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1. Manufacturing Plan and Costing
Mr. P. Waghmare
Miss H. Gwani
Miss V. Varkey
Miss S. Jain
Your Safe delivery… our Mr. D. Igwe
utmost concern Mr. A. Awosusi

2. 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

3. 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

4. Comparison
Existing G7
Technology Technology
S.No. Biochemical Marker
Use of three Marker:Plasma Concentration Manifest
Trimester 1 Trimester 2 Preeclampsia
Use of one -PlGF
Marker: PLGF 1.
-sEng
sflt-1 (Soluble fms- -- high Early increase
-sflt
like tyrosine kinase)
2. Soluble Endoglin -- high Early increase
Fluorescence (sEng) nanoparticle
Gold
antibody for antibody with
quantification 3. fluorescence
Placental Growth low low further
Factor (PlGF) decrease

5. SaphvidTM : Working Principle
Reaction Chamber
PlGF
Array of Antibodies sEng
sflt

6. Product Development of SaphvidTM
Validation of raw Validation
materials Assembly Verification
of strip

7. Product Development : Step 1
Validation of
raw materials

8. Raw Materials Validation
Composition and film
Strip material forming temperature
Nanoparticles N-WCPC Model 3788
Strip Western Blot, TME, IHC
Antibody screening in correlation with WB +
IP in cycles
Polystyrene latex Solubility test
Filter test β-Ratio testing

9. 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

10. Product Development : Step 3
Validation of Strip
Marker Control (pg/mL) Pre-eclampsia
(pg/mL)
Sflt-1 1458.8- 4117.6 1615.7-8274.5
PlGF 65.8-285 47.4-151.8
sEng 3573.8-6238 5401-17617.4
If [sflt- 1]/ [PlGF] > 45 High chances of Pre-eclampsia

11. 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
Product Validation
Feedback
Legal
File patent

12. Product Development: Costing
S.No. Tasks Start Date Duration (days) End Date Cost involved
(£'000)
1 Market and customer analysis 25-07-2010 90 23-10-2010 10
(Business plan draft)
3 Identifying the protein markers 25-07-2010 260 11-04-2011
Nano particles testing 25-07-2010 150 22-12-2010
2 Funding 04-11-2010 90 02-02-2011
4 Screening the Antiobodies 1 and 2 23-12-2010 90 23-03-2011 7
5 Contract with suppliers 12-04-2011 90 11-07-2011 10
6 Design Consutlants/ Manufacturers 11-08-2011 90 09-11-2011 5.85
7 Assembly process and testing 10-11-2011 180 08-05-2012 4
8 Product layout optimization 08-05-2012 90 06-08-2012 1.7
9 Quality Control and Assesment 20
Product Validation 24-03-2011 300 18-01-2012
Product Verification 08-05-2012 120 05-09-2012
Feedback 06-08-2012 30 05-09-2012
10 Legal 10-10-2010 600 01-06-2012 30
filing a patent (UK, Europe, world)
licencing
liability
therapeutical consequences
reliability of results
11 Salary 247
Extras: Capital 100
Lab facility development 25
Total 460.55

13. Clinical Trial Design: UK
10 50 5 Hospitals
Regions Hospitals per Region
Test 20patients per No of • Week 12 Req. 2 Strips/patient
Hospital test • Week 19

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

15. Clinical Trials
• No of Subjects:300
Phase • Target: women-
pregnant & non-
1 pregnant (below
menopause)
• No. of Subject: 500
Phase • Target: All are pregnant
women but with varying
2 degree of vulnerability
(High & Low Risk)
• No. Of Subject:1000
Phase • Pregnant women in week
12 and 19 and with are at
3 high risk (>75% risk of
pre-eclampsia)

16. 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

17. Manufacturing Process: Overview
Specification To • Validated Raw
• Inspection & Manufacturer Materials
Approval • Raw Material • Filter, Polystyrene
• Contract Latex, Antibodies,
• Product & Strip Material
(Agreement) Process
Identify Materials from
Manufacturer Supplier

18. Manufacturing Process- cont.
Manufacturing
• Detailed • Quality Check
Instructions • Define Process • Printing &
• To • Batch Size Labeling
Manufacturer Details
• Quality Check
SOP Packaging

19. 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

20. Manufacturing process information
Process Parameters
Scale Pilot scale
Full scale
Equipment Automated and Programmed
Temperature 15 – 20˚C
Relative Humidity 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

21. EQUIPMENT QUALIFICATION
Design • Verifies system design as per User
Qualification (DQ) Requirement Specification (URS).
Operational • Verifies system operations satisfying all
Qualification (OQ) functional requirements.
Installation • Verifies system installation as specified in
Qualification (IQ) the design.
Performance • Verifying that system performance satisfies
all performance requirements including
Qualification (PQ) those specified in the URS.

