Issue 12: Pharmaceutical regulatory roundup




Catch up with the latest news from around the pharmaceutical industry with issue 12 of our regulatory review, curated by Dr Tim Sandle.


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Concept paper on the development of a guideline on the quality aspects of mRNA vaccines


The European Medicines Agency (EMA) has issued a concept paper with the aim of establishing a guideline on the quality aspects of mRNA vaccines. 

mRNA vaccines work by introducing a piece of mRNA that corresponds to a viral protein - usually a small piece of a protein found on the virus’s outer membrane (note: individuals who get a mRNA vaccine are not exposed to the virus, nor can they become infected with the virus by the vaccine). By using this mRNA, cells can produce the viral protein. As part of a normal immune response, the immune system recognises that the protein is foreign and produces antibodies.

The number of clinical trial applications for human products and marketing authorisation applications for mRNA containing products has significantly increased over the last few years and is expected to increase further in the future. Furthermore, a lot of experience with mRNA vaccines was gained during the COVID-19 pandemic. 

From an analytical and regulatory perspective, mRNA vaccines are interesting since their classification depends on the target and/or whether they are obtained chemically or biologically. mRNA vaccines that are used to protect against infectious diseases must align with the general guidance for human vaccines - however new technology is not fully accounted for in the existing guidance. It is therefore proposed to establish a guideline addressing those specific aspects regarding the manufacturing process, characterisation, specifications and analytical control as well as the definition of active substance and finished product for mRNA vaccines for the prevention of infectious disease.

The scope of the guideline will be limited to mRNA vaccines against infectious diseases (including self-amplifying mRNA). mRNA-based therapeutics will be out of scope of the document. It is not intended to address specific requirements for mRNA vaccines to be used in clinical trials, however the scientific principles described may also be applicable during pharmaceutical development.


To view the paper, see: 




CEP 2.0


CEP stands for ‘Certification of suitability to the monographs of the European Pharmacopoeia’. A review of the format and content of the CEPs is to be implemented in the EU, according to EDQM guidelines (“CEP 2.0”), from 1st September 2023.

The Certification of Suitability (CEP) is a certificate that certifies compliance of the active pharmaceutical ingredients (API) or pharmaceutical ingredients abiding by the rules laid down in the monograph of the European Pharmacopoeia (EP).

CEP is an official procedure implemented by EU Directive. Although not mandatory, it is the preferred option for demonstrating that a substance used in the preparation of a medicinal product complies with the European Pharmacopoeia specifications according to the Note for Guidance on summary requirements for active substances in the quality part of the dossier (CPMP /QWP/297/97 Rev 1 corr; EMEA/CVMP/1069/02).

To support the process, EMA has a document on how to interpret a CEP from a supplier.

A database is available for looking up CEPs registered in the EU, as maintained by EDQM.




ICH and real-world data


Real-world data (RWD) in medicine is data derived from a number of sources that are associated with outcomes in a heterogeneous patient population in real-world settings, including but not limited to electronic health records, health insurance claims and patient surveys. Real-world evidence is clinical evidence on a medical product's safety and efficacy that is generated using real-world data resulting from routine healthcare delivery.

The role of real-world data and real-world evidence (RWE) in supporting the evaluation of medicines across the different stages of their development and lifecycle is evolving. This is the subject of an International Conference on Harmonisation reflection paper. The paper has the lengthy title: “ICH Reflection paper on proposed international harmonisation of real-world evidence terminology and convergence of general principles regarding planning and reporting of studies using real-world data, with a focus on effectiveness of medicine.”

The document seeks to strengthen international collaboration on activities to enable the use of RWE in regulatory decision-making. This requires engagement of regulatory agencies across the globe to address current gaps due to the lack of standardisation of RWD/RWE terminology and formats, the heterogeneity of data quality across RWD sources and the various study designs used depending on the types of diseases, medicines, and regulatory context. 

Addressing these challenges should be supported by common definitions and best practices. Hence, the reflection paper outlines a strategic approach for ICH to address some of these challenges. The goal is to further enable the integration of RWE into regulatory submissions and timely regulatory decision-making.




Concept paper for the revision of the guideline on live recombinant vector vaccines for veterinary use


The European Medicines Agency has issued a concept paper aimed at updating its current “Guideline on live recombinant vector vaccines for veterinary use” (EMEA/CVMP/004/04-FINAL). This was adopted in December 2004 and came into effect on 8 June 2005. 

The document was intended to provide advice to manufacturers seeking marketing authorisation for a live recombinant vector vaccine for use in animals. The objective of this guideline is to define what should be presented in the analytical, safety and efficacy part of the application considering the particular properties of live recombinant vector vaccines in the target and non-target species, including the natural host of the parental organism (where relevant). 

In recent years, experience has been gained within the regulatory network on such vaccines and aspects of the guideline are now considered to be out-of-date, and hence a new guideline is required.

