does not approve a change or exemption for a given justified case.
Provisions containing the expression "should 'are informative or recommended.
In certain articles or other texts, the terms "suitable 'or" corresponding' for the use of a test apparatus, micro-organism, test methods, etc.; if the suitability criteria are not described in the Article, the competent authority shall determine or approve these criteria.
Other provisions concerning general provisions and articles
Quantity
In the purity tests with numerical limits and in the determination of the content, a quantity is prescribed for testing which means the quantity approximate. The quantity actually used, which may differ by no more than 10% from the quantity prescribed, shall be accurately weighted or measured and the result shall be calculated on the basis of that exact quantity. In purity tests where the limit is not numbered, but usually depends on the comparison and behaviour of the comparator under the same conditions, the quantity prescribed for the test shall be used. The probers are also used in prescribed quantities.
The quantity shall be weighted or measured to an accuracy appropriate to the specified degree of accuracy. For weighing, the accuracy of ± 5 units for the last digit (e.g. 0,25 g is 0,245 to 0,255 g). It is important to measure the volume whether the digit behind the decimal point is zero or the number ends in zero (e.g. 10,0 ml or 0,50 ml). In such cases, the volume should be measured by pipette, graduated flask or burette as appropriate. Otherwise, a measuring cylinder or divided pipette may be used. The volumes indicated in microlitres are measured with a micropipette or syringe. In certain cases the accuracy with which the quantities are given does not correspond to the number of figures in force expressed in the numerical requirements given. Weighting and measurement should then be performed with sufficient precision in accordance with analytical practices.
Instruments and procedures
The measuring glass containers comply with the class requirements A corresponding international standards issued by the International Organisation for Standardisation.
Unless otherwise prescribed, analytical procedures shall be carried out at 15 ° C to 25 ° C (room temperature).
The comparative tests, unless prescribed otherwise, shall be carried out using the same test tubes of colourless neutral transparent glass with a flat base and an inside diameter of 16 mm. The same volumes of compared liquids shall be observed from above in the direction of the longitudinal axis of the test tube against the white background or, if necessary, against the black background. The test shall be performed in a diffuse light.
Any solvent used in the purity test or in determining the content at which the indicator is to be used shall first be neutralised to that indicator unless a blank test is prescribed.
Water bath
The term "water bath 'means a bath of boiling water unless another water temperature is indicated. Other heating methods may be used provided the prescribed heating temperature is respected.
Drying or annealing to constant weight
The data "dried to constant weight 'and" ignited to constant weight' mean that the two subsequent weighing scales do not differ by more than 0,5 mg; the second weighing follows a further drying or annealing period appropriate to the nature and quantity of the remainder.
If drying is prescribed using one of the terms "in the desiccator 'or" in vacuum', it is performed under the conditions described in the State Loss by drying (2.2.32).
Tests
The correct implementation of the analytical procedures described in the pharmacopoeia and the reliability of the results depends partly on the quality of the probers used. The examiners are described in the general statum of the examiners (4). The use of analytical grade probers is envisaged. Tests to verify their suitability are included for some probers.
Solvent
If the name of the solvent is not given, the term "solution 'means an aqueous solution. Where the use of water is prescribed or included in the analytical procedures described in the pharmacopoeia or for the preparation of examinations, water complying with the requirements of Aqua purificata shall be used. The term" distilled water' refers to purified water prepared by distillation.
The term "ethanol 'means ethanol 99,0% without any indication. The term" alcohol "used in Ph. Eur. corresponds to 96% [= 96,0% (V / V) ethanol (C2H6O) in ČL 97). Other ethanol dilution shall be marked with" alcohol' indicating the volume percentage of ethanol.
Concentration expression
When expressing concentrations, the expression "percentage '(%) shall be used as appropriate in one of the two meanings:
- the percentage of m / m (by weight, weight) shall indicate the number of grams of the substance in 100 g of the final product. In Article 97, the m / m marking is not usually used. Where the percentages are not specified, the percentage by weight shall be understood.
- the percentage V / V (percentage volume, volume) indicates the number of millilitres of the substance in 100 ml of the final product.
The term ppm (parts per million) used in Ph. Euro corresponds to the weight in weight, unless otherwise stated. In the pharmacopoeia, this expression is replaced, as appropriate, by μg / g or μg / ml, unless otherwise specified.
The percentage by weight and percentage by weight are not allowed in Ph. Euro or in ČL. The necessary concessions are expressed using the relevant units, usually as g / l or ml / kg.
Temperature
Where the analytical procedure indicates a temperature without numerical values, generally used expressions have the following meaning:
| v mrazicím boxu | pod - 15 °C |
| v chladničce | 2 °C až 8 °C |
| za chladu nebo v chladnu | 8 °C až 15 °C |
| při pokojové teplotě | 15 °C až 25 °C |
General States
The materials used for packaging are described in the packaging and packaging material (3). The general names used for materials, especially plastics, cover a product group which differs not only in the characteristics of the constituent but also in the ingredients used. The test methods and limits for materials depend on their composition and are binding only on materials whose composition is defined in the introduction to specifications. The use of materials with a different composition and the test methods and limits required for them shall be subject to the consent of the authorised authority.
Specifications for packaging in the packaging and packaging material (3) have been developed for general use for packaging of specified categories, but due to the wide variety of packaging available and the possible re-publication of the specification does not preclude the use of packaging corresponding to specifications approved by the authorised authority in justified cases.
In the pharmacopoeia, reference may be made to the packaging specifications in this section. General Articles for pharmaceutical forms may require the use of certain types of packaging in the manufacturing section; certain other articles may indicate in the storage section the type of packaging recommended for the use in question.
