Biotest Blood Bank Solutions

March 5th, 2009

Presentation Overview

• Who is Biotest? • Traditional Blood Bank

Reagents– Product offerings

• Biotest Blood Bank Automation– Overview

Biotest – 60+ years of Transfusion Diagnostics

2005 Tango Automated Blood Bank Analyzer launched in US/Canada

2 Manual reagents cleared in Canada and submitted to FDA

3 TANGO optimo launched

4 FDA approves Tango Optimo expanded menu and manual reagents

1948 Introduced World’s First Anti-D test serum

1983 Seraclone, Monoclonal Antibodies for Blood Grouping developed

1985 Erytype introduced, Ready to Use Microplates for Blood Grouping

1946 Founded as BiotestSerum-Institut GmbH

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Biotest Diagnostics CorporationUSA

• Founded in 1982, wholly owned subsidiary of Biotest AG

• Company Headquarters- Rockaway, NJ• Historical Product lines

Transplant HLA• Serological and Molecular Typing Reagents and Automation

Industrial Microbiology- Clean Room Monitoring• Particle counters• Air Samplers• Agar media

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Biotest Diagnostics Corporation • Late 2006

Transfusion Product Lines• Distribution of manual blood bank reagents in

Canada • TANGO Automated Blood Bank System

• March 2008 • Moved to a new facility in Rockaway, NJ• To support growth from new products

and additional customer support activities

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New Biotest Diagnostics Headquarters

• Three state-of-the-art labs

• Customer training facility

• Equipment service center

• Customer service & support

• Warehousing & distribution

BDC Transfusion Management

• Personnel – 40% increase since 2006 to accommodate transfusion

• Upper Management– Bill Weiss – President, BDC

• BS Chemistry, MBA • Abbott - Sales & Marketing Abbott• Immucor – Director of Sales

– Candace Williams – VP, Diagnostics Division• MT(ASCP), SBB• 13 yrs hospital transfusion service• 17 yrs, Olympus blood bank product division

– John Beck – Director of Sales• Immucor - 8 yrs experience sales, sales management and

marketing experience

Traditional Blood Bank Reagents

• Available in Europe, Canada

and USA.• Submitted to U.S.

FDA, approved on August 15th, 2008

Traditional Blood Bank Reagents• ABO/Rh antisera

– A, B, A,B– D Blend – weak D– D 226 – RT, no weak D claim– Control

• Anti-Human Globulin (AHG)

– Anti-IgG– Polyspecific

• Reagent Red Cells – Screening cells – three options– Two panels– A1, B, A2 cells

• Rare Antisera – C, E, c, e, K, k, – Jka, Jkb, S, s, M, N, – Fya, Lea, P1

• Potentiators & Controls

Rh Antisera

-IgM antibodies - anti-D detects D weak but not category D VI-monoclonal => short or no incubation (IS-5’ RT)-high specificity, high avidity- strong reaction-low protein content- suitable for all techniques except antiglobulin test

BS226

MS24

MS33

MS12/MS260

MS16/MS21 /MS63

Seraclone® Anti-D (RH1) Seraclone® Anti-C (RH2)

Seraclone® Anti-c (RH4)

Seraclone® (2) Anti-E (RH3)

Seraclone® (3) Anti-e (RH5)

-3 clones (1 IgM, 2 IgG) suitable for all techniques including Antiglobulin

-detects all D’s

BS242/ BS221/ H411B7 Seraclone® Anti-D (RH1) Blend

FeaturesClonesProduct

Rare Antisera

5’ RT

-5’ RT

-5’ RT

-5’ RT

-5’ RT

-30’ RT

-30’ RT

-5’ RT

-IAT

-IAT

-5’ RT

MS56 (IgM)

Lk1 (IgM)

MS15 (IgM)

MS8 (IgM)

LeA2 (IgM)

BS57 (IgM)

BS41 (IgM)

MS94 (IgM)

P3YAN3 (IgG)

DG-FYA-02 (IgG)

650 (IgM)

Seraclone® Anti-K (KEL1)

Seraclone® Anti-k (KEL2)

Seraclone® Anti-Jka (JK1)

Seraclone® Anti-Jkb (JK2

Seraclone® Anti-Lea (LE1)

