0A4F4F9BD490A749D5437F821CF06DF1
Commission Directive 2005/28/EC
https://ec.europa.eu/health//sites/health/files/files/eudralex/vol-1/dir_2005_28/dir_2005_28_en.pdf
http://leaux.net/URLS/ConvertAPI Text Files/9E87382565B6FC8E1A9E65BEF1D6AC20.en.txt
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| Indicators in focus are typically shown highlighted in yellow; |
Peer Indicators (that share the same Vulnerability association) are shown highlighted in pink; |
"Outside" Indicators (those that do NOT share the same Vulnerability association) are shown highlighted in green; |
Trigger Words/Phrases are shown highlighted in gray. |
Link to Orphaned Trigger Words (Appendix (Indicator List, Indicator Peers, Trigger Words, Type/Vulnerability/Indicator Overlay)
Applicable Type / Vulnerability / Indicator Overlay for this Input
Health / Mentally Incapacitated
Searching for indicator incapable:
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p.(None):
p.(None):
p.(None): (8) The International Conference on Harmonisation (ICH) reached a consensus in 1995 to provide a
p.(None): harmonised approach for Good Clinical Practice. The consensus paper should be taken into account as agreed upon
p.(None): by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency,
p.(None): hereinafter ‘the Agency’, and published by the Agency.
p.(None):
p.(None): L 91/14 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None): (9) It is necessary that sponsors, investigators and other participants take into account the
p.(None): scientific guidelines relating to the quality, safety and efficacy of medicinal products for human use, as
p.(None): agreed upon by the CHMP and published by the Agency, as well as the other phar- maceutical Community
p.(None): guidelines published by the Commission in the different volumes of The rules governing
p.(None): medicinal products in the European Community.
p.(None):
p.(None):
p.(None):
p.(None): (10) In conducting clinical trials on investigational medicinal products for human use, the safety and the
p.(None): protection of the rights of trial subjects should be ensured. The detailed rules adopted by Member States pursuant to
p.(None): Article 3(1) of Directive 2001/20/EC, to protect from abuse indi- viduals who are incapable of giving
p.(None): their informed consent should also cover individuals temporarily incapable of giving their
p.(None): informed consent, as in emergency situations.
p.(None):
p.(None):
p.(None):
p.(None): (11) Non-commercial clinical trials conducted by researchers without the participation of the
p.(None): pharmaceutical industry may be of great benefit to the patients concerned. Directive 2001/20/EC
p.(None): recognises the specificity of these non-commercial clinical trials. In particular, when trials are conducted
p.(None): with authorised medicinal products and on patients with the same characteristics as those covered by the authorised
p.(None): indication, requirements already fulfilled by these authorised medicinal products, as far as manu- facturing
p.(None): or importation are concerned, should be taken into consideration. However, it could also be necessary,
p.(None): due to the specific conditions under which non- commercial trials are conducted, that Member
p.(None): States foresee specific modalities to be applied to these trials not only when conducted with
p.(None): authorised medicinal products and on patients with the same characteristics, in order to comply with the
p.(None): principles imposed by this Directive, in particular as far as the manufacturing or import requirements for
p.(None): authorisation and the documen- tation to be submitted and archived for the trial master file are concerned.
p.(None): The conditions under which the non- commercial research is conducted by public researchers and the places where
p.(None): this research takes place, make the application of certain of the details of good clinical practice
...
Social / Access to Social Goods
Searching for indicator access:
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p.(None): at a later date.
p.(None):
p.(None):
p.(None): 2. An authorisation shall apply only to the premises specified in the application and to the types of
p.(None): medicinal products and pharmaceutical forms specified in that application pursuant to point (a) of Article
p.(None): 10(1).
p.(None):
p.(None):
p.(None): Article 13
p.(None): The holder of the authorisation shall at least comply with the following requirements:
p.(None):
p.(None):
p.(None): (a) to have at his disposal the services of staff that comply with the legal requirements existing in the
p.(None): Member State concerned both as regards manufacture and controls;
p.(None):
p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/17
p.(None):
p.(None):
p.(None): (b) to dispose of the investigational/authorised medicinal products only in accordance with the
p.(None): legislation of the Member State concerned;
p.(None):
p.(None):
p.(None): (c) to give prior notice to the competent authority of any changes he may wish to make to any of the
p.(None): particulars supplied pursuant Article 10(1) and, in particular, to inform the competent
p.(None): authority immediately if the qualified person referred to in Article 13(2) of Directive 2001/20/EC is
p.(None): replaced unexpectedly;
p.(None):
p.(None):
p.(None): (d) to allow agents of the competent authority of the Member State concerned access to his premises at
p.(None): any time;
p.(None):
p.(None):
p.(None): (e) to enable the qualified person referred to in Article 13(2) of Directive 2001/20/EC to carry out his duties,
p.(None): for example by placing at his disposal all the necessary facilities;
p.(None):
p.(None):
p.(None): (f) to comply with the principles and guidelines for good manufacturing practice for medicinal
p.(None): products as laid down by Community law.
p.(None):
p.(None):
p.(None): Detailed guidelines in line with the principles referred to in point (f) of the first paragraph
p.(None): will be published by the Commission and revised where necessary to take account of technical and
p.(None): scientific progress.
p.(None):
p.(None):
p.(None): Article 14
p.(None): If the holder of the authorisation requests a change in any of the particulars referred to in points
p.(None): (a) to (e) of Article 10(1), the time taken for the procedure relating to the request shall not exceed
p.(None): 30 days. In exceptional cases, this period of time may be extended to 90 days.
p.(None):
p.(None):
p.(None): Article 15
p.(None): The competent authority shall suspend or revoke the authori- sation, as a whole or in part, if the holder of
p.(None): the authorisation fails at any time to comply with the relevant requirements.
p.(None):
p.(None):
p.(None): CHAPTER 4
p.(None): THE TRIAL MASTER FILE AND ARCHIVING
p.(None): Article 16
p.(None): The documentation referred to Article 15(5) of Directive 2001/20/EC as the trial master file shall
p.(None): consist of essential documents, which enable both the conduct of a clinical trial and the quality of the
...
p.(None): 2001/83/EC.
p.(None):
p.(None): The trial master file shall provide the basis for the audit by the sponsor’s independent auditor and for the
p.(None): inspection by the competent authority.
p.(None):
p.(None): The content of the essential documents shall be in accordance with the specificities of each phase of
p.(None): the clinical trial.
p.(None):
p.(None): The Commission shall publish additional guidance in order to specify the content of these documents.
p.(None):
p.(None): Article 17
p.(None): The sponsor and the investigator shall retain the essential documents relating to a clinical trial
p.(None): for at least five years after its completion.
p.(None):
p.(None): They shall retain the documents for a longer period, where so required by other applicable requirements
p.(None): or by an agreement between the sponsor and the investigator.
p.(None):
p.(None): Essential documents shall be archived in a way that ensures that they are readily available, upon request, to the
p.(None): competent autho- rities.
p.(None):
p.(None): The medical files of trial subjects shall be retained in accordance with national legislation and in accordance
p.(None): with the maximum period of time permitted by the hospital, institution or private practice.
p.(None):
p.(None): Article 18
p.(None): Any transfer of ownership of the data or of documents shall be documented. The new owner shall assume
p.(None): responsibility for data retention and archiving in accordance with Article 17.
p.(None):
p.(None): Article 19
p.(None): The sponsor shall appoint individuals within its organisation who are responsible for archives.
p.(None):
p.(None): Access to archives shall be restricted to the named individuals responsible for the archives.
p.(None):
p.(None): Article 20
p.(None): The media used to store essential documents shall be such that those documents remain complete and legible
p.(None): throughout the required period of retention and can be made available to the competent authorities upon
p.(None): request.
p.(None):
p.(None): Any alteration to records shall be traceable.
p.(None):
p.(None): L 91/18 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None):
p.(None): CHAPTER 5
p.(None): INSPECTORS
p.(None): Article 21
p.(None): 1. The inspectors, appointed by the Member States pursuant to Article 15(1) of Directive 2001/20/EC, shall
p.(None): be made aware of and maintain confidentiality whenever they gain access to confidential information as a
p.(None): result of good clinical practice inspections in accordance with applicable Community requirements,
p.(None): national laws or international agreements.
