CONTENTS
`
`Scientific Notes
`Collaborative study to assess the reproducibility of a
`reverse-phase LC method to determine the content
`and to estimate the impurities of benzathine
`benzylpenicillin
`System suitability criteria a case study: the
`determination of impurities in dicloxacillin sodium
`Inter-laboratory trials to assess a validation
`procedure for volumetric titrations
`
`Readers’ Tribune
`Near IR spectrometry
`
`Enquiry
`Alkyl mesilate (methanesulphonate) impurities
`in mesilate salts
`
`Certification of Suitability
`of the Monographs of the Ph. Eur.
`List of certificates issued by the EDQM
`
`3
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`3
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`8
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`18
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`26
`26
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`27
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`28
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`45
`45
`47
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`48
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`Official Announcement - Rapid
` Implementation on 01/01/2000
`Magnesium stearate
`Isopropyl alcohol
`Products with risk of transmitting agents of animal
`spongiform encephalopathies
`Minimising the risk of transmitting animal spongiform
`48
`encephalopathy agents via medicinal products (5.2.8)
`Replacement Production statements for monographs on
`52
`TSE-risk products
`Aprotinin
`Aprotinin concentrated solution
`Calcium stearate
`Cholesterol
`Chymotrypsin
`Decyl oleate
`Diethylene glycol monopalmitostearate
`Erythromycin stearate
`Ethyl oleate
`Ethylene glycol monopalmitostearate
`Glycerol distearate
`Glycerol mono-oleates
`Glycerol monostearate 40-55
`Hyaluronidase
`Insulin
`Macrogol stearate
`Macrogol stearyl ether
`Magnesium stearate
`Parnaparin sodium
`Propylene glycol monopalmitostearate
`Stearic acid
`Stearoyl macrogolglycerides
`Trypsin
`Vaccines for human use
`
`52
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`52
`52
`53
`53
`53
`53
`53
`53
`53
`53
`53
`53
`53
`53
`53
`53
`53
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`53
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`53
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`International Conferences
`Mycoplasma Testing the Potentialities & Roles of
`PCR Tests - 13-14 March 2000, Paris, France
`The Future Face of the European Pharmacopoeia
`Current Concerns in Pharmaceutical Analysis
`9-10 October 2000, Lisbon, Portugal
`Tetanus Vaccines for Human Use
`22-23 June 2000, Strasbourg, France
`
`55
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`55
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`59
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`63
`
`PHARMEUROPA 12.1
`January 2000
`
`General Information
`CD-ROM 2000 of the European Pharmacopoeia
`Press release: Conference in Berlin
`Conditions of sale of CRS
`List of CRS adopted in November 1999
`Prepublication brochure (June 1999)
`List of texts published in the June 1999
` prepublication brochure
`List of texts adopted in November 1999
`
`67
`67
`68
`69
`70
`72
`
`73
`74
`
`79
`84
`80
`81
`144
`97
`102
`92
`103
`125
`155
`
`126
`
`Draft monographs for comment
`Arnica tincture
`Assay of human coagulation factor II (2.7...)
`Assay of human coagulation factor X (2.7...)
`Azaperone
`Bovine viral diarrhoea vaccine (inactivated)
`Canine adenovirus vaccine (live)
`Caraway oil
`Carbon dioxide
`Cetyl palmitate
`Dihydroergocristine mesilate
`Diphtheria, tetanus and pertussis
`(acellular, component) vaccine (adsorbed)
`Diphtheria, tetanus, pertussis (acellular, component)
`and haemophilus type b conjugate vaccine (adsorbed) 95
`Diphtheria, tetanus, pertussis (acellular, component)
`and hepatitis B (rDNA) vaccine (adsorbed)
`Diphtheria, tetanus, pertussis (acellular, component)
`and poliomyelitis (inactivated) vaccine (adsorbed)
`Framycetin sulphate
`Gemfibrozil
`Greater celandine
`Heptaminol hydrochloride
`Human coagulation factor VII, freeze-dried
`Human plasma
`(pooled and treated for virus inactivation)
`Human prothrombin complex, freeze-dried
`Hymecromone
`Ibuprofen
`Iodinated (125I) human albumin injection
`Ioxaglic acid
`Java tea
`Levamisole
`Levamisole hydrochloride
`Lobeline hydrochloride
`Marsh mallow leaf
`Mesterolone
`Mint oil, dementholised
`Neomycin sulphate
`Netilmicin sulphate
`Nitrous oxide
`Oak bark
`Orphenadrine citrate
`Orphenadrine hydrochloride
`Phytosterol
`Pipemidic acid trihydrate
`Poloxamers
`Pravastatin sodium
`Rosemary oil
`Sage leaf (salvia officinalis)
`Semi-solid preparations for cutaneous application
`Sodium perborate trihydrate
`Star anise
`Thyme
`Wild pansy (flowering aerial parts)
`Zinc stearate
`
`129
`
`107
`116
`170
`161
`138
`80
`
`168
`79
`157
`148
`110
`141
`87
`153
`150
`140
`167
`146
`88
`119
`122
`105
`162
`137
`135
`165
`133
`172
`114
`99
`163
`112
`126
`164
`82
`90
`159
`
`© PHARMEUROPA Vol. 12, No. 1, January 2000
`
`1
`
`Apotex Exhibit 1023.001
`
`

