Manufacturing Plan and Costing

Mr. P. Waghmare Miss H. Gwani Miss V. Varkey

Miss S. Jain

Your Safe delivery our utmost concern

Mr. D. Igwe Mr. A. Awosusi

Contents
Introduction G7 Technology: Working Principle

Product Development of SaphvidTM

Product Development: Gantt Chart and Costing Clinical Trials and Their Validation Manufacturing process in detail Summary

G 7 Diagnostic kit
Strip: SaphvidTM

Intended Use: Early detection of Pre-eclampsia.

Device Used: Triage Meter

Need of the hour: No effective diagnostic method available 12% of maternal deaths

Comparison
Existing Technology
Use of one Marker: PLGF

G7 Technology
S.No. Biochemical Marker Use of three Marker:Plasma Concentration Trimester 1 Trimester 2

1.

-PlGF -sEng sflt-1 (Soluble fms-sflt like tyrosine kinase)

Manifest Preeclampsia

--

high

Early increase

Fluorescence antibody for quantification

2.

Soluble Endoglin (sEng) nanoparticle Gold

--

high

Early increase

3.

antibody with fluorescence Placental Growth

Factor (PlGF)

low

low

further decrease

SaphvidTM : Working Principle

Reaction Chamber

PlGF

Array of Antibodies

sEng sflt

Product Development of SaphvidTM

Validation of raw materials

Assembly

Validation of strip

Verification

Product Development : Step 1

Validation of raw materials

Raw Materials
Strip material

Validation
Composition and film forming temperature

Nanoparticles Strip

N-WCPC Model 3788

Antibody screening

Western Blot, TME, IHC in correlation with WB + IP in cycles

Polystyrene latex

Solubility test

Filter test

-Ratio testing

Product Development : Step 2

Validation of raw materials

Assembly

Preparation of 3 layer plastic base (strip) Create micro capillary path on the strip Coat the reagents on the strip Integrate filter over reagents

Product Development : Step 3

Validation of Strip
Marker Sflt-1 PlGF Control (pg/mL) 1458.8- 4117.6 65.8-285 Pre-eclampsia (pg/mL) 1615.7-8274.5 47.4-151.8

sEng

3573.8-6238

5401-17617.4

If [sflt- 1]/ [PlGF] > 45 High chances of Pre-eclampsia

Product Development : Gantt Chart

25-Jul-10 02-Nov-10 10-Feb-11 21-May-11 29-Aug-11 07-Dec-11 16-Mar-12 24-Jun-12 Market and customer analysis (Business plan draft)

Identifying the protein markers

Nano particles testing Funding Screening the Antiobodies 1 and 2 Contract with suppliers Design Consutlants/ Manufacturers Assembly process and testing Product layout optimization Quality Control and Assesment Product Validation Product Verification Feedback Legal

File patent

Product Development: Costing

S.No. Tasks Start Date Duration (days) End Date Cost involved ('000) 1 Market and customer analysis (Business plan draft) Identifying the protein markers Nano particles testing 2 4 5 6 7 8 9 Funding Screening the Antiobodies 1 and 2 Contract with suppliers Design Consutlants/ Manufacturers Assembly process and testing Product layout optimization Quality Control and Assesment Product Validation Product Verification Feedback Legal filing a patent (UK, Europe, world) licencing liability therapeutical consequences reliability of results Salary Capital Lab facility development 25-07-2010 90 23-10-2010 10

25-07-2010 25-07-2010 04-11-2010 23-12-2010 12-04-2011 11-08-2011 10-11-2011 08-05-2012

260 150 90 90 90 90 180 90

11-04-2011 22-12-2010 02-02-2011 23-03-2011 11-07-2011 09-11-2011 08-05-2012 06-08-2012 7 10 5.85 4 1.7 20

24-03-2011 08-05-2012 06-08-2012 10-10-2010

300 120 30 600

18-01-2012 05-09-2012 05-09-2012 01-06-2012 30

10

11 Extras:

247 100 25

Total

460.55

Clinical Trial Design: UK

10 Regions

50 Hospitals

5 Hospitals per Region

Test

20patients per Hospital

No of test

Week 12 Week 19

Req.