p.(None):
p.(None): 2. Member States shall ensure that inspectors have completed education at university level, or have
p.(None): equivalent experience, in medicine, pharmacy, pharmacology, toxicology or other relevant fields.
p.(None):
p.(None): 3. Member States shall ensure that inspectors receive appro- priate training, that their training needs
p.(None): are assessed regularly and that appropriate action is taken to maintain and improve their skills.
p.(None):
p.(None): Member States shall also ensure that the inspectors have knowledge of the principles and processes
p.(None): that apply to the development of medicinal products and clinical research. Inspectors shall
p.(None): also have knowledge of applicable Community and national legislation and guidelines applicable to
p.(None): the conduct of clinical trials and the granting of marketing authorisations.
p.(None):
p.(None): The inspectors shall be familiar with the procedures and systems for recording clinical data, and with the organisation
p.(None): and regu- lation of the healthcare system in the relevant Member States and, where appropriate, in third
p.(None): countries.
p.(None):
p.(None): 4. Member States shall maintain up-to-date records of the qualifications, training and experience of
p.(None): each inspector.
p.(None):
p.(None): 5. Each inspector shall be provided with a document setting out standard operating procedures and giving
...
p.(None):
p.(None): (a) before, during or after the conduct of clinical trials;
p.(None):
p.(None): (b) as part of the verification of applications for marketing authorisation;
p.(None):
p.(None): (c) as a follow-up to the granting of authorisation.
p.(None):
p.(None): 2. In accordance with Article 15(1) and (2) of Directive 2001/20/EC, inspections may be requested and
p.(None): coordinated by the European Medicines Agency within the scope of Regu- lation (EC) No 726/2004 of the
p.(None): European Parliament and of the Council (1), especially in connection with clinical trials relating to
p.(None): applications through the procedure established by this Regu- lation.
p.(None):
p.(None): 3. Inspections shall be conducted in accordance with the inspection guidance documents developed to
p.(None): support the mutual recognition of inspection findings within the Community.
p.(None):
p.(None): 4. Improvement and harmonisation of inspection guidance shall be achieved by the Member States, in
p.(None): collaboration with the Commission and the Agency, through joint inspections, agreed processes and procedures
p.(None): and sharing of experience and training.
p.(None):
p.(None): Article 24
p.(None): Member States shall make publicly available within their terri- tories the documents relating to the
p.(None): adoption of good clinical practice principles.
p.(None):
p.(None): They shall establish the legal and administrative framework within which their good clinical practice
p.(None): inspections operate, with definition of the powers of inspectors for entry into clinical trial sites and
p.(None): access to data. In so doing they shall ensure that, on request and where appropriate, inspectors of the
p.(None): competent authority of the other Member States also have access to the clinical trial sites and data.
p.(None): In order to ensure the presence of skills necessary for specific
p.(None):
p.(None): inspections, Member State may appoint teams of inspectors and
p.(None): (1) OJ L 136, 30.4.2004, p. 1.
p.(None):
p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/19
p.(None):
p.(None):
p.(None): Article 25
p.(None): Member States shall provide for sufficient resources and shall in particular appoint an adequate number of
p.(None): inspectors to ensure effective verification of compliance with good clinical practice.
p.(None):
p.(None): Article 26
p.(None): Member States shall establish the relevant procedures for veri- fication of good clinical practice
p.(None): compliance.
p.(None):
p.(None): The procedures shall include the modalities for examining both the study management procedures and the conditions
p.(None): under which clinical trials are planned, performed, monitored and recorded, as well as follow-up measures.
p.(None):
p.(None): Article 27
p.(None): Member States shall establish the relevant procedures for the following:
p.(None):
p.(None): (a) appointing experts for accompanying inspectors in case of need;
p.(None):
p.(None): (b) requesting inspections/assistance from other Member States, in line with Article 15(1) of Directive
p.(None): 2001/20/EC and for cooperating in inspections in another Member State;
p.(None):
p.(None): (c) arranging inspections in third countries.
p.(None):
p.(None): Article 28
p.(None): Member States shall maintain records of national and, if applicable, international inspections
...
Social / Incarcerated
Searching for indicator restricted:
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p.(None): inspection by the competent authority.
p.(None):
p.(None): The content of the essential documents shall be in accordance with the specificities of each phase of
p.(None): the clinical trial.
p.(None):
p.(None): The Commission shall publish additional guidance in order to specify the content of these documents.
p.(None):
p.(None): Article 17
p.(None): The sponsor and the investigator shall retain the essential documents relating to a clinical trial
p.(None): for at least five years after its completion.
p.(None):
p.(None): They shall retain the documents for a longer period, where so required by other applicable requirements
p.(None): or by an agreement between the sponsor and the investigator.
p.(None):
p.(None): Essential documents shall be archived in a way that ensures that they are readily available, upon request, to the
p.(None): competent autho- rities.
p.(None):
p.(None): The medical files of trial subjects shall be retained in accordance with national legislation and in accordance
p.(None): with the maximum period of time permitted by the hospital, institution or private practice.
p.(None):
p.(None): Article 18
p.(None): Any transfer of ownership of the data or of documents shall be documented. The new owner shall assume
p.(None): responsibility for data retention and archiving in accordance with Article 17.
p.(None):
p.(None): Article 19
p.(None): The sponsor shall appoint individuals within its organisation who are responsible for archives.
p.(None):
p.(None): Access to archives shall be restricted to the named individuals responsible for the archives.
p.(None):
p.(None): Article 20
p.(None): The media used to store essential documents shall be such that those documents remain complete and legible
p.(None): throughout the required period of retention and can be made available to the competent authorities upon
p.(None): request.
p.(None):
p.(None): Any alteration to records shall be traceable.
p.(None):
p.(None): L 91/18 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None):
p.(None): CHAPTER 5
p.(None): INSPECTORS
p.(None): Article 21
p.(None): 1. The inspectors, appointed by the Member States pursuant to Article 15(1) of Directive 2001/20/EC, shall
p.(None): be made aware of and maintain confidentiality whenever they gain access to confidential information as a
p.(None): result of good clinical practice inspections in accordance with applicable Community requirements,
p.(None): national laws or international agreements.
p.(None):
p.(None): 2. Member States shall ensure that inspectors have completed education at university level, or have
p.(None): equivalent experience, in medicine, pharmacy, pharmacology, toxicology or other relevant fields.
p.(None):
p.(None): 3. Member States shall ensure that inspectors receive appro- priate training, that their training needs
p.(None): are assessed regularly and that appropriate action is taken to maintain and improve their skills.
p.(None):
...
Social / Trade Union Membership
Searching for indicator union:
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p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/13
p.(None):
p.(None): COMMISSION DIRECTIVE 2005/28/EC
p.(None): of 8 April 2005
p.(None): laying down principles and detailed guidelines for good clinical practice as regards investigational
p.(None): medicinal products for human use, as well as the requirements for authorisation of the
p.(None): manufacturing or importation of such products
p.(None): (Text with EEA relevance)
p.(None):
p.(None):
p.(None): THE COMMISSION OF THE EUROPEAN COMMUNITIES,
p.(None):
p.(None):
p.(None): Having regard to the Treaty establishing the European Community,
p.(None):
p.(None): Having regard to Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on
p.(None): the approx- imation of the laws, regulations and administrative provisions of the Member States relating to the
p.(None): implementation of good clinical practice in the conduct of clinical trials on medicinal products for human
p.(None): use (1), and in particular Article 1(3), Article 13(1) and Article 15(5) thereof,
p.(None):
p.(None): Whereas:
p.(None):
p.(None): (1) Directive 2001/20/EC requires the adoption of principles of good clinical practice and detailed
p.(None): guidelines in line with those principles, minimum requirements for author- isation of the manufacture or
p.(None): importation of investiga- tional medicinal products, and detailed guidelines on the documentation relating to
p.(None): clinical trials to verify their compliance with Directive 2001/20/EC.
p.(None):
p.(None): (2) The principles and guidelines for good clinical practice should be such as to ensure that the
p.(None): conduct of clinical trials on investigational medicinal products, as defined in Article 2(d) of Directive
...
p.(None): the basis of common detailed guidelines, in order to ensure the protection of the trial subject while at
p.(None): the same time allowing a harmonised application in the different Member States of the procedures to
p.(None): be used by Ethics Committees.
