Some of the significant changes in the 2025 version include:

 

• Addition of ASTM 52628 as a normative reference for dosimetry and some other ASTM standards in definitions for calibration
• Removal of reference to ISO 13485 to improve flexibility in using ISO 11137-1 for industries other than medical devices (pharmaceuticals, food, cannabis, non-medical materials modification)
• Increase in the permitted energy limits before activation assessment (10 -> 11 MeV for E-beam and 5 -> 7.5 MeV for X-ray). This will enable more products to be treated by e-beam / X-ray that were previously limited by penetration
• Removal of language implying that dosimetry is required for batch release, allowing for the possibility of parametric or machine based release
• Increased flexibility in dose audit interval from three months to four months with four dose audits per year. This provides more flexibility for manufacturers and should help resolve non-value-added audit observation
• VDmax doses from ISO 11137-2 and ISO 13004 incorporated by reference, providing further support for VDmax doses other than 15 and 25 kGy. This allows manufacturers to use lower doses for greater throughput, efficiency and cost
• A new section for criteria to consider for product adoption

 

Essentially, these steps are designed to help manufacturers to provide products that are safe for patient use, meeting both regulatory and clinical expectations.

 

 

 

Updates to medical device standards

 

The below standards in the medical device sector are being revised:

 
EN 18167 Quality along the patient pathway in medical imaging in Radiology services.

ISO 10524-3 Pressure regulators for use with medical gases. Part 3: Pressure regulators integrated with cylinder valves (VIPRs).

ISO 10322 Ophthalmic optics. Semi-finished blanks.

 

 

 

Bacterial endotoxin testing

 

The European Pharmacopoeia (Ph. Eur.) is updating chapter 2.6.14 for bacterial endotoxin testing.

 

This general chapter has been revised to introduce the fluorimetric end-point method using recombinant factor C (rFC) as the new method G. The proposed technical content concerning method G (in the Introduction, as well as sections 2 and 9) has been imported from general chapter 2.6.32. Test for bacterial endotoxins using recombinant factor C. Some editorial adjustments have also been made to the Introduction and sections 5 and 6 to take account of the new method.

 

General chapter 2.6.32 will become obsolete as a result of the introduction of rFC and will therefore be proposed for suppression. In addition, a revision of general chapter 5.1.13. Pyrogenicity is proposed in the same issue of Pharmeuropa, to take account of these considerations.

 

The draft is accessible via Pharmeuropa (requires a subscription). The deadline for comments is 30 June 2025.

 

 

 

 

Technical conformance study guide

 

The US Food and Drug Administration (FDA) has updated its guidance relating to technical recommendations to sponsors for the submission of animal and human study data and related information in a standardised electronic format in INDs, NDAs, ANDAs and BLAs. The guidance is intended to complement and promote interactions between sponsors and FDA review divisions.

 

The document can be found here: https://www.fda.gov/media/153632/download 

 

 

  

Radioisotopes

 

The shortage of material for the manufacture of radioisotopes continues. The European Heads of Medicines Agencies (HMA) have issued recommendations to address vulnerabilities in the supply chain of radiopharmaceuticals. 

 

These types of medicines contain radioactive forms of chemical elements called radioisotopes and are used to diagnose or treat medical conditions such as cancer. Their use is steadily increasing, while manufacturing capacity in Europe is limited. This has led to occasional shortages in different Member States.

 

The recommendations include the necessity of companies to produce detailed supply chain maps.

 

The guidance can be accessed here: https://www.ema.europa.eu/en/documents/other/recommendations-executive-steering-group-shortages-safety-medicinal-products-mssg-address-vulnerabilities-supply-chain-radiopharmaceuticals_en.pdf 

 

 

 

Clinical trials

 

The European Union Clinical Trials Information System (CTIS) has been designated as a primary registry by the World Health Organisation (WHO) within the International Clinical Trials Registry Platform (ICTRP). Becoming a primary registry means CTIS adheres to specific criteria for content, data quality and validity, accessibility, unique identification, technical capacity and administration. This ensures comprehensive research information is accessible to healthcare decision-makers globally.

 

CTIS has been a registered data provider for WHO since May 2023. Designation as a primary registry represents a significant milestone in facilitating data sharing, promoting transparency and trust in clinical research.

