Introduction

British Pharmacopoeia 2018

The British Pharmacopoeia 2018 supersedes the British Pharmacopoeia 2017. It has been prepared by the British Pharmacopoeia Commission, with the collaboration and support of its Expert Advisory Groups, Panels of Experts and Working Parties and contains approximately 4000 monographs for substances, preparations and articles used in the practice of medicine. Some of these monographs are of national origin and have been elaborated or revised under the auspices of the British Pharmacopoeia Commission whilst others (indicated to users by a chaplet of stars) have been elaborated, or revised, under the auspices of the European Pharmacopoeia Commission, supported by its Groups of Experts and Working Parties, and are reproduced from the European Pharmacopoeia. This edition, together with its companion volume, the British Pharmacopoeia (Veterinary) 2018, incorporates all the monographs of the 9th Edition of the European Pharmacopoeia, as amended by Supplements 9.1 and 9.2. Users of the British Pharmacopoeia thereby benefit by finding within this comprehensively indexed compendium all current United Kingdom pharmacopoeial standards for medicines for human use.

The BP 2018 comprises six volumes as follows.

Effective Date

The effective date for British Pharmacopoeia monographs in this edition is 1 January 2018.

National monographs omitted from this or earlier editions of the British Pharmacopoeia remain effective in accordance with Regulation 252(2)(c) of the Human Medicines Regulations 2012.

Implementation dates regarding European Pharmacopoeia publications are provided in Supplementary Chapter IV B: Dates of Implementation. European Pharmacopoeia monographs are identified by a chaplet of stars alongside the title.

Additions

A list of monographs included for the first time in the British Pharmacopoeia 2018 is given at the end of this introduction. It includes 35 new monographs of national origin and 39 new monographs reproduced from the 9^th Edition of the European Pharmacopoeia, as amended by Supplements 9.1 and 9.2.

Pharmacopoeial public quality standards for biological medicines

In January 2017 the Medicines and Healthcare products Regulatory Agency (MHRA) published a consultation on its strategy for pharmacopoeial public quality standards for biological medicines. This consultation had been prepared by staff from across the MHRA including BP, NIBSC and MHRA assessors and inspectors.

The consultation reflected the increasing importance of biological medicines to global healthcare strategies, together with the need to consider how standards can act as enablers for innovation now and in the future. As a result, the consultation and draft strategy reflected themes around supporting innovation, knowledge building and collaboration. It also acknowledged and supported the MHRA’s wider work in this area, such as the role identified for standards in the Medicines Manufacturing Industry Partnership action plan on advanced therapies manufacturing: http://www.abpi.org.uk/our-work/mmip/documents/advanced-therapies-manufacturing-taskforce-report.pdf.

A public response to the consultation, which closed on 10 April 2017, will be posted on the consultation webpage https://www.gov.uk/government/consultations/strategy-for-pharmacopoeial-public-quality-standards-for-biological-medicines.

Traditional Herbal Medicines; Homoeopathic Preparations

Work is continuing on the development of monographs for herbs used in traditional herbal medicines and homoeopathic medicines. The Latin scientific names cited in BP monographs for herbal drugs are consistent with the advice provided by the Medicinal Plant Names Services at the Royal Botanic Gardens, Kew. As stated in previous editions, the requirements for the quality of the material are provided in the monographs to set the standards for Traditional Herbal Medicines in the UK and to assist the UK Traditional Herbal Medicines Registration Scheme. The British Pharmacopoeia Commission, however, has not assessed the safety and efficacy of the materials in traditional use. Likewise, the British Pharmacopoeia Commission has not assessed the safety and efficacy of materials for use in homoeopathic preparations for which monographs are published.

Four new BP monographs for herbal medicines are included in this edition. They reflect a continued commitment to providing standards for herbal drugs commonly used in the UK and for those known to be used for the preparation of traditional medicines. We have continued to review the fitness-for-purpose of published BP monographs for herbal and complementary medicines, revising them as deemed necessary. We continue to work with our collaborative partners to ensure better understanding of the needs of our users, which in turn focuses attention on producing the standards needed for the future.