p.(None):
p.(None):
p.(None): (7) To secure the compliance of clinical trials with the provisions on good clinical
p.(None): practice, it is necessary that inspectors ensure the practical effectiveness of such provisions. It
p.(None): is essential therefore to provide detailed guidelines on the minimum standards for the qualifi- cation of
p.(None): inspectors, in particular as regards their education and training. For the same reason, detailed
p.(None): guidelines on inspection procedures, in particular on the cooperation of the various agencies,
p.(None): and the follow-up to the inspections, should be laid down.
p.(None):
p.(None):
p.(None): (8) The International Conference on Harmonisation (ICH) reached a consensus in 1995 to provide a
p.(None): harmonised approach for Good Clinical Practice. The consensus paper should be taken into account as agreed upon
p.(None): by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency,
p.(None): hereinafter ‘the Agency’, and published by the Agency.
p.(None):
p.(None): L 91/14 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None): (9) It is necessary that sponsors, investigators and other participants take into account the
p.(None): scientific guidelines relating to the quality, safety and efficacy of medicinal products for human use, as
p.(None): agreed upon by the CHMP and published by the Agency, as well as the other phar- maceutical Community
p.(None): guidelines published by the Commission in the different volumes of The rules governing
p.(None): medicinal products in the European Community.
p.(None):
p.(None):
p.(None):
p.(None): (10) In conducting clinical trials on investigational medicinal products for human use, the safety and the
p.(None): protection of the rights of trial subjects should be ensured. The detailed rules adopted by Member States pursuant to
p.(None): Article 3(1) of Directive 2001/20/EC, to protect from abuse indi- viduals who are incapable of giving
p.(None): their informed consent should also cover individuals temporarily incapable of giving their
p.(None): informed consent, as in emergency situations.
p.(None):
p.(None):
p.(None):
p.(None): (11) Non-commercial clinical trials conducted by researchers without the participation of the
p.(None): pharmaceutical industry may be of great benefit to the patients concerned. Directive 2001/20/EC
...
p.(None):
p.(None):
p.(None):
p.(None): (12) The measures provided for in this Directive are in accordance with the opinion
p.(None): of the Standing Committee on Medicinal Products for Human Use,
p.(None):
p.(None):
p.(None): HAS ADOPTED THIS DIRECTIVE:
p.(None):
p.(None):
p.(None): CHAPTER 1
p.(None): SUBJECT-MATTER
p.(None): Article 1
p.(None): 1. This Directive lays down the following provisions to be applied to investigational medicinal
p.(None): products for human use:
p.(None):
p.(None):
p.(None): (a) the principles of good clinical practice and detailed guidelines in line with those principles,
p.(None): as referred to in Article 1(3) of Directive 2001/20/EC, for the design, conduct and reporting of
p.(None): clinical trials on human subjects involving such products;
p.(None):
p.(None):
p.(None): (b) the requirements for authorisation of the manufacture or importation of such products, as provided
p.(None): for in Article 13(1) of Directive 2001/20/EC;
p.(None):
p.(None):
p.(None): (c) the detailed guidelines, provided for in Article 15(5) of Directive 2001/20/EC, on the documentation
p.(None): relating to clinical trials, archiving, qualifications of inspectors and inspection procedures.
p.(None):
p.(None):
p.(None): 2. When applying the principles, detailed guidelines and requirements referred to in paragraph 1,
p.(None): Member States shall take into account the technical implementing modalities provided for in the
p.(None): detailed guidance published by the Commission in The Rules governing medicinal products in the European
p.(None): Union.
p.(None):
p.(None):
p.(None): 3. When applying the principles, detailed guidelines and requirements referred to in paragraph 1
p.(None): to non-commercial clinical trials conducted by researchers without the participation of the pharmaceutical
p.(None): industry, Member States may introduce specific modalities in order to take into account the specificity of
p.(None): these trials as far as Chapters 3 and 4 are concerned.
p.(None):
p.(None):
p.(None): 4. Member States may take into account the special position of trials whose planning does not require
p.(None): particular manufac- turing or packaging processes, carried out with medicinal products with marketing
p.(None): authorisations within the meaning of Directive 2001/83/EC, manufactured or imported in accordance with the same
p.(None): Directive and conducted on patients with the same characteristics as those covered by the
p.(None): indication specified in the marketing authorisation.
p.(None):
p.(None):
p.(None): Labelling of investigational medicinal products intended for trials of that nature may be subject to
p.(None): simplified provisions laid down in the good manufacturing practice guidelines on investigational medicinal
p.(None): products.
p.(None):
p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/15
p.(None):
p.(None):
p.(None): Member States shall inform the Commission as well as the other Member States of any specific modalities
p.(None): implemented in accordance with this paragraph. These modalities will be published by the Commission.
p.(None):
p.(None):
p.(None): CHAPTER 2
p.(None): GOOD CLINICAL PRACTICE FOR THE DESIGN, CONDUCT, RECORDING AND REPORTING OF CLINICAL TRIALS
p.(None): SECTION 1
p.(None): GOOD CLINICAL PRACTICE
p.(None): Article 2
p.(None): 1. The rights, safety and well being of the trial subjects shall prevail over the interests of science and
p.(None): society.
p.(None):
p.(None): 2. Each individual involved in conducting a trial shall be qualified by education, training, and
p.(None): experience to perform his tasks.
p.(None):
p.(None): 3. Clinical trials shall be scientifically sound and guided by ethical principles in all their
p.(None): aspects.
p.(None):
p.(None): 4. The necessary procedures to secure the quality of every aspect of the trials shall be complied
p.(None): with.
p.(None):
p.(None): Article 3
p.(None): The available non-clinical and clinical information on an inves- tigational medicinal product shall be adequate
p.(None): to support the proposed clinical trial.
p.(None):
p.(None): Clinical trials shall be conducted in accordance with the Declaration of Helsinki on Ethical
p.(None): Principles for Medical Research Involving Human Subjects, adopted by the General Assembly of the World
p.(None): Medical Association (1996).
p.(None):
p.(None): Article 4
p.(None): The protocol referred to in point (h) of Article 2 of Directive 2001/20/EC shall provide for the
...
p.(None): under other applicable requirements.
p.(None):
p.(None):
p.(None): 3. Communication of information between the Ethics Committees and the competent authorities
p.(None): of the Member States shall be ensured through appropriate and efficient systems.
p.(None):
p.(None):
p.(None): SECTION 3
p.(None):
p.(None): THE SPONSORS
p.(None): Article 7
p.(None): 1. A sponsor may delegate any or all of his trial-related functions to an individual, a company, an
p.(None): institution or an organisation.
p.(None):
p.(None):
p.(None): However, in such cases, the sponsor shall remain responsible for ensuring that the conduct of the trials and
p.(None): the final data generated by those trials comply with Directive 2001/20/EC as well as this Directive.
p.(None):
p.(None):
p.(None): 2. The investigator and the sponsor may be the same person.
p.(None):
p.(None):
p.(None): SECTION 4
p.(None): INVESTIGATOR’S BROCHURE
p.(None): Article 8
p.(None): 1. The information in the investigator’s brochure, referred to in Article 2(g) of Directive 2001/20/EC, shall be
p.(None): presented in a concise, simple, objective, balanced and non-promotional form that enables a clinician or
p.(None): potential investigator to understand it and make an unbiased risk-benefit assessment of the appropri- ateness
p.(None): of the proposed clinical trial.
p.(None):
p.(None):
p.(None): The first subparagraph shall apply also to any update of the investigator’s brochure.
p.(None):
p.(None): L 91/16 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None): 2. If the investigational medicinal product has a marketing authorisation, the Summary of Product
p.(None): Characteristics may be used instead of the investigator’s brochure.
p.(None):
p.(None): 3. The investigator’s brochure shall be validated and updated by the sponsor at least once a year.
p.(None):
p.(None):
p.(None): CHAPTER 3
p.(None): MANUFACTURING OR IMPORT AUTHORISATION
p.(None): Article 9
p.(None): 1. Authorisation, as provided for in Article 13(1) of Directive 2001/20/EC, shall be required for both total and
p.(None): partial manu- facture of investigational medicinal products, and for the various processes of dividing
p.(None): up, packaging or presentation. Such authorisation shall be required even if the products manu- factured are
p.(None): intended for export.
p.(None):
p.(None): Authorisation shall also be required for imports from third countries into a Member State.
