1. family and parenting
2. motherhood
3. pregnancy

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CGCC
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CE Technical File
One Step HCG Urine
Pregnancy Test
CONTENTS
No.
Name
I
General Description
II
Quality Control Procedures
III
Design Documents
IV
Production Process
V
Risk Management Report
VI
Essential Requirements
VII
Principle, Test method and Limitation
VIII
Performance Evaluation Data
IX
Labels and Instructions for use
X
Results of Stability Studies
XI
Declaration of Conformity
Appendix I
Test Report
Appendix II
Certificate of Analysis For Biological Products
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Appendix III
Instruction for use
I General Description
1
Product Introduction
2
Classification
3
Characteristic
4
Intended Use
5
List of Components
6
Storage and Stability
7
Warnings & Precautions
We are committed to make diagnostics of diseases easier, faster and less expensive by transferring the benefits of new
research results to the people all around the world.
1. Product Introduction
The One Step HCG Urine Pregnancy Test is a highly sensitive test kit for the determination of HCG in urine specimens.
This test kit is used to obtain a visual, qualitative result for early detection of pregnancy.
2. Classification
Product: One Step HCG Urine Pregnancy Test Classification according to IVD Directive 98/79/EC Annex IV Selftesting Cassette according to IVDD
3. Characteristic
4-1 Easy to use, no additional instrument or reagent is needed;
4-2 Detect within one week of pregnancy;
4-3 Designed for professional and home users;
4-4 High sensitivity and specificity;
4- 5
Each test is enclosed in a moisture proof aluminum pouch with a Silicon Gel for long time storage.
4. Intended Use
5-
1
Cassette: One Step HCG Urine Pregnancy Test measures the presence of the hormone Human Chorionic
Gonadotrophin (HCG) in human urine for the early detection of pregnancy.
5-
2 Strip: One Step HCG Urine Pregnancy Test measures the presence of the hormone Human Chorionic Gonadotrophin
(HCG) in human urine for the early detection of pregnancy.
5-
3 Midstream: One Step HCG Urine Pregnancy Test measures the presence of the hormone Human Chorionic
Gonadotrophin (HCG) in human urine for the early detection of pregnancy.
5. List of Components
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Catalog No.
Product Name
Package
HCG 100
HCG Urine Strip
50tests/Bottle
HCG 110
HCG Urine Strip
100pcs/box
HCG 111
HCG Urine Cassette
25pcs/box
HCG 112
HCG Urine Midstream
1 Test/Pack 36 Pack/Outer
6-1 Human Chorionic Gonadotropin (HCG) Tests Cassettes 61-1 Specification No.
6-1-2 Composition
[Cassette]
Gold conjugates: antip-HCG Antibody
2ug/ml
Test Line: antia-HCG Antibody
1.0-1.2mg/ml
Control line: Rabbit anti Mouse IgG
1.5-2.0mg/ml
Nitrocellulose membrane (S1)
(+0.5mm) 260*19mm
Conjugate pad (S4 )
(+0.5mm) 260*6mm
Absorbent pad (S3)
(+0.5mm) 270*30mm
Fiber glass (S2)
(+0.5mm) 270*24mm
Spinning cloth (S5)
22mm
Double-side plastic tape
58mm
[Strip]
Gold conjugates: Mouse anti-beta HCG monoclonal antibody-gold colloid
1+0.2^g
Test Line: Goat anti HCG
4+0.8^g
Control Line: Goat anti-mouse IgG
2+0.4^g
Nitrocellulose membrane
25+5x4.5+0.9mm
Sample pad
20+4x4.5+0.9mm
Absorbent pad
36+7.2x4.5+0.9mm Sticker of the indication of sample
Sticker for the indication of detection materials
Accessories
Silica Gel Foil
0.5-1.0g/bag
pouch Plastic
60*120mm
Cassette
Size:80*24mm
Midstream
Size:140.3*15mm
Plastic tube
Size: 49*11mm
6-1-3 Biological action
The antibody on the membrane will react specifically with the HCG present in human urine. Mouse anti-beta HCG
monoclonal antibody-gold colloid will react specially with HCG present in human urine/serum.
6-1-4 Appearance
The Human Chorionic Gonadotropin (HCG) Tests Cassette (Strip) has a letter of T and C as “Test Line” and “Control
Line” on the surface of the case. Both the “Test Line” and “Control Line” is used for procedural control. Control line
should always appear if the test procedure is performed properly and the test reagents of control line are working. A
purple “Test Line” will be visible in the result window if there is enough HCG in the sample. If HCG are not present or
are present at very low levels in the sample, there is no color appears in “Test Line”.
A. Cassette
B. Strip
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6-2 HCG Midstream
6-2-1 Characteristic
To squeeze 3 to 4 drops of urine into the sample well. 62-2 Number of droppers
25 tests/kit-25 disposable urine droppers.
100 tests/kit-100 disposable urine droppers.
6-2-3 Biological action N/A
6-2-4 Appearance
Semitransparent polyester like a shape of a club.
6. Storage and Stability
The test kit can be stored at room temperature (2°C to 30°C) in the sealed pouch to the date of expiration. The test kits
should be kept away from direct sunlight, moisture and heat.
7. Warnings & Precautions
8-1 Read directions for use carefully before performing this test. Pay attention to the position of the C and T line.
8-2 Do not use beyond the labeled expiration date.