Medical articles
The pharmaceutical articles (hereinafter referred to as "articles') shall be broken down into parts: the heading of the articles, production, characteristics, identity tests, purity tests, content (efficacy), storage, labelling and impurities. According to its nature, the article does not necessarily contain all parts.
Title of Article
It contains names, including the appropriate indication whether it is a narcotic or psychotropic substance, venenum or separanda, whether it is an article translated from Ph. Eur. It also contains everything that clearly characterises the substance, i.e. the primary formula, the structural formula, the relative molecular (atomic) mass, the CAS number and the definition of the substance with its content range. The formula, the relative molecular (atomic) mass and the CAS number, see below, are not part of the analytical evaluation of the article.
Names. Articles of the ČL are listed by international names approved or recommended by the World Health Organisation under which the names are Czech. If necessary, synonyms are also given (usually the name CSL 4 or Ph. Eur if different).
Patterns. Summaral formulas and structural formulas, if necessary, differ in form from those of Ph. Eur.
Relative atomic and molecular masses. The relative molecular mass (Mr) of the substance, or the relative atomic mass (Ar) of the substance, shall be given where appropriate. Mr. is calculated from the relative atomic mass table and rounded to two decimal places.
CAS number (Chemical Abstracts Service). In Article L these figures are also given for medicinal and auxiliary substances (Ph. Eur. CAS numbers indicate only for examiners).
The definition in Article L is a paragraph defining the active substance, the excipients, the device or the packaging. For chemicals, the definition includes the Czech chemical name created according to the IUPAC (International Union of Pure and Applied Chemistry) principles and the principles of the Czech nomenclature of inorganic and organic chemie1), regardless of the Czech spelling rules.
Content range. Where a range is prescribed it contains the range determined following the method of determination of the test substance content (efficacy).
Plant drugs. Articles for plant drugs shall indicate in the title of the article whether the article is the subject of, for example, the whole drug or the powder drug. As far as the article covers both the whole and the powder drug, the heading of the article clearly states this.
Production
The provisions of paragraph Production draw attention to certain aspects of the production process. They form framework guidelines for manufacturers. They may concern, for example, the source of materials, the production process itself and its validation and control, the ongoing operational checks or testing to be carried out by the manufacturer for the final product, either for selected batches or for each batch before release. These provisions cannot always be verified on a sample of the finished product by an independent analyst. Authorised authority may verify compliance with these guidelines by, for example, examining data obtained from the manufacturer, inspections or testing appropriate samples.
The absence of part Production does not mean that attention should not be paid to what has been mentioned above. The product described in the Article shall be manufactured in accordance with the principles of good manufacturing practice and in accordance with relevant international agreements and supranational and national rules governing products for human and veterinary use.
Where the article for the vaccine in the Part Production defines the characteristics of the vaccine strain, any test methods given to confirm these properties are intended to be provided as examples of appropriate methods.
Characteristics
The provisions in the Properties section are informative and are not pharmaceutical requirements.
Solubility. In the provisions relating to solubility in part Properties, the expressions used in relation to temperatures between 15 and 25 ° C are of the following meaning:
Tab. 1.2-1
| Popisný výraz | Přibližný objem rozpouštědla v mililitrech na gram rozpuštěné látky |
|---|---|
| velmi snadno rozpustný | méně než 1 |
| snadno rozpustný | 1 až 10 |
| dobře rozpustný | 10 až 30 |
| mírně rozpustný | 30 až 100 |
| těžce rozpustný | 100 až 1000 |
| velmi těžce rozpustný | 1000 až 10 000 |
| prakticky nerozpustný | více než 10 000 |
The term "partially soluble 'is used to describe a mixture where only some of the ingredients are dissolved. The term" blending' is used to describe a liquid that is blended in each ratio with that solvent.
Identity tests
Tests referred to in Part Identity tests shall be designed to confirm with an acceptable degree of certainty that the product corresponds to the label on the packaging.
Some articles have additional breakdowns marked "Basic test assembly 'and" Alternative test assembly'. The test or tests consisting of the "Alternative test assembly 'may be used instead of the" Basic test assembly' provided that it can be demonstrated that the substance or preparation can be completely traced to a certified batch which has been completely tested according to the pharmacopoeia and complies with all its requirements.
Purity tests and determination of content or efficiency
Range. The requirements are not designed to take into account all possible impurities. For example, it cannot be assumed that any impurity which is not detectable by the prescribed tests can be tolerated if experience and good pharmaceutical practice require it to be absent. See also the "Impurities" part below.
Calculations. Where the test result is required to be calculated on a dried or anhydrous substance or on another requirement, the determination of the loss shall be made by drying, water content or other characteristics by the method prescribed in the relevant test of the Article.
Range. The prescribed ranges are based on data obtained in normal analytical practice; they shall assume common analytical errors, acceptable changes in production and composition and impairment to the extent deemed acceptable. Changes to the prescribed range cannot be tolerated to determine whether the test product complies with the requirements of the relevant Article.
When determining conformity with the figures, the calculated result of the purity test or determination shall first be rounded to the number of digits indicated, unless otherwise prescribed. The last digit shall be increased by one when the rounded part is equal to or greater than half of the unit, while it does not change when the rounded part is less than half of the unit.
Indication of permitted impurities limit. The approximate range of tolerated impurities or the sum of impurities may be indicated in brackets for information purposes only. If the use of the reference substance for the labelled impurity is not prescribed, its content may be expressed as the nominal concentration of the substance used for the preparation of the comparative solution prescribed in Article, unless otherwise specified. Positive or negative assessment of the impurities shall be determined according to conformity or non-conformity with the test.
