扒哥吃瓜

叠补肠办驳谤辞耻苍诲听

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an organisation comprised of regulatory authorities from ICH Regions and the pharmaceutical industry to discuss scientific and technical aspects relating to the authorisation of medicinal products. 听

The mission of ICH is to achieve greater harmonisation worldwide to ensure that safe, effective, and high-quality medicines are developed and registered. Harmonisation is achieved through the development of ICH guidelines via a process of scientific consensus with regulatory and industry experts working side-by-side.听

Key to the success of this process is .听

As the UK sovereign medicines regulator,听following the UK departure from the听European Union听(EU), the MHRA became a full member of ICH in May 2022.听听

ICH E6 GCP听is an international guideline that has been developed听to facilitate the harmonisation of the听quality of the conduct of clinical trials that are intended to be submitted to a regulatory authority in one or more ICH regions to gain a marketing authorisation approval听(MAA)听for a medicinal product.听

The ICH GCP guideline听is听also applicable to other interventional clinical trials of investigational medicinal products that are not intended to support marketing authorisation applications.听

The (ICH) Expert Working Group for ICH E6听(R3) (EWG) updated the ICH 贰6听(搁2) GCP guideline.听The UK Medicines and Healthcare products Regulatory Agency (MHRA)听represented听the Pharmaceutical Inspection Co-operation Scheme (PIC/s) in the EWG.听The听EWG听involved stakeholders during the revision process, and the guideline was subject to public consultation which the MHRA facilitated for the UK.听听

ICH 贰6听(搁3)听GCP听肠辞苍蝉颈蝉迟蝉听辞蹿听迟丑别 GCP听principles,听two听annexes, appendices A, B and C and a glossary.听听

Compliance with ICH E6 GCP in the United Kingdom听听

The Medicines for Human Use (Clinical Trials) Regulations听2004 (鈥楿K CT Regulations鈥�)听have been updated following United Kingdom鈥檚 departure from the EU and the proposed changes to the legislation were subject to public consultation.听

The听government response to the consultation听on legislative proposals for clinical trials confirmed that the principles of GCP, as set out in ICH E6 GCP,听would replace the current GCP principles in the UK legislation that were based听primarily听on听outdated EU legislation.听

Compliance with the ICH E6 GCP Principles听(as amended from time to time)听and not the entirety of the guideline听becomes听a legal requirement in the UK on 28 April 2026.听This is set out in Regulation 28听of the amended UK CT Regulations, which听states听that:听

鈥�(1) No person shall (a) conduct a clinical trial, or (b) perform the functions of the sponsor of a clinical trial (whether that person is the sponsor or is acting under arrangements made with that sponsor), otherwise than in accordance with the conditions and principles of good clinical practice.鈥�

鈥�(1A) The conditions and principles of good clinical practice include those in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice, as amended from time to time.鈥澨�听

鈥�(1B) (a) For the avoidance of doubt the functions of the sponsor include functions in relation to (i) the development and maintenance of trial specific computerised systems, and (ii) the selection and oversight of a laboratory in relation to the analysis or evaluation of human samples collected as part of the clinical trial; and (b) conducting a trial.鈥澨�听

Training in ICH E6 GCP听

In addition to writing the guidance, the EWG also developed training materials for the E6 (R3)听GCP听guideline.听These training materials are available on the听ICH website.听

Training in ICH E6 GCP and the UK legislation should be proportionate to each individual鈥檚 role in a clinical trial based on their delegated activities.

Sponsors,听service听providers听and investigator听s/institutions听should听use or听consider听the training materials provided by听the E6 (R3) EWG听in their training provision.听ICH听E6听GCP training should be documented.听听

United听Kingdom-specific GCP principles听

Within the Medicines for Human Use (Clinical Trials) Regulations听2004 (鈥淯K CT Regulations鈥�), three UK听specific听principles have been听retained听by the听Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025听(Regulation 37听(which听amends听Schedule 1, Part 2听of the UK CT Regulations)).