8-3 Do not reuse the test Cassettes. Discard it in the dustbin after single use.
8-4 Do not use if pouch is damaged or opened.
8-5 Do not touch the membrane on the strip.
8-6 Once open the pouch, the test Cassette should be used immediately. Prolonged exposure to ambient humidity will cause
product deterioration.
8-7 Treat urine samples and used Cassettes as if they are potentially infectious. Avoid contact with skin.
8-8 Examine if the urine cup exists before usage.
II
Quality Control Procedures
1.
Specification and Control of Raw materials
2.
Specification and Control of Intermediate Products
3.
QC Test Protocol
4.
Specification and Control of the Finished Products
5.
Specification and Control of the Packaging Materials
1. Specification and Control of Raw materials
1.1 Mmouse anti- Human HCG (as Test line)
1-
1-1 Purity
1) Specification: >95%
2) The purity of the protein is determined by check. A sample of the purified material as well as the material before
purification are electrophoresed and stained with Brilliant Blue R.
1-
1-2 Protein Concentration
1) Specification:>1.0mg/ml
2) The protein concentration is determined by check of optical density used by spectrophotometer at 279nm.
(factor OD 1.20=1mg/ml)
1-
1-3 Reactivity
1) Specification: 5-10^m against reactivity of passed reference batch.
2) The purified protein is blotted onto nitrocellulose membranes. The capture antibody coated membrane is
assayed with a reference HCG positive panel as well as a reference HCG negative panel. Approval of the capture
antibody is based on the results meeting the specifications set for the reference panel.
1- 2 Goat anti-mouse IgG (as Control line)
1-
2-1 Protein Concentration
1) Specification:>1.0mg/ml
2) The protein concentration is determined by check of optical density used by spectrophotometer at 279 nm.
(factor OD 1.20=1mg/ml).
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1-
2-2 Purity
1) Specification: >95%
2) The purity of the protein is determined by check..
1- 3
Mouse anti beta HCG monoclonal antibody-gold conjugate
1- 3-1 Optical Density
1) Specification: 10.0+1
2) The optical density of the gold conjugate solution is determined by check by spectrophotometer at 540 nm.
1-
3-2 Reactivity
1) Specification: within+ 10% against reactivity of passed reference batch.
2) The gold conjugate solution is dispensed into conjugate pads. The conjugate pad-assembled with passed coated
membrane is assayed with a reference HCG positive panel as well as a reference HCG negative panel. Approval of
the gold conjugate is based on the results meting the specifications set for the reference panel.
2.
Specification and Control of Intermediate Products
2- 1
Coated Membrane [Reactivity]
1)
Specification: within+10% against reactivity of passed reference batch.
2)
The coated membrane-assembled with passed gold conjugate pad is assayed with a reference HCG positive panel as
well as a reference HCG negative panel. Approval of the coated membrane is based on the results meeting the
specifications set for the reference panel.
2- 2 Mouse anti beta HCG monoclonal antibody-gold conjugate pad
[Reactivity]
1)
Specification: within+10% against reactivity of passed reference batch.
2)
The gold conjugate pad-assembled with passed coated membrane is assayed with a reference HCG positive panel as
well as a reference HCG negative panel. Approval of the gold conjugate pad is based on the results meeting the
specifications set for the reference panel.
2- 3 Laminated (Assembled) Strip [Reactivity]
1)
Specification: within+10% against reactivity of passed reference batch.
2)
The laminated (assembled) strip is assayed with a reference HCG positive panel as well as a reference HCG
negative panel. Approval of the laminated (assembled) strip is based on the results meeting the specifications set
for the reference panel.
3. QC Test Protocol
3- 1 Introduction
Quality control evaluation is performed on all raw materials, intermediate components produced as well as the assembled
kit.
3- 2 Control Procedures
3-
2-1 In-coming QC evaluations are performed on all in-coming raw materials. The quarantined raw materials are
prepared by the respective productions section and are sent to QC section for evaluation.
Upon evaluation, QC section Head will endorse the evaluation data and assign quality status to the raw materials
accordingly.
Only approved raw materials are used for production of products.
3-
2-2 On-line QC inspection and Test
All lots of individual intermediate components produced are inspected and tested on-line. Systematic sampling of
each individual lot of intermediate components is done and the samples are sent to QC for evaluation.
Function tests are performed by assaying the test intermediate component in parallel with a reference
intermediate component on our product. Physical inspections of the test component are also carried out.
Upon analyzing the evaluation results, QC section Head will assign the quality status for the intermediate
components. The approved intermediated components are moved from the quarantined storage area to the approved
storage area. Those components that did not passed the evaluation will be rejected and not used in the production.
3-
2-3 Final QC Test and inspection
Final QC evaluation is carried out once the individual approved intermediate components are assigned to be
assembled into a kit. This test is to ensure that the individual assay components in a kit are properly matched to
produce optimal results during assays.
Evaluation of a in-house QC specificity and sensitivity panel must also meet the specifications before approval.
The QC panel consists of 6 samples, 4 for the sensitivity test and 2 for the specificity test.
Upon QC approval, the individual approved components will be assigned for kit assembly.
Physical inspection is performed on all assembled kits. Physical inspection is performed on all assembled kits.
Physical inspection of kits includes checking the labels, lot number and expiry date of the individual components as
well as the assembled kit.