 

CTIS supports the running of clinical trials for human medicines in the European Union (EU) and the European Economic Area (EEA). The system includes a public searchable database for healthcare professionals, patients and citizens.

 

For details, see: https://euclinicaltrials.eu/search-clinical-trials-reports/?lang=en 

 

 

 

Streamlining biosimilars

 

The European Medicines Agency (EMA) is exploring improvements to the development and evaluation of biosimilar medicines, while upholding strict European Union (EU) safety standards. The aim is to improve access to biosimilars for patients in the EU and ensure that Europe is an attractive market to develop these treatments.

 

The approach is outlined in a new draft reflection paper. The intention is to reduce the amount of clinical data required for the development and approval of biosimilar medicines.

 

For details, see: https://www.ema.europa.eu/en/documents/other/reflection-paper-tailored-clinical-approach-biosimilar-development_en.pdf 

 

 

 

Reducing antimicrobial use

 

Sales of antibiotics for food-producing animals accounted for 98% of total EU sales of veterinary medicines containing substances with antibiotic activity. The highest selling antimicrobial class for food-producing animals were penicillins, followed by tetracyclines and sulfonamides. 

The widespread use of antimicrobials in animal production is fuelling the growth of antimicrobial resistance and this poses health risks to all animals, including humans. According to the AMEG categorisation of antibiotics for use in animals for prudent and responsible use, approximately 65% of total EU sales for food-producing animals corresponded to substances that belong to category D (which should be used as first line treatments, whenever possible), 29% corresponded to category C (which should be considered only when there are no antibiotics in Category D that could be clinically effective), and 6% corresponded to category B (which are critically important in human medicine but use in animals should be restricted to mitigate the risk to public health).

A new paper provides measures to stem the use of antimicrobials in relation farming: 

https://www.ema.europa.eu/en/documents/report/european-sales-use-antimicrobials-veterinary-medicine-annual-surveillance-report-2023_en.pdf 

 

 

 

Epizootic Haemorrhagic Disease 

 

The European Medicines Agency (EMA) has recommended the approval of Hepizovac, the first vaccine against Epizootic Haemorrhagic Disease (EHD) authorised in the EU for use in cattle. This new vaccine provides protection against the recently emerged serotype 8 of the Epizootic Haemorrhagic Disease Virus (EHDV), which has been responsible for recent outbreaks in Europe.

 

EHD is an infectious disease that primarily affects domestic and wild ruminants, like deer. The virus is transmitted through the bite of midges that have fed on infected animals. Infection with EHDV can lead to severe clinical signs in cattle, including fever, nose and mouth sores, drooling, eye inflammation and respiratory distress. In some cases, it can result in death. Despite the severity of the disease in affected animals, the EHDV is not a risk to human health, as it is not known to cause disease in humans under any conditions.

 

Hepizovac contains an inactivated form of the EHDV serotype 8 along with adjuvants to help stimulate the immune response. The vaccine is available as a ready-to-use suspension for injection.

 

For details, see: https://www.ema.europa.eu/en/news/first-vaccine-against-epizootic-haemorrhagic-disease-recommended-approval 

 

 

 

Cutting down on animal testing

 

The US FDA has announced a plan to phase out animal testing requirement for monoclonal antibodies and other drugs.

The new approach is designed to improve drug safety and accelerate the evaluation process, while reducing animal experimentation, lowering research and development costs, and ultimately, drug prices. The FDA’s animal testing requirement will be reduced, refined, or potentially replaced using a range of approaches, including AI, organoid toxicity testing and cell lines. Implementation of the regimen will begin immediately for investigational new drug applications. 

For details, see: https://www.fda.gov/media/186092/download 

 

 

 

Forthcoming European Pharmacopeia changes

 

Revised general chapters for elemental analysis have been published in Pharmeuropa 37.2. Analytical procedures for elemental analysis are described in the following European Pharmacopoeia (Ph. Eur.) general chapters:

• 2.2.22. Atomic emission spectrometry
• 2.2.23. Atomic absorption spectrometry
• 2.2.57. Inductively coupled plasma-atomic emission spectrometry
• 2.2.58. Inductively coupled plasma-mass spectrometry

 

These analytical procedures are essential for ensuring quality and safety of medicines and their ingredients, as well as other articles described in Ph. Eur. monographs, through the quantitation of elements. 

