DKG Møde i GLP arbejdsgruppen

1. DKGMøde i GLP arbejdsgruppen Novo Nordisk A/S 09-Feb-2011

2. DKG møde i GLP arbejdsgruppen Agenda – DKG GLP arbejdsgruppemøde • 14.00-14.15 Velkommen og præsentation af deltagerne • 14.15-14:20  Næste møde og referent • 14:20-15:00  Analyser af prøver fra kliniske forsøg - GCP vs. GLP/GCLP (oplæg fra Novo Nordisk) • 15:00-15:15 Kort pause • 15:15-15:30 Inspektionsnyt • 15:30-16.00 Emner fra deltagerne og eventuelt

3. DKG møde i GLP arbejdsgruppen GLP arbejdsgruppemøde Analyser af prøver fra kliniske forsøg - GCP vs. GLP/GCLP

4. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories What activities are Clinical Labs typically involved in? • Project management at a ”local” level • Kit production and logistics • Sample logistics • Sample analysis • Lab results reporting • Data transfer ~ data management • Storage of materials and documentation

5. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories Sample analysis of: • Whole blood, serum, plasma, urine, tissue, etc. Sample evaluation for: • biochemistry, hematology, coagulation, urinalysis, immunology/antibodies, pharmacogenomics, pharmacokinetics, etc. Techniques used: • Chromatography, immunoassays, cell-based assays, genotyping, flow cytometry, etc.

6. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories • Which laboratories? • Pharma Companies • CROs • Central Labs • Pharmacogenetic Labs • Hospital Labs • Clinics • Investigator Sites • Specialised analytical services

7. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories • Laboratories analysing samples from clinical trials must comply with GCP*. • *: Guideline for Good Clinical Practice E6(R1), ICH June1996, EMEA CPMP/ICH/135/95 January 1997

8. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories • “Systems with procedures that assure the quality of every aspect of the trial should be implemented” – (ICH GCP 2.13) • “Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective task(s)” – (ICH GCP 2.8) • “All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification” – (ICH GCP 2.10)

9. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories • BARQA: Good Clinical Laboratory Practice (2003) • MHRA: Guidance on the maintenance of regulatory compliance in laboratories that perform the analysis or evaluation of clinical trial samples (2009) • EMA: Reflection paper on guidance for laboratories that perform the analysis or evaluation of clinical trial samples (2010)

10. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document: • To date no detailed guidance has been produced which outlines the expectations of national monitoring authorities with respect to the analysis or evaluation of samples collected as part of a clinical trial. In the absence of guidance, some laboratories apply the principles of good laboratory practice when conducting clinical analysis.

11. Organisation Personnel Contracts & agreements Trial conduct Request for add. work Sub-contracting Patient/subject safety Informed consent Sample receipt/chain of custody Method validation Repeat analysis Data recording Reporting Facilities Equipment Computerised systems QA processes Quality control SOPs and facility policies Blinding/unblinding Retention of data Prep. and distr. of kits DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document content:

12. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document: • All staff involved in the analysis or evaluation of clinical trial samples should receive GCP training commensurate with their roles and responsibilities. It is appropriate for laboratory staff to receive periodic GCP refresher training. Such training is especially important following changes to regulations and associated guidance documents. • Example:To what extent should laboratory staff receive training in GCP? • All staff? • Full training in GCP? • Refresher training – who – how often?

13. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document: • Laboratories should not perform any work that is not specified in the original protocol. • Example:In the analytical areas the analytical results obtained from haematology and urine chemistry cannot be “adjusted” according to protocol requirements.There is no procedure or system that would cover the communication between trial management/sponsor and project management/CRO in order to make appropriate arrangements on this issue

14. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document: • There should be a mechanism to ensure that the laboratory is informed in a timely manner if consent is withdrawn to ensure that no further data is generated or collected. • Example:The procedure for trial subjects who has withdrawn their informed consent is that within 24 hours of notification the Project Manager must cancel all pending analysis, discard all tubes received or stored, notify the sponsor of the actions taken and notify the sponsor of the responsibility for taking actions for samples sent to third party labs

15. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document: • On arrival, or prior to processing, each sample and requisition form should be examined to ensure that its label does not display information which may identify the trial subject. • Example:If requisitions are received with patient name on it, a copy of the requisition is taken and the patient name is marked out with a black marker. The original requisition is then returned to the Principal Investigator with an explanatory letter of the error. If patient name appears on the sample tube a blank sticker is used to cover the name.

16. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document: • All computerised systems used for the capture, processing, manipulation, reporting and storage of data should be developed, validated and maintained in ways which ensure the validity, integrity and security of the data. • Examples:- Access to computer systems is not controlled.- System is not validated- No backup of data- An audit trail is not in place

17. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document: • Archive facilities should be available for the secure storage of clinical trial data. • All archive facilities must be secure to prevent unauthorised access to the retained materials. • Non trial-specific data such as equipment validation and maintenance records, staff training records, quality assurance reports, SOPs etc. should be retained in a secure archive • Access to the archive should be restricted to designated member(s) of staff. • Procedures for the removal of material from the archive and its subsequent return should be documented. • Requirements for the archiving of electronic records are the same as those for other record types.

18. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories - EMA document: It is recommended that quality assurance activities include, but are not limited to the following: • Regular facility audits to ensure that the laboratory and associated equipment used to conduct analysis or evaluation of clinical trial samples remain fit for purpose. • Periodic review of the laboratory’s quality systems, including control of standard operating procedures and/or laboratory policies, archiving and the maintenance of training records. • The audit of technical procedures and methodologies used to conduct the analysis or evaluation of clinical trial samples. • Audits performed to assess the conduct of routine and repetitive processes which are common to all trials such as; sample receipt, temperature monitoring, pipette and balance controls, and cleaning procedures. The most robust audit schedules will ensure that all key functions, personnel and procedures are reviewed over the course of one audit cycle. • The audit of documentation generated during the validation of computerised systems or analytical equipment.

19. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories – a QA solution: For departments involved in analysis of samples from clinical trials it has been decided that - • The quality system will be audited both annually based on the audit program, as well as quarterly by process based audits with focus on every aspect of the clinical analytical activities. If certain analytical methods cannot be audited on a process base, these will be included in the scope for the annual audit.

20. DKG møde i GLP arbejdsgruppen ICH GCP requirements relating to Clinical Laboratories EMA document mentions: • Article 15 of EU Clinical Trials Directive 2001/20/EC provides provision for the inspection of laboratories that perform the analysis or evaluation of samples collected as part of a clinical trial and expects Member States to appoint inspectors to verify compliance with good clinical practice. • What is the DMA approach?