Medicines for Human Use (Clinical Trials) Regulations 2004
What this means for your business
- Enforced by
- MHRA
- Applies to
- United Kingdom
- On this page
- 21 compliance obligations, 2 practical guides
What you must do
21 compliance obligations under this legislation — 3 can result in imprisonment.
Appointments 1
Ensure your clinical‑trial sponsor is UK‑based or has a UK legal representative
If your business takes responsibility for starting, managing and funding a clinical trial, you must either be established in the United Kingdom (or an approved country) or appoint a legal representative who is established in the UK. This lets the regulator contact you and ensures the trial can be authorised.
Management duties 6
Conduct clinical trials only as authorised
2 years imprisonmentIf your business runs a clinical trial on a medicinal product, you must follow exactly the approved trial protocol, the terms of the authorisation request, the ethics committee opinion and any conditions set by the licensing authority. In practice this means you cannot change the way the trial is carried out without formal amendment and you must keep evidence that you are complying.
Ensure good clinical practice and free supply of trial medicines
If you run or sponsor a clinical trial, you must have systems in place to follow Good Clinical Practice (GCP) standards and you must give any trial medicines or related devices to participants at no cost (unless NHS rules apply). This means maintaining documented procedures, monitoring, and records throughout the study.
Maintain GMP and allow regulator access
If you hold a manufacturing authorisation for medicines, you must follow good manufacturing practice (GMP) and any specific rules in regulation 40(3). You also have to let the licensing authority inspect your premises whenever they reasonably request, and you must provide the qualified person with the facilities they need to do their job.
Maintain up‑to‑date, unbiased investigator’s brochure
If your company sponsors a clinical trial, you must produce an investigator’s brochure that is clear, balanced and free from promotional language so that doctors can fairly assess the trial’s risks and benefits. You also need to review and refresh the brochure at least once each year.
Manage and record amendments to clinical trial authorisation
When you want to change any part of a clinical trial you have authorised, you must keep a record of the change, send the appropriate notice to the licensing authority (and the ethics committee for substantial changes), and only make the amendment after you have received their written acceptance (or no objection) within the required 35‑day period. Any fee that applies must also be paid.
Meet requirements to obtain a manufacturing authorisation
If you want to manufacture or import investigational medicinal products for clinical trials, you must satisfy the licensing authority’s conditions before they will grant you an authorisation. This means you need the right staff, suitable premises and equipment, a qualified person and you must have complied with the earlier application rules (Regulation 38) and supplied any information the authority asks for. You also need to ensure the details you have given are correct.
Notifications 6
Apply for an ethics committee opinion for your clinical trial
If you are running a clinical trial, the chief investigator must send a written, signed application to a single appropriate ethics committee before the trial starts. The application must be in English and include all documents listed in Schedule 3 Part 1. This ensures the trial has the needed ethical approval.
Notify authorities of urgent safety measures in clinical trial
If you are the sponsor of a clinical trial and you have to take emergency steps to protect participants from an immediate health risk, you must inform the licensing authority and the relevant ethics committee in writing as soon as possible – and no later than three days after the action (or as soon as possible during a pandemic or serious health‑risk period).
Notify licensing authority and ethics committee when trial ends
If your company is the sponsor of a clinical trial you must send a written notice to the licensing authority and the relevant ethics committee as soon as the trial finishes. The notice must be sent within 90 days of a normal conclusion, or within 15 days if the trial is stopped early, and must include the details set out in Part 4 of Schedule 3.
Notify licensing authority of serious trial breaches within 7 days
If you are the sponsor of a clinical trial and a serious breach occurs – for example, something that could seriously affect participants' safety or the scientific value of the study – you must tell the licensing authority in writing within 7 days of finding out. This helps regulators act quickly to protect subjects and maintain trial integrity.
Notify regulator and ethics committee before amending a rejected trial protocol
If a proposed change to your clinical trial protocol has been rejected by the ethics committee or the licensing authority, you may still be able to modify it. You must give written notice to both the licensing authority and the relevant ethics committee at least 14 days before you intend to make the change. If either body sends you a written objection within the next 14 days you must not proceed; if they stay silent you may go ahead.
Submit written authorisation request for clinical trial
Before you start a clinical trial you must send a signed, written application to the licensing authority (the MHRA). The application has to include the specific documents listed in Schedule 3, be in English and be accompanied by any required fee unless you have arranged a later payment.
Offences and prohibitions 2
Breach listed clinical‑trial regulations
2 years imprisonmentIf you (or your company) break any of the specific regulations listed in paragraph 1 (a‑m) – for example regulations 3A, 12, 13, 27‑35, 36‑43 – you commit a criminal offence. The offence covers a wide range of breaches such as failing to obtain authorisation, not keeping proper records, or supplying a product that does not meet the required standards.
Provide false or misleading information in clinical trial applications
2 years imprisonmentIf you give false or misleading information to the MHRA or an ethics committee when applying for an ethics opinion, a clinical‑trial authorisation, a manufacturing authorisation, or when you are conducting, sponsoring or acting as a qualified person on a clinical trial, you commit a criminal offence. A conviction can lead to a fine (potentially unlimited) and/or imprisonment, depending on how the offence is prosecuted.
Record keeping 2
Keep detailed records of all adverse events in clinical trials
If your company sponsors a clinical trial you must maintain a complete record of every adverse event reported by investigators, including serious events, deaths and any events flagged as critical to safety. These records must be kept up to date during the trial and be ready to provide to the licensing authority if it asks for them.
