Last week’s round-up;
29 June – 03 July 2020

published 6 Jul 2020

New Ph.Eur. Test for bacterial endotoxins using recombinant factor C

The new general chapter 2.6.32. Test for bacterial endotoxins using recombinant factor C (rFC) is now available in the Ph. Eur. Supplement 10.3. A revised chapter 5.1.10. Guidelines for using the test for bacterial endotoxins, which has been updated to reflect the new status of rFC-based methods and give prerequisites for their deployment by users of the Ph. Eur., has also been published. The new chapter describes an analytical method for bacterial endotoxins that can be used as an alternative to the classic limulus amoebocyte lysate-based methods for the quantification of endotoxins from gram-negative bacteria. The currently used classic method relies on two endangered species of horseshoe crab as a source of lysate, while the new method involves the use of a recombinant factor C based on the gene sequence of the horseshoe crab and fluorimetric detection. The new method has been developed to help reduce the need for the endangered horseshoe crab. Both chapters will become effective on the 1st January 2021.

EMA: Procedural advice for orphan medicinal product designation

The EMA updated its procedural advice for orphan medicinal product designations on 25th June 2020. Clarification has been provided on the proof of establishment requirements for sponsors that are an individual. If the sponsor is a natural person of a country of the EEA, in order to respect data protection rights and freedoms, they should not include proof of establishment in the portal folder of the submission. Once EMA receives the application, the Orphan Office will e-mail the individual sponsor outside the submission portal to verify their citizenship of a country of the EEA e.g. copy of passport. At the end of the validation process all personal data are deleted from EMA’s systems. The requirements when the sponsor is an organisation remain the same.

Stakeholder comments on PBPK modelling and simulation EMA guidance

An overview of comments received from 12 stakeholders on the ‘Guideline on the qualification and reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation’ has been published by the EMA:

EMA Clinical Trial Information System (CTIS)

At its meeting held in June 2020 the EMA MB endorsed the methodology and next steps to further develop the CTIS ‘Go-Live’ plan. It is proposed to fix the Go-Live date of CTIS to December 2021, which means the Clinical Trial Regulation would also enter in application at that time (i.e. that is the end of the six months after the European Commission publishes its notice in the Official Journal). Further details can be found in the press release from this meeting ( ). And a CTIS newsletter on the topic will be issued twice yearly.

USP novel excipients survey

The US Pharmacopoeia (USP) has conducted an online survey in order to understand how drug formulators view the current state of innovation in excipients, as well as the problems experienced in relation to new or novel excipients. Most pharmaceutical formulators reported that drug development had been limited, at least some of the time, to excipients currently used in FDA-approved drugs. The most cited challenges related to novel excipients include regulatory issues followed by safety concerns. Based on the results of the survey, the USP supports the FDA’s proposal for a pilot review program for the toxicological and quality evaluation of novel excipients intended for use in human medicines. The following article highlights the results of USP’s survey in key areas concerning limitations created by currently used excipients as well as why these limitations have affected innovation and have resulted in reformulations, discontinuations, and delays of pharmaceuticals for the US market:

EMA:New points to consider on implications of COVID-19 on ongoing clinical trials

It is foreseeable that the COVID-19 pandemic will interfere with the conduct of many ongoing trials, not limited to the collection, analysis and interpretation of clinical trial data.The recommendations include pre-planning the capture of systemic deviations. If feasible, data collection should not stop and continue as far as possible. Risk assessment should be performed on the effect of COVID-19 directly on subjects and the ability to conduct the CT. If not already in place an independent DMC should be set up for all affected. Follow up considerations are also outlined.

The document can be found here

Extended consultation re elemental impurities in plastic materials

The consultation period for the new Ph.Eur. general chapter on Elemental Impurities in Plastic Materials for Pharmaceutical Use has been extended to the 30th September 2020 due to high public interest and the importance of the monograph. The new draft chapter covers elemental impurities that may be present in plastic materials used in the manufacture of containers for pharmaceutical preparations. An additional document with supporting information, including a more detailed explanation of the text, has also been published alongside the chapter. This supporting document shows that the impact of elemental impurities in plastic materials, on the quality of the containers produced from these materials, needs to be taken into account even though these are not within the scope of existing texts.

Two other new general chapters on specific plastic materials, Cyclo-olefin polymers (3.1.16) and Cyclo-olefin copolymers (3.1.17), which refer to the general chapter on Extractable elements in plastic materials for pharmaceutical use have also been republished, unchanged, in order to extend the deadline for comments until the 30th September 2020:

ICH: Harmonsation of drug development requirements

Reading an excellent article this morning written by Pär Tellner of EFPIA. He describes the achievements of ICH, which reaches its 30th anniversary in 2020. The article mentions that ‘ICH has encouraged greater collaboration among scientific, technical and medical experts from regulators and companies. It has helped mitigate confusion regarding regulatory processes. ICH has reduced redundancy in requirements at every step of medicine development: in non-clinical studies, clinical trials, submissions, and manufacturing processes.’ He considers that the electronic Common Technical Document (e-CTD) a good concrete example of the level of harmonisation achieved. A very considerable body of guidances (over 80) from about 30 active working groups leads the author to conclude that ICH’s mission has never been more important to ensure the availability of life-changing medicines to patients worldwide. Particularly, bearing in mind, the innovations that are envisaged over the coming years.The article in full can be found here

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