Nitrosamines are formed by a reaction between nitrates or between nitrites and certain amines. Medical reviews have reported a positive association between nitrite and nitrosamine intake and gastric cancer.

 

The update provides new guidance on acceptable intakes (AIs) for N-nitrosamines in APIs such as acebutol, buspirenone, ciprofloxacin, dimetindene, diclofenac, maprotiline, melipramin, propafenone, rivastigmine, valsartan, vanzacaftor and vildagliptin.

 

In addition, the US FDA has published the second revision to the industry guidance on "Control of Nitrosamine Impurities in Human Drugs".

 

 

 

Artificial intelligence

 

The EMA has published guiding principles that set how EU medicine regulators can use large language models (LLMs), a form of generative artificial intelligence (AI), focusing on text generation in regulatory science and for regulatory activities. 

 

Artificial intelligence is a general term referring to any machine-based system designed to operate with varying levels of autonomy. It may exhibit adaptiveness after deployment and infers, from the input it receives, how to generate outputs such as predictions, content, recommendations, or decisions that can influence physical or virtual environments.

 

The document provides high-level recommendations to facilitate LLMs' safe, responsible and effective use, being of interest to anyone who uses or would like to use such AI models in the future.

 

 

 

Pharmaceuticals and environmental assessments

 

The EMA’s Revision of Guideline on Environmental Risk Assessment (ERA) enters into force. This guideline describes the revised requirements for assessing the potential environmental risks of human medicinal products.

 

The requirements for environmental risk assessment will be mandatory for all pharmaceutical companies placing their medicines on the EU market.

 

An ERA must comprise detailed protocols for analysing the environmental impact of drugs, including chemical-physical characterisation, environmental fate and ecotoxicology studies of its active substance(s). The identification of potential hazards of the active substance of a medicinal product is described along with detailed guidance on how to document the results in a risk assessment report, as well as suggested precautionary and mitigation measures.

 

 

 

US regulatory submissions

 

Under section 745A(a) of the Federal Food, Drug and Cosmetic Act (FD&C Act), at least 24 months after the issuance of a final guidance document in which the Food and Drug Administration (FDA or Agency) has specified the electronic format for submitting submission types to the Agency, such content must be submitted electronically as well as in the format specified by FDA.

 

New U.S. FDA guidance describes how sponsors and applicants must organise the content that they submit to the Agency electronically for all submission types under section 745A(a) of the FD&C Act. This guidance also references several technical specification documents and the electronic common technical document (eCTD) Technical Conformance Guide, which provide additional details regarding the organisation of content for electronic submissions.

 

 

 

Withdrawn FDA guidance's

 

The U.S. FDA has withdrawn several guidances relating to biologics during 2024. These include:

 

• Emergency Use Authorization for Vaccines to Prevent COVID-19
• Donor Screening Recommendations to Reduce the Risk of Transmission of Zika Virus by Human Cells, Tissues, and Cellular and Tissue-Based Products
• Policy for Certain REMS Requirements During the Tocilizumab Shortage Related to the COVID-19 Public Health Emergency
• Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Components
• Guidelines for Immunization of Source Plasma (Human) Donors with Blood Substances -
• Guideline for the Uniform Labeling of Blood and Blood Components
• Draft Points to Consider in the Manufacture and Clinical Evaluation of In Vitro Tests to Detect Antibodies to the Human Immunodeficiency Virus Type 1
• Guideline for Collection of Blood or Blood Products from Donors with Positive Tests for Infectious Disease Markers ("High Risk" Donors)
• Draft Points to Consider in the Design and Implementation of Field Trials for Blood Grouping Reagents and Anti-Human Globulin)
• Recommended Methods for Blood Grouping Reagents Evaluation
• Recommended Methods for Evaluating Potency, Specificity, and Reactivity of Anti-Human Globulin
• Guideline for Quality Assurance in Blood Establishments
• Screening and Testing of Donors of Human Tissue Intended for Transplantation
• Year 2000 Date Change for Computer Systems and Software Applications Used in the Manufacture of Blood Products
• Errors and Accidents Regarding Saline Dilution of Samples Used for Viral Marker Testing 

 

The full list can be found here.

 

 

 

Two new monographs published in European Paediatric Formulary

 

Two new monographs, “Flecainide acetate 10 mg/mL oral solution” and “Valaciclovir 20 mg/mL oral solution”, elaborated by the European Paediatric Formulary (PaedF) working party have been added to the European Paediatric Formulary after a successful public consultation phase. The Formulary now comprises nine monographs.

 

The formulations described in the two monographs, which are not legally binding, were selected based on the inclusion and evaluation criteria established for the Formulary that were adopted at the end of 2015.

