European Union (Clinical Trials on Medicinal Products for Human Use) (Principal) Regulations 2022.
Statutory Instruments
Source: Statutory Instruments

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paragraphs: These Regulations may be cited as the European Union (Clinical Trials on Medicinal Products for Human Use) (Principal) Regulations 2022.
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paragraphs: (1) These Regulations apply to all clinical trials conducted in the State.
(2) These Regulations do not apply to non-interventional studies.
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paragraphs: (1) In these Regulations—
(a) a medical practitioner within the meaning of section 2 of the Medical Practitioners Act 2007 (No. 25 of 2007),
(b) a visiting EEA practitioner within the meaning of section 2 of the Medical Practitioners Act 2007 , or
(c) a registered dentist within the meaning of section 2 of the Dentists Act 1985 (No. 9 of 1985);
(a) in relation to an incapacitated subject who is, or is being considered as, a subject for a clinical trial—
(i) a person, other than a person connected with the conduct of the trial, who by virtue of his or her family or other personal relationship with the individual—
(aa) can provide the best interpretation of the will and preferences of the individual based on their knowledge of the individual,
(bb) is available and willing to act for that purpose, or
(ii) if there is no such person, the medical practitioner primarily responsible for the medical treatment provided to the individual where he or she—
(aa) can provide the best interpretation of the will and preferences of the individual based on their knowledge of the individual,
(bb) is not involved in the conduct of the trial,
(cc) is of the view that participation in the trial will not prejudice the health and wellbeing of the individual, and
(dd) is available and willing to act for that purpose, and
(b) in relation to a minor who is, or is being considered as, a subject for a clinical trial, a guardian within the meaning of the Guardianship of Infants Act 1964 (No. 7 of 1964);
(a) the ownership of the investigation data belongs to the non-commercial sponsor from the inception of the clinical trial, and
(b) the design, conduct, recruitment, recording of data and reporting of the results of the investigation remain under the control of the non-commercial sponsor;
(a) in relation to a person receiving services in pursuance of the Health Acts 1947 to 2007—
(i) in a case where a health service body is providing the health care, that body, or
(ii) in any other case, the health service body which entered the arrangements under which the health care is provided, or
(b) in relation to any other person receiving health care, the person primarily responsible for providing that health care;
(2) A word or expression which is used in these Regulations and which is also used in the Clinical Trials Regulation has, unless the context otherwise requires, the same meaning in these Regulations as it has in the Clinical Trials Regulation.
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paragraphs: (1) Save as may be otherwise expressly provided for in these Regulations and subject to paragraph (2)—
(a) the role of Member State, pursuant to the Clinical Trials Regulation, shall be carried out by the Authority and the National Office in conjunction with the nominated ethics committee, each of which—
(i) may communicate information when carrying out their respective functions under the Clinical Trials Regulation, and
(ii) shall keep such communications confidential,
(b) where the State is the reporting Member State under the Clinical Trials Regulation, the Authority and the National Office in conjunction with the nominated ethics committee shall co-ordinate in the review of applications for the conduct of clinical trials and applications for substantial modifications to clinical trials granted authorisation, and perform the functions ascribed to the reporting Member State under the Clinical Trials Regulation within the timelines set out therein,
(c) where the State is a Member State concerned under the Clinical Trials Regulation, the Authority and the National Office in conjunction with the nominated ethics committee shall perform the functions ascribed to the Member State concerned under the Clinical Trials Regulation within the timelines set out therein,
(d) where the State is an additional Member State concerned pursuant to Article 14 of the Clinical Trials Regulation, the Authority and the National Office in conjunction with the nominated ethics committee shall perform the functions ascribed to additional Member States concerned under the Clinical Trials Regulation within the timelines set out therein, and
(e) notifications to the EU portal envisaged at Article 80 of the Clinical Trials Regulation and submissions to the EU database envisaged at Article 81 thereof shall be made by either the Authority or the National Office, as appropriate.