The kits are ready for shipment once they passed this final stage QC inspection.
3- 3 Reference Components used in QC
The reference components used for evaluation of individual intermediated components as well as the final
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assembled kits are approved components from pervious production lots. These reference components are tested to ensure
that results obtained are within the QC specification for the product.
4. Specification and Control of the Finished Products
4- 1 Introduction
The finished products of One Step HCG Urine Pregnancy Test kit includes test Cassette.
Quality control evaluation is performed on every lot of test Cassette.
4- 2 Control Procedures
The quality control procedures used of evaluation of the finished products are:
4-
2-1 Test Cassette’s appearance must be suitable of product-licensing status.
4-
2-2 Performance test for Test Cassette
For the quality testing of the our HCG Cassettes, there are two in-house reference panels, one for HCG positive
while the other for HCG negative.
1) In-house reference panel for the sensitivity test (HCG positive)
(1) The QC panel consist of 4 members, numbered 25,50,250,500 mIU HCG/ml.
(2) An assay is performed using the standard assay procedure with the members of the QC panel.
(3) Each panel is assayed in replicate.
(4) If there is and indication of two lines (C,T), assign a positive result.
(5) If there is an indication of only one line (C), assign a negative result.
(6) Specification: all panels must be interpreted as positive.
2)
In-house reference panel the specificity test (HCG negative)
(1) The QC panel consist of 2 members, 0 mIU HCG/ml, 200m IUhLH/ml.
(2) An assay is performed using the standard assay procedure with the members of the QC panel.
(3) Each panel is assayed in replicate.
(4) If there is an indication of two lines (C,T), assign a positive result.
(5) If there is an indication of only one line (C), assign a negative result.
(6) Specification: all panels must be interpreted as negative.
4- 3 Specification
4-
3-1 Performance test for Test Cassette.
1) In-house reference panel for the sensitivity test (HCG positive)
HCG Concentration
Acceptable Criteria
25 mIU/ml
Weak Positive
50 mIU/ml
Medium Positive
250mIU/ml
Strong Positive
500mIU/ml
Strong Positive
*
Intensity of the overall intensity of the test lines are scored as follows:
- Strong Positive Intensity: 3+
- Medium Positive Intensity: 2+
- Weak Positive Intensity: 1+
- No test lines /Intensity: 2) In-house reference panel for the specificity test (HCG negative)
Concentration
Acceptable Criteria
0 mIU HCG/ml
Negative
200 mIU hLH/ml
Negative
5. Specification and Control of the Packaging Materials
5- 1 Introduction
Packaging materials are materials purchased from vendors for the purposed of production (packaging process).
5- 2 In-coming QC evaluation on the packaging materials are performed upon receipt of goods.
5-
2-1 Plastic Cassette (Cassette)
1) Appearance: No dust and no debris
2) Specification for size: Inner-strip’s frame must be rightly located as a specification.
5-
2-2 Aluminum foil pouch
1) Degree of strictness: Confirmation of maintenance for tightness.
2) Printed contents must be suitable for product for product-licensing status.
5-
2-3 Silica gel
[Confirmation of Drying]
5-
2-4 Instruction for use (Insert)
Printed contents must be suitable for product-licensing status.
5-
2-5 Package
Printed contents must be suitable for product-licensing status.
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III
1.
Parts List
2.
Raw Material Specifications
3.
Drawings
4.
Test Procedure
Design Documents
1. Parts list
Cassette
Strip
Midstream
Test Strip
Test Strip
Test Strip
Cassette
Desiccant
Stick
Urine dropper
Foil pouch
Desiccant
Desiccant
Box
Foil pouch
Foil pouch
Box
Box
2. Raw Material Specifications
2- 1 Specification
Item
Membrane @Sj@
Specification
Cellulose nitrate membrane Thickness 110-160^m Absorption time 0.2750.333mm/sec Intensity > 1 Lb/per inch
Colloidal gold@S4@
Fiber glass@S2@
Particle size: 60nm
Absorbent paper0 S3 0
Absorbent cotton Thickness 15mils Size of the pore 39^m
Spinning cloth0S5@
Plastic Board
Size: 7.9*26cm
Thickness: 0.5mm color: white weight: 11g
2-2 Membrane
Lines on the membrane
Control Line
Material Name
Rabbit anti Mouse IgG
Specification
Classification: IgG1 Activity: ELISA 1:128 Work
Concentration: 1.5-2.0mg/ml Preservative:
0.05%NaN3 Storage: 4°C
Test Line
Anti a-HCG antibody
Classification: IgG1
Purity: SDS-PAGE
Work Concentration: 1.0-1.2mg/ml Preservative: 0.05%NaN3
Storage: 4°C
2-3 Colloidal gold
Material Name
Antibody on the colloidal gold
Anti P-HCG Antibody
Specification
Classification: IgG1 Purity: SDS-PAGE
Work Concentration:2ug/ml Preservative:
0.05%NaN3 Storage: 4°C
2-4 Desiccant
Item
Specification
Silica gel
Gel: white particle and some blue particle Diameter: 1~2mm Water amount: < 4%
Weight: 0.5g, 1.0g
Desiccant package paper
Size: 27cm Color: white & blue
Words: DESICCANT, THROW AWAY, DO NOT EAT
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2-5 Others
Item
strip
Specification
Size:75*3.5mm, 7.5*0.35cm Color: blue handle
Item
Cassette
Specification
Size:80*24mm, 8*2.4cm Color: white, white/pink
Item
midstream
Foil pouch
Specification
Size:140.3*15mm, 4.3* 1.5cm Color: white and purple cup
For strip: 120 *50mm
For Cassette: 120*65mm
For midstream:190*55mm
Sealed in three sides: 5.0±1.0mm
Colored pouch with instruction, English colored pouch
Packing box
Strip: 210*125*55mm (for 50pcs) Casseete:210*125*65mm (for 25pcs)
Midstream:190*60*15mm (for single package)
3. Drawings
3- 1 Cassette
3- 2 Test strip
3- 2 Midstream
Cap
Absorbent Sampler Show Window
Handle
4. Test Procedure
4-1 Strip
4-1-1 Bring the test pouch and urine to room temperature. To begin testing, open the sealed pouch by tearing along the
notch. Remove the test from the pouch..
