What Are the Documents Required for Clinical Trial Applications to Regulatory Authorities in Europe? - Sofpromed (2022)

This is a brief summary of the sections included in the XML CTA:

A. Trial Identification

B. Sponsor Identification

C. Applicant Identification

D. IMP Identification

D. 8 Placebo Information

D. 9 Site(s) where the qualified person certifies batch release

E. General Information on the Trial

F. Population of Trial Subjects

G. Clinical Trial Sites/Investigators in the Member State

H. Competent Authority/Ethics Committee Information

The clinical trial XML file is the building block of the trial application and it will be used to carry out the submission in every participating country.

The regulatory authorities of each EU member state usually have a web-based system or portal used to perform clinical trial application submissions, and these electronic systems require the upload of the completed XML file.

List of Key Documents Required for the Initial Trial Application to the National Regulatory Authority

In short, these are the key documents you will need to submit the initial trial application to the regulatory authority:

  1. Clinical trial application cover letter
  2. Clinical trial application form
  3. Study protocol
  4. Investigator’s Brochure (IB) and/or Summary of Product Characteristics (SmPC)
  5. GMP-related documents (manufacturer/importer authorizations, Qualified Person Declaration)
  6. Investigational Medicinal Product Dossier (IMPD)
  7. Drug labels
  8. Evaluation fees

There might be some study-specific additional documentation to be prepared, but the above list provides an essential checklist for the most important documents.

Let’s proceed to discuss each of these basic pieces of information.

1. Clinical Trial Application Cover Letter

The trial application cover letter is normally completed and generated through the web-based portal of each regulatory authority. In addition, some data expected in the cover letter may already be contained in the EU application form. Then, the information to be included in the cover letter (according to EU guidelines) will be mostly produced electronically.

The cover letter shall specify the EU trial number and the universal trial number and shall draw attention to any particular characteristics of the clinical trial acording to EU instructions (Regulation 536/2014), the cover letter shall include the following aspects:

(a) specific features of the clinical trial population, such as subjects not able to give informed consent, minors and pregnant or breastfeeding women;

(b) whether the clinical trial involves the first administration of a new active substance to humans;

(c) whether scientific advice relating to the clinical trial or the investigational medicinal product has been given by the Agency, a Member State or a third country;

(d) whether the clinical trial is part or is intended to be part of a Paediatric Investigation Plan (PIP) as referred to in Title II, Chapter 3, of Regulation (EC) No 1901/2006 (if the Agency has already issued a decision on the PIP, the cover letter contains the link to the decision of the Agency on its website);

(e) whether investigational medicinal products or auxiliary medicinal products are a narcotic, psychotropic or radiopharmaceutical;

(f) whether the investigational medicinal products consist of or contain a genetically-modified organism or organisms;

(g) whether the sponsor has obtained an orphan designation for the investigational medicinal product for an orphan condition;

(h) a comprehensive list, including the regulatory status, of all investigational medicinal products and a list of all auxiliary medicinal products; and

(i) a list of medical devices which are to be investigated in the clinical trial but which are not part of the investigational medicinal product or products, together with a statement as to whether the medical devices are CE-marked for the intended use.

2. Clinical Trial Application Form

The clinical trial application form is the EU XML file in PDF format. The web portals used to build the CTA and perform the trial submission to competent authorities allow the conversion of the XML contents into the PDF application document.

3. Study Protocol

Based on Regulation (EU) No 536/2014, the protocol shall describe objective, design, methodology, statistical considerations, purpose and organization of the clinical trial.

The protocol shall be identified by:

(a) the title of the clinical trial;

(b) the EU trial number;

(c) the sponsor’s protocol code number specific for all versions of it (if relevant);

(d) the date and number of the version, to be updated when it is amended;

(e) a short title or name assigned to the protocol; and

(f) the name and address of the sponsor, as well as the name and function of the representative or representatives of the sponsor authorized to sign the protocol or any substantial modification to the protocol.