2 Strips/patient

Hospitals in major regions:

University Hospital (Coventry)

West Midlands London Royal Bournemouth (general hospital)South west England East of England Hinching BrookeMajor hospital East midlands Region Royal Berkshire hospital Yorkshire and Humber North east England s Bradford royal infirmary North west England Sunderland royal hospital Wales South west England
The royal london hospital James cook university hospital Countess of chester hospital Trowbridge community hospital
http://www.performance.doh.gov.uk/tables97/index.htm

Clinical Trials
Phase 1 Phase 2 Phase 3
No of Subjects:300 Target: womenpregnant & nonpregnant (below menopause)
No. of Subject: 500 Target: All are pregnant women but with varying degree of vulnerability (High & Low Risk)

No. Of Subject:1000 Pregnant women in week 12 and 19 and with are at high risk (>75% risk of pre-eclampsia)

Steps of Clinical Trials

Approval: Hospital board Patient consent Train staff in proper use of the device Use Saphid strips with traditional methods Review clinical record of the patient Data collection Assessment of The Saphid strip Check for discrepancies between our strip and other methods of diagnosis

Manufacturing Process: Overview

Specification To Manufacturer
Validated Raw Materials Filter, Polystyrene Latex, Antibodies, Strip Material

Inspection & Approval Contract (Agreement)

Identify Manufacturer

Raw Material Product & Process

Materials from Supplier

Manufacturing Process- cont.

Detailed Instructions To Manufacturer SOP

Manufacturing Define Process Batch Size Details Quality Check

Quality Check Printing & Labeling

Packaging

Manufacturing process
Produce the plastic base
Three layers of strip material assembled together

Create the capillary path on the base with a laser

Coat the reagents on the strip

Integrate the filter over the reagents

FINAL STRIP

Manufacturing process information

Process Scale Equipment Temperature Relative Humidity Parameters Pilot scale Full scale Automated and Programmed 15 20C 1- 5%

Sterilisation steps and aseptic conditions to be followed during the entire manufacturing process.

Manufacturer of SaphvidTM :
Raupack Limited 131 High Street, Old Woking, GU22 9LD, United Kingdom, tel: +44 (0)1483 736800 fax: 736810, info@raupack.co.uk

EQUIPMENT QUALIFICATION
Design Verifies system design as per User Requirement Specification (URS). Qualification (DQ)
Operational Verifies system operations satisfying all functional requirements. Qualification (OQ) Installation Qualification (IQ)
Verifies system installation as specified in the design.

Verifying that system performance satisfies Performance all performance requirements including Qualification (PQ) those specified in the URS.

Manufacture Process validation and evaluation

Batches:
Number Batch size Place and date of manufacture Yield Batch purpose (Validation, stability, clinical trial)

Process
Equipment Process parameters Validation protocol

Results
Critical steps In process control Finished product specification.

Manufacturing Process Control of Critical steps and Intermediates

Manufacturing step Test Item Methods Acceptance criteria 99-100% 98-100%

After assembly of strip material After creating capillary path on the base with laser. After coating nanoparticle fluorescent antibodies After coating the antibody array After placing filter and time gate and sample port After placing filter over strip components After strip assembly

Thickness, width and length Depth, diameter of capillary and uniformity Fluorescence

Vernier calliper Laser Micrometer

Fluorometer

99-100%

Quantity and activity Position and diameter

Antigen test and laser micrometer Visual inspection Laser micrometer and vernier calliper Visual inspection Visual inspection, weighing and test with pre-eclamptic blood sample.

99-100% 98-100%

Appearance Appearance, mass, selectivity and specificity.