(f) the Authority shall—
(i) perform the scientific review referred to in Article 4 of the Clinical Trials Regulation,
(ii) validate the aspects covered by the Part I assessment, pursuant to Chapters II and III of the Clinical Trials Regulation,
(iii) be the national contact point for the purposes of Article 83 of the Clinical Trials Regulation,
(iv) perform the inspections envisaged by Articles 63 and 78 of the Clinical Trials Regulation,
(v) collect the fees envisaged by Chapter XVI of the Clinical Trials Regulation,
(vi) be responsible for the enforcement of these Regulations and the prosecution of any offences thereunder.
(g) the National Office, in conjunction with the nominated ethics committee, shall—
(i) perform the ethical review referred to in Article 4 of the Clinical Trials Regulation,
(ii) validate the aspects covered by the Part II assessment, pursuant to Chapters II and III of the Clinical Trials Regulation.
(h) the National Office shall have the additional functions described in S.I. No. 41 of 2022 .
(i) a National Research Ethics Committee shall have the additional functions described in S.I. No. 41 of 2022 .
(2) The Minister may publish guidelines as to the appropriate division of tasks prescribed by the Clinical Trials Regulation, between the Authority, the National Office and the nominated ethics committee, as appropriate.
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paragraphs: (1) Subject to paragraph (2), the Authority shall determine whether the State is willing to be the reporting Member State pursuant to Article 5(1) of the Clinical Trials Regulation, or not, and shall notify any decision to all Member States concerned through the EU Portal.
(2) Before making its determination under paragraph (1), the Authority shall consult with the National Office.
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paragraphs: The Authority shall assess whether the application for authorisation is within the scope of the Clinical Trials Regulation as envisaged by Article 5(3)(a) thereof.
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paragraphs: Subject to the requirements of Regulations 8, 9, and 12, the Authority shall draft Part I of the Assessment Report, and the National Office in conjunction with the nominated ethics committee shall draft Part II of the Assessment Report, and they shall coordinate with each other, as appropriate, to ensure the production of the final Report.
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paragraphs: (1) Subject to paragraph (2), the Authority shall—
(a) review the application in terms of the scientific aspects covered by Part I of the Assessment Report,
(b) draw up Part I of the Assessment Report under Article 6(2) of the Clinical Trials Regulation, and
(c) conclude on the application insofar as Part I of the Assessment Report is concerned, under Article 6(4) of the Clinical Trials Regulation.
(2) In order to assist the Authority in the performance of its functions under paragraph (1)(b) and (1)(c), the nominated ethics committee shall—
(a) review the application in terms of the ethical aspects of the matters covered by Part I of the Assessment Report, and
(b) provide input to the Authority on those ethical aspects, in accordance with Regulation 19 of S.I. No. 41 of 2022 .
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paragraphs: The National Office and the nominated ethics committee shall—
(1) review the application in terms of the matters covered by Part II of the Assessment Report,
(2) draw up part II of the Assessment Report under Article 7(1) of the Clinical Trials Regulation in accordance with Regulation 7, and
(3) conclude on Part II of the Assessment Report under Article 7(2) of the Clinical Trials Regulation.
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paragraphs: (1) In accordance with Article 8(1) or Article 14(3) of the Clinical Trials Regulation, as appropriate, the Authority shall issue an administrative single decision, through the EU portal, as to whether—
(a) a clinical trial is authorised,
(b) a clinical trial is authorised subject to certain conditions, or
(c) authorisation of a clinical trial is refused.
(2) Authorisation of a clinical trial shall be refused pursuant to Article 8(4) or Article 14(10) of the Clinical Trials Regulation, as appropriate, where—
(a) the Authority or the nominated ethics committee disagrees with the reporting Member State’s conclusion as regards Part I of the Assessment Report on any of the grounds stated in the second subparagraph of Article 8(2) or Article 14(4) of the Clinical Trials Regulation, as appropriate,
(b) the nominated ethics committee finds on duly justified grounds, that the aspects addressed in Part II of the Assessment Report are not complied with, or
(c) the nominated ethics committee has issued a negative opinion in relation to the application.
