Substances for Pharmaceutical Use 2034E - uspbpep.com

1 EUROPEAN PHARMACOPOEIA for Pharmaceutical useStandard preparations are calibrated by spectroscopicmeasurements and stored in a state suitable for use overan extended period of time. Hybridisation conditions. The stringency of hybridisationconditions is such as to ensure specific hybridisationbetween probes and standard DNA preparations and thedrug Substances must not interfere with hybridisationat the concentrations techniquesSuitable procedures include: detection of sulphonatedcytosine residues in single-stranded DNA (where DNA isimmobilised on a filter and cytosines are derivatisedin situ,before detection and quantitation using an antibody directedagainst the sulphonated group);detection of single-strandedDNA using a fragment of single-stranded DNA bound to aprotein and an antibody of this protein. Neither procedurerequires the use of specific host or vector DNA as an assaystandard. However, the method used must be validated toensure parallelism with the DNA standard used, linearity ofresponse and non-interference of either the drug substanceor excipients of the formulation at the dilutions used in , TESTS AND ASSAYT herequirementswithwhichthefinalproduct(b ulkmaterialor dose form) must comply throughout its period of validity,as well as specific test methods, are stated in the :2034 SUBSTANCESFOR Pharmaceutical USEC orpora ad usum pharmaceuticumThe statements in this monograph are intended to be readin conjunction with individual monographs on substancesin the Pharmacopoeia.

2 Application of the monographto other Substances may be decided by the for Pharmaceutical use are any organic orinorganic Substances that are used as active substancesor excipients for the production of medicinal products or produced by extraction from raw materials,fermentation or monograph does not apply to herbal drugs, herbal drugpreparations or extracts, which are the subject of separategeneral monographs [Herbal drugs (1433),Herbal drugpreparations (1434),Extracts (0765)].Where medicinal products are manufactured usingsubstances for Pharmaceutical use of human or animalorigin, the requirements of for Pharmaceutical use may be used as such oras starting materials for subsequent formulation to preparemedicinal products. Depending on the formulation, certainsubstances may be used either as active Substances or asexcipients. Solid Substances may be compacted, coated,granulated, powdered to a certain fineness or processedin other ways.

3 Processing with addition of excipients ispermitted only where this is specifically stated in theDefinition of the individual for Pharmaceutical use of special otherwise indicated orrestricted in the individualmonographs, a substance for Pharmaceutical use is intendedfor human and veterinary use, and is of appropriate qualityfor the manufacture of all dosage forms in which it can Individual monographs do not usuallyspecify crystalline or amorphous forms, unless bioavailabilityis affected. All forms of a substance for Pharmaceutical usecomply with the requirements of the monograph, unlessotherwise for Pharmaceutical use are manufacturedby procedures that are designed to ensure a consistentquality and comply with the requirements of the individualmonograph or approved provisions of general to the controlof impurities in Substances for Pharmaceutical or not it is specifically stated in the individualmonograph that the substance for Pharmaceutical use: is a recombinant protein or another substance obtainedas a direct gene product based on genetic modification,where applicable, the substance also complies with therequirements of the general monograph onProducts ofrecombinant DNA technology (0784).

4 Is obtained from animals susceptible to transmissiblespongiform encephalopathies other than by experimentalchallenge, where applicable, the substance also complieswith the requirements of the general monograph onProducts with risk of transmitting agents of animalspongiform encephalopathies (1483); is a substance derived from a fermentation process,whether or not the micro-organisms involved are modifiedby traditional procedures or recombinant DNA (rDNA)technology, where applicable, the substance complieswith the requirements of the general monograph onProducts of fermentation (1468).If solvents are used during production, they are of suitablequality. In addition, their toxicity and their residual levelare taken into consideration ( ). If water is used duringproduction, it is of suitable Substances are produced or processed to yield a certainform or grade, that specific form or grade of the substancecomplies with the requirements of the monograph.

5 Certainfunctionality-related tests may be described to controlproperties that may influence the suitability of the substanceand subsequently the properties of dosage forms preparedfrom substancesmay be processed to obtain a certaindegree of fineness ( ).Compacted substancesare processed to increase the particlesize or to obtain particles of a specific form and/or to active substancesconsist of particles of the activesubstance coated with one or more suitable active substancesare particles of a specifiedsize and/or form produced from the active substance bygranulation directly or with one or more suitable Substances are processed with excipients , these excipientscomply with the requirements of the relevant monograph or,where no such monograph exists, the approved (1)applytoallmonographsandothertexts703 Substances for Pharmaceutical useEUROPEAN PHARMACOPOEIA statements under the heading Characters ( about the solubility or a decomposition point)arenottobeinterpretedinastrictsens eandarenotrequirements.

