Standardised Lab Manual for bioanalytical support in clinical studies : Introducing the harmonised Lab Manual

Transcription

1 Standardised Lab Manual for bioanalytical support in clinical studies : Introducing the harmonised Lab Manual Richard Abbott On behalf of EBF/TT February 2014 NH Sablon Hotel, Brussels

2 Introduction : Background on TT-12 : Issues in Multi-Centre Clinical Trials Initiation May 2012 Regular TCs, c. every 3 weeks Objectives Participation Discussion and concensus on the issues (BA perspective) Create awareness with our clinical colleagues and service providers Wide participation and interest from both Pharma (6) and CRO (4) 2

3 Highlights from 2012/2013 EBF Surveys Sample Chaos 89% of EBF members participating in the surveys voted for an industry standard lab manual Poor labelling (avoid handwritten labels) Different tubes being used by different sites Samples arriving in bags, not boxes Sites using different procedures for sample collection and storage Problems with sample manifests and reconciliation Sample Tracking Shipment arrival notification Poor communication 3

4 TT-12 Generic Lab Manual Initiative Process Improvement Initiative Kick-off meeting 26-Jun-13 Richard Abbott (Facilitator) Sub-Team Carina Ekstrom (Ferring) Rebecca Sleigh (Quotient) Jeff Long (Shire) Requested Material Company lab manuals requested from TT-12 members (9 provided) 4

5 Defining a Generic Lab Manual : the process Brainstorming Review of Main Headings from all individual company lab manuals received Consolidation Agreement to amalgamate common headings to allow document consolidation Draft TOC Draft TOC defined TOC divided between sub-team members for drafting of generic text 5

6 EBF Review : Completion of Stage 1 Review Draft document reviewed by extended TT-12 team Final Draft Final draft produced 02 October 2013 Presentation to EBF Document concept presented to BA community at EBF Symposium in Nov

7 Stage 2 : Clinical Input Input We want your input, ideas, suggestions, edits, deletions Revise We will revise the document to ensure we capture best practice Finalise Objective : a final document which meets and exceeds everyone s expectations 7

8 Hot Topics identified by BA Community Labelling Reconciliation Sample Collection 8

9 Example Labelling Issue The label looks fine until after thawing.. 9

10 Draft Lab Manual Table of Contents Draft Lab Manual previously sent to everyone 1. Purpose and Scope 2. Contacts/Key Personnel/Responsible Staff 3. Documents/Information 4. Precautions during Sampling and Processing 5. Supplies 6. Equipment 7. Labelling 8. Sample Handling and Collection Procedures 9. Storage and Stability 10. Shipping 11. Sample Retention 12. Signatures 13. Appendix 10

11 Chapters 1-2, Purpose and Scope / Contacts, Key Personnel, Responsible Staff Definitions Hopefully, self explanatory Rationale and Benefit Important to identify the specific clinical study of interest and identify the scope of the laboratory processes concerned Likewise, important to reference the key contacts with important roles in the study to facilitate communication 11

12 Chapter 3, Documents/Information Documents needed prior to sample collection Clinical protocol, DTA, Randomisation information Documents required upon sample collection Specimen Inventory Sheet (handwritten, completed at time of sample collection) Documents to be completed prior to sample shipment Sample Shipping List Sample Manifest (QC checked vs sample tube labels) 12

13 Chapter 4, Precautions during Sampling and Processing Rationale Important to consider in each study as molecular properties will vary for each project Examples Avoid exposure to direct sunlight Degradation in presence of light Cover sample tubes Consider yellow light Instability in blood and/or plasma : Chill / place on ice Rapid plasma/serum processing Addition of stabilising reagents o May require accurate pipetting o Consider Day 1 attendance 13

14 Chapter 5-6, Supplies and Equipment Supplies Important to include supplies needed at clinical site. Photos add clarity : Blood collection Plasma/Serum collection Urine collection Equipment Equipment such as a refrigerated centrifuge and -80 C freezer should be specified : Avoids a last minute panic at the clinic and potentially difficult requests to BA to deviate from the protocol 14

15 Chapter 7, Labelling Study # Site Subject Period Day1 Predose Analyte Plasma Aliquot Identified as a key activity by BA All biological samples must be fully labelled with pre-printed, freezersafe labels Label should be applied on tube ensuring barcode is vertical on a tube standing in an upright position Hand-written labels should be minimised, using a specific marker (cover with clear tape) Avoid overwriting barcodes and application of multiple labels (especially those with conflicting information). 15