Unlicensed Medicines

With this new edition, a further 4 monographs for unlicensed formulations have been added. These individual monographs are characterised by a statement that the products are not currently licensed in the United Kingdom. The general and individual monographs are intended to apply to all types of Unlicensed Medicines, that is, those formulations prepared under a Manufacturer’s ‘Specials’ Licence and those prepared extemporaneously under the supervision of a pharmacist.

The Supplementary Chapter on Unlicensed Medicines has been updated to clarify the medicines legislation relating to ‘Specials’ and that relating to formulations prepared under the supervision of a pharmacist and to reflect updated guidance from the Royal Pharmaceutical Society.

Revisions

A significant number (185, comprising 102 technical revisions and 83 editorial revisions) of national monographs have been amended by means of this edition. Of these monographs, those with major technical revisions are listed at the end of this Introduction. For the benefit of the reader this list indicates the section, or sections, of each monograph which has/have been revised.

The list of revisions appended to this Introduction is as comprehensive as practicable. However, to ensure that the reader uses the current standard, it is essential to refer to the full text of each individual monograph.

For those texts reproduced from the European Pharmacopoeia, the European Directorate for the Quality of Medicines & HealthCare (EDQM) database (see below, under Websites) provides information on revisions of the monographs or other texts on a historical basis, beginning from the 5th Edition of the European Pharmacopoeia.

Inhaled Products

The BP Policy on Inhaled Products has been updated following a review of the content and format of specific BP inhaled product monographs and an update to the European Pharmacopoeia General Monograph for Preparations for Inhalation. Nineteen monographs of the BP have been editorially amended to take into account the requirements laid out in the policy; any technical changes required will be revised in a future publication. The updated Inhaled Products Policy can be found in Supplementary Chapter I O: Inhaled Products.

The General Monograph for Preparations for Inhalation of the British Pharmacopoeia has been omitted from this publication and suitable validated alternative methodology for the Content of active ingredient on actuation of the valve test will be established for existing product monographs when available. The Content of active ingredient on actuation of the valve test methodology has been moved to Appendix XII and a cross-reference to this Appendix has been included in monographs where required.

Users should note that the term “pre-dispensed”, previously applied to BP Inhalation product monographs, has been updated to “pre-metered” to align with the appropriate EDQM full Standard Term. The BP legacy title has been included as a subsidiary title for revised monographs. The list of title changes is appended at the end of this Introduction.

Assays Based on the Results of Uniformity Tests

Sixty-one formulated preparation monographs that include Assays based on the average of the results of uniformity tests (Uniformity of content / Uniformity of delivered dose) have been updated. The minor amendment made was to update the wording for Assays based on the average of the results of uniformity tests so that the statement can be applied across monographs of the BP where appropriate, regardless of the number of results obtained in the uniformity test.

Title Changes

Seven monograph titles have been amended in this edition. The list of changes is appended at the end of this Introduction.

Omissions

Ten monographs have been omitted from the British Pharmacopoeia 2018. The list of omissions is appended at the end of this Introduction.

Infrared Reference Spectra

As with the previous edition, the reference spectra are placed in alphabetical order within this edition. Five new spectra have been added to the collection. (Aspirin, Azithromycin, Methylphenidate, Telmisartan and Pantoprazole Sodium).

Appendices

Four new Appendices to harmonise with the European Pharmacopoeia were first published in the British Pharmacopoeia 2017 electronic updates. These have been consolidated in the new edition as follows:

Appendix XV L: Immunonephelometry for Vaccine Component Assay (Ph. Eur. method 2.7.35).

Appendix XI W: High-Performance Thin-Layer Chromatography of Herbal Drugs and Herbal Drug Preparations (Ph. Eur. method 2.8.25).

Appendix XIV O: Host-cell Protein Assays (Ph. Eur. method 2.6.34).

Appendix XIV P: Determination of Bactericidal, Fungicidal or Yeasticidal Activity of Antiseptic Medicinal Products (Ph. Eur. method 5.1.11).