To access the concept paper, see: 




Windsor Framework and supply of medicines to Northern Ireland


The MHRA has updated its guidance on the implementation of labelling and packaging requirements for medicinal products for human use following agreement of the Windsor Framework.

The Windsor Framework sets out the long-term arrangements for the supply of medicines into Northern Ireland. This is to ensure that medicines can be approved and licensed on a UK-wide basis by the Medicines and Healthcare products Regulatory Agency (MHRA) and provides for the disapplication of European Union (EU) Falsified Medicines Directive (FMD) requirements for medicines marketed and supplied in Northern Ireland.

The Windsor Framework is an international arrangement between the UK and the EU under which the parties commit to binding international law obligations, including changes to the Protocol itself.

To preclude onward movement of these medicines into any part of the European Union (EU), while ensuring medicines use the same packaging and labelling across the UK, all medicines on the UK market must be labelled as ‘UK Only’.  These measures will commence on 1 January 2025. This means that from this date:

•    All new medicines and medicines in Northern Ireland that currently fall under the scope of the EU Central Authorisation Procedure will be authorised by the MHRA for the UK market. Separate guidance will be published on the licensing process that will cover the transition of licences in the coming weeks

•    These products will only be able to be sold in the UK and will not be available on the market in Ireland or elsewhere in the EU, other than available in the EU as ‘specials’ subject to EU rules and conditions

•    Packaging for all products, except products with a parallel import licence (PLPI) which have the option to add the label for the UK market, must carry a clearly legible ‘UK Only’ label for the product to be allowed onto the UK market

For further details, see: 




Human albumin solution

Leading scientists at the independent Commission on Human Medicines (CHM) have confirmed that albumin, a critically important medicine for the NHS, can now be safely derived from UK plasma donors.






The European Medicines Agency has released a video outlining the role of the Committee for Proprietary Medicinal Products (CHMP). The organisation is involved with the authorisation of medicines in the European Union (EU). In the centralised procedure, the CHMP is responsible for:

•    Conducting the initial assessment of EU-wide marketing authorisation applications
•    Assessing modifications or extensions ('variations') to an existing marketing authorisation
•    Considering the recommendations of the Agency's Pharmacovigilance Risk Assessment Committee on the safety of medicines on the market and, when necessary, recommending to the European Commission changes to a medicine's marketing authorisation, or its suspension or withdrawal from the market

The CHMP also evaluates medicines authorised at national level referred to EMA for a harmonised position across the EU. For more information, see Referral procedures.

ACT EU: creating a better environment for clinical trials through collaboration


The Accelerating Clinical Trials in the EU (ACT EU) initiative has begun the process of developing a new multi-stakeholder platform to improve clinical trials in the European Union (EU). ACT EU is a collaboration between EMA, the Heads of Medicines Agencies (HMA) and the European Commission (EC) that seeks to transform how clinical trials are initiated, designed and run. The multi-stakeholder platform is a key deliverable of the initiative.

ACT EU aims to place stakeholders at the centre of its activities by giving them the opportunity to steer the direction of the programme. Best approaches to support the implementation of the clinical trial regulation including the role of ethics committees, support to non-commercial sponsors to increase the conduct of multinational clinical trials and how to optimise the coordination of scientific advice to support evidence generation will all be discussed.

New endotoxin standard

The International Organization for Standardization (ISO) has published its new standard Sterilization of health care products — Microbiological methods — Part 3 Bacterial endotoxin testing (ISO 11737-3:2023).

The new ISO standard, released in June 2023, provides information on the following:

•    Guidance on bacterial endotoxin testing (BET)
•    The history and background on the BET
•    Guidance on out of specified limits and failure investigation
•    Guidance on in-process monitoring of manufacturing or component testing
•    Guidance on conducting a risk assessment to support alternatives to batch testing
•    Typical assignment of responsibilities

Endotoxins are the molecular weight lipopolysaccharide (LPS) components of the outer cell wall of gram-negative bacteria, that can cause fever, meningitis and a rapid fall in blood pressure if introduced into the blood stream or certain other tissues of the body. The outer cell wall components, which are composed primarily of proteins, phospholipids and LPS, are constantly released by the cell into the surrounding environment. Endotoxins are ubiquitous in nature, stable, and small enough to pass through conventional sterilising filters. Sterilisation processes will inactivate microorganisms on or in products, but usually do not inactivate endotoxin on products. With controlled processes, endotoxin contamination can be prevented.

It is of interest that this new standard precludes recombinant reagents (a strange decision given the direction in which the endotoxin test industry is moving).

The ISO standard can be purchased here: 

EU GMP Annex 1


As a reminder to readers, EU GMP annex 1 comes into force on 25th August 2023. The new version was issued on 22nd August 2022, giving sterile manufacture one year to prepare.

The Annex is available here: 


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