p.(None):
p.(None): 2. Authorisation, as provided for in Article 13(1) of Directive 2001/20/EC, shall not be required for
p.(None): reconstitution prior to use or packaging, where those processes are carried out in hospitals, health
p.(None): centres or clinics, by pharmacists or other persons legally authorised in the Member States to carry out
p.(None): such processes and if the investigational medicinal products are intended to be used exclusively in those
p.(None): institutions.
p.(None):
p.(None): Article 10
p.(None): 1. In order to obtain the authorisation the applicant must meet at least the following requirements:
p.(None):
p.(None): (a) specify in his application the types of medicinal products and pharmaceutical forms to be manufactured or
p.(None): imported;
p.(None):
...
p.(None):
p.(None): 3. The competent authority of the Member State may require from the applicant further information concerning
p.(None): the parti- culars supplied pursuant to Article 10(1), including in particular information concerning the qualified
p.(None): person at the disposal of the applicant in accordance with point (e) of Article 10(1).
p.(None):
p.(None):
p.(None): Where the competent authority concerned exercises that right, the application of the time-limits laid down in
p.(None): paragraph 2 shall be suspended until the additional data required have been supplied.
p.(None):
p.(None):
p.(None): Article 12
p.(None): 1. In order to ensure that the requirements laid down in Article 10 are complied with, authorisation may
p.(None): be made condi- tional on the carrying out of certain obligations imposed either when authorisation is granted or
p.(None): at a later date.
p.(None):
p.(None):
p.(None): 2. An authorisation shall apply only to the premises specified in the application and to the types of
p.(None): medicinal products and pharmaceutical forms specified in that application pursuant to point (a) of Article
p.(None): 10(1).
p.(None):
p.(None):
p.(None): Article 13
p.(None): The holder of the authorisation shall at least comply with the following requirements:
p.(None):
p.(None):
p.(None): (a) to have at his disposal the services of staff that comply with the legal requirements existing in the
p.(None): Member State concerned both as regards manufacture and controls;
p.(None):
p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/17
p.(None):
p.(None):
p.(None): (b) to dispose of the investigational/authorised medicinal products only in accordance with the
p.(None): legislation of the Member State concerned;
p.(None):
p.(None):
p.(None): (c) to give prior notice to the competent authority of any changes he may wish to make to any of the
p.(None): particulars supplied pursuant Article 10(1) and, in particular, to inform the competent
p.(None): authority immediately if the qualified person referred to in Article 13(2) of Directive 2001/20/EC is
p.(None): replaced unexpectedly;
p.(None):
p.(None):
p.(None): (d) to allow agents of the competent authority of the Member State concerned access to his premises at
p.(None): any time;
p.(None):
p.(None):
p.(None): (e) to enable the qualified person referred to in Article 13(2) of Directive 2001/20/EC to carry out his duties,
p.(None): for example by placing at his disposal all the necessary facilities;
p.(None):
p.(None):
p.(None): (f) to comply with the principles and guidelines for good manufacturing practice for medicinal
p.(None): products as laid down by Community law.
p.(None):
p.(None):
p.(None): Detailed guidelines in line with the principles referred to in point (f) of the first paragraph
p.(None): will be published by the Commission and revised where necessary to take account of technical and
p.(None): scientific progress.
p.(None):
p.(None):
p.(None): Article 14
...
p.(None): for at least five years after its completion.
p.(None):
p.(None): They shall retain the documents for a longer period, where so required by other applicable requirements
p.(None): or by an agreement between the sponsor and the investigator.
p.(None):
p.(None): Essential documents shall be archived in a way that ensures that they are readily available, upon request, to the
p.(None): competent autho- rities.
p.(None):
p.(None): The medical files of trial subjects shall be retained in accordance with national legislation and in accordance
p.(None): with the maximum period of time permitted by the hospital, institution or private practice.
p.(None):
p.(None): Article 18
p.(None): Any transfer of ownership of the data or of documents shall be documented. The new owner shall assume
p.(None): responsibility for data retention and archiving in accordance with Article 17.
p.(None):
p.(None): Article 19
p.(None): The sponsor shall appoint individuals within its organisation who are responsible for archives.
p.(None):
p.(None): Access to archives shall be restricted to the named individuals responsible for the archives.
p.(None):
p.(None): Article 20
p.(None): The media used to store essential documents shall be such that those documents remain complete and legible
p.(None): throughout the required period of retention and can be made available to the competent authorities upon
p.(None): request.
p.(None):
p.(None): Any alteration to records shall be traceable.
p.(None):
p.(None): L 91/18 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None):
p.(None): CHAPTER 5
p.(None): INSPECTORS
p.(None): Article 21
p.(None): 1. The inspectors, appointed by the Member States pursuant to Article 15(1) of Directive 2001/20/EC, shall
p.(None): be made aware of and maintain confidentiality whenever they gain access to confidential information as a
p.(None): result of good clinical practice inspections in accordance with applicable Community requirements,
p.(None): national laws or international agreements.
p.(None):
p.(None): 2. Member States shall ensure that inspectors have completed education at university level, or have
p.(None): equivalent experience, in medicine, pharmacy, pharmacology, toxicology or other relevant fields.
p.(None):
p.(None): 3. Member States shall ensure that inspectors receive appro- priate training, that their training needs
p.(None): are assessed regularly and that appropriate action is taken to maintain and improve their skills.
p.(None):
p.(None): Member States shall also ensure that the inspectors have knowledge of the principles and processes
p.(None): that apply to the development of medicinal products and clinical research. Inspectors shall
p.(None): also have knowledge of applicable Community and national legislation and guidelines applicable to
p.(None): the conduct of clinical trials and the granting of marketing authorisations.
p.(None):
p.(None): The inspectors shall be familiar with the procedures and systems for recording clinical data, and with the organisation
...
p.(None):
p.(None): 3. Inspections shall be conducted in accordance with the inspection guidance documents developed to
p.(None): support the mutual recognition of inspection findings within the Community.
p.(None):
p.(None): 4. Improvement and harmonisation of inspection guidance shall be achieved by the Member States, in
p.(None): collaboration with the Commission and the Agency, through joint inspections, agreed processes and procedures
p.(None): and sharing of experience and training.
p.(None):
p.(None): Article 24
p.(None): Member States shall make publicly available within their terri- tories the documents relating to the
p.(None): adoption of good clinical practice principles.
p.(None):
p.(None): They shall establish the legal and administrative framework within which their good clinical practice
p.(None): inspections operate, with definition of the powers of inspectors for entry into clinical trial sites and
p.(None): access to data. In so doing they shall ensure that, on request and where appropriate, inspectors of the
p.(None): competent authority of the other Member States also have access to the clinical trial sites and data.
p.(None): In order to ensure the presence of skills necessary for specific
p.(None):
p.(None): inspections, Member State may appoint teams of inspectors and
p.(None): (1) OJ L 136, 30.4.2004, p. 1.
p.(None):
p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/19
p.(None):
p.(None):
p.(None): Article 25
p.(None): Member States shall provide for sufficient resources and shall in particular appoint an adequate number of
p.(None): inspectors to ensure effective verification of compliance with good clinical practice.
p.(None):
p.(None): Article 26
p.(None): Member States shall establish the relevant procedures for veri- fication of good clinical practice
p.(None): compliance.
p.(None):
p.(None): The procedures shall include the modalities for examining both the study management procedures and the conditions
p.(None): under which clinical trials are planned, performed, monitored and recorded, as well as follow-up measures.
p.(None):
p.(None): Article 27
p.(None): Member States shall establish the relevant procedures for the following:
p.(None):
p.(None): (a) appointing experts for accompanying inspectors in case of need;
p.(None):
p.(None): (b) requesting inspections/assistance from other Member States, in line with Article 15(1) of Directive
p.(None): 2001/20/EC and for cooperating in inspections in another Member State;
p.(None):
p.(None): (c) arranging inspections in third countries.
p.(None):
p.(None): Article 28
p.(None): Member States shall maintain records of national and, if applicable, international inspections
p.(None): including the good clinical practice compliance status, and of their follow-up.
p.(None):
p.(None): Article 29
p.(None): 1. In order to harmonise the conduct of inspections by the competent authorities of the different
p.(None): Member States, guidance documents containing the common provisions on the conduct of those inspections shall
p.(None): be published by the Commission after consultation with the Member States.
p.(None):
...