Maintain and archive the trial master file for your clinical trial
If your company sponsors a clinical trial you must keep a complete trial master file that holds all essential documents, make it available for inspection, and retain it (and subjects’ medical files) for at least five years after the trial ends. You also need to appoint named staff to manage the archiving, control who can access the files, and record any transfer of ownership.
Registration and licensing 2
Submit a complete written application for manufacturing authorisation
If you want to manufacture an investigational medicinal product for a clinical trial, you must send a written, signed application to the licensing authority. The application must list any standard provisions you want altered, include all details set out in Schedule 6 and the required fee (or a payment arrangement), and it must be in English.
Submit full details with your manufacturing authorisation application
If you want a licence to manufacture a medicinal product for a clinical trial, you must provide a large set of information with your application. This includes who you are, the product types, the manufacturing/assembly/import activities, the addresses and facilities of all sites, staff qualifications, storage and record‑keeping arrangements, and, for modular‑manufacturing (MM) or point‑of‑care (POC) products, a detailed dossier. In short, you need to prepare a comprehensive package of documents before the authority will grant the authorisation.
Reporting and filing 2
Report suspected unexpected serious adverse reactions in clinical trials
If you are the sponsor of a UK clinical trial you must record any serious, unexpected reaction to the investigational medicine. Fatal or life‑threatening reactions have to be reported to the licensing authority and the ethics committee within 7 days, other serious unexpected reactions within 15 days, and any follow‑up information must be sent within 8 days. You also need to let all trial investigators know about each reaction.
Report unexpected serious adverse reactions from overseas trial sites
If your company sponsors a clinical trial that has sites both in the UK and in another country, you must tell the UK licensing authority about any suspected unexpected serious adverse reactions that happen at the foreign sites. Fatal or life‑threatening reactions must be reported within 7 days of you learning of them, all others within 15 days.
Penalties for non-compliance
3 penalties under this legislation. 3 can result in imprisonment. 3 carry an unlimited fine.
Conduct clinical trials only as authorised
Unlimited fine and/or 2 years imprisonment
Breach listed clinical‑trial regulations
Unlimited fine and/or 2 years imprisonment
Provide false or misleading information in clinical trial applications
Unlimited fine and/or 2 years imprisonment
Practical guidance
Our guides explain how to comply with the requirements above.
Running clinical trials in the UK
How to get MHRA authorisation for clinical trials of investigational medicinal products (CTIMPs). Covers combined review process, GCP requirements, safety …
MHRA licensing for medicines and medical devices
MHRA licensing requirements for manufacturing, distributing, and importing medicines and medical devices in the UK.
Sections and provisions
69 classified provisions from this legislation.
Duties 21
- s.3 Sponsor of a clinical trial reference
- Schedule 6 PARTICULARS THAT MUST ACCOMPANY AN APPLICATION FOR A MANUFACTURING AUTHORISATION
- s.14 Application for ethics committee opinion accompanying material
- s.17 Request for authorisation to conduct a clinical trial
- s.24 Amendments by the sponsor
- s.25 Modifying or adapting rejected proposals for amendment
- s.27 Conclusion of clinical trial
- s.28 Good clinical practice and protection of clinical trial subjects
- s.29 Conduct of trial in accordance with clinical trial authorisation etc. person
- s.30 Urgent safety measures immediate hazard
- s.32 Notification of adverse events The sponsor
- s.33 Notification of suspected unexpected serious adverse reactions A sponsor
- s.34 Clinical trials conducted in countries other than the United Kingdom
- s.38 Application for manufacturing authorisation
- s.40 Grant or refusal of manufacturing authorisation provisions
- s.42 Obligations of manufacturing authorisation holder
- Approved country for import Approved country for import
- List of countries for the purpose of the definitio List of countries for the purpose of the definition of “marketing authorization”
- Notification of serious breaches Notification of serious breaches which is likely
- Sponsor’s responsibility for the investigator’s br Sponsor’s responsibility for the investigator’s brochure
- ... and 1 more duties
Powers 14
- s.7 Recognition of ethics committees
- s.8 Revocation of recognition
- s.10 Other functions of the Authority
- s.21 Clinical trials conducted in countries other than the United Kingdom
- s.22 Amendments to clinical trial authorisation
- s.23 Amendments by the licensing authority
- s.44 Variation of manufacturing authorisation
- s.45 Suspension and revocation of manufacturing authorisation
- s.57 Functions in relation to good clinical practice
- s.58 Detailed guidance
- Information sharing Information sharing
- Publication of information Publication of information
- Variation of MM (IMP) master file Variation of MM (IMP) master file
- Variation of POC (IMP) master file Variation of POC (IMP) master file
Definitions 5
Exemptions 13
- Schedule 12 TRANSITIONAL PROVISIONS
- s.13 Supply of investigational medicinal products for the purpose of clinical trials
- s.15 Ethics committee opinion
- s.16 Review and appeal relating to ethics committee opinion
- s.19 Authorisation procedure for clinical trials involving medicinal products for gene therapy etc.
- s.31 Suspension or termination of clinical trial
- s.36 Requirement for authorisation to manufacture or import investigational medicinal products
- s.37 Exemption for hospitals and health centres
- s.43 Qualified persons
- s.46 Labelling
- s.51 Defence of due diligence
- Manufacture of MM investigational medicinal produc Manufacture of MM investigational medicinal products
- Manufacture of POC investigational medicinal produ Manufacture of POC investigational medicinal products