The MHRA has launched a consultation on proposed updates to the definition of gene therapy medicinal products (“GTMPs”) under the UK Human Medicines Regulations 2012 (“HMRs”). The current definition was originally developed in 2007, and was based on a smaller range of technologies. It is no longer considered to reflect the full range of modern gene therapy technologies now available, including therapies involving synthetic genetic material, new forms of genome editing, and highly engineered cells and tissues. This means there may not be a clear path to market for these technologies under the current legislation.

The proposals aim to address these limitations and align the regulatory framework with current scientific developments. The proposed reforms represent a targeted shift towards a more technology-neutral and mechanism-based approach. The proposals do not change the approval process, classification of existing products, or applicable safety and efficacy standards.

The MHRA is seeking input from stakeholders on whether the proposals are appropriate, proportionate and workable, including whether the revisions cover the correct categories of products, and whether these would cause any unintended consequences or operational challenges. The consultation is open until 22 June 2026 and feedback is requested in the form of a survey. Responses can be submitted online here.

Below, we outline the background, the key proposed changes, and the regulatory considerations that have shaped MHRA’s proposals.

Background and current position

Advanced Therapy Medicinal Products (“ATMPs”) represent a category of medicinal product that are based on genes, tissues, or cells and which are often intended to treat serious and/or rare health conditions, including cancer and genetic disorders. ATMPs are often complex in both their design and manufacturing processes. GTMPs are one of the three types of ATMPs defined in the HMRs, along with somatic cell therapy medicinal products and tissue engineered products. Under the HMRs, if a product falls within more than one of these categories including GTMPs, the GTMP definition takes precedence.

The MHRA acknowledges a number of limitations to the current definition and the regulation of GTMPs, including:

• The requirement for GTMPs to be biological in origin, which excludes products based on synthetic nucleic acid constructs that function in the same way;
• The focus on recombinant nucleic acids, which excludes gene editing approaches delivered through non-recombinant nucleic acid systems and potential non-nucleic acid platforms, which could not have been anticipated at the time of the original drafting; and
• The requirement that the therapeutic effect must derive directly from the recombinant sequence, which does not reflect modern designs where genetic modification plays a supporting or enabling role.

According to the MHRA, the current mismatch between legal definitions and scientific reality can lead to uncertainty in classification, inconsistent regulatory oversight, and potential barriers for developers and patient access.

In addition, the MHRA is considering the introduction of a dedicated framework for medicinal products where the active substance is individualised to a patient’s characteristics. Currently, individualisation of ATMPs may be considered on a case-by-case basis. For example, certain individualised mRNA cancer immunotherapies may be classified as ATMPs.

Proposed changes

The consultation proposes amendments to the current GTMP definition set out in Regulation 2A(2) of the HMRs, by removing the necessity for the product to be a biological medicinal product, and outlining an extended list of characteristics, of which the product should fulfil at least one. In summary these are:

• Products that contain or consist of a substance or combination of substances that edit a target genome in a sequence specific manner.
• Products that contain or consist of cells which have been modified, meaning that their genome has been edited in a sequence specific manner.
• Products that contain or consist of a recombinant nucleic acid or synthetic nucleic acid, or consist of cells subjected to a recombinant nucleic acid or synthetic nucleic acid, which are intended to:
  • regulate, replace, or add any nucleic acid sequence; and
  • mediate its effect by being transcribed or translated.

As under the current framework, vaccines against infectious diseases would remain excluded.

The proposed revised definition is based on mechanism of action rather than origin and intended to ensure that all products involving sequence-specific genome editing are clearly captured within the GTMP framework. In addition, medicinal products incorporating synthetic nucleic acids would fall within the ATMP regime alongside products containing recombinant nucleic acids, provided that those nucleic acids mediate their effect through transcription or translation.

The consultation is clear that a key policy objective is to avoid unintentionally bringing established non-expression-based nucleic acid medicines, such as antisense oligonucleotides and certain RNA interference therapies, within the ATMP framework.

Additionally, the MHRA has clarified that there is no intention to further sub-categorise or subclassify GTMPs based on further distinguishing features; although supplementary guidance, based on scientific considerations, may be developed for specific types of products which fall within the definition for GTMPs.