The protocol shall at least include the following information [please note this is an adapted, summarized version of the detailed list included in Regulation (EU) No 536/2014. Refer to the mentioned regulation for the full version of this list]:

(a) a statement that the clinical trial is to be conducted in compliance with the protocol, with EU regulations and with the principles of good clinical practice;

(b) a comprehensive list of all investigational medicinal products and of all auxiliary medicinal products;

(c) a summary of findings from non-clinical studies that potentially have clinical significance and from other clinical trials that are relevant to the clinical trial;

(d) a summary of the known and potential risks and benefits including an evaluation of the anticipated benefits and risks;

(e) where patients were involved in the design of the clinical trial, a description of their involvement;

(f) a description of, and justification for, the dosage, the dosage regime, the route and mode of administration, and the treatment period for all investigational medicinal products and auxiliary medicinal products;

(g) a statement of whether the investigational medicinal products and auxiliary medicinal products used in the clinical trial are authorized;

(h) a description of the groups and subgroups of the subjects participating in the clinical trial;

(i) references to literature and data that are relevant to the clinical trial, and that provide background for the clinical trial;

(j) a discussion of the relevance of the clinical trial;

(k) a description of the type of clinical trial to be conducted and a discussion of the trial design (including a schematic diagram of trial design, procedures and stages, if relevant);

(l) a specification of the primary end-points and the secondary end-points, if any, to be measured during the clinical trial;

(m) a description of the measures taken to minimize bias, including, if applicable, randomization and blinding;

(n) a description of the expected duration of subject participation and a description of the sequence and duration of all clinical trial periods, including follow-up, if relevant;

(o) a clear and unambiguous definition of the end of the clinical trial;

(p) a description of the criteria for discontinuing parts of the clinical trial or the entire clinical trial;

(q) arrangements for the maintenance of clinical trial treatment randomization codes and procedures for breaking codes, if relevant;

(r) a description of procedures for the identification of data to be recorded directly on the Case Report Forms considered as source data;

(s) a description of the arrangements to comply with the applicable rules for the collection, storage and future use of biological samples from clinical trial subjects, where applicable, unless contained in a separate document;

(t) a description of the arrangements for tracing, storing, destroying and returning the investigational medicinal product and unauthorized auxiliary medicinal product;

(u) a description of the statistical methods to be employed, including, if relevant:

— timing of any planned interim analysis and the number of subjects planned to be enrolled;

— reasons for choice of sample size;

— calculations of the power of the clinical trial and clinical relevance;

— the level of significance to be used;

— criteria for the termination of the clinical trial;

— procedures for accounting for missing, unused, and spurious data and for reporting any deviation from the original statistical plan; and

— the selection of subjects to be included in the analyses;

(v) a description of the subject inclusion and exclusion criteria, including criteria for withdrawing individual subjects from treatment or from the clinical trial;

(w) a description of procedures relating to the withdrawal of subjects from treatment or from the clinical trial including procedures for the collection of data regarding withdrawn subjects, procedures for replacement of subjects and the follow-up of subjects that have withdrawn from treatment or from the clinical trial;

(x) a justification for including subjects who are incapable of giving informed consent or other special populations, such as minors;

(y) a justification for the gender and age allocation of subjects and, if a specific gender or age group is excluded from or underrepresented in the clinical trials, an explanation of the reasons and justification for these exclusion criteria;

(z) a detailed description of the recruitment and informed consent procedure, especially when subjects are incapable of giving informed consent;

(aa) a description of the treatments, including medicinal products, which are permitted or not permitted, before or during the clinical trial;

(ab) a description of the accountability procedures for the supply and administration of medicinal products to subjects including the maintenance of blinding, if applicable;

(ac) a description of procedures for monitoring subject compliance, if applicable;

(ad) a description of arrangements for monitoring the conduct of the clinical trial;

(ae) a description of the arrangements for taking care of the subjects after their participation in the clinical trial has ended, where such additional care is necessary because of the subjects’ participation in the clinical trial and where it differs from that normally expected for the medical condition in question;