 

The four general chapters have been revised and are presented in Pharmeuropa 37.2 for comment. Similar recommendations and quality requirements ultimately apply to all of them - this was not previously reflected in their content and structure.

 

Users are encouraged to view the four texts as a package and consider whether a comment on one of them also applies to the others.

 

Please note Pharmeuropa requires a subscription (this is free to access).

 

 

 

New EU Variation Regulation: Commission Delegated Regulation (EU) 2024/1701

 

Based on the experience gained from the COVID-19 pandemic and the adaptations to the variation procedures to change the vaccine composition due to the multiple variant strains, it is appropriate to introduce similar procedures for other vaccines to address a public health emergency.

 

The main proposals are:

 

1) The concept of grouping different Type IA variations is extended to the ‘super-grouping’ concept. The super-grouping allows the submission of one application for Type IA related to different medicinal products (with different Marketing Authorisation numbers) that belong to the same Marketing Authorisation Holder (MAH)

2) The annual notification becomes mandatory for Type IA variations

3) The work sharing procedure becomes mandatory for Type 1B and Type II variations

4) Human coronavirus vaccines - the examination of variations concerning changes to the active substance for the purposes of the annual update is applied also to human coronavirus vaccines

5) Public health emergency. In case of a public health emergency in the EU, the relevant authorities may, where certain pharmaceutical, non-clinical or clinical data is missing, exceptionally and temporarily accept a variation to the terms of marketing authorisations for a human vaccine pertaining to the pathogen causing the public health emergency

6) Not applicable to veterinary medicinal products

7) Medical devices

 

The new Variation Regulation includes variations for medical devices according to the new requirements of the Medical Devices Regulation and the quality guidelines of medicinal products when used with a medical device.

 

For details, see: https://www.ema.europa.eu/en/guidance-application-amended-variations-regulation-1-january-2025#anchor1 

 

 

 

Airflow visualisation

 

Recap: Air pattern or ‘smoke’ studies are designed to demonstrate unidirectional airflow (what used to be called, inaccurately, ‘laminarity’) in relation to EU / WHO GMP Grade A / ISO 14644 class 5 areas. The required airflow appears as a sweeping action over and away from exposed product components (such as vials or stoppers) under dynamic conditions. This requirement also extends to activities such as loading lyophilizers. Such studies should be periodically conducted.

 

Studies are also expected in relation to the areas housing EU / WHO GMP Grade A / ISO 14644 class 5 areas, such as EU / WHO GMP Grade B / ISO 14644 class 7 (in operation) cleanrooms as per conventional aseptic processing (or lower specification area where isolators are used). In these areas the airflow is expected to be turbulent and the main concern is to ensure that air does not move into the EU / WHO GMP Grade A / ISO 14644 class 5 area during activities such as machine set-up or where an intervention is needs to be performed.

 

Other expectations with airflow studies include:

 

• The requirement that they should be well-documented with written conclusions
• Major issues of turbulent airflow in EU / WHO GMP Grade A / ISO 14644 class 5 areas which need to be addressed
• Data which should be used for selecting appropriate environmental monitoring locations, especially with the positioning of settle plates
• Videotape or digital recording mechanisms which have been found to be useful in assessing airflow as well as facilitating evaluation of subsequent equipment configuration changes

 

It is important that all airflow studies are conducted in operation (dynamic state). This is because even successfully qualified systems can be compromised by poor personnel, operational or maintenance practices. Smoke studies and multi-location particulate data are vital when performing qualification studies to assess whether proper particulate control dynamics have been achieved throughout the critical area.  

 

 

 

Particle size analysis

 

The Ph. Eur. is revising chapter 2.9.50. Particle Size Analysis by Dynamic Light Scattering (DLS). Particle size distribution is an important characteristic of dispersed systems such as emulsions, suspensions and liposome formulations.

 

DLS can be used to determine the hydrodynamic size of particles in the submicron range and is therefore particularly suitable for the particle size analysis of dispersed systems that are composed of randomly moving particles measuring up to approximately 1 µm.

 

The update covers an additional procedure for instrument qualification, which has been added in accordance with ISO 13320:2020, as an alternative to the harmonised procedure (local Ph. Eur. requirement).

 

The draft is accessible via Pharmeuropa (requires a subscription). The deadline for comments is 30 June 2025.