Supplementary Chapters

One new Supplementary Chapter to harmonise with the European Pharmacopoeia was first published in the British Pharmacopoeia 2017 electronic updates. It has been consolidated in the new edition as follows:

Supplementary Chapter IV S: Raw Materials of Biological Origin for the Production of Cell-based and Gene Therapy Medicinal Products (Ph. Eur. General Text 5.2.12).

Supplementary Chapter I C: Bacterial Endotoxin Testing This Supplementary Chapter has been updated to reflect current Biological Reference Preparation batch numbers.

European Pharmacopoeia

Co-operation Agreement

As a consequence of the Co-operation Agreement with the EDQM of the Council of Europe, the British Pharmacopoeia Commission is pleased to note the integration of European Pharmacopoeia texts for the British Pharmacopoeia 2017 in-year online updates and for this edition of the British Pharmacopoeia.

In accordance with previous practice, all monographs and requirements of the European Pharmacopoeia are reproduced in this edition of the British Pharmacopoeia or, where appropriate, within its companion edition, the British Pharmacopoeia (Veterinary) 2018.

Where a monograph has been reproduced from the European Pharmacopoeia, this is signified by the presence of a chaplet of stars alongside its title. Additionally, reference to the European Pharmacopoeia monograph number is included immediately below the title in italics in the form ‘Ph. Eur. monograph xxxx’. Where the title in the British Pharmacopoeia is different from that in the European Pharmacopoeia, an approved synonym has been created (see Appendix XXI B) and the European Pharmacopoeia title is included before the monograph number. The entire European Pharmacopoeia text is delineated by two horizontal lines bearing the symbol ‘Ph. Eur.’.

The European Pharmacopoeia texts have been reproduced in their entirety but, where deemed appropriate, additional statements of relevance to UK usage have been added (e.g. action and use statement, a list of British Pharmacopoeia preparations). It should be noted, however, that in the event of doubt of interpretation in any text of the European Pharmacopoeia, the text published in English under the direction of the Council of Europe should be consulted.

Correspondence between the general methods of the European Pharmacopoeia and the appendices of the British Pharmacopoeia is indicated in each appendix and by inclusion of a list at the beginning of the appendices section.

Pharmacopoeial Requirements

It should be noted that any article intended for medicinal use which is described by a name at the head of a monograph in the current edition of the Pharmacopoeia must comply with that monograph ‘whether or not it is referred to as BP’.

It is also important to note that no requirement of the Pharmacopoeia can be taken in isolation. A valid interpretation of any particular requirement depends upon it being read in the context of (i) the monograph as a whole, (ii) the specified method of analysis, (iii) the relevant General Notices and (iv) where appropriate, the relevant General Monograph(s). Familiarity with the General Notices of the Pharmacopoeia will facilitate the correct application of the requirements. Additional guidance and information on the basis of pharmacopoeial requirements is provided in Supplementary Chapter I. This non-mandatory text describes the general underlying philosophy and current approaches to particular aspects of pharmacopoeial control.

Code of Practice

Members of the British Pharmacopoeia Commission and its supporting Expert Advisory Groups, Panels of Experts and Working Parties are required to comply with a Code of Practice on Declaration of Interests in the pharmaceutical industry. Details of the Code are published on the website (www.pharmacopoeia.com).

Recommendations of the Triennial Review of the British Pharmacopoeia Commission

In 2015 the Department of Health conducted a Triennial Review of the British Pharmacopoeia Commission (BPC) to provide assurance to the Department and the public that the functions of the Commission are required and that it is operating effectively. The Triennial Review report, published in March 2015, made a number of minor recommendations. All of the recommendations made in the report have now been completed.

The full report of the Review can be found on the website at www.gov.uk/government/consultations/british-pharmacopoeia-commission-triennial-review.

Websites

British Pharmacopoeia Website

The British Pharmacopoeia website, http://www.pharmacopoeia.com, contains information relating to the British Pharmacopoeia. It allows subscribers to access the British Pharmacopoeia 2018 and British Pharmacopoeia (Veterinary) 2018 online and British Approved Names publications. All users are also able to view and purchase BPCRS products through the website.

