FAQ - Regulatory Requirements (GCP)

May the patient education be carried out within the framework of a clinical trial by a physician?

The physician shall, to a certain extent, give the trial subject access to his or her own medical expertise; he or she shall involve the patient/test subject in his or her activities. Information is part of medical treatment and therefore delegation to non-medical staff is not permitted. According to § 38 AMG ".... may only be performed if .... by a doctor or dentist ..." Thus the physician (graduate of the medical studies) ex lege is eliminated.

In contrast to the graduates of the study of dentistry, the graduates of the study of human medicine are thus not yet entitled to exercise medical activities in the sense of medical law. This is only the case if the Austrian Medical Association has made an entry in the list of doctors.

How are the provisions of § 30 AMG to be interpreted with regard to the necessary performance of pregnancy tests for patients without therapy and healthy volunteers in the context of a clinical trial of drugs?

Section 30 of the AMG as amended is to be interpreted as follows, with reference to the explanatory notes on the AMG for female examiners

  • the provision in § 30 AMG that a pregnancy test must be carried out before the clinical trial cannot be ignored,
  • the interval for carrying out pregnancy tests during the clinical trial can be drawn further than monthly with conclusive justification, e.g. in periods without active substance administration, and
  • When determining the interval, in addition to the protection of the child, the study design, etc., the evaluability of the study must also be taken into account, i.e. whether an emerging pregnancy could not also influence the study results.

How long after the completion of the clinical trial must the completed CRFs be kept at the hospital?

The requirements for the storage of essential study documents, including CRFs, are regulated in the Medicines Act as amended in § 46.

From this it can be deduced that the sponsor must ensure that the essential study documents, including those generated by the study centre, such as study forms etc., are retained for a period of at least 15 years after completion or termination of the clinical trial. The sponsor must satisfy itself as to the retention requirement of the investigator's consent (part of the contractual agreement) and inform the investigator of the end of the retention period.

It should be noted that national legal retention periods (e.g. as prescribed by the Hospital Act) may differ significantly from GCP requirements, depending on the document (e.g. for medical records, imaging diagnostics, etc.).

Attention: In the case of "direct data entry" (data that is entered directly in test forms without additional source data), these must be regarded as part of the medical record, which means that the corresponding national requirements for the archiving periods for medical records (§ 10 Krankenanstaltengesetz KAKuG or Ärztegesetz) must also be extended to completed test forms.

Amendment under Regulation (EU) No 536/2014 on clinical trials of medicinal products for human use: Article 58 : "Archiving of the clinical trial master file" requires: "Except where other Union legislation requires a longer period, the investigator and sponsor shall retain the contents of their master file for at least 25 years after the end of the clinical trial. However, the patient files of the trial subjects shall be kept in accordance with national law."

Is compliance with the ISO 15189, ISO 17025 or EN ISO 9001:2000 standards required in the quality assurance system of a laboratory participating in GCP studies?

Compliance with the above ISO standards in clinical trials is not required by the German Medicines Act. At best, they can be regarded as an indicator of quality. Laboratory analyses that are part of clinical trials shall comply with the provisions of the GCP. If a quality assurance system according to ISO standards already exists in a test facility, it must be ensured that any existing gaps to the requirements of the GCP are closed.

Is it possible to implement a "mobile study team" at our institution, which goes to contractually integrated specialist medical offices "satellite centres", in order to take over the study tasks there?

When setting up satellite centres, various problems arise, e.g.

  • the assumption of responsibility for medical care in the context of the study in accordance with ICH GCP Article 4.3,
  • Qualification and training of personnel and suitability of the facility, e.g. in an emergency,
  • Framework conditions for data collection and transfer as well as data protection aspects, especially in connection with monitoring and necessary inspection of patient files at the satellite centre,
  • Storage of the test medication,
  • Involve the ethics committees responsible for satellite centres,
  • Drafting of contracts,
  • Transparency of the organisational framework conditions in the application documents

Due to the resulting complexity, implementation is not recommended.

Are there regulations for the electronic archiving of study documents?

The requirements for electronic archiving of study documents result from the requirements for documentation and archiving of clinical trials (AMG, guidelines 2001/20/EC, 2005/28/EC, 2001/83/EC, Eudralex Volume 10 chapter V, ICH GCP...), which must also apply to electronic documents.

Excerpts:

Directive 2005/28: Chapter 4 Article 17: Essential documents shall be archived in such a way that they can be rapidly made available to the competent authorities on request. 4 Article 20: The media used to store the essential documents shall be such that they remain complete and legible for the storage period and can be made available to the competent authorities on request. Any changes to the records shall be traceable.

ICH GCP 5.5.3: When using electronic data handling and/or remote electronical trial data systems, the sponsor should a) ensure and document....requirements for completeness, accuracy, reliability, and consistent intended performance (i.e. validation). (b) Maintain SOPs for using these systems. c) Ensure ... that the data changes are documented and that there is no deletion of entered data (audit trail). d) Maintain a security system that prevents unauthorized access to the data. e) Maintain a list of the individuals who are authorized to make data changes. f) Maintain adequate backup of the data. g) Safeguard the blinding, if any (e.g. maintain the blinding during data entry and processing).