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paragraphs: (1) The Authority shall validate the application for a substantial modification and notify the sponsor of the matters at Article 17(2)(a) and (b) of the Clinical Trials Regulation, where the substantial modification concerns—
(a) an aspect covered by Part I of the Assessment Report as envisaged by Article 17 of the Clinical Trials Regulation, or
(b) aspects covered by Parts I and II of the Assessment Report, as envisaged by Article 21 of the Clinical Trials Regulation.
(2) The National Office in conjunction with the nominated ethics committee shall validate the application and notify the sponsor of the matters at Article 20(1)(a) and (b) of the Clinical Trials Regulation, where the substantial modification concerns an aspect covered by Part II of the Assessment Report.
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paragraphs: The following procedure shall apply in relation to the assessment of an application for authorisation of a substantial modification—
(1) the Authority shall perform the scientific review of the Part I assessment in accordance with Articles 18 and 21, as appropriate, of the Clinical Trials Regulation,
(2) in order for the Authority to conclude on the Part I assessment, the National Office, in conjunction with the nominated ethics committee, shall provide an opinion following ethical review of Part I, pursuant to Article 18 or 21 of the Clinical Trials Regulation and Regulation 19 of S.I. No. 41 of 2022 ;
(3) the Authority shall conclude on the Part I assessment in accordance with Article 19 or 23 of the Clinical Trials Regulation, as appropriate,
(4) the nominated ethics committee shall review and conclude on the Part II assessment in accordance with Article 20 or Article 23 of the Clinical Trials Regulation, as appropriate,
(5) the Authority shall submit an administrative single decision on a substantial modification application for authorisation, in accordance with Articles 19 or 23 of the Clinical Trials Regulation,
(6) the National Office shall submit an administrative single decision on a substantial modification application for authorisation in accordance with Article 20 of the Clinical Trials Regulation.
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paragraphs: (1) In accordance with Article 19(1) of the Clinical Trials Regulation and where the substantial modification concerns an aspect covered by Part I of the Assessment Report, the Authority shall notify the sponsor through the EU portal as to whether—
(a) the substantial modification is authorised,
(b) the substantial modification is authorised subject to certain conditions,
(c) authorisation of the substantial modification is refused.
(2) In accordance with Article 20(5) of the Clinical Trials Regulation and where the substantial modification concerns an aspect covered by Part II of the Assessment Report, the National Office (through the Authority if required by the operation of the EU portal) shall notify the sponsor through the EU portal as to whether—
(a) the substantial modification is authorised,
(b) the substantial modification is authorised subject to conditions allowable under Article 20(5) of the Clinical Trials Regulation,
(c) authorisation of the substantial modification is refused.
(3) In accordance with Article 23(1) of the Clinical Trials Regulation and where the modification concerns an aspect covered by Parts I and II of the Assessment Report, the National Office will co-ordinate with the Authority to ensure that the sponsor is notified of the nominated ethics committee’s decision under Article 22 of the Clinical Trials Regulation, to facilitate notification in accordance with a method prescribed under Article 20(5) of the Clinical Trials Regulation
(4) Authorisation of a substantial modification of an aspect covered by Part I of the Assessment Report shall be refused pursuant to Article 19(2), where—
(a) the Authority or the nominated ethics committee disagrees with the reporting Member State’s conclusions as regards Part I of the Assessment Report, on any of the grounds stated in the second subparagraph of Article 19(2) of the of the Clinical Trials Regulation, or,
(b) the nominated ethics committee has issued a negative opinion in relation to the substantial modification,
(5) Authorisation of a substantial modification of an aspect covered by Part II of the Assessment Report shall be refused pursuant to Article 20(7) of the Clinical Trials Regulation, where—
(a) the nominated ethics committee finds that aspects covered by Part II of the Assessment Report are not complied with, or
(b) the nominated ethics committee has issued a negative opinion in accordance with Article 20(7) of the Clinical Trials Regulation.
(6) Authorisation of a substantial modification of an aspect covered by Part I and Part II of the Assessment Report shall be refused where—
(a) the Authority or nominated ethics committee disagrees with the reporting Member State’s conclusions as regards Part I of the Assessment Report, on any of the grounds stated in the second subparagraph of Article 23(2) of the Clinical Trials Regulation,
(b) the nominated ethics committee finds, on duly justified grounds, that the aspects covered by Part II of the Assessment Report are not complied with, or
(c) the nominated ethics committee has issued a negative opinion in relation to the substantial modification.