4-1-2 Immerse the strip into the urine with the arrow end pointing towards the urine. Do not immerse past the MAX
(maximum) line. Take the strip out after 5 seconds and lay the strip flat on a clean, dry, non-absorbent surface (See
the picture).
4-1-3 Wait for colored bands to appear. Depending on the concentration of HCG in the test specimen, Positive results
may be observed in as short as 40 seconds. However, to confirm Negative results, the complete reaction time (5
minutes) is required. So read the result within 5 minutes. Do not read results after 10 minutes.
4-1-4 Discard the test Cassette after single use in the dustbin.
4-2 Cassette
4-2-1 Bring the test pouch and urine to room temperature.
4-2-2 To begin testing, open the sealed pouch by tearing along the notch. Remove the test from the pouch.
4-2-3 Using the sample dropper, draw about 3 drops (approximately 120~150^L) urine sample from the specimen
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cup into the pipette, and dispense it into the sample well on the cassette. (Please send the “Slip Shutter” to sample
well if it has.)
4-2-4 Wait for the colored bands to appear. Depending on the concentration of hCG in the test specimen, positive results
may be observed in as short as 40 seconds. However, to confirm negative results, the complete reaction time (5
minutes) is required. So read the result within 5 minutes. Do not read results after 10 minutes.
4-2-5 Discard the test Cassette after single use in the dustbin.
4-3 Midstream
4-3-1 To begin testing, open the sealed pouch by tearing along the notch. Remove the test kit from the pouch and use it as
soon as possible.
4-3-2 Hold the handle of the test with one hand. Use the other hand to remove the cap and expose the absorbent. Put the
cap aside for now.
4-3-3 Point the absorbent tip downward; place the absorbent tip in urine stream for at least 10 seconds to be thoroughly
wet. Otherwise, you can collect your urine into a clean container (not provided ) and dip half of the absorbent pad into
the urine for at least 10 seconds
4-
3-4 Re-cap the Cassette and wait for colored bands to appear. Depending on the concentration of hCG, positive
results may be observed in as soon as 40 seconds. However, to confirm negative results, the complete reaction time of
5 minutes is required. It is important that the background is clear before the result is read. Do not read result after
more than 10 minutes.
4-
3-5 Discard the test Cassette after single use in the dustbin.
IV
Production Process
1.
Overall Flow Chart of Production Process
2.
Raw Materials Production
3.
Test Cassette Components Production
4.
Cassette Assembly and Sealing
5.
Packaging Process
6.
In-process Control of Production Process
1. Overall Flow Chart of Production Process
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000 Reagent making
000
S4 00
S5 00
S2 00
Membrane coating
S4 making
S5 making
S2 making
Preparation of reaction
membrane
S2: 0000
Fiber glass
S1000000
cellulose nitrate membrane
S3: 000
Absorbent paper
S4: 000
Colloidal gold
S5: 000
Spinning cloth
0 0 0 0 0 Sealing used
by foil pouch printed
2.
Raw Materials Production
2-1 Manufacturing of goat anti HCG (as Test line)
2-1-1 Acquiring of human chorionic gonadotrophin in urine of pregnant woman.
2-1-2 Isolation, purification of immunogen (HCG)
The desired immunogen was made as following procedures.
1) The urine of pregnant woman is purified by monoclonal antibody to HCG coupled sepharose gel, and then eluted by
0.1M glycine solution.
2)
After dialyzing of eluted HCG, it uses as a immunogen.
3)
The immunogen is made up by mixing purified HCG, Freund’s adjuvant, complete and saline.
2-1-3 Injection of 2-1-2 immunogen to goat.
2-1-4 Collecting whole blood from 2-1-3 immunized goat and then centrifuge to get serum.
2-1-5 Titration of goat anti HCG in goat serum used by ELISA method.
2-1-6 After purification of goat anti HCG, protein concentration is determined by BCA method.
2-1-7 Goat anti HCG solution as test line is prepared with 1.0 mg/ml.
2-2 Manufacturing of goat anti-mouse IgG (as Control line)
2-2-1 Isolation and purification of mouse IgG from mouse serum by using of protein A gel.
2-2-2 Preparation of immunogen. The immunogen is made up by mixing purified mouse IgG, Freund’s adjuvant,
complete and saline.
2-2-3 Injection of 2-2-2 immunogen to goat (body weight about 30kg) 4 times as the interval of 1 month.