6 They are given for a substance may show polymorphism, this may bestated under Characters in order to draw this to the attentionof the user who may have to take this characteristic intoconsideration during formulation of a under Identification an individual monographcontains subdivisions entitledFirst identificationandSecond identification, the test or tests that constitute theFirst identificationmay be used in all circumstances. Thetest or tests that constitute theSecond identificationmaybe used for identification, provided it can be demonstratedthat the substance is fully traceable to a batch certified tocomply with all the other requirements of the ( ).Ifthenatureofacrystallineoramorphous form imposes restrictions on its use inpreparations, the nature of the specific crystalline oramorphous form is identified, its morphology is adequatelycontrolled and its identity is stated on the Substances .

7 Unless otherwise prescribed or justifiedand authorised, organic impurities in active Substances areto be reported, identified wherever possible, and qualifiedas indicated in Table thresholds may be applied for impurities knownto be unusually potent or to produce toxic or unexpectedpharmacological the individual monograph does not provide suitablecontrol for a new impurity, a suitable test for control mustbe developed and included in the specification for requirements above do not apply to biological andbiotechnological products, peptides, oligonucleotides,radiopharmaceuticals, products of fermentation andsemi-synthetic products derived therefrom, to crude productsof animal or plant origin or herbal solventsare limited according to the principlesdefined in , using general another suitable method. Where a quantitativedetermination of a residual solvent is carried out and a testfor loss on drying is not carried out, the content of residualsolvent is taken into account for calculation of the assaycontent of the substance, the specific optical rotation andthe specific quality.

8 Individual monographs giveacceptance criteria for microbiological quality whereversuch control is necessary. Table Acceptancecriteria for microbiological quality of non-sterilesubstances for Pharmaceutical usein quality of Pharmaceutical preparationsgives recommendations on microbiological quality that areof general relevance for Substances subject to microbialcontamination. Depending on the nature of the substanceand its intended use, different acceptance criteria may ( ). If intended for use in the manufactureof sterile dosage forms without a further appropriatesterilisation procedure, or if offered as sterile grade, thesubstance for Pharmaceutical use complies with the test endotoxins( ). If offered as bacterialendotoxin-free grade, the substance for Pharmaceutical usecomplies with the test for bacterial endotoxins. The limitandtestmethod(ifnotgelationmethodA) arestatedintheindividual monograph.

9 The limit is calculated in accordancewithTest for bacterial endotoxins: guidelines( ),unless a lower limit is justified from results from productionbatches or is required by the competent authority. Where atest for bacterial endotoxins is prescribed, a test for pyrogensis not ( ). If the test for pyrogens is justified ratherthan the test for bacterial endotoxins and if a pyrogen-freegrade is offered, the substance for Pharmaceutical usecomplies with the test for pyrogens. The limit and testmethod are stated in the individual monograph or approvedby the competent authority. Based on appropriate testvalidation for bacterial endotoxins and pyrogens, the test forbacterial endotoxins may replace the test for properties. Control of additional properties ( characteristics, functionality-related characteristics)may be necessary for individual manufacturing processesor formulations. Grades (such as sterile, endotoxin-free,pyrogen-free) may be produced with a view to manufacture ofpreparations for parenteral administration or other dosageforms and appropriate requirements may be specified in anindividual justified and authorised, contents of Substances forpharmaceutical use are determined.

10 Suitable methods general, labelling is subjectto supranational and nationalregulation and to international agreements. The statementsunder the heading Labelling therefore are not comprehensiveand, moreover, for the purposes of the Pharmacopoeiaonly those statements that are necessary to demonstratecompliance or non-compliance with the monograph aremandatory. Any other labelling statements are includedas recommendations. When the term label is used in thePharmacopoeia, the labelling statements may appear on thecontainer, the package, a leaflet accompanying the packageor a certificate of analysis accompanying the article, asdecided by the competent appropriate, the label states that the substance is: intendedforaspecificuse; of a distinct crystalline form;Table Reporting, identification and qualificationof organic impurities in active substancesUseMaximum dailydoseReportingthresholdIdentificatio nthresholdQualificationthresholdHuman use or human andveterinary use 2g/day> > of > mg (whicheveris the lower)> of > mg (whicheveris the lower)Human use or human andveterinary use>2g/day> > > use onlyNot applicable> > > the information section on general monographs (cover pages)EUROPEAN PHARMACOPOEIA for human use of a specific degree of fineness; compacted; coated; granulated; sterile.