Monograph Development Process for the European Pharmacopoeia: How to participate in the work programme of the European Pharmacopoeia Dr Claude Coune Head of the Publication and IT division Dr Claude Coune Head of the Publication and IT division

4 procedures Procedure 1: group of experts Procedure 2: adaptation of existing national monograph Procedure 3: direct co-operation with innovator, work co-ordinated by national pharmacopoeia Procedure 4: direct co-operation with innovator, work co-ordinated by EDQM Procedure 1: group of experts Procedure 2: adaptation of existing national monograph Procedure 3: direct co-operation with innovator, work co-ordinated by national pharmacopoeia Procedure 4: direct co-operation with innovator, work co-ordinated by EDQM

Stages in elaboration All four procedures : –Addition to work programme by Commission: public announcement (industry associations, Pharmeuropa, web site) –Interested parties can (and should!) express an interest –Elaboration, experimental checking of draft –Publication in Pharmeuropa (3-month comment period) All four procedures : –Addition to work programme by Commission: public announcement (industry associations, Pharmeuropa, web site) –Interested parties can (and should!) express an interest –Elaboration, experimental checking of draft –Publication in Pharmeuropa (3-month comment period)

Stages in elaboration (2) –Study of comments by group of experts/working party –Submission to Commission for adoption –Publication within 6 months –Implementation 1 year after adoption Overall timescale: minimum 2-3 years –Study of comments by group of experts/working party –Submission to Commission for adoption –Publication within 6 months –Implementation 1 year after adoption Overall timescale: minimum 2-3 years

Work status Key to information on status: 0 = on the work programme, no first draft 1 = first draft (new or revised monograph) 2 = published (or in press) in Pharmeuropa 3 = submitted to the Commission 4 = adopted, ready for publication 5 = published Key to information on status: 0 = on the work programme, no first draft 1 = first draft (new or revised monograph) 2 = published (or in press) in Pharmeuropa 3 = submitted to the Commission 4 = adopted, ready for publication 5 = published

Work programme Based on proposals from: –National delegations –Groups of experts –EDQM Manufacturers can submit proposals via one of the above Based on proposals from: –National delegations –Groups of experts –EDQM Manufacturers can submit proposals via one of the above

Work programme (2) Additions announced on web site Search engine at for complete work programmewww.pheur.org Communication via industry associations Additions announced on web site Search engine at for complete work programmewww.pheur.org Communication via industry associations

New monographs: actives For active substances, aim is to have monograph ≥ 2 years before patent expiry Addition to programme depends on: –therapeutic importance –extent of use –number of countries in which product is approved – known quality problems For active substances, aim is to have monograph ≥ 2 years before patent expiry Addition to programme depends on: –therapeutic importance –extent of use –number of countries in which product is approved – known quality problems

New monographs: excipients For excipients, important criteria are: –extent of use –type of use (parenteral, oral, etc) –number of preparations in which the excipient is used –known quality problems For excipients, important criteria are: –extent of use –type of use (parenteral, oral, etc) –number of preparations in which the excipient is used –known quality problems

How to participate Participation depends on the procedure used For all procedures it is in your interest to provide samples for testing Information on actives and excipients in approved products is needed Participation depends on the procedure used For all procedures it is in your interest to provide samples for testing Information on actives and excipients in approved products is needed

Procedure 1 Declare an interest in the monograph being elaborated or revised Indicate willingness to provide samples and to work with the group EDQM will organise contact with co- ordinator for the monograph Declare an interest in the monograph being elaborated or revised Indicate willingness to provide samples and to work with the group EDQM will organise contact with co- ordinator for the monograph

Direct participation Join a group of experts: contact your national pharmacopoeia authority, which makes proposals for experts Work as a co-opted expert for a particular project that is of interest: short-term commitment Join a group of experts: contact your national pharmacopoeia authority, which makes proposals for experts Work as a co-opted expert for a particular project that is of interest: short-term commitment

Procedures 3 & 4 EDQM contacts the innovator to determine willingness to work on monograph Close co-operation during elaboration Will be used systematically for single- source products in future EDQM contacts the innovator to determine willingness to work on monograph Close co-operation during elaboration Will be used systematically for single- source products in future

Proposing a new monograph Contact your National Pharmacopoeia Authority (in Europe) or EDQM (outside Europe) Initial data: countries where the product is approved Data package: –Current specification –Validation reports –Samples of substances and impurities –Full description of data package is available Contact your National Pharmacopoeia Authority (in Europe) or EDQM (outside Europe) Initial data: countries where the product is approved Data package: –Current specification –Validation reports –Samples of substances and impurities –Full description of data package is available

Pharmacopoeia liaison EDQM wishes to have a pharmacopoeia liaison contact for each major manufacturer/user Channel information and requests from manufacturer to EDQM Reception point for contact by EDQM Benefits for both sides EDQM wishes to have a pharmacopoeia liaison contact for each major manufacturer/user Channel information and requests from manufacturer to EDQM Reception point for contact by EDQM Benefits for both sides