p.(None): 1. Member States shall lay down all necessary rules to ensure that confidentiality is respected by inspectors and
p.(None): other experts. With regard to personal data, the requirements of Directive 95/46/EC of the European
p.(None): Parliament and of the Council (1) shall be respected.
p.(None):
p.(None): 2. Inspection reports shall be made available by the Member States only to the recipients referred to in
p.(None): Article 15(2) of Directive 2001/20/EC, in accordance with national regulations of the Member States and
p.(None): subject to any arrangements concluded between the Community and third countries.
p.(None):
p.(None): CHAPTER 7
p.(None): FINAL PROVISIONS
p.(None): Article 31
p.(None): 1. Member States shall bring into force the laws, regulations and administrative provisions necessary to
p.(None): comply with this Directive by 29 January 2006 at the latest. They shall forthwith communicate to
p.(None): the Commission the text of those provisions and a correlation table between those provisions and this Directive.
p.(None):
p.(None): When Member States adopt these provisions, they shall contain a reference to this Directive or be accompanied
p.(None): by such a reference on the occasion of their official publication. Member States shall determine how such
p.(None): reference is to be made.
p.(None):
p.(None): 2. Member States shall communicate to the Commission the text of the main provisions of national law which they
p.(None): adopt in the field covered by this Directive.
p.(None):
p.(None): Article 32
p.(None): This Directive shall enter into force on the twentieth day following that of its publication in
p.(None): the Official Journal of the European Union.
p.(None):
p.(None): Article 33
p.(None): This Directive is addressed to the Member States. Done at Brussels, 8 April 2005.
p.(None): For the Commission Günter VERHEUGEN Vice-President
p.(None):
p.(None):
p.(None):
p.(None):
p.(None):
p.(None):
p.(None):
p.(None):
p.(None):
...
Social / Victim of Abuse
Searching for indicator abuse:
(return to top)
p.(None): and the follow-up to the inspections, should be laid down.
p.(None):
p.(None):
p.(None): (8) The International Conference on Harmonisation (ICH) reached a consensus in 1995 to provide a
p.(None): harmonised approach for Good Clinical Practice. The consensus paper should be taken into account as agreed upon
p.(None): by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency,
p.(None): hereinafter ‘the Agency’, and published by the Agency.
p.(None):
p.(None): L 91/14 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None): (9) It is necessary that sponsors, investigators and other participants take into account the
p.(None): scientific guidelines relating to the quality, safety and efficacy of medicinal products for human use, as
p.(None): agreed upon by the CHMP and published by the Agency, as well as the other phar- maceutical Community
p.(None): guidelines published by the Commission in the different volumes of The rules governing
p.(None): medicinal products in the European Community.
p.(None):
p.(None):
p.(None):
p.(None): (10) In conducting clinical trials on investigational medicinal products for human use, the safety and the
p.(None): protection of the rights of trial subjects should be ensured. The detailed rules adopted by Member States pursuant to
p.(None): Article 3(1) of Directive 2001/20/EC, to protect from abuse indi- viduals who are incapable of giving
p.(None): their informed consent should also cover individuals temporarily incapable of giving their
p.(None): informed consent, as in emergency situations.
p.(None):
p.(None):
p.(None):
p.(None): (11) Non-commercial clinical trials conducted by researchers without the participation of the
p.(None): pharmaceutical industry may be of great benefit to the patients concerned. Directive 2001/20/EC
p.(None): recognises the specificity of these non-commercial clinical trials. In particular, when trials are conducted
p.(None): with authorised medicinal products and on patients with the same characteristics as those covered by the authorised
p.(None): indication, requirements already fulfilled by these authorised medicinal products, as far as manu- facturing
p.(None): or importation are concerned, should be taken into consideration. However, it could also be necessary,
p.(None): due to the specific conditions under which non- commercial trials are conducted, that Member
p.(None): States foresee specific modalities to be applied to these trials not only when conducted with
p.(None): authorised medicinal products and on patients with the same characteristics, in order to comply with the
p.(None): principles imposed by this Directive, in particular as far as the manufacturing or import requirements for
p.(None): authorisation and the documen- tation to be submitted and archived for the trial master file are concerned.
...
Social / education
Searching for indicator education:
(return to top)
p.(None):
p.(None): (4) With regard to the protection of trial subjects and to ensure that unnecessary clinical
p.(None): trials will not be conducted, it is important to define principles and detailed guidelines of
p.(None): good clinical practice whilst allowing the results of the trials to be documented for use in a later
p.(None): phase.
p.(None):
p.(None):
p.(None): (5) To ensure that all experts and individuals involved in the design, initiation, conduct and recording of
p.(None): clinical trials apply the same standards of good clinical practice, prin- ciples and detailed guidelines of
p.(None): good clinical practice have to be defined.
p.(None):
p.(None):
p.(None): (6) Provisions for the functioning of the Ethics Committees should be established in each Member State on
p.(None): the basis of common detailed guidelines, in order to ensure the protection of the trial subject while at
p.(None): the same time allowing a harmonised application in the different Member States of the procedures to
p.(None): be used by Ethics Committees.
p.(None):
p.(None):
p.(None): (7) To secure the compliance of clinical trials with the provisions on good clinical
p.(None): practice, it is necessary that inspectors ensure the practical effectiveness of such provisions. It
p.(None): is essential therefore to provide detailed guidelines on the minimum standards for the qualifi- cation of
p.(None): inspectors, in particular as regards their education and training. For the same reason, detailed
p.(None): guidelines on inspection procedures, in particular on the cooperation of the various agencies,
p.(None): and the follow-up to the inspections, should be laid down.
p.(None):
p.(None):
p.(None): (8) The International Conference on Harmonisation (ICH) reached a consensus in 1995 to provide a
p.(None): harmonised approach for Good Clinical Practice. The consensus paper should be taken into account as agreed upon
p.(None): by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency,
p.(None): hereinafter ‘the Agency’, and published by the Agency.
p.(None):
p.(None): L 91/14 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None): (9) It is necessary that sponsors, investigators and other participants take into account the
p.(None): scientific guidelines relating to the quality, safety and efficacy of medicinal products for human use, as
p.(None): agreed upon by the CHMP and published by the Agency, as well as the other phar- maceutical Community
p.(None): guidelines published by the Commission in the different volumes of The rules governing
p.(None): medicinal products in the European Community.
p.(None):
p.(None):
p.(None):
p.(None): (10) In conducting clinical trials on investigational medicinal products for human use, the safety and the
p.(None): protection of the rights of trial subjects should be ensured. The detailed rules adopted by Member States pursuant to
...
p.(None):
p.(None):
p.(None): 4. Member States may take into account the special position of trials whose planning does not require
p.(None): particular manufac- turing or packaging processes, carried out with medicinal products with marketing
p.(None): authorisations within the meaning of Directive 2001/83/EC, manufactured or imported in accordance with the same
p.(None): Directive and conducted on patients with the same characteristics as those covered by the
p.(None): indication specified in the marketing authorisation.
p.(None):
p.(None):
p.(None): Labelling of investigational medicinal products intended for trials of that nature may be subject to
p.(None): simplified provisions laid down in the good manufacturing practice guidelines on investigational medicinal
p.(None): products.
p.(None):
p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/15
p.(None):
p.(None):
p.(None): Member States shall inform the Commission as well as the other Member States of any specific modalities
p.(None): implemented in accordance with this paragraph. These modalities will be published by the Commission.
p.(None):
p.(None):
p.(None): CHAPTER 2
p.(None): GOOD CLINICAL PRACTICE FOR THE DESIGN, CONDUCT, RECORDING AND REPORTING OF CLINICAL TRIALS
p.(None): SECTION 1
p.(None): GOOD CLINICAL PRACTICE
p.(None): Article 2
p.(None): 1. The rights, safety and well being of the trial subjects shall prevail over the interests of science and
p.(None): society.
p.(None):
p.(None): 2. Each individual involved in conducting a trial shall be qualified by education, training, and
p.(None): experience to perform his tasks.
p.(None):
p.(None): 3. Clinical trials shall be scientifically sound and guided by ethical principles in all their
p.(None): aspects.
p.(None):
p.(None): 4. The necessary procedures to secure the quality of every aspect of the trials shall be complied
p.(None): with.
p.(None):
p.(None): Article 3
p.(None): The available non-clinical and clinical information on an inves- tigational medicinal product shall be adequate
p.(None): to support the proposed clinical trial.