98-100% 99-100%

Gantt Chart: Manufacturing (Pilot )

07-Sep-12 Identify Manufacturer Contract (Agreement) Raw material specification Process Specification + SOP Phase 1: 300 (630) Phase 3: 1000 (2070) Quality Check Instructions (define and printing) Packaging 04-Feb-13 04-Jul-13

Identifying centres Protocol for conducting clinical trials Analysis of Results Regulatory Approval

Cost of manufacturing (Pilot scale)

S.No. Tasks Start Date Duration (days) End Date Costing (000) GBP 1 Identify Manufacturer 07-09-2012 25 02-10-2012 2.5

Inspection and Approval Contract (Agreement) Raw material specification Product specification Process Specification + SOP

22-09-2012 13-10-2012 04-11-2012 13-10-2012 19-11-2012

20 10 15 20 75

12-10-2012 23-10-2012 19-11-2012 02-11-2012 02-02-2013

Manufacturing (Batch Size) Phase 1: 300 (630) Phase 2: 500 (1050) Phase 3: 1000 (2070) Quality Check Instructions (define and printing) Labels Packaging Quality Check Storage Transport Clinical Trials Identifying centres Consent from patients and hospitals Protocol for conducting clinical trials Documentation Analysis of Results Regulatory Approval Salary R&D Manager Manufacturing Manager Marketing analyst Total

03-02-2013 15-08-2013 01-03-2014 11-02-2013 19-02-2013 27-02-2013 07-03-2013 15-03-2013 23-03-2013 26-03-2013

7 10 20 7 7 7 7 7 2 1

10-02-2013 25-08-2013 21-03-2014 18-02-2013 26-02-2013 06-03-2013 14-03-2013 22-03-2013 25-03-2013 27-03-2013

12.6 18.9 37.26 0.5 0.075 0.12 0.375 0.5 0 2

5 6

7 8 9

04-11-2012 24-11-2012 04-11-2012 28-03-2013 05-04-2013 16-04-2013

60 60 30 7 10 180

03-01-2013 23-01-2013 04-12-2012 04-04-2013 15-04-2013 13-10-2013

5 0.1 0.1 3.5 88 45 28 15 189.74

10 11

Cost of manufacturing (full scale)

S. No. Activity 1 2 3 4 5 6 7 8 9 Salary Manufacturing the strip Packaging Instructions Labelling Quality Check Transport Documentation Analysis Total Cost GBP (000)(1st year) Cost GBP (000)(2nd year) 299 4500 87.5 30 25 3 2.5 1.5 3.5 4952 Cost GBP (000)(3rd year) 310 5610 115.5 39.6 33 3 3.5 1.5 4 6120.1

299
4000 80 24 30 3 2 1.5 3 4442.5

Suppliers:
Raw Materials Strip material Filter material Specification Plastic material PA66, Polyamide Suppliers Millipore Corporation Yuexing sailaqi gauze filter co. Ltd.

Fluorescent nanoparticle- linked antibody

FluoroNanogold-anti-human Fab'- Universal Biologicals Alexa Fluor 488 PlGF

Secondary antibodies

Human Endoglin/CD105 MAb (Clone 166713), Mouse IgG1

Human VEGF R1 (Flt-1) MAb (Clone 49560

R & D systems

Packaging

25 packs

Strip wrapped in foil to keep out moisture

Instruction manual

Failure mode and effect

Failure mode Mistakenly switching Review samples effectiveness of and report
corrective actions

Possible effect 1.Identify finding (review) Wrong result

Corrective action Proper labelling of event Assessment/ raw material trays Report Proper storage of raw materials Print out the measurement file 2.Evaluate finding (disposition)

Contamination of raw materials

Unreliable result

Wrong analysis for the Unreliable result samples analysed from 4.Close finding key steps (verification)

Corrective action tracking and implementation 3.Resolve finding (implementation)

Corrective action plan.

Summary
Cost of product development estimated at GBP 460,000 Steps involved in clinical trials

Estimated units of strips to be manufactured:

Year 1: 4,000,000

Total costs associated with manufacturing:

Year 1: GBP 4,442,500

THANK YOU !