Eudralex Vol. 10 Chapter V: 4) Quality of essential documents: Essential documents should be complete, legal, accurate, and unambiguous; They should be signed and dated as appropriate; 5) Media to be used: Particular attention ... electronic, magnetic, optical, or other non-indelible media. Controls... to ensure that these records cannot be altered without appropriate authorisation and the creation of an audit trail. Original records ...transferred to other media for archiving, the system of transfer should be validated to ensure that information will not be lost or altered. Such transfers should be certified for accuracy and completeness by someone with appropriate authority (e.g. trial manager), as part of the quality assurance system.

It is important that inspections should not be delayed, made more difficult or impossible by electronic archiving. The EMA GCP Inspectors Working Group has worked on a Reflection Paper on this topic, which is available at the following link

Amendment under Regulation (EU) No 536/2014 on clinical trials of medicinal products for human use: Article 58 : "Archiving of the clinical trial master file" requires: "Except where other Union legislation requires a longer period, the investigator and sponsor shall retain the contents of their master file for at least 25 years after the end of the clinical trial. However, the patient files of the trial subjects shall be kept in accordance with national law."

Is it possible for non-medical study staff to report the SAE to the sponsor? Does the proof of the time of the notification have to be available at the trial centre?

The SAE report of the investigator to the sponsor and the causal assessment necessary for this is an essential basis for the case evaluation by the sponsor and for the possibly necessary "expedited" report to authorities and ethics committees in the case of a SUSARS.

This message and medical evaluation by an investigator (does not have to be the PI) cannot be replaced by a message and evaluation by non-medical personnel.

It is also not sufficient if the medical evaluation is available exclusively in the source data, since the medical causality assessment and evaluation must be immediately apparent to the sponsor through the notification.

As legal references, AMG § 36 clause 9 in conjunction with § 41d as well as Article 4.3.1 ICH GCP are to be used. This requirement applies equally regardless of the form of the SAE report (paper, eCRF, fax, etc.).

In general, it should also be noted that regardless of the type of report, the timely report to the sponsor at the trial site must also be comprehensible, e.g. via fax confirmation, the eCRF audit trail, etc.

Is one calibration of a balance sufficient if it is used to determine the weight during a clinical trial. Is calibration required in addition to calibration?

Balances which are used or kept ready in the health service are subject to calibration according to §11 Abs 2 des Maß- und Eichgesetzes, BGBl. Nr. 152/1950 in der geltenden Fassung. Recalibration and error limits are also defined by law. Whether calibrated balances with a valid sticker require additional calibration (note: calibration is basically a special form of calibration) depends on the measurement requirements or on the local quality system and manufacturer recommendations.

If the accuracy to be checked is greater than that covered by the calibration or if the accuracy and function are to be checked at shorter intervals, calibration would also be required for a calibrated balance. The time intervals between calibrations must therefore be adapted to the requirements and should take the manufacturer's recommendations into account.

No special calibration intervals are prescribed by the BASG. During inspections, however, the justification for the periodic functional tests and the suitability of a balance in principle (e.g. sufficient accuracy) can be questioned.

Is it possible to use electronic subject information and a declaration of consent?

This is only possible if the electronic signature meets the following requirements:

  • According to § 39 para. 2 AMG, the consent of a volunteer to participate in a clinical trial requires written form. Writing in terms of § 886 ABGB means that a contract is only concluded after the signature of the parties. A replica of the handwritten signature by technical means is only sufficient where it is customary in business transactions. This is generally not the case for medical interventions and in particular for clinical trials.
  • According to § 4 para. 1 Signaturgesetz only the qualified electronic signature fulfils the legal requirement of a handwritten signature of the possible electronic signature types. In this regard, reference is made to the definitions in §2 Signaturgesetz.
  • Conformity with Art. 4.8.8 ICH GCP must also be ensured when an electronic signature is used. This means that both the respondent and the examiner or their authorised representative must sign the declaration of consent using a qualified signature.

Please note that even if an electronic declaration of consent form is used, the respondent must receive copies of the respondent's information and signed declaration of consent. These must be checked for conformity with the original as defined in Art. 1.63 ICH GCP by signature or as part of a validated process.

Independently of this, additional electronic information may be used for educational purposes (e.g. film, audio, interactive programmes), provided that it is validated and approved by the Ethics Committee.

What is the classification of a change in the staff of the test centre with regard to amendments and what are the reporting obligations?

The change in the auditor ("Principle Investigators") is a substantial change for the Ethics Committee and must therefore be approved by the Ethics Committee. A new auditor may only take up his function after approval by the Ethics Committee.

Other changes in the investigator's team are classified as non-substant changes and are therefore not subject to approval. However, in the case of changes in medical study personnel ("sub-investigators"), the changes must be brought to the attention of the Ethics Committee before they take up their duties.

Information to the BASG is only required if contents of the EudraCT notification form are concerned. This notification can also be made subsequently, provided that it is made promptly.

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