p.(None):
p.(None): Clinical trials shall be conducted in accordance with the Declaration of Helsinki on Ethical
p.(None): Principles for Medical Research Involving Human Subjects, adopted by the General Assembly of the World
p.(None): Medical Association (1996).
p.(None):
p.(None): Article 4
p.(None): The protocol referred to in point (h) of Article 2 of Directive 2001/20/EC shall provide for the
p.(None): definition of inclusion and exclusion of subjects participating in a clinical trial, monitoring and publication
p.(None): policy.
p.(None):
p.(None): The investigator and sponsor shall consider all relevant guidance with respect to commencing and conducting a
p.(None): clinical trial.
p.(None):
p.(None): Article 5
p.(None): All clinical trial information shall be recorded, handled, and stored in such a way that it can be
p.(None): accurately reported, inter- preted and verified, while the confidentiality of records of the trial subjects
p.(None): remains protected.
p.(None): SECTION 2
p.(None): THE ETHICS COMMITTEE
p.(None): Article 6
...
p.(None): Any transfer of ownership of the data or of documents shall be documented. The new owner shall assume
p.(None): responsibility for data retention and archiving in accordance with Article 17.
p.(None):
p.(None): Article 19
p.(None): The sponsor shall appoint individuals within its organisation who are responsible for archives.
p.(None):
p.(None): Access to archives shall be restricted to the named individuals responsible for the archives.
p.(None):
p.(None): Article 20
p.(None): The media used to store essential documents shall be such that those documents remain complete and legible
p.(None): throughout the required period of retention and can be made available to the competent authorities upon
p.(None): request.
p.(None):
p.(None): Any alteration to records shall be traceable.
p.(None):
p.(None): L 91/18 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None):
p.(None): CHAPTER 5
p.(None): INSPECTORS
p.(None): Article 21
p.(None): 1. The inspectors, appointed by the Member States pursuant to Article 15(1) of Directive 2001/20/EC, shall
p.(None): be made aware of and maintain confidentiality whenever they gain access to confidential information as a
p.(None): result of good clinical practice inspections in accordance with applicable Community requirements,
p.(None): national laws or international agreements.
p.(None):
p.(None): 2. Member States shall ensure that inspectors have completed education at university level, or have
p.(None): equivalent experience, in medicine, pharmacy, pharmacology, toxicology or other relevant fields.
p.(None):
p.(None): 3. Member States shall ensure that inspectors receive appro- priate training, that their training needs
p.(None): are assessed regularly and that appropriate action is taken to maintain and improve their skills.
p.(None):
p.(None): Member States shall also ensure that the inspectors have knowledge of the principles and processes
p.(None): that apply to the development of medicinal products and clinical research. Inspectors shall
p.(None): also have knowledge of applicable Community and national legislation and guidelines applicable to
p.(None): the conduct of clinical trials and the granting of marketing authorisations.
p.(None):
p.(None): The inspectors shall be familiar with the procedures and systems for recording clinical data, and with the organisation
p.(None): and regu- lation of the healthcare system in the relevant Member States and, where appropriate, in third
p.(None): countries.
p.(None):
p.(None): 4. Member States shall maintain up-to-date records of the qualifications, training and experience of
p.(None): each inspector.
p.(None):
p.(None): 5. Each inspector shall be provided with a document setting out standard operating procedures and giving
p.(None): details of the duties, responsibilities and ongoing training requirements. Those procedures shall be
p.(None): maintained up to date.
p.(None):
p.(None): 6. Inspectors shall be provided with suitable means of iden- tification.
p.(None):
p.(None): 7. Each inspector shall sign a statement declaring any financial or other links to the parties
...
Social / philosophical differences/differences of opinion
Searching for indicator opinion:
(return to top)
p.(None): indication, requirements already fulfilled by these authorised medicinal products, as far as manu- facturing
p.(None): or importation are concerned, should be taken into consideration. However, it could also be necessary,
p.(None): due to the specific conditions under which non- commercial trials are conducted, that Member
p.(None): States foresee specific modalities to be applied to these trials not only when conducted with
p.(None): authorised medicinal products and on patients with the same characteristics, in order to comply with the
p.(None): principles imposed by this Directive, in particular as far as the manufacturing or import requirements for
p.(None): authorisation and the documen- tation to be submitted and archived for the trial master file are concerned.
p.(None): The conditions under which the non- commercial research is conducted by public researchers and the places where
p.(None): this research takes place, make the application of certain of the details of good clinical practice
p.(None): unnecessary or guaranteed by other means. Member States will ensure in these cases, when
p.(None): providing for specific modalities, that the objectives of the protection of the rights of patients who
p.(None): participate in the trial, as well as, in general, the correct application of the good clinical practice principles,
p.(None): are achieved. The Commission will prepare a draft with guidance in this respect.
p.(None):
p.(None):
p.(None):
p.(None): (12) The measures provided for in this Directive are in accordance with the opinion
p.(None): of the Standing Committee on Medicinal Products for Human Use,
p.(None):
p.(None):
p.(None): HAS ADOPTED THIS DIRECTIVE:
p.(None):
p.(None):
p.(None): CHAPTER 1
p.(None): SUBJECT-MATTER
p.(None): Article 1
p.(None): 1. This Directive lays down the following provisions to be applied to investigational medicinal
p.(None): products for human use:
p.(None):
p.(None):
p.(None): (a) the principles of good clinical practice and detailed guidelines in line with those principles,
p.(None): as referred to in Article 1(3) of Directive 2001/20/EC, for the design, conduct and reporting of
p.(None): clinical trials on human subjects involving such products;
p.(None):
p.(None):
p.(None): (b) the requirements for authorisation of the manufacture or importation of such products, as provided
p.(None): for in Article 13(1) of Directive 2001/20/EC;
p.(None):
p.(None):
p.(None): (c) the detailed guidelines, provided for in Article 15(5) of Directive 2001/20/EC, on the documentation
p.(None): relating to clinical trials, archiving, qualifications of inspectors and inspection procedures.
p.(None):
p.(None):
p.(None): 2. When applying the principles, detailed guidelines and requirements referred to in paragraph 1,
p.(None): Member States shall take into account the technical implementing modalities provided for in the
p.(None): detailed guidance published by the Commission in The Rules governing medicinal products in the European
p.(None): Union.
p.(None):
p.(None):
p.(None): 3. When applying the principles, detailed guidelines and requirements referred to in paragraph 1
...
General/Other / Public Emergency
Searching for indicator emergency:
(return to top)
p.(None): hereinafter ‘the Agency’, and published by the Agency.
p.(None):
p.(None): L 91/14 EN Official Journal of the European Union
p.(None): 9.4.2005
p.(None):
p.(None):
p.(None): (9) It is necessary that sponsors, investigators and other participants take into account the
p.(None): scientific guidelines relating to the quality, safety and efficacy of medicinal products for human use, as
p.(None): agreed upon by the CHMP and published by the Agency, as well as the other phar- maceutical Community
p.(None): guidelines published by the Commission in the different volumes of The rules governing
p.(None): medicinal products in the European Community.
p.(None):
p.(None):
p.(None):
p.(None): (10) In conducting clinical trials on investigational medicinal products for human use, the safety and the
p.(None): protection of the rights of trial subjects should be ensured. The detailed rules adopted by Member States pursuant to
p.(None): Article 3(1) of Directive 2001/20/EC, to protect from abuse indi- viduals who are incapable of giving
p.(None): their informed consent should also cover individuals temporarily incapable of giving their
p.(None): informed consent, as in emergency situations.
p.(None):
p.(None):
p.(None):
p.(None): (11) Non-commercial clinical trials conducted by researchers without the participation of the
p.(None): pharmaceutical industry may be of great benefit to the patients concerned. Directive 2001/20/EC
p.(None): recognises the specificity of these non-commercial clinical trials. In particular, when trials are conducted
p.(None): with authorised medicinal products and on patients with the same characteristics as those covered by the authorised
p.(None): indication, requirements already fulfilled by these authorised medicinal products, as far as manu- facturing
p.(None): or importation are concerned, should be taken into consideration. However, it could also be necessary,
p.(None): due to the specific conditions under which non- commercial trials are conducted, that Member
p.(None): States foresee specific modalities to be applied to these trials not only when conducted with
p.(None): authorised medicinal products and on patients with the same characteristics, in order to comply with the
p.(None): principles imposed by this Directive, in particular as far as the manufacturing or import requirements for
p.(None): authorisation and the documen- tation to be submitted and archived for the trial master file are concerned.
p.(None): The conditions under which the non- commercial research is conducted by public researchers and the places where
p.(None): this research takes place, make the application of certain of the details of good clinical practice
p.(None): unnecessary or guaranteed by other means. Member States will ensure in these cases, when
...