Plant drugs. For plant drugs, sulphate ash, total ash, water soluble substance, alcohol 96% soluble substance, water content, oil content and active substance content shall be calculated by reference to a substance which has not been separately dried unless otherwise prescribed in the article.
Equivalent. In the case of the indication of the equivalent of a substance, those numbers shall be used for pharmaceutical purposes if the requirements of a particular Article are to apply.
Biological tests. When using animals to determine the efficacy and other biological tests, Act No. 246 / 1992 Coll., for the protection of animals against abuse must be observed.
Storage
The information and recommendations set out in the section Storage are not fully binding. Authorised authority may prescribe special storage conditions to be observed. In addition, the Czech Pharmacopoeia prescribes special storage conditions for the following groups of drugs against Ph. Eur: narcotic drugs, psychotropic substances, vena and separanda, see Tables I to III. In that order the superiority of their retention shall apply. This superiority was also used to compile the above tables. The products described in the Pharmacopoeia shall be stored in such a way as to prevent contamination and, if possible, degrade them. Where special storage conditions, including type of packaging, are recommended, see also 3.2, and storage temperatures, are provided in the article.
The following terms shall be used in the articles in the part marked "Storage '. Protected from moisture means that the product is stored in an airtight container. In a moist atmosphere, the package should be opened carefully. A low moisture content may be achieved, if necessary, by using a desiccant in the packaging provided that no direct contact of the desiccant with the product is made.
Protected from light means that the light-sensitive product is stored either in a material packaging that sufficiently absorbs the actinic light and thereby protects the content from the change caused by it, or in a packaging that also provides such protection, or is stored in a place that is completely protected from light.
Labelling
Labelling is usually the subject of transnational and national regulations and international agreements. The provisions set out in the Labelling section are incomplete and, moreover, only those provisions which are necessary to demonstrate the consent or disagreement with the Article are binding for pharmaceutical purposes. Any other labelling provisions are included in the Pharmacopoeia as a recommendation. The pharmaceutical provisions concerning labelling may be indicated on the inner or outer packaging or in the package leaflet, as decided by the authorised authority.
Warning
The materials described in the articles and the examiners intended for use in the pharmacopoeia may be harmful to health if appropriate safety measures are not complied with. The principles of good practice in the control laboratory and the provisions of the related rules should be maintained at all times. Substances particularly dangerous are referred to in certain articles by means of warning notices; the absence of such notifications does not mean that there is no danger.
Impurities
A list of all known and potential impurities to be checked by tests in a particular article may be provided for information in the Impurity section. The list may be divided into two parts: "qualified impurities' and" other detachable impurities'. Qualified impurities are impurities which have been accepted as such by a pre-authorised authority; impurities considered to be qualified in other ways (e.g. impurities occurring as natural metabolites) may also be included. Other detachable impurities are such possible impurities that were not detected in any sample of the substance during the preparation of the article or that occur in quantities below 0,1% but limited by purity tests.
Critical physical characteristics
A list of critical physical properties not subject to official requirements but still relevant to the use of a substance may be attached to the article for information, see also General provisions mentioned above.
Reference substances, reference preparations and reference spectrum
Some articles prescribe the use of a reference substance, a reference product or a reference spectrum. These are prepared in the light of their intended use as prescribed in the Articles and may not be appropriate in other circumstances. Czech Pharmacopoeia prescribes reference materials one to be prepared by the European Pharmacopoeia Committee for Articles translated from Ph. Eur. and reference materials prepared by the Medical Commission of the Czech Republic for articles representing Czech specifics. The Commission shall not take responsibility for any errors arising from uses other than those prescribed for reference materials.
Reference substances, reference preparations and reference spectrum for testing according to articles translated from Ph. Eur may be ordered in the Technical Secretariat of the European Pharmacopoeia Commission. These are official reference materials to be used in the case of arbitration. The list of reference substances, reference preparations and reference spectra may be obtained in the Technical Secretariat. The list of reference materials for testing according to articles representing Czech specificity is published in the Bulletin of the State Institute for Drug Control in Prague and reference materials can be ordered in the Secretariat of the Medical Commission of the Ministry of the Czech Republic.
Working standards may be used for routine analyses of substances according to articles translated from Ph. Eur.
Any information necessary for the correct use of Ph. Eur. reference materials shall be indicated on the label, in the package leaflet or in the catalogue. Where the conditions for drying are not stated in the package leaflet or on the package leaflet, the substance should be used as supplied. The European Pharmacopoeia Commission does not provide analytical certificates or other data not related to the prescribed use of the product. The date of application shall not be stated; the reference materials may be used from the date of receipt for at least 6 months if they are stored as described in the package leaflet; their use after this period must be notified to the Technical Secretariat of the European Pharmacopoeia Commission. cannot be guaranteed the stability of the contents of open packages.
Chemical reference substances. The abbreviation CRL (in Ph. Eur. CRS) refers to the chemical reference substance declared by the European Pharmacopoeia Commission or the reference substance declared by the Pharmacopoeia Commission of the Czech Republic. Some chemical reference substances are used for the microbiological determination of antibiotics and their efficacy is reported in international units, inter alia (in Ph. Eur. marked by U.l.) in the package leaflet or on the packaging and defined in the same way as biological reference products.
Biological reference products. Most of the primary reference products listed in both Ph. Eur and ČL are international standards and international reference products declared by the World Health Organisation. As these reference materials are usually available only in limited quantities, the European Pharmacopoeia Commission declares biological reference products (referred to by BRP) where appropriate. The efficacy of biological reference products is expressed in international units marked, inter alia (in Ph.Eur marked U.I.). For certain biological reference products where there is no international standard or international reference product, the efficacy is expressed in the European Pharmacopoeia Ph.Eur.j. units (Ph.Eur. designated as Ph.Eur.U.).