Chromatograms for information to support new monographs published in the British Pharmacopoeia 2018 have been added to the example test results gallery to aid users of British Pharmacopoeia monographs. This service will increase year-on-year to allow users to examine chromatograms obtained during the practical evaluation of new monographs by the British Pharmacopoeia Commission Laboratory.

A regular review schedule for draft texts is included on the website, with draft new and revised monographs being posted at the start of each quarter and available for comment for a period of three months thereafter. This free service allows greater visibility of the BP’s work programme and enables stakeholder contributions to monograph development.

Subscribers to the BP online will find that draft texts and example test results are also linked with relevant texts and directly accessible from the BP online content. Additionally, BPCRS products are also linked with relevant BP monographs and subscribers to the BP online will be able to purchase these directly from the BP online. BPCRS customers are able to make purchases through invoice or credit card orders.

An email subscription feature allows users to keep abreast with BP news. Additionally, users can subscribe to receive BPCRS updates, which are now posted monthly.

Access to previous editions of the BP is available as a BP archive product for purchase by new and existing BP online subscribers. The content of the archive starts from the BP 2014 onwards and grows year-on-year as superseded editions are added to the archive.

A policy of continuous improvement allows the BP website to keep up to date and respond to users. Customers are therefore invited to provide the Secretariat with feedback on their experience.

European Pharmacopoeia Websites

https://extranet.edqm.eu/publications/recherches_sw.shtml For those texts reproduced from the European Pharmacopoeia, the EDQM website provides access to a database (the Knowledge database) containing information of various sorts related to monographs and intended to facilitate their proper use. Information is provided on chromatographic columns used in monograph development, suppliers of reagents and equipment that may be difficult to find for some users, the status of monographs (in development, adopted, published, under revision), revisions of the monographs on a historical basis, beginning from the 5th Edition of the European Pharmacopoeia as well as other useful information.

https://pharmeuropa.edqm.eu/homeThe European Pharmacopoeia Forum, Pharmeuropa, is published quarterly as an aid for the elaboration of monographs and as a vehicle for information on pharmacopoeial and related matters. Pharmeuropa is available as a free on-line publication.

International Collaboration

Therapeutic Goods Administration, Australia The British Pharmacopoeia Commission is pleased to continue its long-standing co-operation with the Australian Department of Health Therapeutic Goods Administration (TGA). The TGA continues to provide advice to British Pharmacopoeia Commission Expert Advisory Groups, to participate in inter-laboratory evaluation of British Pharmacopoeia monographs and to review data jointly. This collaboration has enabled the production of robust, high quality monographs for users.

Chinese Pharmacopoeia The British Pharmacopoeia Commission is pleased to continue its collaboration with the Chinese Pharmacopoeia on the development of monographs and staff exchanges to support mutually agreed projects.

The Croatian Agency for Medicinal Products and Medical Devices (“HALMED”) Following the signing of a Cooperation Agreement in February 2015, the Medicines and Healthcare products Regulatory Agency has granted HALMED a licence to use the information in the British Pharmacopoeia on unlicensed medicines.

The Japanese Pharmacopoeia The British Pharmacopoeia has collaborated with the Japanese Pharmacopeia for the development of informally harmonised standards and knowledge sharing in a number of areas of mutual interest.

State Pharmacopoeia of the Republic of Kazakhstan Following the signing of a Collaboration Agreement in April 2016, the Medicines and Healthcare products Regulatory Agency has granted the Committee on Surveillance of Medical and Pharmaceutical Activities of the Ministry of Health of the Republic of Kazakhstan a licence to continue to use relevant contents of the British Pharmacopoeia in the State Pharmacopoeia of the Republic of Kazakhstan.

State Pharmacopoeia of Ukraine Following the signing of a Collaboration Agreement in 2016, the Medicines and Healthcare products Regulatory Agency has continued to grant the Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines a licence to use relevant contents of the British Pharmacopoeia in the State Pharmacopoeia of Ukraine.