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paragraphs: (1) Without prejudice to the Clinical Trials Regulation, a person shall not—
(a) conduct a clinical trial,
(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), or
(c) perform the functions of the investigator of a clinical trial,
in the State, otherwise than in accordance with paragraph (2).
(2) The activities at paragraph 1(a) to (c) shall be conducted in accordance with—
(a) the Clinical Trials Regulation,
(b) these Regulations,
(c) the Declaration of Helsinki,
(d) the authorisation to conduct that clinical trial as notified to the sponsor under Regulation 10 or 13 of these Regulations,
(e) any clinical trial protocol relating to a particular clinical trial,
(f) any particulars or documents, other than the clinical trial protocol, accompanying a clinical trial application, as may be modified from time to time in accordance with Articles 17 to 23 of the Clinical Trials Regulation,
(g) the conditions and principles of good clinical practice, and
(h) any other relevant guidance, including guidance published by the Agency or the European Commission.
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paragraphs: (1) Subject to paragraph (2) and for the purposes of Article 92 of the Clinical Trials Regulation, the sponsor of a clinical trial shall ensure that—
(a) any investigational medicinal products or auxiliary medicinal products used in the clinical trial, and
(b) any medical devices used for the administration of such products,
(2) Paragraph (1) shall not apply to a non-commercial clinical trial conducted by a non-commercial sponsor, except in circumstances where the sponsor has obtained the products or devices referred to in paragraph (1) free of charge, in which case clinical trial subjects shall not bear any cost relating to such products or devices.
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paragraphs: A clinical trial shall not be authorised under these Regulations, or conducted in the State, unless there is in place a policy of insurance or indemnity scheme to provide compensation for any damage suffered by a subject resulting from participation in the clinical trial, which policy or scheme shall be appropriate to the nature and the extent of the risk.
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paragraphs: (1) Subject to paragraph (3), a clinical trial shall not be conducted in the State other than in accordance with the general rules laid down in Article 28 of the Clinical Trials Regulation.
(2) For the purposes of Article 28(1)(d), national law in relation to privacy and data rights of individuals shall also apply, in particular the Data Protection Acts 1988 to 2018.
(3) Article 28(1)(b) and (c), Article 31(1)(a) and (b), and Article 32(1)(a) and (b) of the Clinical Trials Regulation may be derogated from in emergency situations in the manner prescribed by Article 35 of the Clinical Trials Regulation.
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paragraphs: (1) For clinical trials in the State, informed consent shall be given or obtained in accordance with Article 29 of the Clinical Trials Regulation.
(2) For clinical trials in the State, the interview prescribed by Article 29(2)(c) of the Clinical Trials Regulation shall be conducted by the investigator or by—
(a) a registered medical practitioner,
(b) a registered dentist, or
(c) a registered nurse
whose training, experience and qualifications have been assessed by the investigator and determined to be appropriate to qualify him, or her, to conduct the interview.
(3) For the purposes of Article 29(8) of the Clinical Trials Regulation, in addition to the informed consent given by a guardian, a minor who is capable of forming an opinion and assessing the information given to him or her, shall also assent in order to participate in a clinical trial.
(4) For clinical trials which are to be conducted exclusively in the State, the investigator may obtain informed consent by simplified means, in accordance with Article 30 of the Clinical Trials Regulation, provided all conditions therein are met.
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paragraphs: Without prejudice to the general obligations on sponsors and investigators under Article 57 of the Clinical Trials Regulation in relation to the keeping of a clinical trial master file, the clinical trial master file shall—
(1) contain information—
(a) sufficient to demonstrate whether the principles and guidelines of good clinical practice, Annex I and, where applicable, Annex II to the Clinical Trials Regulation, have been complied with, and
(b) which is specific to each phase of the clinical trial,
(2) be readily available for inspection by the Authority and directly accessible upon request, and
(3) form the basis for the Authority’s inspection as envisaged by Article 78 of the Clinical Trials Regulation.