If the ČL contains an article for which a biological reference product not prepared by the European Pharmacopoeia Commission is required for testing, it shall ensure that such biological reference product is prepared by the Czech Pharmacopoeia Commission following the relevant reference product of the World Health Organisation.
Reference substances for radiopharmaceuticals are substances with defined purity, always accompanied by an appropriate certificate indicating the quality and shelf life. They are obtained from the Czech Metrology Institute - Inspectorate for Ionizing Radiation, Radiová 1, Prague 10.
Reference spectrum. The reference spectrum (for infrared spectrophotometers) is accompanied by information concerning the conditions used in the preparation of the substance for testing and recording of spectrum. Reference spectrum required for testing according to articles translated from Ph. Eur may be ordered in the Technical Secretariat of the European Pharmacopoeia Commission. The reference spectrum required for testing according to articles representing Czech specifics can be ordered in the Secretariat of the Medical Commission of the Czech Republic.
1.3 Tags and symbols
| A | absorbance |
| specifická absorbance | |
| Ar | relativní atomová hmotnost |
| specifická optická otáčivost | |
| BRP | biologický referenční přípravek |
| CRL | chemická referenční látka |
| relativní hustota | |
| λ | vlnová délka |
| m.j. | mezinárodní jednotka |
| Mr | relativní molekulová hmotnost |
| index lomu | |
| Ph.Eur.j. | Ph. Eur. jednotka |
| R | zkoumadlo |
| RF | retenční faktor používaný v chromatografii vyjadřující poměr vzdálenosti středu skvrny zkoušené látky ke vzdálenosti čela mobilní fáze, měřeno od místa nanášení |
| RS | roztok zkoumadla |
| Rst | poměr vzdálenosti středu skvrny zkoušené látky od místa nanášení ke vzdálenosti středu skvrny porovnávací látky od místa nanášení používaný v chromatografii |
| TT | teplota tání |
| TV | teplota varu |
| VR | základní látka pro odměrnou analýzu |
| VS | odměrný roztok |
Abstracts used in immune serum cells, immunoglobulins and vaccines
| CCID50 | Statisticky stanovené množství viru, u něhož lze předpokládat, že infikuje 50 % buněčných kultur, do nichž bylo přidáno. |
| ED50 | Statisticky stanovená dávka vakcíny, u níž lze v podmínkách zkoušek předpokládat, že u 50 % zvířat navodí tvorbu protilátek na antigeny související s vakcínou. |
| EID50 | Statisticky stanovené množství viru, u něhož lze předpokládat, že infikuje 50 % ptačích embryí, do nichž bylo inokulováno. |
| ID50 | Statisticky stanovené množství viru, u něhož lze předpokládat, že infikuje 50 % zvířat, jimž bylo inokulováno. |
| L+/10 dávka | Nejmenší množství toxinu, které v podmínkách zkoušky smícháno s 0,1 m.j. antitoxinu a podáno specifikovaným způsobem usmrtí v daném období pokusná zvířata. |
| L+ dávka | Nejmenší množství toxinu, které v podmínkách zkoušky smícháno s 1 m.j. antitoxinu a podáno specifikovaným způsobem usmrtí pokusná zvířata. |
| LD50 | Statisticky stanovené množství látky, u něhož po podání specifikovaným způsobem lze předpokládat, že v daném období usmrtí 50 % pokusných zvířat. |
| Lf dávka | Množství toxinu nebo toxoidu, které v nejkratším období vyvločkuje s 1 m.j. antitoxinu. |
| Lo/10 dávka | Největší množství toxinu, které v podmínkách zkoušky smícháno s 0,1 m.j. antitoxinu a podáno specifikovanýmn způsobem nezpůsobí v daném období pokusným zvířatům toxické příznaky. |
| Lp/10 dávka | Nejmenší množství toxinu, které v podmínkách zkoušky smícháno s 0,1 m.j. antitoxinu a podáno specifikovaným způsobem paralyzuje v daném období pokusná zvířata. |
| Lr/100 dávka | Nejmenší množství toxinu, které v podmínkách zkoušky smícháno s 0,01 m.j. antitoxinu a intrakutánně vstříknuto způsobí v daném období charakteristickou reakci v místě podání. |
| MLD | nejmenší smrtná dávka |
| PD50 | Statisticky stanovená dávka vakcíny, u níž lze v podmínkách zkoušek předpokládat, že ochrání 50 % zvířat před čelenžní dávkou toxinů nebo mikroorganismů, proti nimž je účinná. |
| PFU | jednotky vytvářející poky nebo jednotky vytvářející plaky |
| SPF | prostý specifikovaných patogenů |
Collection of micro-organisms
| ATCC | American Type Culture Collection |
| 12301 Parklawn Drive | |
| Rockville, MD 20852, USA | |
| C.I.P. | Collection de Bactéries de l’Institut Pasteur |
| B.P.52, 25 Rue du Dr Roux | |
| 75724 Paris Cedex 15, France | |
| I.P. | Collection Nationale de Culture de Microorganismes (C.N.C.M.) |
| Institut Pasteur | |
| 25 Rue du Dr Roux | |
| 75724 Paris Cedex, France | |
| NCIMB | National Collection of Industrial and Marine Bacteria Ltd. |
| 23 St Machar Drive | |
| Aberdeen AB2 IRY, Great Britain | |
| NCPF | National Collection of Pathogenic Fungi |
| London School of Hygiene and Tropical Medicine | |
| Keppel Street | |
| London WC1E 7HT, Great Britain | |
| NCTC | National Collection of Type Cultures |
| Central Public Health Laboratory | |
| Colindale Avenue | |
| London NW9 5HT, Great Britain | |
| NCYC | National Collection of Yeast Cultures |
| AFRC Food Research Institute | |
| Colney Lane | |
| Norwich NR4 7UA, Great Britain | |
| S.S.I. | Statens Serum Institut |
| 80 Amager Boulevard, Copenhagen, Denmark | |
| CCM | Česká sbírka mikroorganismů |
| Přírodovědecká fakulta Masarykovy univerzity | |
| Tvrdého 14, 602 00 Brno | |
| CNCTC | Česká národní sbírka typových kultur mikroorganismů |
| Státní zdravotní ústav | |
| Centrum epidemiologie a mikrobiologie | |
| Šrobárova 48, 100 42 Praha 10 |
1.4. International System Units (SI) used in the Pharmacopoeia and relation to other units
International Unit System (SI)
The International Unit System comprises three groups: basic units, derived units and supplementary units (1). The basic units and their definitions contain Table 1.4-1.