2-2-4 Collecting whole blood from 2-2-3 immunized goat and then centrifuge to get serum.
2-2-5 Titration of goat anti-mouse IgG in goat serum used by ELISA method.
2-
2-6 The goat serum is then purified by mouse IgG coupled sepharose 4B gel.
2-
2-7 Eluted solution containing specific goat anti-mouse IgG are then pooled together and protein concentration is
determined with BCA protein assay.
2-
2-8 Solution as control line is prepared with 1 mg/ml.
2- 3 manufacturing of mouse anti beta HCG monoclonal antibody-gold conjugate
2-
3-1 Acquiring of human chorionic gonadotro-phine in urine of pregnant woman.
1-
3-2 Manufacturing of Immunogen (HCG)
The desired immunogen was made as following procedures;
1-
3-3 Injection of 2-1-2 immunogen to balb/c mouse.
1-
3-4 Making hybridoma for producing of mouse anti beta HCG.
2-
3-5 Isolation of cell line to produce mouse anti beta HCG and culture of cell line.
2-
3-6 Inoculation of the cell line into abdominal cavity of mouse.
2-
3-7 Purification of mouse anti beta HCG, acquiring of mouse anti beta HCG monoclonal antibody.
2-
3-8 Preparation of gold chloride solution. This solution is made up by mixing 0.01% gold chloride and 0.1%
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sodium citrate.
2-3-9 Adding 1^g/ml of mouse anti beta HCG monoclonal antibody and 0.2MK2CO3 solution to 2-3-1 solution, and then
stirring the mixture for 3 minutes.
2-3-10 Adding 1% stopping solution.
2-
3-11 Solution as gold conjugate is prepared with the O.D 10 at 540 nm using by spectrophotometer.
3. Test Cassette Components Production
3- 1 Manufacturing of Coated Membrane
3-
1-1
Preparation for membrane lamination: Fix a 25mm x 300mm of nitrocellulose membrane onto the 300mm
x 68mm of plastic card.
3-
1-2 Dispensing of materials for control line and test line at the concentration of above 2-1 and 2-2.
3-
1-3 The coated membranes are then dried in a 370 incubator for 1 hour.
3- 2 Manufacturing of Conjugate pad.
2-
2-1 Preparation of pad material (glass fiber).
2-
2-2 Immerse prepared conjugate pad materials in of mouse anti beta HCG monoclonal antibody-gold conjugate
solution at the concentration of above 2-3.
2-
2-3 And then the conjugate pads are dried in a 400 incubator for 2 hours.
3-
2-4 Above dried conjugate pads are then cut into the size of 7mm x 30mm with a cutter.
3- 3
Preparation of sample pad, Absorbent Pad.
3-
3-1 Preparation of sample pad material at the size of 20mm x 30mm.
3-
3-2 Preparation of absorbent pad material (cellulose pad) at the size of 18mm x 30mm.
4. Cassette Assembly and Sealing
4- 1
Lamination
Laminating of above 2-1~3-3 materials as below.
[Cross Section Scheme of Lamination]
1)
2)
6)
3)
7)
1) Sample pad
2) Gold-conjugate pad
3) Coated nitrocellulose membrane
4)
5)
4) Test line
5) Control line
6) Absorbent pad
7)
Plastic card
4- 2 Cutting
Laminated plastic cards are cut into the size of 4.5mm x 68mm with a cutter.
4- 3 Plastic Cassette Assembly
Assemble cut-strips into the complete plastic Cassette.
4- 4
Sealing
Individual Cassettes are sealed together with silica gel using aluminum foil pouch. The pouch is clearly labeled with lot
number and an expiry date.
5. Packaging Process
5- 1
5-
For final kit assembly, the required QC approved components are issued from the components’ storage area.
2 All the components are issued according to the lot numbers on the packaging detail list. The kit is then
assembled. The number of a component type issued, corresponds to the number of kits assembled.
5- 3
Final kit inspection of the outgoing kits is carried out by QC technicians prior to shipment.
6. In-process Control of Production Process
6- 1
Introduction
The in-process control steps are introduced at strategic steps to monitor the quality of products. The in-process controls
performed, within the various levels of production, are in accordance with in-house standard operating procedure.
6- 2 Raw materials Production
6-
2-1 The in-process control steps are introduced at strategic steps of goat anti-HCG (as Test line), goat antimouse immunoglobulin (as Control line) and of mouse anti beta HCG monoclonal antibody-gold conjugate
production to monitor the quality of products. The in-process controls performed are in accordance with in-house
standard operating procedure.
6-
2-2 Goat anti-HCG (as Test line) production
1) Titration of hybridoma cell line to produce goat anti-HCG is used by ELISA method.
2)
The protein concentration of acquired goat anti-HCG is determined with optical density of spectrometer at
280nm (factor: 0D1.20=1.0mg/ml).
6-
2-3 Goat anti-mouse immunoglobulin G (as Control line) production.
1) Titration of goat anti-mouse IgG in goat serum used by ELISA method.
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2)
The protein concentration of the acquired goat ant-mouse IgG is determined with optical density of
spectrophotometer at 280nm. (factor OD 1.39»1.0mg/ml)
6-
2-4 Mouse anti beta HCG monoclonal antibody-gold conjugate production.
1) Optical density of prepared gold conjugate is determined at 540 nm using by spectrophotometer.
2) Check the migration appearance of prepared gold conjugate.