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paragraphs: Without prejudice to the general obligations on sponsors and investigators under Article 58 of the Clinical Trials Regulation in relation to archiving—
(1) the clinical trial master file shall be archived—
(a) for at least 25 years after the end of a clinical trial, or such longer period as may be agreed between the sponsor and investigator, and
(b) in a manner which ensures that it can be made available for inspection by the Authority.
(2) the medical files of trial subjects shall be retained for the maximum period of time permitted or required by the hospital, entity, or private practice at which the trial is conducted.
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paragraphs: The Authority and the National Office in conjunction with the nominated ethics committee shall supervise clinical trials authorised for conduct in the State, and may communicate with each other in regard to same. All such communications shall be confidential.
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paragraphs: The Authority is designated as the competent authority for inspections pursuant to Article 78 of the Clinical Trials Regulation and shall carry out the functions of the competent authority in that regard.
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paragraphs: (1) Subject to paragraphs (3) and (4), where the State is a Member State concerned and the Authority has justified grounds for considering that the requirements set out in the Clinical Trials Regulation are no longer met, the Authority may take any corrective measure set out under Article 77(1) of the Clinical Trials Regulation, in accordance with the procedure set out therein.
(2) Any corrective measure taken by the Authority under paragraph (1) shall be notified by the Authority to the sponsor or investigator and shall specify the date on which the measure shall take effect.
(3) Before the Authority takes a measure under Article 77(1) of the Clinical Trials Regulation, it shall, except where immediate action is required, ask the sponsor or the investigator for their opinion, which opinion shall be delivered within 7 days.
(4) When considering whether the requirements of the Clinical Trials Regulation continue to be met, the Authority may consult with—
(a) the National Office, or
(b) the nominated ethics committee, or
(c) other Member States concerned,
(5) Where a measure is taken by the Authority under Article 77(1) of the Clinical Trials Regulation and paragraph (1) of this Regulation, the Authority shall immediately inform all Member States concerned through the EU portal, in accordance with Article 77(3) of the Clinical Trials Regulation.
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paragraphs: For clinical trials in the State—
(1) investigators and sponsors shall comply with the reporting obligations to which they are subject under Articles 41, 42, and 43 of the Clinical Trials Regulation,
(2) the Authority may, by way of notification, require the sponsor to send it the records referred to in Article 41(3) of the Clinical Trials Regulation, or copies thereof.
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paragraphs: For the purposes of Article 44(2) and (3) of the Clinical Trials Regulation, the Authority—
(1) shall cooperate with other Member States concerned in assessing the information reported under Articles 42 and 43 of the Clinical Trials Regulation, and
(2) may consult with the National Office or the nominated ethics committee in the performance of its obligations under paragraph (1).
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paragraphs: Without prejudice to the obligations on safety reporting under Chapter VII of the Clinical Trials Regulation, the sponsor shall maintain records of all adverse events and serious adverse events relating to a clinical trial which are reported by the investigators for that trial.
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paragraphs: In accordance with Article 61(1) of the Clinical Trials Regulation, the manufacturing and importation of investigational medicinal products shall be subject to the holding of a manufacturer’s authorisation.
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paragraphs: (1) For the purposes of Article 61(5) of the Clinical Trials Regulation, setting out the conditions on which an exemption to the holding of an authorisation may apply—
(a) “pharmacists” means “registered pharmacist” as defined in Regulation 3(1) of these Regulations,
(b) “other persons legally authorised in the Member State concerned” means a registered medical practitioner, or a registered dentist, as defined in Regulation 3(1) of these Regulations, and
(c) a “clinic” includes a retail pharmacy business as defined in the Pharmacy Act 2007 (No. 20 of 2007).
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paragraphs: (1) For the purposes of ensuring safety and reliability and robustness of the data generated in the clinical trial as required by Article 61(6) of the Clinical Trials Regulation, the Authority—
(a) shall maintain a register of processes specified in Article 61(5) of the Clinical Trials Regulation that are undertaken in hospitals, clinics and health centres that are exempt from the requirements of Article 61(1) of the Clinical Trials Regulation, defined as “Register of Exemptions” in Regulation 3(1), and
(b) the Minister may publish guidelines prescribing further appropriate and proportionate requirements as may be required to ensure the objectives of Article 61(6) of the Clinical Trials Regulation are met.