 

Flecainide acetate oral solution monograph (registration required to view): https://paedform.edqm.eu/app/epf/content/default/F0021E.htm 

Valaciclovir oral solution monograph (registration required to view): https://paedform.edqm.eu/app/epf/content/default/F0023E.htm 

 

 

 

Inspection arrangements

 

The EMA maintains a compilation of inspection-related procedures and templates used by the GMP and GDP inspectorates in the European Union (EU) and European Economic Area (EEA).

 

These procedures and templates cover the basis for national procedures that form part of 
the national inspectorates' quality system. This facilitates cooperation between EU Member States, supporting the harmonisation and exchange of inspection-related information.

 

The compilation includes procedures to support inspections of manufacturers and wholesale distributors.

 

To access, see: https://www.ema.europa.eu/en/human-regulatory-overview/research-development/compliance-research-development/good-manufacturing-practice/compilation-union-procedures-inspections-exchange-information 

 

 

 

New European Pharmacopeial texts

 

The following texts appear for the first time in the European Pharmacopoeia. They will be implemented on 1 April 2025.

 

General Chapters

 

• 2.4.35. Extractable elements in plastic materials for pharmaceutical use
• 5.33. Design of experiments
• 5.34. Additional information on gene therapy medicinal products for human use

 

Monographs

 

• Gene therapy medicinal products for human use (3186)
• Radiopharmaceutical preparations and starting materials for radiopharmaceutical preparations
• Lutetium (177Lu) zadavotide guraxetan injection (3170)

 

 

 

Raw materials of biological origin

 

The European Pharmacopoeia is revising the chapter “5.2.12. Raw materials of biological origin for the production of cell-based and gene therapy medicinal products”.

 

The revision is the consequence of the publication in the same Ph. Eur. Supplement of the 
new general monograph Gene therapy medicinal products for human use (3186), which 
replaces general chapter Gene transfer medicinal products for human use (5.14).

 

 

 

Gene therapy medicinal products for human use

 

The European Pharmacopoeia is revising the chapter “5.34. Additional information on gene therapy medicinal products for human use”.

 

This general chapter provides recommendations in addition to the requirements of the general 
monograph gene therapy medicinal products for human use (3186) and comprises individual 
sections covering gene therapy medicinal products (GTMPs) that have not yet been approved 
on the European market.

 

The general requirements for GTMP production, for recombinant vectors and for 
genetically modified cells for human use, are outlined in a dedicated section in the general 
monograph 3186. The statements therein are not repeated in the individual sections of the general monograph or this general chapter.

 

 

 

Inhalers and fluorinated greenhouse gases

 

The European Medicines Agency has issued a document on inhalers and CFCs, titled “Questions and answers on labelling requirements for centrally authorised metered dose inhalers containing  fluorinated greenhouse gases”.

 

The aim is to provide operational guidance on labelling requirements for metered dose inhalers containing fluorinated greenhouse gases (F-gases).

 

The guidance can be found here: https://www.ema.europa.eu/en/documents/other/questions-answers-labelling-requirements-centrally-authorised-metered-dose-inhalers-containing-fluorinated-greenhouse-gases_en.pdf 

 

 

 

Disinfectants

 

Sterilants and disinfectants are regulated in a variety of ways in Australia, depending on the intended purpose of the product as discerned from the claims made in the instructions for use, labelling and promotional material.

 

To outline the requirements in Australia, the Therapeutic Group Association (TGA) has updated its guidance: https://www.tga.gov.au/resources/resource/guidance/disinfectants-sterilants-and-sanitary-products 

 

 

 

EU Clinical Trials

 

The Clinical Trials Regulation (EU) No 536/2014 (CTR) was adopted in 2014. However, one of the requirements of the CTR is the use of a newly developed, single electronic submission portal called Clinical Trial Information System (CTIS).

 

Due to a delayed technical development of this portal, the CTR officially came into force on the 31st of January 2022, together with the go live of CTIS. From that date on, the CTR repealed the CTD.

 

Phase 3 of the process begins from January 31, 2025 – onwards. This date marks the end of the transition period. All ongoing clinical trials that were approved under the CTD must now fully be transitioned to comply with the CTR. If not transitioned by this date, this will have serious consequences. Such trials are considered non-compliant and in breach of the CTR, meaning that sponsors could be subject to corrective measures and penalties by Member states, and subject to civil and criminal liability.

 

For details, see the EMA: https://www.ema.europa.eu/en/news/clinical-trials-transition-new-eu-system-one-year-left 

 

 

 

FDA issues “New Drugs Regulatory Program Modernization – Impact Narrative.” 

 

In 2017, FDA began an initiative to modernise its New Drugs Regulatory Program (NDRP), to continuously improve regulatory science and review. A new report provides a detailed look at the strategic objectives and impact of NDRP modernisation, as well as continued efforts toward reaching the program’s goals.

 

For details, see: https://www.fda.gov/drugs/cder-conversations/modernizing-new-drugs-regulatory-program