(af) a specification of the efficacy and safety parameters as well as the methods and timing for assessing, recording, and analysing these parameters;

(ag) a description of ethical considerations relating to the clinical trial if those have not been described elsewhere;

(ah) a statement from the sponsor (either in the protocol or in a separate document) confirming that the investigators and institutions involved in the clinical trial are to permit clinical trial-related monitoring, audits and regulatory inspections, including provision of direct access to source data and documents;

(ai) a description of the publication policy;

(aj) duly substantiated reasons for the submission of the summary of the results of the clinical trials after more than one year;

(ak) a description of the arrangements to comply with the applicable rules on the protection of personal data;

(al) a description of measures that will be implemented to ensure confidentiality of records and personal data of subjects;

(am) a description of measures that will be implemented in case of data security breach.

The protocol shall also describe the procedures for:

(a) eliciting and recording adverse events by the investigator, and the reporting of relevant adverse events by the investigator to the sponsor;

(b) reporting by the investigator to the sponsor of those serious adverse events which have been identified in the protocol as not requiring immediate reporting;

(c) reporting of suspected unexpected serious adverse reactions by the sponsor to the Eudravigilance database; and

(d) follow-up of subjects after adverse reactions including the type and duration of follow-up.

4. Investigator’s Brochure (IB) and/or Summary of Product Characteristics (SmPC)

In the context of a clinical trial, regulatory authorities require the submission of the investigator’s brochure (IB) and/or the Summary of Product Characteristics (SmPC) of the drugs under investigation.

According to Annex I of Regulation (EU) No 536/2014 (Section E; 26, 27, 28):

“The purpose of the IB is to provide the investigators and others involved in the clinical trial with information to facilitate their understanding of the rationale for, and their compliance with, key features of the protocol, such as the dose, dose frequency/interval, methods of administration, and safety monitoring procedures.

The information in the IB shall be presented in a concise, simple, objective, balanced and non-promotional form that enables a clinician or investigator to understand it and make an unbiased risk-benefit assessment of the appropriateness of the proposed clinical trial. It shall be prepared from all available information and evidence that supports the rationale for the proposed clinical trial and the safe use of the investigational medicinal product in the clinical trial and be presented in the form of summaries.

If the investigational medicinal product is authorised, and is used in accordance with the terms of the marketing authorisation, the approved summary of product characteristics (SmPC) shall be the IB. If the conditions of use in the clinical trial differ from those authorised, the SmPC shall be supplemented with a summary of relevant non-clinical and clinical data that support the use of the investigational medicinal product in the clinical trial. Where the investigational medicinal product is identified in the protocol only by its active substance, the sponsor shall select one SmPC as equivalent to the IB for all medicinal products that contain that active substance and are used at any clinical trial site.”

5. GMP-related Documents (Manufacturer/Importer Authorizations, Qualified Person Declaration)

Regarding the documents related to GMP compliance of the drug product to be used in the clinical trial, no documentation is to be submitted to the regulatory authority if the drug is authorized in the EU and is not modified, whether or not it is manufactured in Europe.

If the investigational medicinal product (IMP) is not authorized in the EU, and is not manufactured in Europe, the following documents will be required:

(a)A copy of the importer/manufacturer authorization: This is an authorization granted by EU national regulatory authorities to the local companies (e.g. depots, CDMOs) in charge of drug product import, manufacturing, testing, and handling.

(b)QP Declaration: A certification by the qualified person (QP) in the EU that the manufacturing complies with GMP at least equivalent to the GMP in Europe. For more information about the QP Declaration, please read this article.

In all other cases, a copy of the manufacturer authorization shall be submitted.

6. Investigational Medicinal Product Dossier (IMPD)

The IMPD is a very important document that provides data on the quality of IMPs, including drug substance and drug product manufacturing, testing, analysis, and control aspects, as well as data related to non-clinical and clinical studies.

Quality data shall be submitted according to the Guideline on the requirements for the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials.