Derived units may be formed by combining basic units according to algebraic relationships between corresponding variables. Some of these derived units have special names and symbols. SI units used in Ph. Euro are shown in Table 1.4-2.
Some important, generally used secondary units are shown in Table 1.4-3.
The prefixes given in Table 1.4-4 are used to create the names and symbols of decadic multiples and SI units.
Tab. 1.4-1 Basic SI units
| Veličina | Jednotka | Definice | ||
|---|---|---|---|---|
| Název | Symbol | Název | Symbol | |
| délka | l | metr | m | Metr je délka dráhy, kterou proběhne světlo ve vakuu za 1/299 792 458 sekundy. |
| hmotnost | m | kilogram | kg | Kilogram je hmotnost mezinárodního prototypu kilogramu, uloženého v Mezinárodním úřadě pro váhy a míry v Sévres. |
| čas | t | sekunda | s | Sekunda je trvání 9 192 631 770 period záření odpovídajícího přechodu mezi dvěma velmi jemnými hladinami základního stavu atomu cesia 133. |
| elektrický proud | I | ampér | A | Ampér je stálý elektrický proud, který při průtoku dvěma rovnoběžnými přímými a nekonečně dlouhými vodiči zanedbatelného kruhového průřezu, umístěnými ve vakuu ve vzájemné vzdálenosti 1 metru vyvolá mezi nimi stálou sílu 2.10-7 newtonu na metr délky. |
| termody-namická teplota | T | kelvin | K | Kelvin je 1/273,16 termodynamické teploty trojného bodu vody. |
| látkové množství | n | mol | mol | Mol je látkové množství soustavy, která obsahuje právě tolik elementárních jedinců (entit), kolik je atomů v 0,012 kg uhlíku 12* |
| svítivost | Iv | kandela | cd | Kandela je svítivost zdroje, který v daném směru vysílá monochromatické záření o kmitočtu 540.1012 hertzů a jehož zářivost v tomto směru je 1/683 wattu na steradián. |
* Elemental entities should be specified when indicating the substance level; may be atoms, molecules, ions, electrons, other particles or a specified particle grouping.
Table 1.4-2 Units used in the Pharmacopoeia and corresponding to other units
| Veličina | Jednotka | Převod jiných jednotek na jednotky SI | ||||
|---|---|---|---|---|---|---|
| Název | Symbol | Název | Symbol | Základní jednotka SI | Jiné jednotky SI | |
| vlnočet | v | reciproký metr | 1/m | m-1 | ||
| vlnová délka | λ | mikrometr nanometr | μm nm | 10-6 m 10-9 m | ||
| plošný obsah | A, S | čtverečný metr | m2 | m2 | ||
| objem | V | krychlový metr | m3 | m3 | 1 ml = 1 cm3 = = 10-6 m3 | |
| kmitočet | f, v | hertz | Hz | s-1 | ||
| hustota | ρ | kilogram na krychlový metr | kg/m3 | kg.m-3 | 1 g/ml = 1 g/cm3 = = 103 kg.m-3 | |
| rychlost | v | metr za sekundu | m/s | m.s-1 | ||
| síla | F | newton | N | m.kg.s-2 | 1 dyn = 1 g.cm.s-2 = = 10-5 N | |
| 1 kp = 9,80665 N | ||||||
| tlak, mechanické napětí | p | pascal | Pa | m-1.kg.s-2 | N.m-2 | 1 dyn/cm2 = 10-1 Pa = = 10-1. N.m-2 |
| 1 atm = 101325 Pa = 101,325 kPa | ||||||
| 1 bar = 105 Pa = = 0,1 MPa | ||||||
| 1 mm Hg = = 133,322387 Pa | ||||||
| 1 Torr = = 133,322368 Pa | ||||||
| 1 psi = 6,894757 kPa | ||||||
| dynamická viskozita | η | pascalsekunda | Pa.s | m-1.kg.s-1 | N.s.m-2 | 1 P = 10-1 Pa.s = = 10-1 N.s.m-2 |
| 1 cP = 1 mPa.s | ||||||
| kinematická viskozita | v | čtverečný metr za sekundu | m2/s | m2.s-1 | Pa.s.m3.kg-1 N.m.s.kg-1 | 1 St = 1cm2.s-1 = = 10-4 m2.s-1 |
| energie | E, W | joule | J | m2.kg.s-2 | N.m | 1 erg = 1 cm2.g.s-2 = = 1 dyn.cm = 10-7 J |
| 1 cal = 4,1868 J | ||||||
| výkon (tepelný tok) | P | watt | W | m2.kg.s-3 | N.m.s-1 J.s-1 | 1 erg/s = = 1 dyn.cm.s-1 = = 10-7W = = 10-7 N.m.s-1 = = 10-7 J.s-1 |
| pohlcená dávka (radiační energie) | D | gray | Gy | m2.s-2 | J.kg-1 | 1 rad = 102 Gy |
| elektrické napětí, elektromotorické napětí | U | volt | V | m2.kg.s-3.A-1 | W.A-1 | |
| elektrický odpor | R | ohm | Ω | m2.kg.s-3.A-2 | V.A-1 | |
| elektrický náboj | Q | coulomb | C | A.s | ||
| aktivita nuklidu | A | becquerel | Bq | s-1 | 1 Ci = 37.109 Bq = = 37.109 s-1 | |
| látková koncentrace, molární koncentrace | c | mol na krychlový metr | mol/m3 | mol.m-3 | 1 mol/1 = 1 M = = 1 mol/dm3 = = 103 mol.m-3 | |
