Source: https://www.swissmedic.ch/bewilligungen/00155/00242/00327/00345/index.html?lang=en
Timestamp: 2017-10-23 20:39:04
Document Index: 369413973

Matched Legal Cases: ['art. 5', 'art. 54', 'art. 46', 'art. 62', 'art. 60', 'art. 3', 'art. 33', 'art. 46']

GCP and GVP Inspections - Swissmedic -
Submission of changes
Clinical trials on transplant products / gene therapy / genetically modified organisms
Below you can find information about GCP inspections regarding clinical trials with medicinal products, as well as information on Pharmacovigilance (GVP) inspections.
GCP inspections:
Clinical trials with medicinal products in humans are regulated in the Federal Act on Medicinal Products and Medical Devices of 15 December 2000 (Therapeutic Products Act, TPA, SR 812.21) as well as the new Federal Law on Research on Human Subjects of 30 September 2013 (Human Research Act, HRA, RS 810.30) and the related ordinances (Ordinance on clinical trials in human research, ClinO, SR 810.305 and Organisation ordinance on the Human Research Act, org-HRA, SR 810.308).
The ICH Good Clinical Practice Guidelines are directly anchored in the Swiss legislation (art. 5, para 1 ClinO) and apply to all clinical trials with medicinal or therapeutic products performed in Switzerland.
In accordance with art. 54, para. 5, TPA and art. 46 ClinO, Swissmedic is authorised to carry out or mandate inspections at any time in order to verify that trial conduct complies with applicable national law. In this authority, Swissmedic is entitled to visit the premises of all parties involved in a clinical trial, including but not limited to sponsor, contract research organisations, investigational sites and laboratories / pharmacies and to access all documentation and data relating to the clinical trial.
The relevant ethics committee and cantonal authority are to be informed of the inspection and may take part therein as well. All attendees of the regulatory and cantonal authorities are bound by professional secrecy.
Where it has objective grounds, Swissmedic may interrupt a clinical trial, impose regulatory requirements regarding its execution, or prohibit it. In addition, the Institute may take legal actions in accordance with art. 62 and 63 HRA.
With the exception of immediate actions to be taken in order to protect the study participants («Sofortmassnahmen», “mesures immédiates”), the inspectee is given the possibility to take position on all legal measures planned before their coming into effect.
GVP inspections:
The requirements for Pharmacovigilance systems are defined in the TPA, the Medicinal Products Licensing Ordinance (MPLO, SR 812.212.1), the Ordinance on Medicinal Products (VAM, SR 812.212.21) and the Ordinance on Clinical Trials (ClinO). In accordance with art. 60 TPA, art. 3, let. B, MPLO, art. 33 VAM and art. 46 ClinO, Swissmedic is entitled to carry out GVP inspections at any time.
B. Inspection types
There are three different approaches for conducting GCP inspections:
routine inspections (based on yearly planning);
for cause inspections (ad hoc inspection, based on complaints or a suspected violation of regulations (including fraud); may be announced or not;
inspections triggered by marketing authorisation application- (request from the internal Division of Marketing Authorisation).
There are three GCP inspection procedures:
systems inspections (sponsor, CRO, laboratory): GCP systems inspections focus on the key elements of the quality system of an organisation involved in clinical research. This includes review and evaluation of whether the company’s quality system and relevant subsystem procedures are suitably designed and address basic requirements in different domains. A further element is the analysis of whether the quality system is adequately implemented (=controlled, maintained and documented) to fulfil the objectives for which it has been set up.
site inspection (trial site): GCP site inspections focus on the quality and integrity of the recorded data as well as on the procedures implemented to safeguard the rights, safety and well-being of study participants.
combined systems inspection: combined systems inspections involve one or more trial specific site inspections followed by a systems inspection at the sponsor and / or CRO premises. On that occasion, deviations observed during (a) preceding inspection(s) are followed-up and the company’s respective actions and reactions are analysed.
GVP inspections (Pharmacovigilance):
There are no different types of GVP inspections. GVP inspections are mainly carried out at companies holding the marketing authorisation for a marketed product in Switzerland (MAH). They can, however, also be conducted at CROs or research organisations which assume pharmacovigilance tasks for others. These inspections are generally systems based, meaning that inspectors examine the systems and procedures used by the inspected organisation to comply with existing national / international pharmacovigilance regulations and guidance.
GVP inspections can be carried out either as routine or "for cause" inspections.
C. Criteria for selecting routine inspection targets
Routine GCP and GVP Inspection sites are selected based on one or more of the objective criteria described below.