The IMPD shall also contain summaries of non-clinical pharmacology and toxicology data for any investigational medicinal product used in the clinical trial. It shall contain a reference list of studies conducted and appropriate literature references.

Non-clinical pharmacology and toxicology data shall be submitted in a logical structure, such as that of Module 4 of the ICH Common Technical Document format.

Data from previous clinical trials and human experience shall be submitted according to Module 5 of the ICH Common Technical Document format.

The IMPD will also include an overall risk and benefit assessment in the form of a summary that critically evaluates the non-clinical and clinical data in relation to the potential risks and benefits of the investigational medicinal product in the proposed clinical trial unless this information is already provided in the protocol.

7. Drug Labels

Study drug label designs must be submitted to regulatory authorities when sending the clinical trial application.

Following the general rules of Annex VI (EU Regulation 536/2014) for unauthorized IMPs (section A.1), this information must appear on the immediate and the outer packaging of the drug:

(a) name, address and telephone number of the main contact for information on the product, clinical trial and emergency unblinding; this may be the sponsor, contract research organisation or investigator (for the purpose of this Annex this is referred to as the ‘main contact’);

(b) the name of the substance and its strength or potency, and in the case of blind clinical trials the name of the substance is to appear with the name of the comparator or placebo on the packaging of both the unauthorised investigational medicinal product and the comparator or placebo;

(c) pharmaceutical form, route of administration, quantity of dosage units;

(d) the batch or code number identifying the contents and packaging operation;

(e) a clinical trial reference code allowing identification of the trial, site, investigator and sponsor if not given elsewhere;

(f) the subject identification number and/or the treatment number and, where relevant, the visit number;

(g) the name of the investigator (if not included in (a) or (e));

(h) directions for use (reference may be made to a leaflet or other explanatory document intended for the subject or person administering the product);

(i) ‘For clinical trial use only’ or similar wording;

(j) the storage conditions;

(k) period of use (expiry date or re-test date as applicable), in month and year format and in a manner that avoids any ambiguity; and

(l) ‘Keep out of reach of children’, except when the product is for use in trials where the product is not taken home by subjects.

8. Evaluation Fees

Finally, regulatory authorities will normally charge fees for the efforts made to evaluate a clinical trial application. Different prices may apply depending on the characteristics of the clinical study. For instance, you can check the fees of the Spanish regulatory authority (Spanish Agency of Medicines and Medical Devices, AEMPS) in the image below.

FAQs

What are the documents required for clinical trials? ›

The essential documents for clinical trials are the following: Investigator's Brochure. Clinical Study Protocol. Subject Information and Informed Consent Form.
...
CLINICAL STUDY PROTOCOL
  • Study Plan.
  • Study schedule.
  • Study Visits.
  • Study Assessments / Procedures.
  • Definition of efficacy endpoints.
  • Treatment cycles.

What is included in a clinical trial application? ›

A Clinical Trial Application provides comprehensive information about the investigational medicinal product(s) and planned trial, enabling regulatory authorities to assess the acceptability of conducting the study.

What is clinical trial authorization application? ›

A Clinical Trials Application (CTA) is the application/submission to the competent National. Regulatory Authority(ies) for authorization to conduct a clinical trial in a specific country.

What are essential documents in GCP? ›

Essential documents are commonly referred to as regulatory documents. ICH GCP guidance defines essential documents as “those documents which individually and collectively permit evaluation of the conduct of the clinical trial and the quality of the data produced.

What is clinical trial regulatory? ›

The Clinical Trials Regulation harmonises the processes for assessment and supervision of clinical trials throughout the EU. The evaluation, authorisation and supervision of clinical trials are the responsibilities of EU Member States and European Economic Area (EEA) countries.

What are the regulatory documents? ›

Regulatory Documents means all dossiers, filings, applications, modifications, amendments, supplements, revisions, reports, submissions, authorizations and approvals, including any IND or NDA, and any reports or amendments necessary to maintain Regulatory Approvals.