United States Pharmacopeia Close collaboration with the United States Pharmacopeia continues, building on the success of the programme of work to informally harmonise drug product monographs, with joint participation in conferences and symposia and knowledge sharing in areas of mutual interest.

World Health Organization The British Pharmacopoeia continues to support the work of the WHO, including collaboration and information exchange with the International Pharmacopoeia and supporting the international non-proprietary names programme.

Forward Look

Electronic Updates The British Pharmacopoeia 2018 online updates will be published on the website, www.pharmacopoeia.com, to enable users to keep up to date with monographs published in the European Pharmacopoeia. These updates will be integrated annually with the publication of the main edition of the British Pharmacopoeia.

Acknowledgements

The British Pharmacopoeia Commission is greatly indebted to the members of its Expert Advisory Groups, Panels of Experts and Working Parties for their dedicated enthusiasm and assistance in the preparation of this edition.

Close co-operation has continued with many organisations at home and overseas. These include the Medicines and Healthcare products Regulatory Agency, the Veterinary Medicines Directorate, the Royal Pharmaceutical Society, the Association of the British Pharmaceutical Industry, the British Association of Homoeopathic Manufacturers, the United Kingdom Herbal Forum, The China Food and Drug Administration, the Chinese Pharmacopoeia Commission, the European Pharmacopoeia Commission and the European Directorate for the Quality of Medicines & HealthCare, the Therapeutic Goods Administration (Australia), the Health Products and Food Branch of Health Canada, the United States Pharmacopeia, the Quality Assurance and Safety: Medicines Department of the World Health Organization (WHO), the Health Sciences Authority of Singapore and the Royal Botanic Gardens, Kew.

The British Pharmacopoeia Commission wishes to thank the European Directorate for the Quality of Medicines & HealthCare for their support and assistance in the reproduction of the European Pharmacopoeia texts and monographs. The British Pharmacopoeia Commission acknowledges the importance of the work of the European Pharmacopoeia (Ph. Eur.) Commission and its Groups of Experts and Working Parties. The British Pharmacopoeia Commission is also grateful for the generous contribution by the UK experts to the work of the Groups of Experts and Working Parties of the European Pharmacopoeia Commission.

The revision to the monograph for Aspirin Tablets was completed in conjunction with the University of Sunderland Pharmacy Department. Analysis performed by MPharm students under the supervision of Dr John Lough provided valuable input into the new method for Related substances.

The British Pharmacopoeia Commission acknowledges the contribution of Professor Frederick A Senese, Department of Chemistry, Frostburg State University, USA, for his kind permission to reproduce the indicator colour chart.

The British Pharmacopoeia Commission also acknowledges and appreciates the advice of the publishing team at The Stationery Office, in particular, Ms Nichola Billington, Mr Colin Hackett, Mr Paul Allard, Mr Paul Relfe and Mr Ian Webb, in the production of this edition.

The British Pharmacopoeia Commission acknowledges the contribution of Ms Charlotte Hill and Mr Jonathan Ware, two members of the Civil Service Fast Stream programme who each spent six months working with the British Pharmacopoeia Secretariat.

Additions

The following monographs of the British Pharmacopoeia 2018 were not included in the British Pharmacopoeia 2017.