Criteria to select GCP inspection targets:
involvement of a vulnerable trial population (e.g. paediatric trials)
trials with a high(er) risk (e.g. FIM , medical emergency setting)
company or contractual partner unknown to Swissmedic
high activity in clinical research
inexperienced sponsor (representative) and / or trial site
Criteria to select GVP inspection targets:
quality of individual case safety reports
risk management and risk minimization activities
products associated with special risks
poor outcome in previous inspections
D. The inspection process
The inspection process of GCP and GVP inspections share the following similarities:
Organisations / trial sites selected for a routine inspection are notified of the inspection at least 4 weeks in advance. At the same time a request for information is issued in order to prepare the inspection. For a systems inspection this typically includes, but is not limited to, company’s organisational charts, list of standard operating procedures (SOPs), key contact details and details of clinical trial activities (number and status of clinical trials in Switzerland, key service providers etc.). For site inspections typically the delegation of responsibility log, copies of study-specific working instructions and a list of ongoing clinical trials is requested. The competent Ethics Committee and the relevant cantonal authority receive a copy of the notification for information. In the case of investigator initiated trials, the hospital management is informed as well.
An inspection agenda, detailing activities, resource needs and timing will be provided to the inspectee about one week prior to the inspection. Any comments or questions relating to this plan can be discussed with the Lead Inspector at this time to make sure the availability of relevant staff members.
During the on-site inspection:
A GCP or GVP inspection is usually carried out by two inspectors. The inspectors should be made available a room for the documentation review and the conduct of the interviews. Furthermore access to a photocopier and a phone should be organised. The inspectee should appoint a contact person for the inspectors, who is available throughout the inspection. All relevant documentation must be readily available. For systems inspections this typically includes but is not limited to the trial master file (TMF), SOPs and training documentation and for site inspections the investigator site file (ISF), patient medical records, CRFs and signed informed consent forms.
The inspection will start with an opening meeting where the Lead Inspector will outline the scope and purpose of the inspection and confirm the tentative agenda.
During the inspection, interviews with relevant personnel, generally as per the inspection plan, are conducted. Time is built into the inspection for the review of documentation. The inspectors may request additional documentation and the organisation should be prepared to provide this promptly during the inspection. Copies of relevant documentation may be taken and are recorded in a form for the sake of transparency. The inspectors may visit any facilities involved in clinical trials, for example archives, pharmacy or laboratories and these visits may be pre-arranged for logistical reasons or decided upon during the inspection.
Timing as defined in the agenda is approximate and may be subject to change based on the inspection progress.
At the end of the inspection a closing meeting will be held where verbal feedback on any non-compliances is provided to the organisation.
After the on-site inspection:
Once the inspection has been completed, an inspection report is prepared by the Lead Inspector, reviewed by the Co-inspector and approved by the Head of the GCP and GVP inspectorate. The findings observed are classified as «critical», «major» or «minor». In addition, inspectors may include comments in the inspection report. For the underlying definitions reference is made to section E.
The inspected organisation is requested to provide a response to the inspection report as well as a corrective action and preventative action (CAPA) plan. Once adequate responses have been received from the organisation, an official letter will be issued by Swissmedic stating that the CAPA plan has been accepted and that the inspection is closed.
The competent Ethics Committee, the relevant cantonal authority as well as the sponsor (site inspection, study-specific systems inspection of CRO) receive a copy of the inspection report, CAPA plan and closing letter.
The outcome of the inspection might trigger subsequent inspections such as other site or systems inspections and / or a re-inspection.
Following the inspection the inspected organisation (systems inspection) / sponsor (site inspection, study-specific systems inspection of CRO) will receive an invoice. In accordance with the Ordinance on Fees levies by the Swiss Agency for Therapeutic Products, Article 3, para. 1, Article 4, para. 1 in connection with letter B, section I of Annex 5 (HgebV) Swissmedic levies fees for carrying out inspections. The fees are based on time spent per hour and per inspector (rate: CHF 200.00 per hour), and include the pre- and post-inspection work in addition to the on-site inspection time.
E. Classification of findings
Inspection findings are classified in accordance with the criteria defined by the European Commission and applied by the EMA (EUDRALEX Volume 10 - Clinical trials, of the publications “The rules governing medicinal products in the European Union”. Chapter IV: Guidance for the preparation of Good Clinical Practice inspection reports).
Conditions, practices or processes that adversely affect the rights, safety or well being of the subjects and/or the quality and integrity of data. Critical observations are considered totally unacceptable.
Remark Observations classified as critical may include a pattern of deviations classified as major, bad quality of the data and/or absence of source documents. Fraud belongs to this group.
Definition Conditions, practices or processes that might adversely affect the rights, safety or well-being of the subjects and/or the quality and integrity of data. Major observations are serious deficiencies and are direct violations of GCP principles.
Remark Observations classified as major, may include a pattern of deviations and/or numerous minor observations.
⇒ MINOR
Definition Conditions, practices or processes that would not be expected to adversely affect the rights, safety or well being of the subjects and/or the quality and integrity of data.
Observations classified as minor, indicate the need for improvement of conditions, practises and processes.
Remark The observations might lead to suggestions on how to improve quality or reduce the potential for a deviation to occur in the future.
Definition The observations might lead to suggestions on how to improve quality or reduce the potential for a deviation to occur in the future.