What are the essential documents? ›

Essential documents are those documents that individually and collectively allow the evaluation of the conduct of a trial and the quality of the data generated.
...
References
  • Case Record Form (CRF)
  • Informed Consent Documents (ICD)
  • Investigator's Brochure (IB)
  • Trial Master File (TMF)
  • Laboratory Related Documents.

What are the documents required for clinical trial applications to regulatory authorities in Europe? ›

The key documents for a clinical trial application to regulatory authorities in the EU are: the cover letter, the application form, the study protocol, the IB/SmPC, the manufacturer/importer authorizations, the Qualified Person Declaration, the IMPD, the drug labels, and the evaluation fees (payment receipts).

What is the equivalent of an IND in Europe? ›

In the United States, the initial submission to permit use of an investiga- tional drug in a clinical setting is called an investigational new drug (IND) application. In the European Union, this documen- tation is submitted within a clinical trial application (CTA).

Which FDA Act permits clinical trials to be conducted internationally? ›

Under the Food and Drug Administration Safety and Innovation Act of 2012, the FDA is required to accept data from overseas trials to approve or clear a device as long as it was collected in conformance with good clinical practice, the Regulatory Affairs Professional Society points out.

Who approves clinical trials in EU? ›

In Europe clinical trial approval is granted by a regulatory authority and requires favourable opinion by a Research Ethics Committee (REC). The CT Directive set out the minimum requirements for clinical trials with a specific sub-category of medicines called 'investigational medicinal products' (IMPs).

What is EU CTR regulation? ›

he European Union Clinical Trial Regulation 536/2014 (EU-CTR) aims to standardize and harmonize the conduct and management of interventional clinical trials across the European Economic Area (EEA), with legally binding rules on requirements and increased transparency.

Is clinical trials Authorisation required? ›

All clinical trials of medicines and studies on medical devices also need to be authorised by the Medicines and Healthcare Products Regulatory Agency (MHRA). This is called Clinical Trial Authorisation (CTA).

Why documentation is important in clinical trials? ›

The most important purpose of source documentation in a clinical trial is to reconstruct the trial as it happened. It should enable an independent observer to reconfirm the data. Documentation should be such that it is able to provide audit trail to permit investigation if and when required.

What documents are in a trial master file? ›

Includes site selection, set-up, initiation, management and general information. Consists of safety documentation, trial status reporting and general safety reports. Includes oversight, capture, database, electronic data capture management and general data management sections.

What are the purposes of filing essential documents? ›

Essential documents serve to demonstrate compliance with the standards of Good Clinical Practice (GCP) and with all applicable regulatory requirements. These document files may be audited by the sponsor and regulatory authorities to confirm the validity of the clinical research conduct and integrity of the data.

What is regulatory approval process? ›

For the purposes of clinical trials, regulatory approvals include any approvals by government or health authorities regarding any research that includes human subjects. Additional approvals will be necessary if the research involves the use of an FDA regulated product.

What regulatory approval is needed before conducting a human clinical trial? ›

Role in Clinical Trial Approval Process

In accordance with 21CFR56 and 21CFR312, the Food & Drug Administration (FDA) must review an investigational new drug application (IND) and an EC must review and approve the proposed study prior to a sponsor initiating a clinical trial.

What is being replaced by the EU clinical trials regulation? ›

Effective 31 January 2022, a new regulation designed to simplify and harmonise clinical trials in the EU begins replacing EU-CTD. EU Clinical Trial Regulation 536/2014 (EU-CTR) aims to overcome EU-CTD's shortcomings.

What are the 3 main GCP principles? ›

Subject's Rights, Safety, and Bell-Being. ICH GCP Principle 3 states that the rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.

What is export regulatory documents? ›

(a) Regulatory Documents:

Refers to the pre-shipment documents prescribed by the exporting country. The compliance of these documents is mandatory for an export contract.

