how to use the european pharmacopoeia and how to contribute · how to use the european...

How to use the European Pharmacopoeia and how to contribute

18th European Symposium on Radiopharmacy and Radiopharmaceuticals

Ellen Pel, Scientific Officer

European Pharmacopoeia DepartmentEuropean Directorate for the Quality of Medicines & HealthCare (EDQM)

Outline

• Purpose of the European Pharmacopoeia (Ph. Eur.)• Place of the Ph. Eur. in the regulatory network• General principles – general organisation• Elaboration of Ph. Eur. Texts• Setting of limits• Opportunities for you to contribute to the Ph.Eur.

Ellen Pel ©2016 EDQM, Council of Europe. All rights reserved.

Mihaela Buda ©2015 EDQM, Council of Europe. All rights reserved.

The purpose of the European Pharmacopoeia is to promote public health by the provision of recognised common standards for the quality of medicines and their components. Such standards are to be appropriate as a basis for the safe use of medicines by patients.

Introduction



Place of the Ph. Eur. within the regulatory network

Ø Lays down common, compulsory quality standards for all medicinal products in Europe.

Ø Mandatory on the same date in 37 states (CoE) and the EU.

Ø The Ph. Eur. is legally binding. The legislation also includes a mechanism to provide the pharmacopoeia authority with information on the quality of products on the market;

Ø The European Pharmacopoeia needs to keep pace Ø with the regulatory needs of licensing, control and inspection authorities

in the public health area, Ø with technological and scientific advances, and with industrial constraints.

Ph. Eur. – General organisation


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Introduction

General notices

General chapters

General monographs

Individual monographs



………..

§ apply to all monographs and other texts of the Ph. Eur.

§ instructions to understand texts, conventional expressions

§ essential reading before starting to use general chapters and monographs

Introduction

1. General notices

General chapters

General monographs


Flexibility in the Ph. Eur. – Alternative methods

“The tests and assays described are the official methods upon which the standards of the Pharmacopoeia are based. With the agreement of the competent authority, alternative methods of analysis may be used for control purposes, provided that the methods used enable an unequivocal decision to be made as to whether compliance with the standards of the monographs would be achieved if the official methods were used. In the event of doubt or dispute, the methods of analysis of the Pharmacopoeia are alone authoritative.”General Notices


Ø Ph. Eur. tests are reference methods, essential in cases of dispute.

Ø Compliance is required, but alternative methods may be used as long as they lead to the same pass/fail result.

Ø It is the responsibility of the user to demonstrate their suitability. Approval of the competent authority is necessary in many cases.

Flexibility in the Ph. Eur. – Waiving of tests

“An article is not of Pharmacopoeia quality unless it complies with all the requirements stated in the monograph. This does not imply that performance of all the tests in a monograph is necessarily a prerequisite for a manufacturer in assessing compliance with the Pharmacopoeia before release of a product. The manufacturer may obtain assurance that a product is of Pharmacopoeia quality from data derived, for example, from validation of the process and from validation studies of the manufacturing process and from in-process control”.

General Notices (3rd Edition to Supplement 8.1)




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Introduction

General notices

General chapters

General monographs


2 - Methods of analysis

2.2.66 – Detection andmeasurement of radioactivity

Reference in the General Monograph ofRadiopharmaceutical Preparations:




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Introduction

General notices

General chapters

General monographs


2 - Methods of analysis3 - Materials for containers

and containers4 - Reagents5 - General texts



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Introduction

General notices

General chapters

General monographs


2 - Methods of analysis3 - Materials for containers

and containers4 - Reagents5 - General texts

5.19 – Extemporaneouspreparation ofradiopharmaceuticals

Example of a general text




………..

Introduction

General notices

General chapters

General monographs


23 general monographs + Dosage forms monographsin Ph. Eur. 8.8

- Pharmaceutical preparations- Radiopharmaceutical

preparations- Parenteral preparations- Chemical precursors for

radiopharmaceuticalpreparations

...



………..

Introduction

General notices

General chapters

General monographs


More than 2500 monographs- Chemicals- Herbals- Antibiotics- Biologicals- Vaccines- Fats- Radiopharmaceuticals- ….

Elaboration of monographs (1):- Ideally monographs cover the preparations used all over

Europe, produced by different routes of synthesis. - Individual routes are not explicitly mentioned in a monograph,

but a hint to the routes examined during the elaboration mightbe given in the knowledge database.

- Knowledge about the routes of synthesis, starting materials, intermediates, by-products, degradants (potential impurities/efficiency of the purification procedure) is needed.

=> Input from producers is crucialwww.edqm.eu


Elaboration of monographs (2)Preparation having a marketing authorisation

- Specifications and tests are based upon those of the marketed preparations.

- But specifications can be different, in case batch data support this and if thereis no objection from e.g. efficacy or(radio)toxicological side.

- Validation data are examined. Methodsare validated in case of changes.

- Methods are experimentally verified.

Preparation without a marketing authorisation

Note: it is exceptional that mono-graphs are elaborated on substances/ preparations not already authorised in at least one Ph. Eur. member state.

- Elaboration often „from scratch“.

- Methods are developed and validated.

- Limits are based upon efficacy, toxicology considerations and analyticalmethod capabilities and supported bybatch data.

- Methods are verified in a secondlaboratory.


Basis for limit setting• Authorised specifications• Batch data of frequently used preparations• Toxicology data• Efficacy data• Analytical method capabilities

Quality systems. The quality standards represented by monographs are valid only where the articles in question are produced within the framework of a suitable quality system. The quality system must assure that the articles consistently meet the requirements of the Pharmacopoeia.


Example for limits: Alovudine (18F) injection

Limits: in the chromatogram obtained with the spectrophotometer:

– alovudine: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (a) (0.1 mg/V);

– impurity C: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (b) (0.1 mg/V);

– any other impurity: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 mg/V);

– total: not more than 5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 mg/V);

– disregard limit: 0.3 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.03 mg/V).

Pass/fail decision



Participating in the work of theEuropean Pharmacopoeia

https://www.edqm.eu/Knowledge-Database-707.html

Knowledge database: example of additional information


Contributions depend on state of work


State of work

0 No draft available

1 Draft available to the experts

2 Draft published in Pharmeuropa

3 Draft will be presented to the Ph.Eur. Commission

4 Draft adoped by the Ph.Eur. Commission

5 Monograph is published


http://pharmeuropa.edqm.eu/home/


Thank you very much!


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