One requiring compliance with the Declaration of Helsinki (see guidance on听Declaration of Helsinki and Clinical Trial Regulations听alignment), a second relating to the provision of insurance, and a third one as follows:听

鈥淭he investigator and sponsor must have regard to all relevant guidance with respect to听commencing听and conducting a clinical trial.鈥�

This means that the听annexes听to ICH E6 (R3)听GCP听cannot be ignored听as they are relevant guidance.听As the principles of听ICH E6听GCP are听high level, the听annexes听provide听more detailed guidance听on how compliance with听the principles could听be achieved.听

The sponsor and investigator must give due regard to the Annexes when commencing or conducting a clinical trial.

Disapplication听and听interpretation听of听aspects听of the听guidance contained听in the听ICH E6 GCP annexes听for trials not intended for marketing authorisation applications听

ICH E6 (R3) GCP听introduction and structure听contains听the following text:听

鈥淭his guideline applies to interventional clinical trials of investigational products that are intended to be听submitted听to regulatory authorities. The Principles of GCP in this guideline may also听be applicable听to other interventional clinical trials of investigational products that are not intended to support marketing authorisation applications听in accordance with听local requirements.鈥�

鈥淭he Annexes provide the basis for the听appropriate interpretation听and application of the principles and should therefore be appropriately considered; however, various approaches to the provisions in the Annexes may be considered provided they are justified and achieve the intended purpose of the application of the principles.鈥�

鈥淭he principles outlined in this guideline may be satisfied using differing approaches and should be applied to fit the intended purpose of the clinical trial.鈥澨�听

As a result, for trials that are not related to a MAA, disapplication and specific interpretation of some aspects of the Annexes may occur or be required. Clinical trials of medicines that are not used for marketing authorisation purposes may nevertheless impact on public health, for example, the publication of the trial results may impact prescribing practice.

It is important such trials generate reliable results when used for decision making and that trial participants鈥� rights, safety and well-being are protected. In accordance with the UK-specific principle outlined above, which requires the sponsor and investigator have regard to all relevant guidance when commencing and conducting a clinical trial, a robust rationale must be provided for any such disapplication or alternative methods used to satisfy the ICH E6 GCP principles.听

Disapplication听of听aspects of听annex听guidance听may be on a trial or听a听quality system听level;听the latter therefore applies to all the trials conducted using the quality system. Rationale for the departure and details of any mitigation or other means to ensure that the relevant principle(s) are met听should be documented.听

It is recommended that such considerations are made proactively and early in the trial lifecycle and could be part of a trial risk assessment and accompany the consideration of critical to quality factors.

A line-by-line assessment of Annex 1 is not required to be documented. Documentation should be retained that demonstrates that consideration of the Annexes was undertaken and that any disapplication that could potentially impact on compliance with ICH E6 GCP principles was mitigated or how compliance was maintained by other means. This then would demonstrate that this UK principle had been complied with respect to GCP.

The MHRA may conduct a GCP inspection of a trial conducted in the United Kingdom against the UK legislative requirements including the ICH E6 GCP principles.听For trials conducted to support marketing authorisations and/or where the sponsor organisation claims compliance with ICH E6 GCP for its clinical trials, compliance with the Annexes in addition to the principles would be expected.听

Proportional听application听of听aspects听of the听guidance contained听in the ICH E6 GCP Annexes听听

ICH E6 (R3) GCP Principles听contains听the following听text:听

鈥淭he Principles of GCP are designed to be flexible and applicable to a broad range of clinical trials. This guideline, along with ICH E8(R1), encourages thoughtful consideration and planning to address specific and potentially unique aspects of an individual clinical trial. This includes evaluation of trial characteristics, such as the design elements, the investigational product being evaluated, the medical condition being addressed, the characteristics of the participants, the setting in which the clinical trial is being conducted, and the type of data being collected. Careful consideration of factors relevant to ensuring trial quality is needed for each clinical trial.鈥澨�听

鈥淐linical trial processes and risk mitigation strategies implemented to support the conduct of the trial should be proportionate to the importance of the data being collected and the risks to trial participant and the reliability of trial results.鈥�

Amendments to the UK CT Regulations (made by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025),听implemented on 28 April 2026,听contains听the following top-level principle from ICH E6 (R3) GCP:听