What are the commercial documents? ›

Commercial documents
  • Sales contract. The sales contract is the initial document that specifies the seller's obligation to deliver the agreed-upon goods and the buyer's obligation to pay for them. ...
  • Pro forma invoice. ...
  • Commercial invoice. ...
  • Packing list. ...
  • Letter of credit. ...
  • Certificate of insurance.
7 Jul 2020

What are the five source documents? ›

Some examples of source documents include:
  • Bank Statements.
  • Payroll Reports.
  • Invoices.
  • Leases & Contracts.
  • Check Registers.
  • Purchase Orders.
  • Deposit Slips – not included on a bank statement.
  • Check Copies – not included on a bank statement.
20 Jan 2017

Who of the following must maintain essential documents when involved in a clinical trial? ›

The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

Which of the following is the primary European law for the EU directive? ›

Treaties are the starting point for EU law and are known in the EU as primary law. The body of law that comes from the principles and objectives of the treaties is known as secondary law; and includes regulations, directives, decisions, recommendations and opinions.

Why is it important to have regulations implemented for clinical trials? ›

It promotes more transparent research, helps to maintain the validity of evidence based medicine and availability of reliable data for the meta-analysis. Therefore, the implementation of these regulations is intended to safe guard the integrity of clinical research.

How many volumes are there in EudraLex? ›

Volumes. EudraLex consists of 10 volumes: Concerning Medicinal Products for Human use: Volume 1 - Pharmaceutical Legislation.

Is FDA approval required in Europe? ›

The FDA must approve all high-risk medical devices in the United States, but in Europe, some high-risk devices, such as those that are not intended for “distribution and/or use on the Community Market,” are not approved under the Medical Devices Directive.

What is the difference between EU and FDA approval? ›

The FDA historically developed as a consumer protection agency, whereas the regulations from the European Commission arose out of a need to harmonize inter-state commercial interests while preserving national "autonomy." Thus, whereas the FDA has the advantages of centralization and common rules, the European Union ...

Does FDA accept foreign clinical trials? ›

Food and Drug Administration (FDA) regulations permit the acceptance of foreign clinical studies in support of an application for marketing approval of a human drug, biological product, or device if certain conditions are met.

Can you do clinical trials abroad? ›

If a suitable trial is taking place in your country, it is best to try and join it there. Some trials take place in many countries because they can recruit the patients more quickly that way. This is particularly important for rare cancers. You could try looking at overseas trial information databases.

Can foreigners participate in US clinical trials? ›

The NIH Clinical Center conducts clinical research on a broad spectrum of diseases and health problems. On occasion, NIH accepts international patients as clinical research participants.

How many clinical trials are in Europe? ›

In the EU / EEA, approximately 4,000 clinical trials are authorised each year.

Who is competent authority in Europe? ›

A Competent Authority belongs to the government of a Member State of the European Union (EU) and is responsible for transposing the requirements of European regulations into national legislation.

How many clinical trials are conducted in the EU annually? ›

Every year, some 4000 clinical trials are authorised in the EU.

How long is the EU CTR transition period? ›

The CTR foresees a three-year transition period. Member States will work in CTIS immediately after the system has gone live.

When did EU Ctr take effect? ›

The updated European Union (EU) pharmaceutical legislation for the Clinical Trials Regulation (CTR) entered into application on January 1, 2022. The CTR aligns processes for the assessment and supervision of clinical trials throughout the EU.

What is Regulation EU No 536 2014? ›

Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16th April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC [1], establishes a new set of harmonised rules that all member states are required to apply in all clinical trials performed throughout ...

What is included in a clinical trial application? ›

A Clinical Trial Application provides comprehensive information about the investigational medicinal product(s) and planned trial, enabling regulatory authorities to assess the acceptability of conducting the study.

What are clinical trial regulations? ›

Per law, it is mandatory that all clinical research that falls under the ambit of Schedule Y complies with the necessary requirements. It has 12 appendices, formats for clinical trial protocols, informed consent forms, ethics committee (EC) approval templates and a format for serious adverse event (SAE) reporting.