6- 3 Test Cassette Components Production
The three kinds of production capacity of One Step HCG Urine Pregnancy Test is approximately 28,800 tests, 57,600
tests and 115,200 test per production run, respectively. The in-process controls performed are:
6-
3-1 Membrane Coating (C, T line)
1) 100% visual inspection of all nitrocellulose membranes to make sure that none are damaged or moldy.
2) The dispensing volume is calibrated at the start of the process by checking the accuracy of the dispensing
volumes.
3) 100% visual inspection to ensure that the designated areas on all the membranes are spotted with the antibody
for test line and antibody for control line.
4)
6-
Visual inspection of membranes to ensure that all membranes are dried before cutting (100% sampling).
3-2 Immersing the conjugated pad in mouse anti beta HCG monoclonal antibody-gold conjugate solution.
1) 100% visual inspection of all conjugate pads during the immersing stage to ensure that the conjugate pads are
submerged under the solutions.
2) Visual inspection of all conjugate pads to ensure that all conjugate pads are dried before cutting (100%
sampling).
6- 4 Assembly into plastic Cassettes
100% visual inspection of assembled Cassettes to check the membranes are properly attached and assembled.
6- 5 Assembly of Final Kit
6-
5-1 Inspection of component being issued for assembly is carried.
6-
5-2 Checks on the assembled kits are carried out at the completion of assembly. This is done prior to the final
out-going QC inspection being performed by the QC section.
V
Risk Management Report
1. General Information
2. About Product
3. Implementation of risk analysis procedure
4. Result of the risk analysis
1. General Information
1.1 Summary
1.1.1 For in vitro diagnostic medical devices, taking into account the particularities and specific aspects of these
medical devices, the large majority of such devices do not constitute a direct risk to patients and are used by
competently trained professionals, and the results obtained can often be confirmed by other means, however, indirect
risks may result from hazards associated with in vitro diagnostic medical device, leading or contributing to erroneous
decisions. In addition, whereas specimens from any patient could be infected with bloodborne pathogens, use-related
hazards and their associated risks should be considered.
1.1.2 This document is a risk analysis for One Step HCG Urine Pregnancy Test (hereinafter called HCG). All hazards
and each potential reason causing the relevant hazard have been judged in this document. This document also
estimates the degree of harm caused by all kinds of hazards and the possibility of occurrence of the hazards. If there
are acceptable ways to reduce the risk, descriptions have been made and the remaining risk level after making the
ways has been estimated.
1.1.3 Note: The HCG product has twelve years history of production in marketing this product in world. For this existing
product, this risk management will be performed retrospectively. In the unlikely case that the retrospectively
performed risk analysis for this product, which is already on the market shows an unacceptable risk, the product has to
be re-designed before CE marking.
1.1.4 Result: By means of considerable ways, all risks, which may cause hazards, are reduced to an acceptable level, and
the total number of all kinds of hazards is reduced to an acceptable level. Risk is proportional to usability.
1.2 Purpose
1.2.1 The main purpose of this risk analysis is to make judgment to the risk that may be caused by HCG and to determine
the diagnostic requirements for this product. Furthermore, description of necessary measurement shall be made to
reduce the risk to an acceptable level.
1.2.2 The description makes a requirement to the HCG product, and will be reevaluated after finishing the
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improvement.
1.3 Scope
The HCG product concerning in this risk analysis consists of the following mode:
A. Cassette
B. Strip
C. Midstream
1.4 Reference
1.4.1 Reference to Standards
1.4.1.1 Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic
medical devices (IVD)
1.4.1.2 EN ISO 14971:2000 Medical devices - Application of risk management to medical devices
1.4.2 Specification
See ALK-CE-HCG “General Description”
1.4.3 Other information or data
For estimating risks, other information or data can be obtained, for example, from —scientific technical
data —field data from same or similar medical devices already in use including published reported incidents
—usability tests employing typical users —clinical evidence
—feedback information from customer —observation and research of market requirement —information during the
development —material diagnostic safety data sheet from Material vendor —expert opinion
—external quality assessment schemes
2. About Product
2.1 General Description and Intended Use
2.1.1 General Description
The HCG product is a highly sensitive test kit for the determination of HCG in urine specimens. This test kit is
used to obtain a visual, qualitative result for early detection of pregnancy. There characteristics are: (1) easy to use,
no additional instrument or reagent is needed; (2) detect within one week of pregnancy; (3) designed for
professional and home users; (4) high sensitivity and specificity; (5) each test is enclosed in a moisture proof
aluminum pouch with a Silicon Gel for long time storage.
2.1.2 Intended Use
2.1.2.1 Cassette: HCG measures the presence of the hormone Human Chorionic Gonadotrophin (HCG) in
human urine for the early detection of pregnancy.
2.1.2.2 Strip: HCG measures the presence of the hormone Human Chorionic Gonadotrophin (HCG) in
human urine for the early detection of pregnancy.
2.1.2.3 Midstream: HCG measures the presence of the hormone Human Chorionic Gonadotrophin (HCG) in human
urine for the early detection of pregnancy.
