European Pharmacopoeia (Ph. Eur.) Commission adopts new monographs and makes a number of revisions

They will come into effect in July 2017

The Ph. Eur. Commission has adopted nine new monographs, one new general chapter, 46 revised monographs and 15 revised general chapters, as well as a new version of the glossary. These will be published in the Ph. Eurcome Supplement 9.2 and come into effect in July 2017.

The new general chapter, Determination of bactericidal, fungicidal or yeasticidal activity of antiseptic medicinal products (5.1.11), provides a method to assess the main quality parameter for this product class. It describes a test that can be used to determine antimicrobial activity in antiseptic medicinal products, miscible with water and intended for administration by direct contact with the skin or mucous membranes.

The revised monographs include:

  • Omega-3-acid Ethyl Esters 90 (1250). This represents a step forward in the quality control of the substance which is used as an active ingredient in medicinal products approved in Europe for treatment of hypertriglyceridemia, and in adjuvant treatment in secondary prevention after myocardial infarction. Limits for several persistent organic pollutants have been included under the Production section. In addition, tests and limits for unidentified fatty acid ethyl esters and cholesterol have been introduced. The test for peroxide value has also been revised to avoid the use of chloroform, and finally the chromatogram of the Assay for content of EPA and DHA ethyl esters has been updated.
  • Ethylcellulose (0822). This has been revised to acknowledge the possibility of including a suitable antioxidant in this excipient. In addition, the assay procedure has been modernised: the use of a GC capillary column will be implemented, as already prescribed in the harmonised monographs on Hydroxypropylcellulose (0337) and Hydroxypropylcellulose, low substituted (2083). This modification is based on a collaborative study performed worldwide.

The revised general chapters include:

  • Volumetric Analyses (4.2.2): This describes the preparation and standardisation of volumetric solutions and has been revised to introduce more direct ways of standardisation. As a corollary, the chapter Primary standards for volumetric solutions (4.2.1) has been revised to introduce new substances (e.g. trometamol).
  • Microbial Examination of cell-based Preparations (2.6.27): Microbiological control for these preparations poses significant challenges, as their shelf-life ranges from days to only a few hours and they are usually available only in very small volumes. This revised chapter provides guidance on the best approach to use with regard to the constraints associated with cell-based preparations.
  • Methods of preparation of sterile products (5.1.1) and Biological Indicators in the Preparation of Sterile Products (5.1.2): These two chapters have been completely rewritten to make them state-of-the-art in terms of approaches to sterilisation.
  • Alternative Methods for Control of Microbiological Quality (5.1.6): This takes account of the latest technological developments in the field. It is hoped that it will facilitate the development and validation of methods known to be more rapid and technologically advanced than conventional methods.
  • Monocyte-activation test (2.6.30) This has been revised to make it more widely usable and thus facilitate a reduction in testing on laboratory animals. This extensive revision of the general chapter – first published in the Ph. Eur. in 2010 – is the result of a wide-ranging consultation with industry representatives, academics, regulatory authorities and Official Medicines Control Laboratories.
  • Five general chapters regarding polyolefin materials for pharmaceutical use (plastic containers and closures): Polyolefins (3.1.3), Polyethylene without additives for containers for parenteral preparations and for ophthalmic preparations (3.1.4), Polyethylene with additives for containers for parenteral preparations and for ophthalmic preparations (3.1.5), Polypropylene for containers and closures for parenteral preparations and ophthalmic preparations (3.1.6) and Poly(ethylene - vinyl acetate) for containers and tubing for total parenteral nutrition preparations (3.1.7).

The Ph. Eur. Commission reviewed the pilot phase for elaborating texts on monoclonal antibodies, using infliximab as a case study. In view of the extent of conclusive experimental data generated by Ph. Eur. experts in support of the elaboration of a monograph on Infliximab concentrated solution (2928), the Ph. Eur. Commission agreed to publish this draft monograph in Pharmeuropa to collect comments from users. At this stage, it has not been decided whether a final monograph will be adopted for publication in the Ph. Eur.

A new general chapter on Process Analytical Technology (PAT) was added to the Ph. Eur. Commission’s work programme. The future chapter 5.25 (for information only) will highlight the various modifications that have been made to the Ph. Eur. to support PAT applications. In addition, this general chapter will address the different approaches to interfacing PAT techniques with manufacturing processes and will introduce definitions of terminology used.

List of new monographs adopted:

  • Terlipressin (2646)
  • Milbemycin oxime for veterinary use (2536)
  • Remifentanil hydrochloride (2644)
  • Isopropyl isostearate (2867)
  • Lutetium (177Lu) solution for radiolabelling (2798)
  • Selenium for homoeopathic preparations (2844)
  • Egg phospholipids for injection (2315)
  • Sodium pyrophosphate for radiopharmaceutical preparations (2552)
  • Evodia fruit (2718)