| hmotnostní koncentrace | p, ρ | kilogram na krychlový metr | kg/m3 | kg.m-3 | 1 g/l = 1 g/dm3 = = 1 kg.m-3 | |
Tab. 1.4-3 Side Units
| Veličina | Jednotka | Hodnoty v SI jednotkách | |
|---|---|---|---|
| Název | Symbol | ||
| čas | minuta hodina den | min h d | 1 min = 60 s 1 h = 60 min = 3 600 s 1 d = 24 h = 86400 s |
| rovinný úhel | stupeň | ° | 1° = (𝜋/180) rad |
| objem | litr | 1 | 1 l = 1 dm3 = 10-3 m3 |
| hmotnost | tuna | t | 1 t = 103 kg |
| frekvence otáčení | otáčka za minutu | ot/min | 1 ot/min = (1/60) s-1 |
Tab. 1.4-4 Decadent multiples and unit parts
| Činitel | Předpona | Značka | Činitel | Předpona | Značka |
|---|---|---|---|---|---|
| 1018 | exa | E | 10-1 | deci | d |
| 1015 | peta | P | 10-2 | centi | c |
| 1012 | tera | T | 10-3 | mili | m |
| 109 | giga | G | 10-6 | mikro | μ |
| 106 | mega | M | 10-9 | nano | n |
| 103 | kilo | k | 10-12 | piko | p |
| 102 | hekto | h | 10-15 | femto | f |
| 101 | deka | da | 10-18 | atto | a |
Remarks
1. A Celsius temperature scale (symbol is t) is used in the Pharmacopoeia. It is defined by:
t = TTO,
in which: This is defined as 273.15 K. The Celsius or 100-degree scale is expressed in degrees Celsius (symbol ° C). The unit "degree Celsius" is equal to the unit "kelvin."
2. The terms for concentrations used in the pharmacopoeia are defined in the General Principles.
3. The radian is the plane angle between the two radius of the circle, which on the circumference dissects the arc of the same length as the radius.
4. The centrifugation conditions are defined in the Pharmacopoeia by comparing acceleration and normal acceleration of gravity (gn):
gn = 9,80665m.s-2.
5. Some quantities without dimensions are used in the Pharmacopoeia: relative density (2.2.5), absorbance (2.2.25), specific absorbance (2.2.25) and refractive index (2.2.6), as well as quantities expressed in other units, such as specific optical rotation (2.2.7).
6. Microcatal is defined as an enzyme efficiency that transforms 1 micromole of substrate per second under defined conditions (e.g. hydrolysis).
7. The energy of particles and electromagnetic radiation is expressed in joules (J) and, where appropriate, in test tubes (eV):
1eV = 1,602177.10-19J.
Relative atomic mass table
The following table was prepared by the Commission on Atomic Weights and Isotopic Abundances and published in 1996 by the International Union of Pure and Applied Chemistry (IUPAC). The National Centre of IUPAC for the Czech Republic prepared the documentation for publication of the tablet in the Pharmacopoeia.
| Název latinský (český) | Symbol | Atomové číslo | Relativní atomová hmotnost |
|---|---|---|---|
| Actinium (aktinium) | Ac | 89 | [227] |
| Aluminium (hliník) | Al | 13 | 26,981538(2) |
| Americium (americium) | Am | 95 | [243] |
| Argentum (stříbro) | Ag | 47 | 107,8682(1) |
| Argon (argon) | Ar | 18 | 39,948(1) |
| Arsenum (arsen) | As | 33 | 74,92160(2) |
| Astatium (astat) | At | 85 | [210] |
| Aurum (zlato) | Au | 79 | 196,96654(3) |
| Barium (baryum) | Ba | 56 | 137,327(7) |
| Berkelium (berkelium) | Bk | 97 | [247] |
| Beryllium (beryllium) | Be | 4 | 9,012182(3) |
| Bismuthum (bismut) | Bi | 83 | 208,98038(2) |
| Borum (bor) | B | 5 | 10,811(7) |
| Bromum (brom) | Br | 35 | 79,904(1) |
| Cadmium (kadmium) | Cd | 48 | 112,411(8) |
| Caesium (cesium) | Cs | 55 | 132,90545(2) |
| Calcium (vápník) | Ca | 20 | 40,078(4) |
| Californium (kalifornium) | Cf | 98 | [251] |
| Carboneum (uhlík) | C | 6 | 12,0107(8) |
| Cerium (cer) | Ce | 58 | 140,116(1) |
| Chlorum (chlor) | Cl | 17 | 35,4527(9) |
| Chromium (chrom) | Cr | 24 | 51,9961(6) |
| Cobaltum (kobalt) | Co | 27 | 58,933200(9) |
| Cuprum (méď) | Cu | 29 | 63,546(3) |
| Curium (curium) | Cm | 96 | [247] |
| Dysprosium (dysprosium) | Dy | 66 | 162,50(3) |
| Einsteinium (einsteinium) | Es | 99 | [252] |
| Erbium (erbium) | Er | 68 | 167,26(3) |
| Europium (europium) | Eu | 63 | 151,964(1) |
| Fermium (fermium) | Fm | 100 | [257] |