2.2 Principle of the function
2.2.1 The HCG assay is a rapid one-step test, based on an immunochromato graphic technology. A membrane with an
absorbent pad overlapping a strip of fiber glass paper that is impregnated with a lyophilized colloidal conjugate of gold
particles and monoclonal solid phase antibodies to HCG. Other absorbent pads at the end of the assay absorb excess
sample fluid. The urine sample is introduced into the device, and moves along the absorbent pad, then laterally onto a
chromatographic membrane. As it contacts the membrane, the sample dissolves the lyophilized conjugate. In a reactive
sample, the HCG antigen will attach to the antibodies in the colloidal solution. As the conjugate moves forward on the
membrane, anti-HCG monoclonal antibody affixed on the test zone (“T”) will bind the HCG-gold conjugate complex,
forming a pink line (“T”). Any sample will cause a pink colored line to appear in the control zone (“C”).
2.2.2 This line is formed by the binding of the polyclonal antibodies (Anti-mouse IgG) affixed onto the control zone to the
sample-colloidal gold conjugate. Presence of this line indicates that the test has been carried out correctly. In less than
5 minutes, levels of HCG as low as 25mlU/ml can be detected.
2.3 Applicable environment
20-300
2.4 Reference data of risk analysis
3. Implementation of risk analysis procedure
According to ISO14971:2000 method for Implementation of risk analysis can refer to the list of judgment of risk analysis
report in following:
3.1 Urine samples
3.1.1 168 randomly selected urine samples from specimen bank which is maintained in Dept. of Obstetrics and
Gynecology at the Hospital.
3.1.2 Positive panels-25. 50, 250, 500mIU/ml HCG.
3.1.3 Negative Positive panels-0 mIU/ml HCG, 200miu/ml HLH
Normal urine samples including 200mIU/ml HLH
Normal urine samples including 1000mIU/ml HFSH
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Normal urine samples including 1000mIU/ml Htsh.
3.1.4 Analysis of the Results
The sensitivity and specificity will be calculated as follows:
No. of urine samples with positive results
Sensitivity (%) =100X ----------------------------------------------------------------------------No. of positive urine samples confirmed as pregnancy
No. of urine samples with negative results
Specificity (%) =100X----------------------------------------------------------------------------No. of negative urine samples confirmed as non-pregnancy
3.2 Classification of the result of risk analysis
The detailed result of risk analysis is classified: 1) very serious; 2) Serious; 3) Mild; 4) Trivial
3.3 Judgement of potential hazards
3.3.1 Definition of ‘ ‘hazard”
Occurrence of hazard is usually a result of causality. It begins with technical (mostly can not be copied) and trivial
psychological causes, bringing harm to human, property and environment. This risk analysis define “hazard” as a link
between the first point in the casual chain and the sufferer (the person or the product)
3.3.2 Relevant potential hazards
According to clinical use of products in many users, relevant information, professional knowledge and experience
acquired, EC team judged the potential hazard of HCG product as follows:
3.3.2.1 Hazard to the person (the person subjected to examination/user/other person)
The time that becomes pregnant to be short.
3.3.2.2 Hazard to the product
A. Some kind of component has falls off (i.e. Colloidal Gold layer)
B. Product term of validity
3.3.3 Existing and Foreseeable Hazards to Human Bodies During the Using Process of HCG test kits (Three Formats)
Strips
Version/Rev. B/1
Number
01
02
Cassette
Number
Risk
Description
Causes
Grade of harms to human
Specific harms to
Preventive
body (1, Negligible; 2,
human body
Measures that
Marginal; 3, Critical)
can be taken
False Positive Negligible
The effect of Perform lab analysis Make a mistake
interfering with every lot of conclusion
substances products
False
Negative
Risk
Description
Negligible
The effect of Perform lab analysis Make a mistake
interfering with every lot of conclusion
substances products
Grade of harms to human Causes
body (1, Negligible; 2,
Marginal; 3, Critical)
Preventive Measures that Specific harms
to human body
can be taken
01
False
Positive
Negligible
The effect of
interfering
substances
Perform lab analysis with Make a
every lot of products
mistake
conclusion
02
False
Negative
Negligible
The effect of
interfering
substances
Perform lab analysis with Make a
every lot of products
mistake
conclusion
Midstream
Number
Risk
Description
Grade of harms to human Causes
body (1, Negligible; 2,
Marginal; 3, Critical)
Preventive Measures that Specific harms
can be taken
to human body
01
False
Positive
Negligible
The effect of
interfering
substances
Perform lab analysis with Make a
every lot of products
mistake
conclusion
02
False
Negative
Negligible
The effect of
interfering
substances
Perform lab analysis with Make a
every lot of products
mistake
conclusion
If not totally avoidable, what extra measures can we take to reduce harms to human body.
Beside above measures, we can also reduce potential hazards by performing test for more than one time.
3.4 Estimation of the occurrence probability of each reason No. Class
Likelihood (events per year and device)
1 Incredible < 10-6
2 Improbable 10-4 - 10-6
3 Remote 10-2 - 10-4
4 Occasional 10-1 - 10-2
5 Probable 1 - 10-1
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6 Frequent > 1
The assumed occurring probability to the potential reasons of each hazard is recorded in the column “W” of the risk
management table with the type of classification number (1-6).
3.5 Estimation of risks and relevant measure
3.5.1 Two risk parameters are summarized for each item of hazard/cause: the degree of harm and the occurring probability.
Therefore, the risk is identified. According to the proposal of Annex E, IS014971:2000, three “risk scope” are
defined.
