1. Validation of new systems in an ISO 9001 certified environment Emma Davis CIGMR University of Manchester

2. Overview What is BioBanking Solutions What is ISO 9001 Validation of Chemagic STAR

3. What is Biobanking Solutions? BioBanking Solutions (BBS) is: o a research project based at Centre for Integrated Genomic Medical Research (CIGMR), UoM o a 15 strong team of academics, project managers, IT specialists and technical staff o an ISO 9001:2008 certified biobanking solution provider for projects with sample handling requirements o A provider of services and advice for banking and distributing biological samples. http://www.biobankingsolutions.ac.uk/

4. We provide Project management Labelling solutions Sample tracking for multiple sample types DNA extraction (manual and robotic) DNA measurement (Nanodrop and PicoGreen) Sample storage (room temperature, -80C) Sample distribution Sample replenishment

5. Biobanking process Biobank Study Design Storage Processing Aggregation Quality control Collectors Collaborators

6. What is ISO 9001 Current version is ISO 9001:2008 Quality management system standard Based upon mapped processes Requires a customer focus, management commitment and continual improvement of your systems We have been ISO 9001 certified since 2005 We are audited by an external auditor

7. Mapped process In order to ensure that all of our services are run in a controlled and standardised way we have: – Mapped core and support processes – Validated core machinery – Trained to SOPs – Developed a Quality Management System (QMS) which is certified to ISO 9001:2008

8. What is a Quality Management System (QMS)? The web definition is: A quality management system is a set of documented, interrelated or interacting elements that organizations use to direct and control how quality policies are implemented and quality objectives are achieved.

9. What does this mean? Meeting the quality expectations of upstream and downstream users through monitoring of your procedures and continual improvement. OR Doing all aspects of your work in the best way you can.

10. Mapped BBS processes

11. Example of a mapped process Our processes detail basic steps Supported by detailed flowcharts and SOPs Controlled and reviewed by senior staff

12. Introducing a new system into the Biobank We implement a 2 stage approach when introducing a new system or procedure into the biobank: – Method development – Validation These of both fall under the R&D process

13. Method development in the R&D process This section is performed by a senior member of laboratory staff : – Scoping the system – Initial tests of the system – Changes are made to the system to fulfil requirements – Drafting SOP – Develop validation test plan – Hand-over to validation staff

14. Method Validation Validation is a procedure that is used to check that a product, service or system meets requirements and fulfils its intended purpose. Validation is required when working to ISO 9001 and is important when you are providing a service. (section 7.3 – design and development)

15. Method Validation in the R&D process Performed by specifically trained individuals – Thorough testing of every function of the system – Completion of the test plan – Additional testing where necessary – Assessment of the SOP – Activation of the system – Probationary period

16. Example section of a test plan Restart the Method. Select the matrix to matrix files for both user prompts. User prompt: Please choose the quantification technique used. Absorbance. Fluorescence. Click Abort. Method Aborts. Restart the Method. Select the matrix to matrix files for both user prompts for the worklists. User prompt: Please choose the quantification technique used. Absorbance. Fluorescence. Select Absorbance, Click OK. The Destination plate type prompt appears. Click Abort. Method Aborts.

17. Why we validate Ensure traceability and sample identification Maintain the integrity of the samples Provide accurate data Prevent loss of sample Prove the system does what is supposed to do Peace of mind for collectors and collaborators

18. Frequency of validation Core systems should be validated after any change to the system The level of validation can range from: – A single test run after minor changes – A full system check after upgrades

19. VALIDATION OF THE CHEMAGIC STAR

20. Chemagic overview The Chemagic STAR, with the 24 rod head, can run 2 sets of 24 samples in one run Each set takes approximately 1.5hrs to run It can process up to 4mls of blood or saliva It uses magnetic bead extraction It is integrated with our LIMS and includes barcode reading

21. Chemagic – critical procedure DNA extraction is a service BBS provides High quality DNA extraction is important for our collectors Failure of DNA extraction results in loss of the sample Repeat samples are not always available Poor quality DNA extraction may cause DNA to degrade over time

22. Plan for validation of the Chemagic 24-rod head Run various numbers of samples in simulation for both blood and saliva E.g. <24, 24, 24+1, 2x24, 2x24-1 (testing the programming) Run the same tests with water Testing the robotics, labware definitions and liquid handling Run at least 24 saliva kits and bloods Samples should ideally be from one donor for blood and a mixture of donors for saliva Check the user interface for errors and check volume calculations

23. Plan for validation continued Validate connection to LIMS and transfer of data Validate chemistry Assess DNA quality and quantify by Nanodrop, picogreen, Gel, rtPCR/PCR Use extracted DNA to assess stability Repeat process for 12 rod head.

24. Example of simulation test data Purpose of the test was to see which methods could be run with different combinations of labware

25. Looking for patterns 154.3171.3658.32180.81 184.335227.03165.65526.39 202.87515.22231.64174.465 229.705197.31230.49510.825 214.055217.72221.76227.335 167.15215.78170.529.61 Data from before head was changed(16/1) average conc ng/ul199.1 Average yeild per ml (ug)24.8 Average 260/2801.932368421 Average 260/2302.008421053 Highest value cellCell 9231.64 Lowest value cellCell 78.32 Standard deviation80.39 164.77299.435213.17191.1 226.98245.18227.805225.21 242.665243.26238.915225.805 231.875234.605241.675223.51 254.595234.91233.885228.735 204.18244.72237.545225.14 Date from after head was changed (09/3) average conc ng/ul230 Average yeild per ml (ug)28.8 Average 260/2801.917291667 Average 260/2302.0575 Highest value cellCell 13299.435 Lowest value cellCell 19164.77 Standard deviation24.11015

26. Post validation Generate a report detailing all issues and fixes SOPs undergo a probationary process Samples are being run routinely Data is being collected to monitor the extraction technique

27. Thanks Bill Ollier Martin Yuille Kate Dixon Andrew Platt Debbie Payne Biobanking team All CIGMR Staff Collectors & Collaborators Hamilton and Chemagen Support