General/Other / Relationship to Authority
Searching for indicator authority:
(return to top)
p.(None):
p.(None): (a) specify in his application the types of medicinal products and pharmaceutical forms to be manufactured or
p.(None): imported;
p.(None):
p.(None): (b) specify in his application the relevant manufacture or import operations;
p.(None):
p.(None): (c) specify in his application, where relevant as in the case of viral or non-conventional agents’
p.(None): inactivation, the manufac- turing process;
p.(None):
p.(None): (d) specify in his application the place where the products are to be manufactured or have at his disposal,
p.(None): for their manu- facture or importation, suitable and sufficient premises, technical equipment and
p.(None): control facilities complying with the requirements of Directive 2003/94/EC as regards the manufacture,
p.(None): control and storage of the products;
p.(None):
p.(None): (e) have permanently and continuously at his disposal the services of at least one qualified
p.(None): person as referred to in Article 13(2) of Directive 2001/20/EC.
p.(None):
p.(None): For the purposes of point (a) of the first subparagraph, ‘types of medicinal products’ include blood products,
p.(None): immunological products, cell therapy products, gene therapy products, biotech- nology products, human or animal
p.(None): extracted products, herbal products, homeopathic products, radiopharmaceutical products and products containing
p.(None): chemical active ingredients.
p.(None):
p.(None):
p.(None): 2. The applicant shall provide with his application docu- mentary evidence that he complies with
p.(None): paragraph 1.
p.(None):
p.(None):
p.(None): Article 11
p.(None): 1. The competent authority shall issue the authorisation only after verifying the accuracy of the
p.(None): particulars provided by the applicant pursuant to Article 10 by the means of an inquiry carried out by
p.(None): its agents.
p.(None):
p.(None):
p.(None): 2. Member States shall take all appropriate measures to ensure that the procedure for
p.(None): granting an authorisation is completed within 90 days of the day on which the competent
p.(None): authority receives a valid application.
p.(None):
p.(None):
p.(None): 3. The competent authority of the Member State may require from the applicant further information concerning
p.(None): the parti- culars supplied pursuant to Article 10(1), including in particular information concerning the qualified
p.(None): person at the disposal of the applicant in accordance with point (e) of Article 10(1).
p.(None):
p.(None):
p.(None): Where the competent authority concerned exercises that right, the application of the time-limits laid down in
p.(None): paragraph 2 shall be suspended until the additional data required have been supplied.
p.(None):
p.(None):
p.(None): Article 12
p.(None): 1. In order to ensure that the requirements laid down in Article 10 are complied with, authorisation may
p.(None): be made condi- tional on the carrying out of certain obligations imposed either when authorisation is granted or
p.(None): at a later date.
p.(None):
p.(None):
p.(None): 2. An authorisation shall apply only to the premises specified in the application and to the types of
p.(None): medicinal products and pharmaceutical forms specified in that application pursuant to point (a) of Article
p.(None): 10(1).
p.(None):
p.(None):
p.(None): Article 13
p.(None): The holder of the authorisation shall at least comply with the following requirements:
p.(None):
p.(None):
p.(None): (a) to have at his disposal the services of staff that comply with the legal requirements existing in the
p.(None): Member State concerned both as regards manufacture and controls;
p.(None):
p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/17
p.(None):
p.(None):
p.(None): (b) to dispose of the investigational/authorised medicinal products only in accordance with the
p.(None): legislation of the Member State concerned;
p.(None):
p.(None):
p.(None): (c) to give prior notice to the competent authority of any changes he may wish to make to any of the
p.(None): particulars supplied pursuant Article 10(1) and, in particular, to inform the competent
p.(None): authority immediately if the qualified person referred to in Article 13(2) of Directive 2001/20/EC is
p.(None): replaced unexpectedly;
p.(None):
p.(None):
p.(None): (d) to allow agents of the competent authority of the Member State concerned access to his premises at
p.(None): any time;
p.(None):
p.(None):
p.(None): (e) to enable the qualified person referred to in Article 13(2) of Directive 2001/20/EC to carry out his duties,
p.(None): for example by placing at his disposal all the necessary facilities;
p.(None):
p.(None):
p.(None): (f) to comply with the principles and guidelines for good manufacturing practice for medicinal
p.(None): products as laid down by Community law.
p.(None):
p.(None):
p.(None): Detailed guidelines in line with the principles referred to in point (f) of the first paragraph
p.(None): will be published by the Commission and revised where necessary to take account of technical and
p.(None): scientific progress.
p.(None):
p.(None):
p.(None): Article 14
p.(None): If the holder of the authorisation requests a change in any of the particulars referred to in points
p.(None): (a) to (e) of Article 10(1), the time taken for the procedure relating to the request shall not exceed
p.(None): 30 days. In exceptional cases, this period of time may be extended to 90 days.
p.(None):
p.(None):
p.(None): Article 15
p.(None): The competent authority shall suspend or revoke the authori- sation, as a whole or in part, if the holder of
p.(None): the authorisation fails at any time to comply with the relevant requirements.
p.(None):
p.(None):
p.(None): CHAPTER 4
p.(None): THE TRIAL MASTER FILE AND ARCHIVING
p.(None): Article 16
p.(None): The documentation referred to Article 15(5) of Directive 2001/20/EC as the trial master file shall
p.(None): consist of essential documents, which enable both the conduct of a clinical trial and the quality of the
p.(None): data produced to be evaluated. Those documents shall show whether the investigator and the sponsor have
p.(None): complied with the principles and guidelines of good
p.(None): clinical practice and with the applicable requirements and, in particular, with Annex I to Directive
p.(None): 2001/83/EC.
p.(None):
p.(None): The trial master file shall provide the basis for the audit by the sponsor’s independent auditor and for the
p.(None): inspection by the competent authority.
p.(None):
p.(None): The content of the essential documents shall be in accordance with the specificities of each phase of
p.(None): the clinical trial.
p.(None):
p.(None): The Commission shall publish additional guidance in order to specify the content of these documents.
p.(None):
p.(None): Article 17
p.(None): The sponsor and the investigator shall retain the essential documents relating to a clinical trial
p.(None): for at least five years after its completion.
p.(None):
p.(None): They shall retain the documents for a longer period, where so required by other applicable requirements
p.(None): or by an agreement between the sponsor and the investigator.
p.(None):
p.(None): Essential documents shall be archived in a way that ensures that they are readily available, upon request, to the
p.(None): competent autho- rities.
p.(None):
p.(None): The medical files of trial subjects shall be retained in accordance with national legislation and in accordance
p.(None): with the maximum period of time permitted by the hospital, institution or private practice.
p.(None):
p.(None): Article 18
p.(None): Any transfer of ownership of the data or of documents shall be documented. The new owner shall assume
p.(None): responsibility for data retention and archiving in accordance with Article 17.
p.(None):
p.(None): Article 19
p.(None): The sponsor shall appoint individuals within its organisation who are responsible for archives.
p.(None):
p.(None): Access to archives shall be restricted to the named individuals responsible for the archives.
p.(None):
p.(None): Article 20
...
p.(None):
p.(None): (c) as a follow-up to the granting of authorisation.
p.(None):
p.(None): 2. In accordance with Article 15(1) and (2) of Directive 2001/20/EC, inspections may be requested and
p.(None): coordinated by the European Medicines Agency within the scope of Regu- lation (EC) No 726/2004 of the
p.(None): European Parliament and of the Council (1), especially in connection with clinical trials relating to
p.(None): applications through the procedure established by this Regu- lation.
p.(None):
p.(None): 3. Inspections shall be conducted in accordance with the inspection guidance documents developed to
p.(None): support the mutual recognition of inspection findings within the Community.
p.(None):
p.(None): 4. Improvement and harmonisation of inspection guidance shall be achieved by the Member States, in
p.(None): collaboration with the Commission and the Agency, through joint inspections, agreed processes and procedures
p.(None): and sharing of experience and training.
