Molecular Diagnostics

Mike NugentGlobal Market Segment DirectorBD Molecular Diagnostics/BD MAX

B.A Life ScienceMBA – Robert Smith School, U of MD

Pace of change in growth based microbiology has been slow over time…• Blood plate invented 1881• Blood plate commercially 

available 1950’s• Incubators• Microscopes• Reagents

Although innovation has been accelerating in the last 10 years:

Maldi TofMicrobiology Lab automation 

(Kiestra, WASP)

Molecular diagnostics landscape on the other hand…

Many changes in the 31 years since PCR was first developed…

1983 – PCR invented

2014 

Separate Rooms

Single room

Singleplex/tube 20+ Multiplexing

Isothermal methods

Sample to 

answerMultiple instrumentssystems required

Single instrumentamplificationdetection

These rapid changes in molecular diagnostics technologies are creating several market forces that will fuel growth in the future

Automation and multiplexing simplifying workflows

Conversion from conventional to

molecular diagnostics

Decreasing costs making molecular testing more affordable

Shift toward syndromic panels

• Accessibility• Molecular 

available to the masses

• Laboratory labor relief

• Clinician benefits

MDX outlook by diagnostic area looks very strong in the near term and beyond…

Virology

5.3

BloodScreening

+7.6%

4%

20%

30%

22%

Oncology

Microbiology

12%

9%

2012

8%

5%

22%

27%

25%

7.6

2017

Other

Histology

15%

Other includes: Prenatal, Coagulation, Tissue Typing, Oncology, CTC, Pharmacodiagnostic

Molecular Diagnostics market forecastUSD Billion

Multiple areas for growth exist in the broad WW  Molecular Diagnostics market

• Molecular Diagnostics WW is anticipated to grow from a $6.1B market in 2014 to over $10B in 2024

• The largest areas of growth in this time period are Histology/Cancer Diagnostics and Infectious Disease Diagnostics.

• Infectious Disease Diagnostics is expected to see a CAGR of 9.4% over the next 3 years.

US and Europe remain the biggest users of MDX technologies, but emerging markets are growing quickly…

Clinical Molecular testing remains a phenomenon of the developed world

US dominates the molecular market: - Centralization and rationalization of testing

Europe continuing healthcare reforms- Economical pressures result in centralization of diagnostic labs and testing rationing

China 2nd largest laboratory market in Asia:- Fastest growing IVD market for modern lab instrumentation and tests and primary care tests and

devices

India rapidly growing diagnostic lab segment:- Driven by the demand from the private health sector and hospital are upgrading services

Questions that manufacturers should consider for assay development

Will the assay change/impact 

therapeutic decision?

Is there a significant lab benefit:  

Time/Labor/Materials?

Will the technology increase accuracy or 

detection?What is the cost 

position for the assay?

What is the disease prevalence?

BD’s vision for molecular testing is built to address the most critical clinical issues using intelligent assay design

…leading to flexible, cost effective diagnostic tools that impact clinical outcomes

Evolving clinical and patients challenges (emerging diseases, cost, time to result)

Technical Capabilities 

(Instrumentation and molecular chemistry)

Laboratory  requirements (accuracy, 

productivity, efficiency)

Smart assay design is a patient centric approach to assay development…

• Focused panels• Multiplex assays• Open System Reagents

Syndromic approach based on:• Patient and clinical 

consideration• Disease prevalance• Test methods tailored to the 

patient

Hospital based laboratories today are faced with unprecedented internal and external pressures…

…forcing them to identify approaches to diagnostics solutions…

REGIONAL LABS

REGIONAL LABS

REGIONAL LABS

Clinicianexpectations

Challengingnew

pathogens

Reduction in 

SkilledLabor

Time and Space 

Constraints

Molecular testing for enterics

Study Design – Examine cost and turn around time for conventional methodologies for 206 stool cultures 

•Costs of all media and tests•Time required (Labor) for processing•10 consecutive days / 5 MTs of varying levels of expertise

•TAT from time received to time finalizedConclusion  Summary ‐ Costs associated with conventional testing are substantial when considering time to result and labor requirements. 

•Cost of finding a positive is $427 due to the low prevalence and amount of labor and false positivework ups.•63% of negative stool cultures require additional testing beyond primary media.

