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Susanne Keitel, MD, is head of the European Directorate for the Quality of Medicines of the Council of Europe. EDQM is responsible for the European Pharmacopoeia.
Revisions and updates for the 9th Edition of the European Pharmacopoeia result in changes to more than half of the content.
In July 2016, the European Directorate for the Quality of Medicines & HealthCare (EDQM) will release the 9th Edition of the European Pharmacopoeia (Ph. Eur.), Europe’s legal and scientific benchmark for pharmacopoeial standards, which contributes to delivering high-quality medicines in Europe and beyond. As a single reference-work for official European quality standards, the Ph. Eur. responds in a timely manner to developments in the pharmaceutical world-new substances and products, changes in regulatory processes, or scientific and technological advances-while maintaining focus on the quality and safety of medicines based on scientific rigor.
This 9th Edition, which is applicable from Jan. 1, 2017 in 37 European countries and the EU as such and will be used in more than 100 countries worldwide, contains updates and modifications made in response to developments over the course of the past three years: 109 new monographs, 12 new general chapters, and 1403 revised texts. The new edition will include, for example, 760 individual monographs revised to align the pharmacopoeia with the newly adopted International Council on Harmonization (ICH) Q3D Guideline for Elemental Impurities (Q3D). The absence of elemental impurities (including heavy metals) tests from an individual monograph, however, does not release manufacturers from the obligation to control the level of such elements in their products, where and if relevant.
New and updated texts and monographs
In addition to the changes made in the 9th Edition, the Ph. Eur. Commission decided to reproduce in the general chapter currently entitled “Metal catalysts or metal reagents residues” (5.20), the principles set out in the ICH Q3D guideline. The Ph. Eur. intends to introduce a cross-reference to revised chapter 5.20 in the general monograph “Pharmaceutical preparations” (2619), thus making application of the ICH Q3D guideline legally binding for all the medicinal products within the scope of ICH Q3D. The revised version of general monograph 2619 is expected to be published in Ph. Eur. Supplement 9.3 on July 1, 2017, thus making chapter 5.20 legally binding as of Jan. 1, 2018.
A revised version of the general monograph “Substances for pharmaceutical use” (2034) was also published for public enquiry. This monograph was revised to clarify how to handle substances used in pharmaceutical products outside the scope of the ICH Q3D guideline and is also expected to be published in Ph. Eur. Supplement 9.3. The general method currently entitled “Determination of metal catalysts or metal reagent residues” (2.4.20) will undergo a revision, initially to align its wording with the ICH Q3D guideline, and is also expected to be published in Ph. Eur. Supplement 9.3. In parallel, general chapter 5.20 is part of the work program of the Pharmacopoeial Discussion Group.
Compared to the 8th Edition, 57% of the content of the 9th Edition will be new or updated. In addition to more than 350 general texts, it will contain approximately 2300 monographs covering categories such as chemically defined substances (55%), herbals (13%), human and veterinary vaccines (7%), antibiotics (6%), biologicals (4%), and blood derivatives (1%). Of the 109 new monographs, 55% relate to APIs representing the key treatment areas (e.g., anti-cancer drugs, immunosuppressants, antiretrovirals, antivirals, antiemetics, anti-infectives, and drugs for cardiac therapy).
Ph. Eur. responds to industry trends
This investment by the Ph. Eur. Commission in texts that reflect developing trends in existing and innovative treatments is further demonstrated by the 12 new general chapters, which include “Raw materials of biological origin for the production of cell-based and gene therapy medicinal products for human use” (5.2.12). This general chapter, published for information in the Ph. Eur. and therefore not legally binding, aims to help stakeholders in ensuring that raw materials of biological origin used for the production of advanced therapy medicinal products (ATMP) are of suitable quality and safety, and to foster harmonization in the qualification practices and standards to be applied. It contains sections on quality requirements and examples of the critical quality attributes specific to each class of raw material.
An example of the Ph. Eur. responding to technological developments is the complete rewriting and restructuring of the general chapter on “Raman Spectroscopy” (2.2.48), which came into effect on April 1, 2016. This general chapter, published for information to help users when and if needed, was first presented in the 4th Edition of the Ph. Eur. in 2002. Since then, Raman spectroscopy has received increasing attention in pharmaceutical applications, and nowadays is used regularly for the identification and characterisation of materials. Newer Raman technologies have become available, and existing ones have been developed further, including hand-held instruments. This thorough revision contains separate sections covering: the potential use of this technique within a process analytical technology (PAT) environment; updated requirements, adaption to different instrument types available on the market; and the presentation of qualitative and quantitative uses.
Also, by elaborating and adopting a new general monograph on “Chemical precursors for radiopharmaceutical preparations” (2902), the Ph. Eur. Commission filled a gap in a rapidly evolving field. For many substances, no marketing authorizations or drug master files exist. The product lifecycles of chemical precursors can be relatively short and the substances employed can change rapidly (e.g., in positron emission tomography [PET]), and materials can become redundant due to technological and scientific advances in the field. Consequently, information on the quality control of the substance is often not readily available, and for this reason, a general monograph was deemed appropriate. This new general monograph, which will become legally binding with the entry into force of Ph. Eur. Supplement 8.8 on July 1, 2016, provides a self-contained set of quality criteria for chemical precursors and gives guidance on further aspects to be considered. This text is also an important complementary monograph to the existing general monograph for “Radiopharmaceutical Preparations” (0125), which has been updated accordingly.
The 9th Edition will also contain the first monograph on a finished product containing a chemically-defined active substance, Sitagliptin tablets. Such monographs at the European level will facilitate assessment of marketing authorization applications and will provide those in charge of market surveillance studies with useful tools to test medicinal products that are on the market, thus reducing the burden on both regulators and industry across Europe and beyond.
Supplements to the 9th Edition
The 9th Edition will be complemented by three annual supplements, the first of which will contain the revised monograph on “Water for Injections” (0169), which will become legally binding as of April 1, 2017. The revised monograph takes into account technological advances and current manufacturing practices using methods other than distillation for producing water for injection, and is supported by the evidence provided in the document “Reverse osmosis in Ph. Eur. monograph Water for injections (0169),” published in Pharmeuropa Issue 27.2 (April 2015) (1). The revised monograph also states that the use of non-distillation technologies for the production of water for injection requires that notice is given to the supervisory authority of the manufacturer before implementation.
Recognizing the impact of the dramatic changes to the pharmaceutical world over the past 50 years, which have resulted in a truly globalised environment, the Ph. Eur. Commission has now decided to revise its working procedures to allow experts from all over the world to become involved in its work – an evolution that will lay the foundations for subsequent Editions of the Ph. Eur.
1. EDQM, Pharmeuropa, Pharmeuropa Bio, & Scientific Notes.
Article DetailsPharmaceutical Technology
Vol. 40, No. 5
When referring to this article, please cite it as S. Keitel, "Significant Revisions and Updates to the European Pharmacopoeia," Pharmaceutical Technology 40 (5) 2016.