Who approves a clinical trial protocol? ›

Each federally supported or conducted clinical study and each study of a drug, biological product, or medical device regulated by FDA must be reviewed, approved, and monitored by an institutional review board (IRB). An IRB is made up of doctors, researchers, and members of the community.

What are the documents required for clinical trials? ›

The essential documents for clinical trials are the following: Investigator's Brochure. Clinical Study Protocol. Subject Information and Informed Consent Form.
...
CLINICAL STUDY PROTOCOL
  • Study Plan.
  • Study schedule.
  • Study Visits.
  • Study Assessments / Procedures.
  • Definition of efficacy endpoints.
  • Treatment cycles.

What are source documents for clinical trials? ›

Common source documents are participant medical records, phone encounters or notes, lab and diagnostic test results, participant diaries and specific research worksheets used to document key research data elements. If data are entered directly into a computer system, the electronic record is considered the source.

What are the essential documents? ›

Essential documents are those documents that individually and collectively allow the evaluation of the conduct of a trial and the quality of the data generated.
...
References
  • Case Record Form (CRF)
  • Informed Consent Documents (ICD)
  • Investigator's Brochure (IB)
  • Trial Master File (TMF)
  • Laboratory Related Documents.

What is the difference between TMF and ISF? ›

PAID MESSAGE – The Trial Master File (TMF) is held by the sponsor and represents the story of the study of the study. The Investigator Site File (ISF) is held by the site and represents the story of the study at the site.

What is a trial master file in clinical research? ›

A Trial Master File (TMF) is a collection of all essential trial documentation that enables effective monitoring, data integrity, and compliance throughout the lifecycle of a clinical trial. Because the TMF confirms regulatory compliance, it is integral to clinical trial success.

What is TMF full form? ›

Trial Master File (TMF) – Clinical Trial Medical Monitoring Plan | Online Clinical Research Courses In India.

What are clinical regulatory documents? ›

Resources permitting evaluation of the conduct of a clinical trial and the quality of produced data. Essential documents are commonly referred to as regulatory documents.

What are the regulatory documents? ›

Regulatory Documents means all dossiers, filings, applications, modifications, amendments, supplements, revisions, reports, submissions, authorizations and approvals, including any IND or NDA, and any reports or amendments necessary to maintain Regulatory Approvals.

Who is responsible for final approval on trial and process documents? ›

1 The investigator/institution should conduct the trial in compliance with the protocol agreed to by the sponsor and, if required, by the regulatory authority(ies) and which was given approval/favourable opinion by theIRB/IEC.

What are the 3 phases of FDA approval? ›

Phase 1 studies (typically involve 20 to 80 people). Phase 2 studies (typically involve a few dozen to about 300 people). Phase 3 studies (typically involve several hundred to about 3,000 people). The pre-NDA period, just before a new drug application (NDA) is submitted.

What is regulatory permission? ›

The Regulatory Permissions are the only permissions and permits required by the Regulated Companies in order to carry on their business as presently conducted and each Regulated Company has, at all material times, held and (so far as the Seller is aware) complied with all permissions and permits required from all ...

What are the documents required for clinical trial applications to regulatory authorities in Europe? ›

The key documents for a clinical trial application to regulatory authorities in the EU are: the cover letter, the application form, the study protocol, the IB/SmPC, the manufacturer/importer authorizations, the Qualified Person Declaration, the IMPD, the drug labels, and the evaluation fees (payment receipts).

Who approves clinical trials in EU? ›

In Europe clinical trial approval is granted by a regulatory authority and requires favourable opinion by a Research Ethics Committee (REC). The CT Directive set out the minimum requirements for clinical trials with a specific sub-category of medicines called 'investigational medicinal products' (IMPs).

What is EU CTR regulation? ›

he European Union Clinical Trial Regulation 536/2014 (EU-CTR) aims to standardize and harmonize the conduct and management of interventional clinical trials across the European Economic Area (EEA), with legally binding rules on requirements and increased transparency.