Medicinal and Pharmaceutical Substances

Animal Epithelia and Outgrowths for Allergen Products*

Aprepitant*

Clopidogrel Besilate^*

Clopidogrel Hydrochloride*

Egg Phospholipids for Injection*

Escitalopram*

Gadodiamide Hydrate*

Hydroquinone

Hydroxychloroquine Sulfate*

Hymenoptera Venoms for Allergen Products*

Irinotecan Hydrochloride Trihydrate*

Isopropyl Isostearate*

Mites for Allergen Products*

Moulds for Allergen Products*

Pollens for Allergen Products*

Remifentanil Hydrochloride*

Tacalcitol Monohydrate*

Temozolomide*

Teriparatide*

Terlipressin*

Tobramycin Sulfate

Formulated Preparations: Specific Monographs

Azithromycin Capsules

Azithromycin for Infusion

Azithromycin Oral Suspension

Azithromycin Tablets

Benzoyl Peroxide and Clindamycin Gel

Ceftazidime Injection

Ciclosporin Capsules

Sterile Doxorubicin Concentrate

Doxorubicin for Infusion

Heparin Flush Solution

Loperamide Oral Suspension

Methylphenidate Tablets

Morphine Capsules

Prolonged-release Morphine Capsules

Morphine Granules for Oral Suspension

Morphine Oral Solution

Pantoprazole for Injection

Gastro-resistant Pantoprazole Tablets

Pramipexole Tablets

Prolonged-release Pramipexole Tablets

Orodispersible Sildenafil Films

Sildenafil Injection

Sildenafil Powder for Oral Suspension

Sildenafil Tablets

Chewable Sildenafil Tablets

Orodispersible Sildenafil Tablets

Telmisartan Tablets

Tobramycin Oral Solution

Tretinoin, Hydrocortisone and Hydroquinone Cream

Herbal Drugs, Herbal Drug Preparations and Herbal Medicinal Products

Akebia Stem*

Andrographis Herb*

Cape Jasmine Fruit*

Chinese Goldthread Rhizome*

Standardised Capsicum Oleoresin

Capsicum Tincture

Codonopsis Root*

Dioscorea Nipponica Rhizome*

Evodia Fruit*

Horse-chestnut Fruit*

Standardised Horse-chestnut Dry Extract*

Liquorice Liquid Extract

Lycopus Lucidus Herb*

Red Peony Root*

White Peony Root*

Polygonum Cuspidatum Rhizome and Root*

Polygonum Orientale Fruit*

Tribulus Terrestris Fruit

Uncaria Stem with Hooks*

Zanthoxylum Bungeanum Pericarp*

Materials for use in the Manufacture of Homoeopathic Preparations

Magnesium Fluoratum for Homoeopathic Preparations*

Selenium for Homoeopathic Preparations*

Radiopharmaceutical Preparations

Lutetium (¹⁷⁷Lu) Solution for Radiolabelling*

Sodium Pyrophosphate Decahydrate for Radiopharmaceutical Preparations*

Omissions

The following monographs of the British Pharmacopoeia 2017 are not included in the British Pharmacopoeia 2018.

Medicinal and Pharmaceutical Substances

Hydroxychloroquine Sulfate (superseded by new Ph. Eur. monograph)

Formulated Preparations: General Monographs

Preparations for Inhalation of the British Pharmacopoeia

Formulated Preparations: Specific Monographs

Clofibrate Capsules

Doxorubicin Injection

Iofendylate Injection

Iopanoic Acid Tablets

Methoxamine Injection

Mexenone Cream

Herbal Drugs, Herbal Drug Preparations and Herbal Medicinal Products

Peppermint Spirit

White Peony Root (superseded by new Ph. Eur. monograph)

Technical Changes

The following monographs in the British Pharmacopoeia 2018 have been technically amended since the publication of the British Pharmacopoeia 2017, or have had a significant editorial change. This list does not include revised monographs of the European Pharmacopoeia. An indication of the nature of the change or the section of the monograph that has been changed is given in italic type in the right hand column.

Medicinal and Pharmaceutical Substances

Formulated Preparations: Specific Monographs

Herbal Drugs, Herbal Drug Preparations and Herbal Medicinal Products

In addition to the changes listed above, the following changes have also been made to BP monographs in this edition.

The tests for Uniformity of content and Uniformity of delivered dose have been amended to refer to the “average of the individual results obtained …” rather than specifying the number of units tested.

Appropriate changes have been made to relevant monographs for Inhaled Products to reflect the updated policy for these formulations.

Changes in Title

The following list gives the alterations in the titles of monographs of the British Pharmacopoeia 2017 that have been retained in the British Pharmacopoeia 2018.

Medicinal and Pharmaceutical Substances

Formulated Preparations