| Ferrum (železo) | Fe | 26 | 55,845(2) |
| Fluorum (fluor) | F | 9 | 18,9984032(5) |
| Francium (francium) | Fr | 87 | [223] |
| Gadolinium (gadolinium) | Gd | 64 | 157,25(3) |
| Gallium (gallium) | Ga | 31 | 69,723(1) |
| Germanium (germanium) | Ge | 32 | 72,61(2) |
| Hafnium (hafnium) | Hf | 72 | 178,49(2) |
| Helium (helium) | He | 2 | 4,002602(2) |
| Holmium (holmium) | Ho | 67 | 164,93032(2) |
| Hydrargyrum (rtuť) | Hg | 80 | 200,59(2) |
| Hydrogenium (vodík) | H | 1 | 1,00794(7) |
| Indium (indium) | In | 49 | 114,818(3) |
| Iodium (jod) | I | 53 | 126,90447(3) |
| Iridium (iridium) | Ir | 77 | 192,217(3) |
| Kalium (draslík) | K | 19 | 39,0983(1) |
| Krypton (krypton) | Kr | 36 | 83,80(1) |
| Lanthanum (lanthan) | La | 57 | 138,9055(2) |
| Lawrentium (lawrencium) | Lr | 103 | [262] |
| Lithium (lithium) | Li | 3 | 6,941(2) |
| Lutetium (lutecium) | Lu | 71 | 174,967(1) |
| Magnesium (hořčík) | Mg | 12 | 24,3050(6) |
| Manganum (mangan) | Mn | 25 | 54,938049(9) |
| Mendelevium (mendelevium) | Md | 101 | [258] |
| Molybdaenum (molybden) | Mo | 42 | 95,94(1) |
| Natrium (sodík) | Na | 11 | 22,989770(2) |
| Neodymium (neodym) | Nd | 60 | 144,24(3) |
| Neon (neon) | Ne | 10 | 20,1797(6) |
| Neptunium (neptunium) | Np | 93 | [237] |
| Niccolum (nikl) | Ni | 28 | 58,6934(2) |
| Niobium (niob) | Nb | 41 | 92,90638(2) |
| Nitrogenium (dusík) | N | 7 | 14,00674(7) |
| Nobelium (nobelium) | No | 102 | [259] |
| Osmium (osmium) | Os | 76 | 190,23(3) |
| Oxygenium (kyslík) | 0 | 8 | 15,9994(3) |
| Palladium (palladium) | Pd | 46 | 106,42(1) |
| Phosphorus (fosfor) | P | 15 | 30,973761(2) |
| Platinum (platina) | Pt | 78 | 195,078(2) |
| Plumbum (olovo) | Pb | 82 | 207,2(1) |
| Plutonium (plutonium) | Pu | 94 | [244] |
| Polonium (polonium) | Po | 84 | [209] |
| Praseodymium (praseodym) | Pr | 59 | 140,90765(2) |
| Promethium (promethium) | Pm | 61 | [145] |
| Protactinium (protaktinium) | Pa | 91 | 231,03588(2) |
| Radium (radium) | Ra | 88 | [226] |
| Radon (radon) | Rn | 86 | [222] |
| Rhenium (rhenium) | Re | 75 | 186,207(1) |
| Rhodium (rhodium) | Rh | 45 | 102,90550(2) |
| Rubidium (rubidium) | Rb | 37 | 85,4678(3) |
| Ruthenium (ruthenium) | Ru | 44 | 101,07(2) |
| Samarium (samarium) | Sm | 62 | 150,36(3) |
| Scandium (skandium) | Sc | 21 | 44,955910(8) |
| Selenium (selen) | Se | 34 | 78,96(3) |
| Silicium (křemík) | Si | 14 | 28,0855(3) |
| Stannum (cín) | Sn | 50 | 118,710(7) |
| Stibium (antimon) | Sb | 51 | 121,760(3) |
| Strontium (stroncium) | Sr | 38 | 87,62(1) |
| Sulfur (síra) | S | 16 | 32,066(6) |
| Tantalum (tantal) | Ta | 73 | 180,9479(1) |
| Technetium (technecium) | Tc | 43 | [98] |
| Tellurium (tellur) | Te | 52 | 127,60(3) |
| Terbium (terbium) | Tb | 65 | 158,92534(2) |
| Thallium (thallium) | Tl | 81 | 204,3833(2) |
| Thorium (thorium) | Th | 90 | 232,0381(1) |
| Thulium (thulium) | Tm | 69 | 168,93421(2) |
| Titanium (titan) | Ti | 22 | 47,867(1) |
| Wolframium (wolfram) | W | 74 | 183,84(1) |
| Uranium (uran) | U | 92 | 238,0289(1) |
| Vanadium (vanad) | V | 23 | 50,9415(1) |
| Unnilennium (unnilennium) [Meitnerium] | Une [Mt] | 109 | [266] |
| Unnilhexium (unnilhexium) [Seaborgium] | Unh [Sg] | 106 | [263] |
| Unniloctium (unniloctium) [Hassium] | Uno [Hs] | 108 | [265] |
| Unnilpentium (unnilpentium) [Dubnium] | Unp [Db] | 105 | [262] |
| Unnilquadium (unnilquadium) [Rutherfordium] | Unq [Rf] | 104 | [261] |
| Unnilseptium (unnilseptium) [Bohrium] | Uns [Bh] | 107 | [262] |
| Ununnilium (ununnilium) | Uun | 110 | [269] |
| Unununium (unununium) | Uuu | 111 | [272] |
| Xenon (xenon) | Xe | 54 | 131,29(2) |
| Ytterbium (ytterbium) | Yb | 70 | 173,04(3) |
| Yttrium (yttrium) | Y | 39 | 88,90585(2) |
| Zincum (zinek) | Zn | 30 | 65,39(2) |
| Zirconium (zirkonim) | Zr | 40 | 91,224(2) |
Note: Square brackets for numbers in the column Relative atomic mass indicate the variation in the value of the last digit and round brackets indicate the variation in the value of the number given in brackets.
