AXIS-SHIELD DIAGNOSTICS LTD.

PIPS STUDENTSHIPS

JEFF BRADY

Summary• Why Axis-Shield is a good place for the students• Why student placements are good for Axis-Shield• Questions / Discussion

Axis-Shield Diagnostics Ltd. – Key Focus

Identify, develop and commercialise in-vitro diagnostic

tests

Using our World class

facility with our world class

teams

Producing World class Products – ‘Changing lives’

Axis-Shield Diagnostics Ltd. - Dundee

Axis-Shield Diagnostics Ltd. – Our History

Pre Merg

er

• 1982 – Shield Immunologicals formed by Scientists spinning out of Dundee University • 1984 – Axis Biochemical created from spin out of Oslo University • 1987 – Shield Immunologicals renamed Shield Diagnostics following capital investment• 1993 – Shield Diagnostics listed on London Stock Exchange• 1998 – Move to current building – 100 employees

Early Merg

er

• 1999 - Merger of Axis Biochemicals ASA (Norway) and Shield Diagnostics Ltd (Scotland)

• 2003 – AxSYM xtra licence deal signed & Autoimmune range divested

• 2004 – Laboratory Division consolidated in Dundee

Current

• 2010 – Enzymatic Homocysteine technology acquired from Catch Inc.

• 2011 – Acquired by Alere Inc.

Axis-Shield Diagnostics Ltd. – Our Key Partners

Partner since 1997• 20 + product launches• Multiple Systems (IMx, AxSYM & ARCHITECT)

Partner since 2001• Homocysteine on BNII – launched 2005• Centaur agreements - Anti-CCP -2011/ Active B12 - 2013

Partner since 2009• Anti-CCP clinical chemistry• Enzymatic Homocysteine

Axis-Shield Diagnostics Ltd. – Key Products

Vitamin B12 DeficiencyActive B12 - improved diagnosis of vitamin b12 deficiency in at risk groups e.g. Elderly

DiabetesHbA1c - Diabetes

diagnosis and monitoring of

glycemic (or glucose) control

Rheumatoid ArthritisAnti-CCP - RA patient stratification for early

therapeutic intervention

Severe SepsisHeparin Binding Protein – Identify patients who will progress to severe illness in infection related conditions

CardiovascularHomocysteine - key risk factor determination

Laboratory Division – Product Pipeline

45329880

Practical (laboratory and Clinical) ‘Proof-of-Concept’

work being undertaken

Undergoing detailed

non-practical assessment (including IP)

Markers reviewed and rejected

Potential markers identified

45329880

Practical (laboratory and Clinical) ‘Proof-of-Concept’

work being undertaken

Undergoing detailed

non-practical assessment (including IP)

Markers reviewed and rejected

Potential markers identified

Axis-Shield Laboratory Division– Product Pipeline

Laboratory Division – Our People 137 people Onsite

Average length of service is 8.5 years. 48% have been with the company for over 10

years of which a further 14% over 20 years service

55% of our employees have a first level degree or higher.

Axis-Shield Diagnostics Ltd. – Our People

R&D Structure

Axis-Shield Diagnostics Ltd. – Operations

Reagents –Protein purification & conjugation

Technical Manuf. Bulk manufacture & test (SPC), solid phase coating

Filling - Fully Automated fill lines with built in full IPC

Kit Packing & Label –Label Vision inspection system

Support –

Supply chain

Technical support incl. technical transfer

C.I.Site wide 5sCI Coach Training

World

Class

Produc

ts

•5 Patented Products (HcY, Anti-CCP, Active B12, HbA1c & HBP)•Excellent on market product quality & delivery performance

World

Class

Facility

•Compliant Quality System that fosters a culture of continuous improvement•Continuous improvement embedded in the culture e.g. 5s maintained site wide

World

Class

People

•Experienced & Knowledgeable Staff with •30 years research & development •20 years working with major OEM’s•19 years production transfer

Axis-Shield Diagnostics Ltd. – Summary

PIPS Project On-Market Group• As working on “On-Market” products (FDA approved)

• high burden of proof• Bureaucratically, difficult to change

• 3 months; must be compact• Student needs to be independent (supervision time limited)

• Lab work• Experimental planning• Experimental analysis• Write-up

PIPS project• Improved in-house assay for S-adenosyl

homocysteine lyase

L-Hcy Adenosine

SAHase

SAH

+ + H2O

Good, basic biochemistry

Vmax = 0.020034 dA min-1

Km = 0.1673mM

[Substrate]~ 10x Km value. ∴ between 1- 2mM

0 2 4 6 8 10 12 14 160

100

200

300

400

500

600

700

800

f(x) = 49.9163858975139 x + 8.3486278981178R² = 0.999756279291766

[S][S

]/v

3 replicates for each data point!

PIPS project

• Took R&D model for assay• Feasibility• Optimisation• Validation

Robust Design approachUnderstand key design requirements

Risk Assess methods and formulations to capture key variables

Perform DoEs to optimise/characterise parameters

Experimental design training• Training given by our stats department• Advantages over One Factor At a Time (OFAT)

experiments• Stats input to experimental design and interpretation

CurHigh

Low0.74787D

Optimal

d = 0.74787

Minimum%CV

y = 2.0085

0.74787DesirabilityComposite

0.020

0.060

0.050

0.150µParts(%Conj (µg

[0.0995] [0.0576]

DOE Robustness Experiments

Variables tested:• Temperature• [Substrate]• [DTNB]• pH

Conclusions:• No variables significantly influence output• Conditions for assay set at

37oC pH 8.5 1.2mM SAH 12mM DTNB

Summary- what we got• Ciaran -excellent contribution to SAH-ase assay

project• Achieved goals for project• Assay passed to Reagents for implementation• Report written• Presentation to senior managers

• Additional support to us for protein engineering aspects (ASD opportunity)• Suggested codon optimisation• Helped with SNP project

Summary what Ciaran got• Especially crafted induction process

• GMP• Rigorous recording of experiments (SOP driven)

• Exposure to Experimental design driven experimentation• Input from Quality Engineers etc.

• Participation in Social events• Gin tasting !• Beer festival !