22. 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.

23. Manufacturing Process Control of Critical steps and Intermediates
Manufacturing step Test Item Methods Acceptance
criteria
After assembly of strip Thickness, width and Vernier calliper 99-100%
material length
After creating capillary Depth, diameter of Laser Micrometer 98-100%
path on the base with capillary and uniformity
laser.
After coating nano- Fluorescence Fluorometer 99-100%
particle fluorescent
antibodies
After coating the Quantity and activity Antigen test and laser micrometer 99-100%
antibody array
After placing filter and Position and diameter Visual inspection 98-100%
time gate and sample Laser micrometer and vernier
port calliper
After placing filter over Appearance Visual inspection 98-100%
strip components
After strip assembly Appearance, mass, Visual inspection, weighing and 99-100%
selectivity and test with pre-eclamptic blood
specificity. sample.

24. Gantt Chart: Manufacturing (Pilot )
07-Sep-12 04-Feb-13 04-Jul-13
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
Identifying centres
Protocol for conducting clinical trials
Analysis of Results
Regulatory Approval

25. 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
2 Inspection and Approval 22-09-2012 20 12-10-2012 2
Contract (Agreement) 13-10-2012 10 23-10-2012
3 Raw material specification 04-11-2012 15 19-11-2012
Product specification 13-10-2012 20 02-11-2012 1
Process Specification + SOP 19-11-2012 75 02-02-2013
4 Manufacturing (Batch Size)
Phase 1: 300 (630) 03-02-2013 7 10-02-2013 12.6
Phase 2: 500 (1050) 15-08-2013 10 25-08-2013 18.9
Phase 3: 1000 (2070) 01-03-2014 20 21-03-2014 37.26
5 Quality Check 11-02-2013 7 18-02-2013 0.5
6 Instructions (define and printing) 19-02-2013 7 26-02-2013 0.075
Labels 27-02-2013 7 06-03-2013 0.12
Packaging 07-03-2013 7 14-03-2013 0.375
Quality Check 15-03-2013 7 22-03-2013 0.5
7 Storage 23-03-2013 2 25-03-2013 0
8 Transport 26-03-2013 1 27-03-2013 2
9 Clinical Trials
Identifying centres 04-11-2012 60 03-01-2013
Consent from patients and hospitals 24-11-2012 60 23-01-2013 5
Protocol for conducting clinical trials 04-11-2012 30 04-12-2012
Documentation 28-03-2013 7 04-04-2013 0.1
Analysis of Results 05-04-2013 10 15-04-2013 0.1
10 Regulatory Approval 16-04-2013 180 13-10-2013 3.5
11 Salary 88
R&D Manager 45
Manufacturing Manager 28
Marketing analyst 15
Total 189.74

26. Cost of manufacturing (full scale)
S. No. Activity Cost GBP (000)(1st year) Cost GBP (000)(2nd year) Cost GBP (000)(3rd year)
1 Salary 299 299 310
2 Manufacturing the strip 4000 4500 5610
3 Packaging 80 87.5 115.5
4 Instructions 24 30 39.6
5 Labelling 30 25 33
6 Quality Check 3 3 3
7 Transport 2 2.5 3.5
8 Documentation 1.5 1.5 1.5
9 Analysis 3 3.5 4
Total 4442.5 4952 6120.1

27. Suppliers:
Raw Materials Specification Suppliers
Strip material Plastic material Millipore Corporation
Filter material PA66, Polyamide Yuexing sailaqi gauze
filter co. Ltd.
Fluorescent FluoroNanogold-anti-human Fab'- Universal Biologicals
nanoparticle- linked Alexa Fluor 488
antibody
PlGF
Human Endoglin/CD105 MAb
Secondary (Clone 166713), Mouse IgG1 R & D systems
antibodies
Human VEGF R1 (Flt-1) MAb
(Clone 49560

28. Packaging
25 packs
Strip wrapped in foil to
keep out moisture
Instruction manual

29. Failure mode and effect
Failure mode Possible effect Corrective action
1.Identify finding
Mistakenly switching (review)
Wrong result Proper labelling of event
Assessment/ raw
Review samples effectiveness of
and report material trays
Report
corrective actions
Contamination of raw Unreliable result Proper storage of raw
materials materials
Wrong analysis for the Unreliable result Print out the
samples analysed from
4.Close finding measurement file
2.Evaluate finding
key steps (verification) (disposition)
Corrective action tracking
and implementation Corrective action plan.
3.Resolve finding
(implementation)

30. 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

31. THANK YOU !