Seraclone® Anti-M (MNS1)

Seraclone® Anti-N (MNS2)

Seraclone® Anti-S (MNS3)

Seraclone® Anti-s (MNS4)

Seraclone® Anti-Fya (FY1)

Seraclone® Anti-P1 (P1)

Test MethodClonesProduct

Reagent Red Cell Products• Antibody Screen

– Pooled cell– 2 cell

• R1R1 (CDe/CDe) and R2R2 (cDE/cDE)• Homozygous expression of Jka

– 3 cell screen• R1R1 (CDe/CDe), R2R2 (cDE/cDE), and rr (cde/cde)

• Homozygous expression of Jka and Fya

• Antibody Identification – 8 cell, 11 cell panels– 4 ml fill volume

• ABO– A1, A2 and B cells

Additional Manual Reagents• AHG Reagents

– Anti-IgG (light chain)– Polyspecific Anti-IgG + C3d

• IgG Coated Control RBC

• LISS (MLB2)

Traditional Reagents: The Biotest Advantage

• Biotest antisera all monoclonal• Biotest rare antisera do not require

antiglobulin phase except anti-s & anti-Fya

• Biotest panels have 4 ml vs. 3 ml fill volume

• 16 of 20 Biotest antisera specificities represent new clones for the US market

Traditional Reagent Evaluation

• Mike Charapata, Manager, Transfusion Services, Puget Sound Blood Center

• Presented at 2008 AABB Annual Meeting, Montreal, 2008

• Evaluated Biotest rare antisera in comparison to Immucor and Ortho

Results of Rh Antisera Evaluation

Biotest Significantly Outperforms

61496Anti-e

108

110

110

97

Number of samples tested

Roughly Equivalent

1014Anti-c

Roughly Equivalent

53Anti-E

Roughly Equivalent

2914Anti-C

Roughly Equivalent

1814Anti-D Blend

Conclusion# Stronger with Biotest Rgts

# Stronger

with Reference

Rgts

Antisera

Rare Antisera Evaluation

Biotest Outperforms

17231Anti-s

Biotest Outperforms

10031Anti-S

Roughly Equivalent

6230Anti-N

Roughly Equivalent

0111Anti-k

Equivalent0041Anti-K

Conclusion# Stronger with Biotest Rgts

# Stronger with Reference Rgts

# Samples testedAntisera

Rare Antisera Evaluation

Roughly Equivalent

4030Anti-Lea

Biotest Outperforms

10018Anti-P1

Roughly Equivalent

2231Anti-Jkb

Roughly Equivalent

3831Anti-Jka

Biotest Outperforms

11031Anti-Fya

Conclusion# Stronger with Biotest Rgts

# Stronger with Reference Rgts

# Samples testedAntisera

Rare Antisera Evaluation Conclusions

• Performance qualification– Anti-e significantly outperforms reference reagents– Anti-S, -s, -Fya, and –P1 shows stronger reactivity

than reference reagent– All reagents show at least equivalent reactivity

– Test Methodology = ease-of-use

– Labor and time savings due to number of antisera not requiring antiglobulin phase

Traditional Reagents: The Biotest Advantage

• Biotest antisera all monoclonal• 16 of 26 Biotest antisera specificities represent

new clones for the US market• Biotest rare antisera do not require antiglobulin

phase except anti-s & anti-Fya

– 5’ RT - Anti-S, anti-K, anti-k, anti-P1– 15’ RT - Anti-Jka, anti-Jkb, anti-Lea

• Biotest panels have 4 ml vs. 3 ml fill volume• Many of the Rh and Rare antisera exhibit greater

avidity (reaction strength) and ease-of-use vs. other supplier’s products

Fully-automated instrument for the hospital transfusion service, prenatal testing and donor centers.

Features• Flexibility

– Batch or random access analyzer– Two, Three or Pooled antibody screening options– 2 STAT modes (Emergency and Express)

• User-Friendly - As easy as 1-2-3. (Load sample, confirm order, press start).

