Validation of new systems in an ISO 9001 certified environment

Emma Davis CIGMR

University of Manchester

Overview

• What is BioBanking Solutions

• What is ISO 9001

• Validation of Chemagic STAR

What is Biobanking Solutions?

• BioBanking Solutions (BBS) is:o a research project based at Centre for Integrated Genomic Medical

Research (CIGMR), UoMo a 15 strong team of academics, project managers, IT specialists and

technical staffo an ISO 9001:2008 certified biobanking solution provider for projects

with sample handling requirementso A provider of services and advice for banking and distributing

biological samples.

http://www.biobankingsolutions.ac.uk/

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

Biobanking process

Biobank•Study Design•Storage•Processing•Aggregation•Quality control

Collectors Collaborators

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

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

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.”

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.

Mapped BBS processes

Example of a mapped process

• Our processes detail basic steps• Supported by detailed flowcharts and SOPs• Controlled and reviewed by senior staff

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

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

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)

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

Example section of a test planRestart 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.

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

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

VALIDATION OF THE CHEMAGIC STAR

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

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

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 salivaCheck the user interface for errors and check

volume calculations

Plan for validation continued

Validate connection to LIMS and transfer of data

Validate chemistry◦Assess DNA quality and quantify by Nanodrop,

picogreen, Gel, rtPCR/PCRUse extracted DNA to assess stabilityRepeat process for 12 rod head.

Example of simulation test data

• Purpose of the test was to see which methods could be run with different combinations of labware

protocol Medium VolumeSample Type Kit

Output 1ml tips 5ml tips 1ml tips 5ml tips 1ml tips 5ml tips 1ml tips 5ml tips 1ml tips 5ml tipsBlood Kit 1 (medium) Abgene x x x No x x x No x x

Greinerbioone x x x No x x x No x xMatrix x x x x x x x No x x

Blood Kit 2 (medium) Abgene x x x No x x x No x xGreinerbioone x x x No x x x No x xMatrix x x x x x x x No x x

Blood Kit 3 (medium) Abgene x x x No x x x No x xGreinerbioone x x x No x x x No x xMatrix x x x x x x x No x x

Saliva Kit 1(medium) Abgene x x x No x x x No x xGreinerbioone x x x No x x x No x xMatrix x x x x x x x No x x

Input LabwareSaliva TekLab 1ml Teklab 5ml Vacuette 1ml Vacuette 5ml

x = compatibleChecked in simulation mode

Looking for patterns154.3 171.365 8.32 180.81

184.335 227.03 165.655 26.39

202.875 15.22 231.64 174.465

229.705 197.31 230.495 10.825

214.055 217.72 221.76 227.335

167.15 215.78 170.52 9.61

Data from before head was changed(16/1)average conc ng/ul 199.1

Average yeild per ml (ug) 24.8Average 260/280 1.932368421Average 260/230 2.008421053Highest value cell Cell 9 231.64Lowest value cell Cell 7 8.32Standard deviation 80.39

164.77 299.435 213.17 191.1

226.98 245.18 227.805 225.21

242.665 243.26 238.915 225.805

231.875 234.605 241.675 223.51

254.595 234.91 233.885 228.735

204.18 244.72 237.545 225.14

Date from after head was changed (09/3)average conc ng/ul 230

Average yeild per ml (ug) 28.8Average 260/280 1.917291667Average 260/230 2.0575Highest value cell Cell 13 299.435Lowest value cell Cell 19 164.77Standard deviation 24.11015

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

Thanks Bill Ollier Martin Yuille Kate Dixon Andrew Platt Debbie Payne Biobanking team

All CIGMR Staff

Collectors & Collaborators

Hamilton and Chemagen Support