§ Section 2 (2) AMG defines the term "non-clinical trial" as the pharmacological or toxicological testing of a medicinal product that is not carried out on humans. GLP must be applied to such tests if data from them are to be used in the authorisation of a medicinal product or in the authorisation of a clinical trial. According to § 9a (1) lit. 19 AMG, non-clinical data must be included with the application for authorisation. According to § 28 (1) AMG, clinical trials may only be conducted if meaningful results of non-clinical trials are available that have been conducted in accordance with the current state of scientific knowledge. Such trials must be carried out in a standardised form for the purpose of comparability and reconstructability, so that the BASG may only accept data from a non-clinical trial if the GLP standard is complied with. According to the Ordinance on GLP, Federal Law Gazette II No. 450/2006, the principles of GLP listed in the Annex to Directive 2004/10/EC must be observed in non-clinical trials.
The BASG's monitoring mandate is specified in the Ordinance on GLP, Federal Law Gazette II No. 450/2006:

• § 4 The BASG must carry out a periodic inspection to monitor compliance with GLP in the form of a company audit within the meaning of § 67 AMG.
• § 5 Conformity must be certified by the BASG in the form of a GLP certificate.
• § 6 A report on GLP in Austria must be published annually (by the end of March of the following year) (see www.basg.at and www.oecd.org)
• § 7 The European Commission and the OECD must be informed if non-conformity is detected.

The Regulation on GLP, Federal Law Gazette II No. 450/2006, transposes the GLP principles of the OECD into national law via Directive 2004/10/EC, so that international recognition of non-clinical tests lawfully carried out in Austria is ensured, provided that a valid GLP certificate from the BASG is available for the time of performance. GLP inspections are carried out with a periodicity of 2 years.

The quality assurance system and studies are usually inspected during each inspection. Depending on the risk situation, the emphasis can be shifted to the system or to the studies conducted. However, the specific content of an inspection depends on the field of activity of the inspection organisation and the frequency of non-clinical studies carried out. Directive 2004/09/EC on inspection procedures specifies the organisational procedure and the conditions under which a GLP inspection must be planned, performed and recorded by the monitoring authority. It can be used as a source of information on the expected inspection process. The test standard for a GLP inspection is the principles of GLP according to the OECD, which are incorporated into Directive 2004/10/EC and form part of national law according to the Regulation on GLP, Federal Law Gazette II No. 450/2006. All legal standards relevant for a GLP test facility are listed under Applicable legal bases (in the Preliminary information on the inspection of good laboratory practice (GLP)).

The presence of the inspectors at the test facility depends largely on the size of the test facility and the complexity of the non-clinical tests and can vary between one and four days. As a rule, inspections are carried out by two inspectors.

Relevant specialised inspectors (e.g. experts in special fields of chemical analysis) or external experts (e.g. experts for special test systems) can also be called in to examine specific issues.

Typically, the part of an inspection carried out at the test facility consists of the following elements:

• Opening of the inspection in the form of a meeting;
• Inspection of the test facility to check the facilities (premises, logbooks, temperature recording, qualification, etc.) and to observe/interview the personnel involved in conducting studies;
• Study documents and interview personnel at the test facility;
• At the end of the inspection, coordination of the inspectors and then the final meeting with the announcement of the observations.

In principle, the inspectors can check any documentation (specifications and evidence) that is related to data quality. This includes, for example (non-exhaustive list):

• Organisation chart of the test facility (incl. job descriptions and proof of qualification of key personnel)
• Master schedule
• Quality assurance system
• Procedural instructions
• Records
• Qualification & validation documents
• Training system (incl. personnel training records)
• Delegation of responsibilities
• All specifications and records for completed or ongoing non-clinical examinations

In the case of GLP inspections, a distinction must be made between deficiencies that are directly attributable to a non-clinical trial and deficiencies that are attributable to the quality system. Once a completed study has been inspected, it is generally no longer possible to correct a deficiency. In such a case, the reliability of a non-clinical trial is assessed taking into account the defects that cannot be corrected.

The rectification of any deficiencies affecting the quality assurance system can begin immediately - even during the inspection.

The identified deficiencies are addressed in the final meeting, but not classified. The preliminary classification of the deficiencies is made in the initial report. In the course of finalising the report, the severity of deficiencies can be upgraded or downgraded, taking into account the right to be heard (Section 45 (3) AVG). The final classification of the deficiencies is therefore made in the final report.

In order to categorise a deficiency as remedied, it is necessary to provide written evidence in the course of the response to the initial report that proves the remediation of a deficiency on the basis of suitable measures (e.g. photo documentation, drafts of documents, etc.).

Declarations of intent do not lead to the elimination of a deficiency; concrete corrective and preventive measures must be taken. The action plan should be submitted collectively as a statement for the hearing of the parties.

If any deficiencies found in the action plan are not addressed with corrective and preventive measures or are not rectified within the agreed period, there is a risk of official measures up to and including the non-issue of the GLP certificate or the cancellation of an existing GLP certificate, followed by a complaint. In addition, information about the lack of compliance with the applicable legal requirements will be published on the homepages of the BASG and the OECD. A further consequence is the information of all European authorisation authorities in order to ensure the exclusion of the affected non-clinical data from the authorisation processes.

GLP test facilities are inspected every 2 years, unless the risk situation requires a shorter inspection interval.

The BASG approaches the test facility automatically.

Further information can be found on the BASG website.

If your question is still not answered there, please send an e-mail to inspektionen@ages.at.