• Seven day on-board reagent and microplate storageIn addition:• Batch or single sample result validation • Enhanced automated maintenance• Automated QC testing – only once per day

Microplate Storage•10 plates•7 days on-board

Plate Loading•Plate barcodes•Strip barcodes

Transport Channel•Individual strips •Test setup and mixing•RT and 37C incubation

Transport Channel•Centrifugation•Washing•Add AHG, if required

Results Interpretation•Measurement chamber•Transport belt to waste

Liquid Reagent Storage•7 day on-board storage•RT and refrigerated storage•Continuous access•Reads barcodes

Sample Loading•Continuous loading•Holds 144 samples

Erytype and Solidscreen Platform

• Eight wells/strip• Strips move through

instrument – not plates

• 12 strips/plate

• Barcoded strips and plates– Product – Strip number– Lot number– Strip type– Expiration date

Superior Reagent Stability

Microplates• Erytype Strips• Solidscreen StripsLiquid Reagents• AHG/IgG• MLB (LISS)• Reverse Cells• Screen Cells• Bromelin

On-board– 7 Days– 7 Days

– 7 Days– 7 Days– 7 Days– 7 Days– 24 Hours

Shelf-life– 18 months– 2 years

– 2 years– 18 months– 5 weeks– 5 weeks– 6 months

ABO/Rh Methodology Erytype S• Standard

hemagglutination testing

• Monoclonal antisera dried in microwells– Reduces waste from

dead volume– Reduces reagent loading– Reduces solid waste

• 7 day onboard shelf-life• 18 month product

shelf-life

ABO/Rh Method• Wells coated with dried monoclonal

antisera

• Red cells suspended in bromelin are pipetted into wells

• Antisera dissolves, test mixture incubated

• Centrifugation and resuspension of test mixture

• TANGO interprets well images

TANGO ABO/Rh Results• Grades reactions• Makes interpretation• Compares with historical results • Stores results and interpretations (~15,000 patients)

Field Trial ABO/Rh NTD Rates

• 51% ABO NTD due to patients condition, multiple transfusions, oncology, bone marrow transplant, etc.

• 24% due to clots/fibrin

• 21% due to weak isohemagglutinins

• 4 % Miscellaneous causes

0.1%Rh

0.03%Rh

ABO

ABO

0.7%Donor Samples

n = 3,208

1.8%Patient Samples

n = 3,449

NTD Rate after repeat testing

Antiglobulin Test MethodologySolidscreen II

– Microplate configuration– Strip and plate barcode process controls– On-board shelf-life is 7 days

– Product shelf-life is 2 years– Unique solidscreen methodology

• Microplate well contains a layer of Protein A, which has a high affinity for the Fc portion of the Anti-Human Globulin (Anti-IgG)

• Screening RBC’s are coated with patient antibodies, if antibodies are present in serum/plasma

•Plasma or serum added to well, followed by MLB (modified LISS) and screening cells

•Incubates for 20 min

at 37 degrees

• Sensitized RBC’s and Anti-IgG bind with Protein A on well surface

• Unsensitized RBC’s form button at bottom of well

•Wells are washed with PBS

•Anti-IgG is added to the wells

Solidscreen II Reaction Patterns

Positive Antibody Screen

Negative Antibody Screen

Field Trial Sensitivity by Method

# Positive with

SolidScreen on TANGO

TANGO Sensitivity

(%)Reference

Method

# Positive with reference method

Reference Method

Sensitivity (%)

36 35 97.2% Immucor Capture 33 91.6%

64 60 93.7% LISS Manual Tube 53 82.8%

19 17 89.5% Ortho Gel 17 89.5%

119 112 94.1% All Methods 103 86.5%

TANGO Reference Methods

# Samples containing antibodies

Antibodies Not Detected

By TANGO• Passive anti-D• Anti-E (3)

– IgM (1)

– +/- LISS (1)

• Anti-C – (Gel -, LISS w+)

• Anti-M (2)

By Reference Method

• Anti-D• Anti-E (3)• Anti- E, K

• Anti-K

• Anti-E, Jka• Anti-M• Anti-Lua

Linauts S, Lammers C, Transfusion, Vol. 44, No. 9S, 2004, p. 123A.