What is the equivalent of an IND in Europe? ›

In the United States, the initial submission to permit use of an investiga- tional drug in a clinical setting is called an investigational new drug (IND) application. In the European Union, this documen- tation is submitted within a clinical trial application (CTA).

What documents are in a trial master file? ›

Includes site selection, set-up, initiation, management and general information. Consists of safety documentation, trial status reporting and general safety reports. Includes oversight, capture, database, electronic data capture management and general data management sections.

Why documentation is important in clinical trials? ›

The most important purpose of source documentation in a clinical trial is to reconstruct the trial as it happened. It should enable an independent observer to reconfirm the data. Documentation should be such that it is able to provide audit trail to permit investigation if and when required.

Who is responsible to prepare essential documents like protocol? ›

#9. Whose responsibility is to prepare essential documents like protocol/ investigators brochure/ informed consent form/ case report form in clinical trials?
  • Investigator.
  • Ethics committee.
  • Scientist.
  • Sponsor.

How can I get HRA approval? ›

If your project is eligible for HRA Approval there are four main steps that should be completed in the following order: Complete a research application form on the Integrated Research Application System (IRAS) Prepare your study documents. Book your application in through the Online Booking Service.

What is the difference between TMF and ISF? ›

PAID MESSAGE – The Trial Master File (TMF) is held by the sponsor and represents the story of the study of the study. The Investigator Site File (ISF) is held by the site and represents the story of the study at the site.

What is a trial master file in clinical research? ›

A Trial Master File (TMF) is a collection of all essential trial documentation that enables effective monitoring, data integrity, and compliance throughout the lifecycle of a clinical trial. Because the TMF confirms regulatory compliance, it is integral to clinical trial success.

What is TMF full form? ›

Trial Master File (TMF) – Clinical Trial Medical Monitoring Plan | Online Clinical Research Courses In India.

What are good documentation practices standards? ›

Good Documentation Practice Standards

It requires that documentation must be created and retained to provide a traceable, historical record of all activities as well as be readily accessible for product investigations, periodic product reviews, or any internal or external (e.g., FDA, EMA) audits.

Why are paper forms considered as source documents? ›

A source document is an original record which contains the detail that supports or substantiates a transaction that will be (or has been) entered in an accounting system. In the past, source documents were printed on paper. Today, the source documents may be an electronic record.

Which two elements are major causes of documentation problems? ›

Documentation suffers from a number of potential problems:
  • Expensive, time-consuming; the cost of the documentation may outstrip its value.
  • Written by people who can't write or who don't know the material.
  • Hard to read; too dry, too terse.
  • Vague; not clear.
  • Incomplete.
  • Assumes knowledge readers don't possess.

Who prepares essential documents in clinical trials? ›

The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.

Who is responsible for final approval on trial and process documents? ›

1 The investigator/institution should conduct the trial in compliance with the protocol agreed to by the sponsor and, if required, by the regulatory authority(ies) and which was given approval/favourable opinion by theIRB/IEC.

Who provides approval for conducting clinical trials? ›

As set forth in the 2019-CTRules and the Hdbk-ClinTrial, the Central Drugs Standard Control Organization (CDSCO) is the regulatory authority responsible for clinical trial oversight, approval, and inspections in India.

How long does Ira application take? ›

How long does IRAS approval take? IRAS applications involve several stages: application development, internal ethical approval, confirmation of indemnity, REC review and contractual collaboration arrangements. Combined these can take approximately three months.

How do I submit my IRA application? ›

Clicking on "Proceed to Submission" under the Submission tab will store the application in your Submission History in IRAS and generate a submission code, which will appear at the foot of each page of the form for reference. You will then be able to save and/or print the completed form for submission.

How long does it take to get HRA approval? ›

The Committee must notify you of their decision within 60 calendar days of receiving your valid application and 21 days for studies accepted for proportionate review. After meeting, you will be notified of the REC's decision, usually within 10 working days.

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