Removal of the requirement for GTMPs to be “biological” medicinal products

Under the current definition, GTMPs are required to qualify as “biological medicinal products”. Under the new proposal, any synthetic or biologically derived products could qualify as a GTMP provided that they satisfy the revised classification criteria. The MHRA still encourages developers to follow the most appropriate chemical or biological regulatory guidance on a case-by-case basis using a risk-based approach.

Synthetic and recombinant nucleic acids included only where transcribed or translated

The MHRA notes that allowing chemically synthesised products to fall within the GTMP definition raises a parallel challenge: ensuring that products that were not previously considered ATMPs do not fall within the updated definition, as this could create “substantial regulatory disruption”.

To mitigate this challenge, the proposed definition only classifies products containing recombinant or synthetic nucleic acids as GTMPs, where those nucleic acids undergo transcription and translation. Conversely, an active substance that contains a naturally occurring nucleic acid will not be classified as a GTMP (e.g., unmodified bacteriophage or unmodified oncolytic viruses). Similarly, any (manufactured) active substances where the nucleic acid is not transcribed or translated (typically antisense oligonucleotides, small interfering RNAs, small activating RNAs, micro RNAs, etc.) will also not be considered a GTMP.

Genome editing mechanism of action

The MHRA proposes to regulate any medicinal product with a mechanism of action which incorporates genome editing as a GTMP. This aims to ensure that the regulatory framework covers new modalities as scientific advances are made, not only recombinant nucleic acid-based mechanisms (on which most gene editing approaches to date have relied). Genome editing will be interpreted to encompass effects on the genome only and the sequence-specific edit will be regarded as an intentional and design feature of the product, to ensure that products causing broad, non-targeted genome changes are not caught by the definition.

Removal of requirement for “direct therapeutic, prophylactic or diagnostic effect”

The proposal removes the requirement for the recombinant or synthetic nucleic acid to be directly responsible for the therapeutic, prophylactic or diagnostic effect, to ensure that classification reflects the role of genetic modification in modern therapies, even where it is not the primary driver of efficacy.

The current definition requires that the relevant effect must relate directly to the recombinant nucleic acid sequence it contains, or to the product of genetic expression of this sequence. According to the MHRA, this may exclude products where the genetic modification performs an important manufacturing, safety or enabling function, rather than being directly responsible for therapeutic activity.

The proposal focuses instead on the properties of the active substance or the product’s mechanism of action. This is particularly relevant for engineered cell therapies and platform technologies where the genetic modification may serve an enabling, persistence, manufacturing or safety function rather than constituting the primary therapeutic mechanism.

The MHRA notes that this change does not diminish the overarching requirement for such a product to meet the definition of a medicinal product under Regulation 2 of the HMRs.

Clarification that GTMPs do not need to act directly on human cells

The consultation proposes that GTMPs do not need to act directly on human cells to fall within the ATMP framework. According to the MHRA, products may still qualify as GTMPs where recombinant or synthetic nucleic acids are administered to humans and exert their effect through expression of that sequence, including where modifications occur in donor cells or intermediate biological systems.

International regulatory definitions

The consultation reflects the MHRA’s broader objective of maintaining international regulatory alignment while ensuring sufficient flexibility to accommodate emerging technologies. The proposed revisions move the UK framework closer to contemporary scientific and regulatory approaches adopted internationally.

At the same time, the MHRA appears to be pursuing a more technology-neutral and future-focused drafting approach than some existing international frameworks, particularly by focusing on mechanism of action and sequence-specific genome editing rather than narrower concepts tied exclusively to recombinant biological products. This may help reduce future classification uncertainty as new modalities emerge.

For developers operating internationally, however, classification divergence risks are likely to remain. If the proposals are taken forward, products classified as GTMPs in the UK may not necessarily be regulated identically in the EU or the United States, particularly where synthetic nucleic acids, non-viral delivery systems or novel genome editing mechanisms are involved. Developers will therefore need to continue assessing classification and regulatory strategy on a jurisdiction-specific basis.