• anti-C

• anti-Jka

• anti-C+Jka

• anti-E

• anti-K

• anti-D

• anti-c+Jka

• anti-c x2

• anti-I

• anti-M x 2

• anti-C (wk +)

• anti-D (micro +) 59509Total

161602 to 3+

30255w to 1+

1394Neg

TotalPositiveNegative

LISS Tube Results (post-thaw)

Solidscreen II Results

Known Antibody Positive Samples (n=59)

Comparison of Solid-Phase Antibody Screening Tests with

Pooled Red Cells in Blood Donors

Reference: Vox Sang 1996;71:37-42

Solid-phase antibody screening in 10,008 blood donorsTechnique number of Detection of donors with

donors detected IgG Antibodies (n=41)

IgGa nonspecificb sensitivity specificity test

% % efficiency c

Capture R Ready Screen 40 61 97.6 99.39 1.40

Solidscreen II (polyspecific AHG) 39 11 95.1 99.88 1.89

Solidscreen II – (Anti-IgG) 38 2 92.7 99.98 1.95

Total d 41 67

a Correct positive test result: IgG antibody with blood group specificity detected.

b False-positive test result: nonspecific positive reactions with all panel cells including the autocontrol.

c The test efficiency (result validity) is the sum of the predictive values for positive and negative test results. A value of 2.0 indicates an optimal test efficiency.

Comparative Studies in Antibody Screening of Blood Donations with Three Different Pooled Red Blood Cell

ReagentsO. Mannherz, B. Siebert, E. A. Scharberg Biotest Medical Diagnostics, Dreieich,

Germany; DRK-BSD-Nord, Institut Lütjensee,Germany; DRK-BSD Baden-Württemberg-Hessen, Institut Baden-Baden,

Germany

• Tested 19,130 using pooled reagent red cells for Solidscreen II and Capture R

• Used semi-automated methods (workstations)

Specificity Sensitivity – Solidscreen II 100% 89.2%– Capture R 99.8% 90%

• Positive Predictive value (probability that when the test is positive that it contains an antibody

– Solidscreen II 97.9%– Capture R 45% (80 positive results/ only 32 were true antibodies)

• Conclusion– “Extremely low rate of false positives with Solidscreen II is highly beneficial by

reducing the amount of extra work required to resolve false positives.”

Load and walk away

144 sample loading capacity

• 12 Racks with 12 samples each

• Continuous availability for sample loading and unloading

Ordering Tests• Random Access Analyzer

– LIS ordering via bidirectional interface– Operator ordering via touchscreen/keyboard/mouse

• Individually by sample• All samples on screen

• Batch Analyzer– Barcoded sample rack – orders same tests for all samples in

rack• Stat Testing

– Add Stat samples at any time– Change sample status to Stat at any time prior to sampling– TANGO skips routine samples and pipettes stats as first

sample in next “mini-batch” (4 samples)

Sample Requirements• Use of primary tubes

– Serum or plasma samples for antibody screening– All common tubes can be used simultanously

(10-16,5mm diameter, 20-115 mm height)

• Positive sample identification– All common barcodes can be read including ISBT code 128

• Sample requirements– 500 ul minimum

• Barcodes on sample rack– The rack barcodes can be used to define single tests or test

profiles.

Reagent Loading and Storage• 12 cooled/ 6 RT positions

• Cells are kept in suspension

• Automatically reads reagent barcodes upon loading

• True level sensing

• 7-day on-board shelf-life for all reagents except bromelin

• Tracks on-board shelf-life

• Can load multiple vials or lot numbers of same reagent

Sample Throughput

• 25 ABO/Rh tests per hour• 60 Antibody screens per hour (2 wells)• 50 ABO/Rh Confirmations per hour• Time to complete

– One ABO/Rh 17 minutes– Four ABO/Rh 22 minutes– One Type and Screen 32 minutes– Four Type and Screens 37 minutes

The Advantage

• Easy to operate:– Flexible operations; continuous access capability– Load samples, request tests, press start– Stores reagents for multiple assay types– Happier techs! - Easy to use by generalists & dedicated staff

• Low Operating Costs:– QC only once a day – Controls not required with each sample or batch– Two, three or pooled screen cell options– Excellent specificity/sensitivity = fewer repeats– On-board reagent storage (7 days) = minimal reagent waste

• Increased Productivity– True Stat capability - Linear rack system means no lock out period– Daily maintenance in less than 10 minutes– Excellent process control– Less reagent manipulation