`

`THE EUROPEAN PHARMACOPOEIA
`THE EUROPEAN PHARMACOPOEIA
`
`Paper Version
`3rd Edition 1997 + Supplement 2000
`
`Price :
`
`456 Euro (Europe)
`
`509 Euro (Outside Europe)
`
`Supplement 2000
`
`Price :
`
`140 Euro (Europe)
`
`170 Euro (Outside Europe)
`
`— PHARMEUROPA — SPECIAL ISSUE —
`
`“List of Standard Terms” 2000 Edition
`
`The present List of Standard Terms is a revised List of Standard Terms which was drawn up in response
`to a request from the European Commission. It covers both medicines for human and veterinary use.
`Those Standard Terms are to be used in answering the questions 2, 2.1 and 2.2 of part IA and sections
`3 and 6.5 of part IB (Summary of the Product Characteristics) of the EU application format.
`The current issue of Standard Terms is composed of :
`— an Introduction :
`• a section of general principles and instructions for the use of Standard Terms,
`• the summary of the changes (amendments, additions, deletions) performed since the last
` publication (February 1998),
`• procedure for the addition, deletion or modification of terms in the list of Standard Terms,
`— three lists of standard terms :
`• list of pharmaceutical forms,
`• list of routes and/or methods of administration,
`• list of containers, closures and administration devices.
`
`The previous edition contained translations in sixteen European languages : Croatian, Danish, Dutch,
`English, Finnish, French, German, Greek, Italian, Norwegian, Portuguese, Slovak, Slovenian, Spanish,
`Swedish and Turkish). The present lists have further been enlarged by adding the Bulgarian, Czech,
`Hungarian, Icelandic and Polish Terms.
`
`Price: 38 Euro (Europe) - 42 Euro (Outside Europe) .
`
`Information and orders:
`Council of Europe
`European Department for the Quality of Medicines (EDQM)
`BP 907 - F67029 Strasbourg Cedex 1
`tel. : +33 (0)3 88 41 20 36 - fax : + 33 (0)3 88 41 27 71
`E-mail : pub@ pheur.org
`
`2
`
`© PHARMEUROPA Vol. 12, No. 1, January 2000
`
`Apotex Exhibit 1023.002
`
`

`

`Readers’ tribune
`
`tifically sound rationale be used when building
`libraries and or calibrations. This rationale may vary
`depending on the application and products For ex-
`ample, in a quantitative calibration, correlation may
`not be a good indicator of performance, particularly
`when the calibration range is small and the error
`associated with primary method is comparatively
`large.
`
`— Based on the definition of the identity test, NIR can
`be used for identification of mixtures. Depending on
`the requirements of the application, as long as the
`
`method is shown to be sensitive to significant changes
`in composition (selectivity - this may be difficult
`when concentrations are low), along with the other
`validation requirements, it should be considered
`acceptable. For example, if distinction between two
`different dosage strengths of a single product in
`tablet form is required, one should be able to use NIR
`for this purpose if the method is shown to be
`validatable and thus sensitive to the differences in
`composition. Therefore we do not believe that dis-
`cussions should focus on the identification of single
`active ingredients or excipients.
`
`Enquiry
`
`ALKYL MESILATE (METHANESULPHONATE) IMPURITIES
`IN MESILATE SALTS
`
`The need for limits on methyl, ethyl and isopropyl
`mesilate esters in active substances presented as mesilates
`has recently been discussed by the European Pharmaco-
`poeia Commission. These esters are highly toxic and
`assurance is needed that they are not present in unaccept-
`able quantities in medicinal products. However, they are
`also very reactive and it is therefore possible that in
`practice the level of contamination is negligible. Readers
`of Pharmeuropa are asked to inform EDQM of their
`opinion on the need for a test and limit in the light of their
`experience with mesilate salts. Information on analytical
`methods and the level of such impurities found in prac-
`tice would be extremely valuable. Seven monographs on
`mesilates are at present included in the European Phar-
`macopoeia and would be concerned if a test and limit
`were to be added:
`
`Betahistine mesilate
`Bromocriptine mesilate
`Deferoxamine mesilate
`Dihydroergocristine mesilate
`Dihydroergotamine mesilate
`Pefloxacin mesilate dihydrate
`Phentolamine mesilate
`
`Please send your replies to:
`Council of Europe
`European Directorate for the Quality of Medicines
`B.P. 907
`67029 Strasbourg Cedex 1
`France
`Fax: + 33 (0)3 88 41 27 71.
`E-mail: info@pheur.org.
`
`© PHARMEUROPA Vol. 12, No. 1, January 2000
`
`27
`
`Apotex Exhibit 1023.003
`
`