•Time required by MTs working up stool cultures limits time spend on more complex, higher value diagnostic tests.

•Time to result varies from 48 hours to 96 hours 

ASM 2013 Abstract … Quantifying Stool Culture Costs and Time to Results 

Beal et al, ASM 2013 Denver, CO USA

Cost Tables:

Total Cost / Stool w STEC Screen 24.86$    

Media and Labor Supplemental Tests

* STEC EIA not performed in Lab during this study

Review of cost calculations … STEC screening added to analysis  

Total Cost / Stool 9.86$      

Cost :MacConkey 0.21$          XLD 0.28$          Sheep Blood Agar 0.18$          Campy Agar + pouch 4.37$          Selenite Broth  0.43$          XLD from Selenite Broth 0.28$          

5.75$          STEC EIA* 15.00$        

Labor per stool (8 min / $27 per hr)  3.06$          

Labor & Media Cost per stool 8.81$          

# of tests Cost (ea) Total CostOxidase 58 0.05$           2.90$      Gram Stain 54 0.80$           43.20$    Restreak to BAP 52 0.18$           9.36$      Wet Prep 35 0.50$           17.50$    TSI 31 0.41$           12.71$    LIA 29 0.44$           12.76$    Restreak to MAC 15 0.21$           3.15$      Spot Indole 15 0.05$           0.75$      ID/AST 14 3.95$           55.30$    Vanc Screen Agar 7 0.90$           6.30$      MDG 6 4.51$           27.06$    StrepQuick Card 4 4.80$           19.20$    Restreak to XLD 3 0.28$           0.84$      PYR 3 1.50$           4.50$      Catalase 2 ‐$             ‐$        Total (206 stools) 215.53$  

Cost / stool 1.05$      

Beale et al, ASM 2013 Denver, CO USA

We have developed a differentiated menu that will enable transition to molecular based diagnostic solutions

Enteric Assay Example

… To rapid, accurate  molecular diagnostics

Sample received by lab - culture setup

Incubate 35o/2 days

Incubate 35o/1 day

Incubate 42o/3 days

Incubate 25o/2 days

24 hours 48 hours 72+ hours

Sample received by lab - BD MAX setup

2 hours

Sample in tube load MAX

• Test for E. coli• Re incubate 24 hr• Plate review• Subculture suspect colonies

• Plate review• Subculture suspect colonies

• Screen for Campy• Incubate Campy 24 hr

From conventional culture based methods…

15

Sample Preparation

1. Vortex unpreserved or Cary-Blair preserved samples at high speed for 15 seconds.

2. Remove the clear cap from the SBT and inoculate as follows:

a. Insert a 10 μL disposable inoculation loop until the entire loop portion is submerged in the sample.

3. Place the SBT in a rack compatible with a multi-tube vortex mixer.

4. Add inoculated SBT to BD MAX rack.

• Proceed to MAX:1. Remove the required number of URS(s), Extraction 

Tube(s) and Master Mix Tube(s) from their protective pouches from the BD MAX Enteric Bacterial Panel kit. 

2. For each sample to be tested, place one (1) URS on the BD MAX System Rack and snap 1  Extraction Tube and (1) Master Mix Tube) into each URS.

3. Add the required PCR Cartridges to MAX4. Start Run.

BD MAX ENTERIC BACTERIAL WORKFLOW

• Highlights:• 4242 diarrheal stool samples 

(3457 Prospective / 785 Retrospective)

• Reference Method – Culture and Shiga‐toxin EIA

• Discordant analysis – Alt PCR and Sequencing

• Total run time of the EBP including sample processing, PCR, and result reporting is 2h 35 min.

16Mortensen et al, ECCMID 2014 Barcelona, Spain*Table presented at BD Meet the Experts ECCMID

Data Summary (Post-discrepant analysis)*

Multiple other areas where Molecular Diagnostics can be implemented for efficiency, accuracy

• Antibiotic Resistance Marker detection– CRE– ESBL– MRSA

• Other instances where culture based methods are either lower yield or labor intensive– Cdiff

• Low prevalence disease areas– Open System reagents for specific analytes

Thank You