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paragraphs: (1) Subject to paragraph (2), processes specified in Article 61(5) of the Clinical Trials Regulation shall not be carried out unless they have been included on the Register of Exemptions.
(2) Notwithstanding paragraph (1), a process that has not been included on the register specified in Regulation 30, may be carried out if—
(a) the related clinical trial had commenced prior to 31 January 2022 and is being conducted under Directive 2001/20/EC, or
(b) the process relates to a clinical trial conducted under the Clinical Trials Regulation whereby an application to be added to the Register of Exemptions has been submitted to the Authority pursuant to Regulation 32 by 31st of January 2023.
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paragraphs: (1) An application for entry on to the register shall be—
(a) made in writing, in accordance with any form and manner as the Authority at its discretion may require,
(b) signed by or on behalf of the applicant, whether in ink or by means of electronic signature,
(c) accompanied by any fee which may be payable in connection with the application,
(d) subject to Regulation 31, be submitted prior to the intended commencement of the activity.
(2) The applicant shall notify the Authority without delay of any changes to the details of the registered process.
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paragraphs: Following the receipt of an application for entry on the Register of Exemptions, the Authority may carry out an inspection of the process, as determined by risk assessment.
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paragraphs: The Authority may not include a process on the Register of Exemptions where—
(a) conditions for entry on to the register are not satisfied,
(b) the information submitted is false or misleading.
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paragraphs: The Authority may withdraw a registered process from the Register of Exemptions where—
(a) it does not comply with these Regulations or a condition of entry on to the Register of Exemptions,
(b) the applicant requests the withdrawal of the process,
(c) it transpires that the information submitted in the application for entry to the Register of Exemptions is false or misleading.
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paragraphs: (1) An application for the grant of a manufacturer’s authorisation under Article 61 of the Clinical Trials Regulation shall be—
(a) made in writing to the Authority,
(b) signed by or on behalf of the applicant, whether in ink or by means of an electronic signature, and
(c) accompanied by—
(i) a written undertaking that in the event of the authorisation being granted, the applicant will ensure fulfilment of the obligations arising by virtue of the terms and conditions of the authorisation, and
(ii) any fee which may be payable in connection with that application.
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paragraphs: (1) Subject to the provisions of this Regulation, the Authority shall consider a valid application for a manufacturer’s authorisation and grant or refuse to grant same within a period not exceeding 90 days from the date the application is received.
(2) Following receipt of an application, the Authority shall, by means of inspection or otherwise, confirm the accuracy of the particulars provided in the application and may give a notice in writing to the applicant requesting him or her to provide further information relating to the said particulars.
(3) Where the Authority gives a notice pursuant to paragraph (2), the period specified in paragraph (1) shall be suspended from the date the notice is given and shall recommence only on receipt of the information requested.
(4) The expiry of the period of 90 days referred to in paragraph (1) shall not confer any rights on the applicant, and in particular shall not —
(a) confer a default or tacit manufacturer’s authorisation on an applicant, or
(b) be taken to imply that a manufacturer’s authorisation has been granted or will be granted.
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paragraphs: (1) The Authority shall not grant a manufacturer’s authorisation unless it is satisfied that—
(a) the particulars supplied pursuant to Regulation 36 are accurate,
(b) the applicant has—
(i) complied with the requirements of Regulation 36, and of Article 61 of the Clinical Trials Regulation, and
(ii) provided any additional information to the Authority as may have been required under Regulation 37.
(2) Subject to paragraph (1), the Authority may—
(a) grant a manufacturer’s authorisation in respect of any or all of—
(i) the types and pharmaceutical forms of the investigational medicinal product manufactured or imported,
(ii) the premises, and
(iii) the manufacturing or importation operations specified in the application,
(b) grant a manufacturer’s authorisation in accordance with the application, but subject to the carrying out of certain obligations by the authorisation holder,
(c) grant a manufacturer’s authorisation otherwise than in accordance with the application, or
(d) refuse to grant a manufacturer’s authorisation.