Names and marks given in square brackets for elements with atomic number 104, 105, 106, 107, 108, 109 as recommended by the International Union of Pure and Applied Chemistry of 30.8.1997.
2.1. Instruments and apparatus for testing
2.1.1. Drops
If the term "drop 'is used, this means a drop obtained using the standard dropper described below.
The standard dropper, see Figure 2.1.1.1, is made of practically colourless glass and ends at the bottom with a circular hole in a plane perpendicular to the dropper axis.
Other droplets may be used if they comply with the following test.
The dropper is carefully cleaned and fixed in a vertical position. 20 drops of water R which, at a temperature (20 ± 1) ° C, freely drip from the dropper at a constant rate of 1 drop / s, weighs (1000 ± 50) mg.
Three determinations shall be made with each dropper. The results of individual determinations do not differ from the average of the three determinations by more than 5%.
Fig. 2.1.1-1 Standard dropper
Dimensions in millimetres
2.1.2 Correlation table of porosity grades for sintered stock filters 1)
Tab. 2.1.2-1
| Stupeň pórovitosti (Ph. Eur.)* | Maximální průměr pórů v mikrometrech | Německo | Francie | Velká Británie |
|---|---|---|---|---|
| 1,6 | méně než 1,6 | 5f | - | - |
| - | 1 - 2,5 | 5 | - | 5 |
| 4 | 1,6 - 4 | - | - | - |
| - | 4 - 6 | - | 5 | - |
| 10 | 4 - 10 | 4f | - | 4 |
| 16 | 10 - 16 | 4 | 4 | - |
| 40 | 16 - 40 | 3 | 3 | 3 |
| - | 40 - 50 | - | - | 2 |
| 100 | 40 - 100 | 2 | 2 | - |
| - | 100 - 120 | - | - | 1 |
| 160 | 100 - 160 | 1 | 1 | - |
| - | 150 - 200 | 0 | 0 | - |
| 250 | 160 - 250 | - | - | - |
| - | 200 - 500 | - | 00 | - |
* The European Pharmacopoeia adopted a system that was declared by the International Organisation for Standardisation (ISO, taken over by ČSN 70 4850).
Diameters in micrometres
Special use
| < 2,55 | - bakteriologická filtrace |
| 4 až 10 | - ultra-jemná filtrace, dělení mikroorganismů velkého průměru |
| 10 až 40 | - analytická filtrace, velmi jemná filtrace rtuti, velmi jemná disperze plynů |
| 40 až 100 | - jemná filtrace, filtrace rtuti, jemná disperze plynů |
| 100 až 160 | - filtrace hrubých materiálů, disperze a promývání plynů, předfiltry při použití jiných filtračních materiálů |
| 160 až 500 | - filtrace velmi hrubých materiálů, disperze a promývání plynů |
2.1.3 Ultraviolet lamps for analytical purposes
Ultraviolet lamps for analytical purposes are usually composed of a mercury discharge lamp that serves as a source of ultraviolet light and a suitable filter that eliminates the visible part of the spectrum emitted by the discharge lamp. If a pharmacopoeia prescribes in the test the use of ultraviolet light of a wavelength of 254 nm or 365 nm, a lamp consisting of a mercury lamp and a filter whose emission zone has a maximum intensity at 254 nm or 365 nm shall be used. The lamp used enables reliable detection of a standard spot of sodium salicylate about 5 mm in diameter on the G R silica gel layer if the stain is observed in normal position relative to the source of radiation.
For the verification of this requirement, 5 μl of sodium salicylate R (0,4 g / l) solution is applied in 96% R2 alcohol for lamps at 254 nm and 5 μl of solution (2 g / l) for 96% R3 alcohol for lamps at 365 nm. The distance between the lamp and the chromatographic plate set in the test referred to in the pharmacopoeia cell shall not exceed the distance set in this verification.
2.1.4. Network
Sieves with square openings made of suitable materials shall be used. For non-analytical purposes, sieves with circular openings whose internal diameters are 1,25 times the size of square openings of the corresponding sieve may be used. The material from which the sieve is made shall not react with the sieve material. The degree of fragmentation is prescribed in the individual articles so that the sieve number corresponding to the nominal size of holes in micrometres is shown in brackets after the name of the substance.
Limit deviation3) Single hole size (+ X): The aperture size does not exceed the rated aperture size by more than X, calculated from the relation:
X = 2w0,753 + 4w0,25,
in which it indicates:
w - size of holes in μm.
Limit deviation of aperture size for average aperture size (± Y): the average aperture size does not deviate from the nominal aperture size by more than ± Y, calculated from the relation:
Y = w0,9827 + 1,6.
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Regulation Information
| Citation | Decree of the Ministry of Health No. 1 / 1998 Coll., laying down quality requirements, procedure for the preparation, testing, storage and dosing of medicinal products (Czech Pharmacopoeia 1997) |
|---|---|
| Regulation Type | - |
| Author | - |
| Collection | Code of Laws |
| Date of Promulgation | 15.01.1998 |
|---|---|
| Effective from | 01.02.1998 |
| Effective until | - |
| Status | Valid |
The regulation text is for informational purposes only.
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