Revision Types of revision: –Correction of a monograph/general chapter –Minor revision –Routine revision –Rapid revision Types of revision: –Correction of a monograph/general chapter –Minor revision –Routine revision –Rapid revision

Corrections Correction of obvious errors (typos, etc.) Dealt with by Secretariat, notification to Commission and national authorities No Pharmeuropa publication Effective from the official publication date of the edition/supplement Occasionally used for rapid implementation of a true revision Correction of obvious errors (typos, etc.) Dealt with by Secretariat, notification to Commission and national authorities No Pharmeuropa publication Effective from the official publication date of the edition/supplement Occasionally used for rapid implementation of a true revision

Minor revision Minor technical changes that do not need to be published for consultation in Pharmeuropa Adopted by Commission on the basis of a briefing note Implemented with other revisions in next edition/supplement Minor technical changes that do not need to be published for consultation in Pharmeuropa Adopted by Commission on the basis of a briefing note Implemented with other revisions in next edition/supplement

Routine revision Based on request for revision with sufficient data Studied by group of experts Published in Pharmeuropa Adopted by Commission Implemented in next edition/supplement Based on request for revision with sufficient data Studied by group of experts Published in Pharmeuropa Adopted by Commission Implemented in next edition/supplement

Rapid revision Special procedure intended for use where there is a serious public health concern Cumbersome (publication of resolution and in official journal of each Member State) and not very rapid Rarely used nowadays, “correction” preferred (faster and simpler) Special procedure intended for use where there is a serious public health concern Cumbersome (publication of resolution and in official journal of each Member State) and not very rapid Rarely used nowadays, “correction” preferred (faster and simpler)

Revision programme Work programme is announced via web site Declare an interest for relevant items Make sure you see Pharmeuropa for revision proposals Provide samples, test draft proposal Work programme is announced via web site Declare an interest for relevant items Make sure you see Pharmeuropa for revision proposals Provide samples, test draft proposal

Revision: why? New sources have new impurity profiles Quality improves, monograph should keep in line New quality issues arise Analytical methods change: more convenient methods, more powerful methods, more reliable methods become available International harmonisation (PDG, ICH, VICH) New sources have new impurity profiles Quality improves, monograph should keep in line New quality issues arise Analytical methods change: more convenient methods, more powerful methods, more reliable methods become available International harmonisation (PDG, ICH, VICH)

Revision: why? (2) FAQ: “Why did you revise the monograph on…?” You can find out via: –Briefing notes in Pharmeuropa –Collected briefing notes posted on the web site for each new edition/supplement There is no briefing note for corrections FAQ: “Why did you revise the monograph on…?” You can find out via: –Briefing notes in Pharmeuropa –Collected briefing notes posted on the web site for each new edition/supplement There is no briefing note for corrections

How to request revision Commission decides on revision Based on proposals from: –National delegations –Groups of experts –EDQM Manufacturers should submit via one of these Commission decides on revision Based on proposals from: –National delegations –Groups of experts –EDQM Manufacturers should submit via one of these

How to request revision (2) Europe: via national pharmacopoeia authority (address list in Pharmeuropa) Outside Europe: contact EDQM which will refer the matter to a group of experts or to the Commission Make clear what needs revising and if possible make a concrete proposal Europe: via national pharmacopoeia authority (address list in Pharmeuropa) Outside Europe: contact EDQM which will refer the matter to a group of experts or to the Commission Make clear what needs revising and if possible make a concrete proposal

Data for revision Revision can only be undertaken if the request is backed up by sufficient data Give batch data, sample chromatograms, etc. to enable a decision on the need for revision Revision can only be undertaken if the request is backed up by sufficient data Give batch data, sample chromatograms, etc. to enable a decision on the need for revision

Special revision programme Instituted in 2004 to replace TLC by quantitative methods in about 140 monographs on APIs Phase 1: , 40 monographs on APIs + 20 amino acids Manufacturers invited to submit data Information available on web site Instituted in 2004 to replace TLC by quantitative methods in about 140 monographs on APIs Phase 1: , 40 monographs on APIs + 20 amino acids Manufacturers invited to submit data Information available on web site

Traditional Medicines 50 Chinese Traditional Medicines (herbals), –About 15 published, or about to be published Other traditions: Indian (?), South America 50 Chinese Traditional Medicines (herbals), –About 15 published, or about to be published Other traditions: Indian (?), South America

Knowledge database The whole programme of the European Pharmacopoeia –All published monographs –All monographs under elaboration –All monographs accepted for elaboration –Links to the catalogue of reference standards –Links to the Certification database –Additional information The whole programme of the European Pharmacopoeia –All published monographs –All monographs under elaboration –All monographs accepted for elaboration –Links to the catalogue of reference standards –Links to the Certification database –Additional information