p.(None):
p.(None): Article 24
p.(None): Member States shall make publicly available within their terri- tories the documents relating to the
p.(None): adoption of good clinical practice principles.
p.(None):
p.(None): They shall establish the legal and administrative framework within which their good clinical practice
p.(None): inspections operate, with definition of the powers of inspectors for entry into clinical trial sites and
p.(None): access to data. In so doing they shall ensure that, on request and where appropriate, inspectors of the
p.(None): competent authority of the other Member States also have access to the clinical trial sites and data.
p.(None): In order to ensure the presence of skills necessary for specific
p.(None):
p.(None): inspections, Member State may appoint teams of inspectors and
p.(None): (1) OJ L 136, 30.4.2004, p. 1.
p.(None):
p.(None): 9.4.2005 EN Official Journal of the European Union
p.(None): L 91/19
p.(None):
p.(None):
p.(None): Article 25
p.(None): Member States shall provide for sufficient resources and shall in particular appoint an adequate number of
p.(None): inspectors to ensure effective verification of compliance with good clinical practice.
p.(None):
p.(None): Article 26
p.(None): Member States shall establish the relevant procedures for veri- fication of good clinical practice
p.(None): compliance.
p.(None):
p.(None): The procedures shall include the modalities for examining both the study management procedures and the conditions
p.(None): under which clinical trials are planned, performed, monitored and recorded, as well as follow-up measures.
p.(None):
p.(None): Article 27
p.(None): Member States shall establish the relevant procedures for the following:
p.(None):
p.(None): (a) appointing experts for accompanying inspectors in case of need;
p.(None):
p.(None): (b) requesting inspections/assistance from other Member States, in line with Article 15(1) of Directive
p.(None): 2001/20/EC and for cooperating in inspections in another Member State;
p.(None):
p.(None): (c) arranging inspections in third countries.
p.(None):
p.(None): Article 28
...
Orphaned Trigger Words
p.(None):
p.(None): COMMISSION DIRECTIVE 2005/28/EC
p.(None): of 8 April 2005
p.(None): laying down principles and detailed guidelines for good clinical practice as regards investigational
p.(None): medicinal products for human use, as well as the requirements for authorisation of the
p.(None): manufacturing or importation of such products
p.(None): (Text with EEA relevance)
p.(None):
p.(None):
p.(None): THE COMMISSION OF THE EUROPEAN COMMUNITIES,
p.(None):
p.(None):
p.(None): Having regard to the Treaty establishing the European Community,
p.(None):
p.(None): Having regard to Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on
p.(None): the approx- imation of the laws, regulations and administrative provisions of the Member States relating to the
p.(None): implementation of good clinical practice in the conduct of clinical trials on medicinal products for human
p.(None): use (1), and in particular Article 1(3), Article 13(1) and Article 15(5) thereof,
p.(None):
p.(None): Whereas:
p.(None):
p.(None): (1) Directive 2001/20/EC requires the adoption of principles of good clinical practice and detailed
p.(None): guidelines in line with those principles, minimum requirements for author- isation of the manufacture or
p.(None): importation of investiga- tional medicinal products, and detailed guidelines on the documentation relating to
p.(None): clinical trials to verify their compliance with Directive 2001/20/EC.
p.(None):
p.(None): (2) The principles and guidelines for good clinical practice should be such as to ensure that the
p.(None): conduct of clinical trials on investigational medicinal products, as defined in Article 2(d) of Directive
p.(None): 2001/20/EC, is founded in the protection of human rights and the dignity of the human being.
p.(None):
p.(None): (3) Manufacturing requirements to be applied to investiga- tional medicinal products are
p.(None): provided for by Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines
p.(None): of good manu- facturing practice in respect of medicinal products for human use and investigational
p.(None): medicinal products for human use (2). Title IV of Directive 2001/83/EC of the European Parliament and of the
p.(None): Council of 6 November 2001 on the Community code relating to medicinal products for human use (3)
p.(None): contains the provisions applied for the authorisation for the manufacture of medicinal products as part
p.(None): of the requirements needed for the application for a marketing authorisation. Article 3(3) of that Directive
p.(None): establishes that these requirements are not applicable for medicinal products intended for
p.(None):
p.(None): (1) OJ L 121, 1.5.2001, p. 34.
p.(None): (2) OJ L 262, 14.10.2003, p. 22.
p.(None): (3) OJ L 311, 28.11.2003, p. 67. Directive as last amended by Directive 2004/27/EC (OJ L 136, 30.4.2004, p. 34).
p.(None): research and development trials. It is therefore necessary to lay down minimal requirements regarding
p.(None): applications for and management of authorisations to manufacture or import investigational medicinal products, as
p.(None): well as for the granting and the content of the authorisations, in order to guarantee the quality
p.(None): of the investigational medicinal product used in the clinical trial.
p.(None):
p.(None):
...
p.(None): with.
p.(None):
p.(None): Article 3
p.(None): The available non-clinical and clinical information on an inves- tigational medicinal product shall be adequate
p.(None): to support the proposed clinical trial.
p.(None):
p.(None): Clinical trials shall be conducted in accordance with the Declaration of Helsinki on Ethical
p.(None): Principles for Medical Research Involving Human Subjects, adopted by the General Assembly of the World
p.(None): Medical Association (1996).
p.(None):
p.(None): Article 4
p.(None): The protocol referred to in point (h) of Article 2 of Directive 2001/20/EC shall provide for the
p.(None): definition of inclusion and exclusion of subjects participating in a clinical trial, monitoring and publication
p.(None): policy.
p.(None):
p.(None): The investigator and sponsor shall consider all relevant guidance with respect to commencing and conducting a
p.(None): clinical trial.
p.(None):
p.(None): Article 5
p.(None): All clinical trial information shall be recorded, handled, and stored in such a way that it can be
p.(None): accurately reported, inter- preted and verified, while the confidentiality of records of the trial subjects
p.(None): remains protected.
p.(None): SECTION 2
p.(None): THE ETHICS COMMITTEE
p.(None): Article 6
p.(None): 1. Each Ethics Committee established under Article 6(1) of Directive 2001/20/EC shall adopt the
p.(None): relevant rules of procedure necessary to implement the requirements set out in that Directive and, in
p.(None): particular, in Articles 6 and 7 thereof.
p.(None):
p.(None):
p.(None): 2. The Ethics Committees shall, in every case, retain the essential documents relating to a clinical
p.(None): trial, as referred to in Article 15(5) of Directive 2001/20/EC, for at least three years after
p.(None): completion of that trial. They shall retain the documents for a longer period, where so required
p.(None): under other applicable requirements.
p.(None):
p.(None):
p.(None): 3. Communication of information between the Ethics Committees and the competent authorities
p.(None): of the Member States shall be ensured through appropriate and efficient systems.
p.(None):
p.(None):
p.(None): SECTION 3
p.(None):
p.(None): THE SPONSORS
p.(None): Article 7
p.(None): 1. A sponsor may delegate any or all of his trial-related functions to an individual, a company, an
p.(None): institution or an organisation.
p.(None):
p.(None):
p.(None): However, in such cases, the sponsor shall remain responsible for ensuring that the conduct of the trials and
p.(None): the final data generated by those trials comply with Directive 2001/20/EC as well as this Directive.
p.(None):
p.(None):
p.(None): 2. The investigator and the sponsor may be the same person.
p.(None):
p.(None):
p.(None): SECTION 4
p.(None): INVESTIGATOR’S BROCHURE
p.(None): Article 8
p.(None): 1. The information in the investigator’s brochure, referred to in Article 2(g) of Directive 2001/20/EC, shall be
p.(None): presented in a concise, simple, objective, balanced and non-promotional form that enables a clinician or
p.(None): potential investigator to understand it and make an unbiased risk-benefit assessment of the appropri- ateness
p.(None): of the proposed clinical trial.
...
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| abuse | Victim of Abuse |
| access | Access to Social Goods |
| authority | Relationship to Authority |
| education | education |
| emergency | Public Emergency |
| incapable | Mentally Incapacitated |
| opinion | philosophical differences/differences of opinion |
| restricted | Incarcerated |
| union | Trade Union Membership |
Indicator Peers (Indicators in Same Vulnerability)
Trigger Words
consent
ethics
protect
protection
risk
Applicable Type / Vulnerability / Indicator Overlay for this Input