鈥�7. Clinical trial processes,听measures听and approaches should be implemented in a way that is proportionate to the risks to participants and to the importance of the data collected and that avoids unnecessary burden on participants and investigators.鈥�

This means that a risk proportionate approach to how the trial is designed, set-up, conducted and reported must be implemented.听听

The ICH E6 (R3)听GCP听principles include further听proportionate听requirements in relation to processes and systems for ensuring the quality of the information from the trial and for computerised systems being fit for purpose as follows:听听

鈥�9.2 Systems and processes that aid in data capture, management and analyses, as well as those that help ensure the quality of the information generated from the trial, should be fit for purpose, should capture the data required by the protocol and should be implemented in a way that is proportionate to the risks to participants and the importance of acquired data.鈥�

鈥�9.3 Computerised systems used in clinical trials should be fit for purpose (e.g., through risk-based validation, if听appropriate), and factors critical to their quality should be addressed in their design or adaptation for clinical trial purposes to ensure the integrity of relevant trial data.鈥�

The MHRA therefore expects sponsors to have undertaken a robust risk assessment to facilitate the implementation of a risk-based approach. Additionally, the annex guidance specifically requires sponsors to implement implementation of risk-proportionate approaches and an appropriate risk-based quality management system (see ICH E6 (R3) Introduction to section 3 and section 3.10).

Further guidance is available for this in听.

All aspects of the guidance should be interpreted in the context of the risks to the reliability of the trial results and to the rights,听safety听and well-being of trial participants. As a result听of the flexibility afforded in ICH E6 (R3)听GCP听it is expected that specific processes applied during the trial听will听vary from trial to trial听and how听aspects of听the guidance听were听implemented would vary as a result.

It is expected that the sponsor鈥檚 interpretation of compliance with the guidance听would be traceable to a robust justification in a risk assessment.听听

Sponsors should understand that MHRA GCP Inspectors aim to evaluate compliance with the Annexes proportionately and pragmatically in relation to the risks to the reliability of the trial results and the protection of the participants鈥� rights, safety and well-being and will make use of the sponsor鈥檚 risk assessment as part of this process.

The responses to the ICH E6 R3 consultation听identified听a need for consistency of approach and assessment of risk proportionality across regulators. The MHRA collaborates via the Pharmaceutical Cooperation Inspection Scheme (PIC/S) to enhance consistency across regulators and to discuss differences in approach and interpretation听

Implementation of ICH E6 (R3) GCP for ongoing trials on 28 April 2026听

Updating the Medicines for Human Use (Clinical Trials) Regulations2004 (鈥淯K CT Regulations鈥�) to implement the ICH E6 GCP principles has been a known intention for some time.

It was听stated听in the听government response to consultation听on legislative proposals for clinical trials听which听published听on听21 March 2023)听and听contained in the legislation听that听was听laid听before parliament on 12 December 2024听(that amended the UK CT Regulations).听

The ICH E6 (R3) GCP principles and Annexe 1 reached Step 4 on 06 January 2025 and the date for听implementation of the updated legislation of 12 months after the legislation came into law became clear on 10 April 2025.听

It听is听expected that sponsors should听have听assessed听ICH E6 (R3)听GCP principles and听Annexe听1听to听determine听necessary changes to their quality management system to ensure compliance from 28 April 2026.听This assessment should be听documented,听and it听could be examined听during听MHRA GCP inspections.听

For听trials that听commenced听prior to 28 April 2026, there should be a听documented听impact assessment of the听GCP听updates听on the trial.听During this assessment consideration should be given to the status of the trial听when the implementation date was announced听and the expected duration of the trial after 28听April 2026.听听

It is understood that for some aspects of the updated guidance it would be inappropriate to apply updated procedures to the听trial,听and such justifications should be part of the assessment.听

This would be dependent upon the trial and its timing, for example, trials that were being set up and started between dates听10 April 2025听and 28 April 2026 and听anticipated听to continue after that date would be expected to have fewer required deviations than听those trials started听a lot听earlier听and continuing only for a short period of time after听28听April 2026.听

Such prospective听deviations from the updated quality management system听should be documented and听should be听limited to the affected trials.