16 Chapter , Sample Handling and Collection Procedures (Blood, Plasma and Serum) Another key activity identified by BA Blood sample collection and processing o Anti-coagulant spray vs liquid o Volume/time/temperature o Clot time for serum Plasma/serum sample processing o Minimum volume required o Backups (maybe for discussion) Storage temperature details Tabular or Diagram Representation Choose tabular or diagram representation as required Any preference from clinical colleagues? 16

17 Chapter 8.3, Urine Sample Handling and Collection Procedure Urine sample collection Volume / Time period required Specify container, any required additives and storage temperature during collection Urine sample processing Ensure appropriate mixing if combining collections Do not overfill sample aliquot tubes to allow for sample mixing following freeze/thaw Addition of surfactants/stabilisers as required Specify storage temperature Tabular or Diagram Representation Choose tabular or diagram representation as required 17

18 Chapter 9, Storage and Stability Rationale Stability of a molecule can vary enormously between projects. Documenting known stability information in the lab manual should remind both BA and clinical scientists of any critical stability windows as well as the appropriate storage conditions Important Note Please ensure that primary and backup samples are stored in different refrigerators/freezers, otherwise the value of the backup is rather diminished 18

19 Chapter 10-11, Shipping/Sample Retention Shipping Sample Retention Another key activity identified by BA Ship with sufficient dry ice for 72h Organise in storage container with individual compartments Follow all necessary Gov and IATA regulations Avoid scheduling sample arrival at the weekend Full shipping address details Please provide tracking details and estimated arrival date For unstable samples, consider use of temperature data logger Document process for retention of samples so that there is no ambiguity. Always consult Sponsor prior to sample disposal 19

20 Chapter 12/13, Signatures and Appendices Signatures Signatures indicate acceptance Clinical Study Manager Clinical PI Central Lab Manager Sponsor BA Study Manager CRO BA Responsible Scientist Too many? For Discussion Appendices For Clarity : Example Sample Manifest Example Sample Receipt Form Example Urine Handling Sheet Relationship : rpm/rcf Others? 20

21 Hot Topics identified by BA Community Labelling Reconciliation Sample Collection 21

22 Reconciliation Sponsor Clinical Site Bioanalytical Lab Central Lab 22

23 Example Reconciliation Issues Scenario 1 Sample Manifest Sent to Bioanalytical Lab Information contained added to LIMS Information from Clinic updated: Central Lab database updated and don t tell Bioanalytical Lab Unfortunately once in LIMS and analysed database cannot be updated Scenario 2 Unscheduled samples sent to Bioanalytical Lab Request for information requested as to how samples should be logged in No answer 23

24 Example of Potential Clinic-to-Clinic Variability Several phase 1 trials had been conducted to test a novel iron chelator for treatment of chronic iron overload Data from one of two sites both recruiting to the same trial showed a level of iron chelation 5-10X greater than ever seen before Site in question used the same clinical supplies and followed the same sample collection procedure Subjects were fed the same meals and samples at both sites were stored at the correct temperature and freezers were in specification Bioanalytical bias ruled out as backup samples gave same results Conclusion: There was a subtle difference in sample collection and/or processing between sites that impacted the bioanalytical results 24

25 Hot Topics identified by this group This group may have a different perspective Hopefully there will be overlap : Equilibrium desired Sample Logistics Clinical PK Clin Ops / Study Monitors Phase I Unit Central Labs Regulatory Bioanalytical Community 25

26 Review and Objective Bioanalytical Review Quick review of the lab manual from a BA viewpoint Highlighted some issues for consideration Clinical Partner Input We need your input to ensure we have a practical, workable document Really important : we want groups to use it and see the benefits Objective A Standardised Lab Manual which will minimise issues and realise efficiencies in the successful conduct of multi-centre PK studies 26

27 So, In order to arrive at a Standardised Lab Manual which will minimise issues and realise efficiencies in the successful conduct of multi-centre PK studies, we need your input to ensure we have a practical, workable and endorsed document 27

28 Acknowledgement EBF Steering Committee Supporting companies in TT-12 include : Bayer Celerion Ferring Janssen R&D Merck&Co PRA Quotient BioAnalytical Sciences Shire Thanks for contributing company lab manuals TT-12 members and reviewers : Benno Ingelse Bernd Matthes Bernhard Beckermann Bernhard Schmid Carina Ekstrom Carolyn Mailer Cecilia Eskilsson Iris Vanwelkenhuysen Jeff Long Jose Groenboom Klaus Pusecker Marianne Scheel Fjording Philip Timmerman Ray Briggs Rebecca Sleigh Richard Abbott Stephen White Terry Holland 28

29 Questions? 29