1. Not acceptable region
2. Broadly acceptable region
3. Risk as low as reasonable practicable (ALARP)
3.5.2The degree of harm and occurring probability of each group are fallen under the three classes in the following table.
Severity
Likelihood
Class
No
1
Negligible
2
Marginal
3
Critical
-------------------------6
Frequent
5
Probable
4
Occasional
3
Remote
AK
2
Improbable
AK
AK
1
Incredible
AK
AK
AK
NAK = not acceptable
AK = broadly acceptable
ALARP = risk as low as reasonable practicable
The evaluated risk of each hazard/cause is recorded in the column “R” of the risk management table with the type of
the classification of risk scope (NAK/AK/ALARP).
3.5.3 Definition of measure
Supposed estimated risk is not to be recorded in risk scope “AK” as no measure has been taken, it is necessary to
specify the measure for each hazard/cause. Should there be many measures at the same time, it is necessary to refer
to the result brought by all measures using together for its effect. Drafted measures are recorded in Column
“Relevant Measure” in the Form of Risk Management and marked as “M...”.
3.5.4 Estimation of risk after taking measure
It is supposed to limit damage or reduce its occurrence, or both will minimize after applying relevant treatment. To
what degree a group of treatment can limit the causes of risk, generally speaking it is hardly to
judge the degree of reduction (degree of damage or probability of occurrence) as a fixed item. This estimation is a
summarization of essence from members of EC team in company.
Each change is recorded in column “Applying Relevant Treatment” in the form of Risk Management and marked as
“M...”.
Remaining risk of each hazard/cause can be judged from the above table for risk scope (NAK/AK/ALARP) to which
it belongs.
RemarkB ALARP does not mean fulfill the goalBbut risk scope “Acceptable” Bonly if the fee caused by measure
taken to reduce risk further more is larger than the profit it broughtBALARP as remaining risk can be acceptable. If
result of reducing risk is ALARPBit is necessary to make an explanation why it is impractical to reduce the risk
further more.
4. Result of the risk analysis
4.1 As displayed on the risk management table, the remaining risk of each hazard/cause is reduced to the region of AK or
ALARP. Meanwhile, an explanation is made to each ALARP situation why it’s impractical to reduce the risk farther more.
4.2 In the following table, the number of the hazard/cause item in every column under the situation of applying treatment
and not applying treatment are showed. Thus it can be seen that under the situation of not applying treatment, there are 2
NAK and 1 ALARP. While under the situation of applying treatment, NAK doesn’t appear any more.
Not applying relevant treatment
1
Applying relevant treatment
Severity
23
Probability
6
5
4
3
2
1
¥//s?/A
In this way, the total number of remaining risk can be considered acceptable.
Because is broadly used in developed countries for many years, and also used in partial developing countries over recent
years, and the clinical effect of the HCG product is obvious, the benefit refer to ALK-CE-HCG Device Description, the
benefit needn’t explain here. Therefore, the remaining risk keeps under a low level, and the risk is proportional to the
benefit.
VI
Essential Requirements
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1. List of European Standards and International Standards
2. Essential Requirements Checklist
1. List of European Standards and International Standards
No.
Standard Reference
Titles
1
IVDD 98/79/EC
2
EN 376:2002
3
EN 13532:2002
testing
General requirements for in vitro diagnostic medical Device for self-testing
4
EN 13640: 2002
Stability testing of in vitro diagnostic medical Device
5
EN 13641: 2002
6
EN 13612: 2001
Performance evaluation of in vitro diagnostic medical Device
7
EN 980:2002
Graph and symbol used in the label of medical Device
8
EN 928:1995
Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998
on in vitro diagnostic medical Device
Information supplied by the manufacturer with in vitro diagnostic reagents for self-
Elimination or reduction of risk of infection related to in vitro diagnostic reagents
In vitro diagnostic systems - Guidance on the application of EN29001 and EN46001
and of EN29002 and EN46002 for in vitro diagnostic medical Device
9
ISO 13485: 2003
The demand of quality management system of medical Device and standard Quality
10
ISO 14971: 2000
systems Medical Device
Usage of risk analysis and management on medical Device
11
EN 540:1993
Clinical investigation of medical Device
2. Essential Requirements Checklist
Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
ISO 14971:2000 EN
ALK-CE-HCG
I. General requirements
1. The Device must be designed and manufactured in such a way that,
A
when used under the conditions and for the purposes intended, they will
540:1993
not compromise, directly or indirectly, the clinical condition or the
(Risk
Management
safety of the patients, the safety or health of users or, where applicable,
Report)
other persons, or the safety of property. Any risks which may be
ALK-CE-HCG
associated with their use must be acceptable when weighed against the
(Clinical Data)
benefits to the patient and be compatible with a high level of protection
of health and safety.
2. The solutions adopted by the manufacturer for the design and
A
ISO 14971:2000
construction of the Device must conform to safety principles, taking
ALK-CE-HCG
(Risk
account of the generally acknowledged state of the art.
Management
Report)
In selecting the most appropriate solutions, the manufacturer must apply
the following principles in the following order:
— eliminate or reduce risks as far as possible (safe design and
construction),
— where appropriate take adequate protection measures in relation to
risks that cannot be eliminated,
— inform users of the residual risks due to any shortcomings of the
protection measures adopted.
3. The Device must be designed and manufactured in such a way that
A
EN 980:2002
ALK-CE-HCG
they are suitable for the purposes referred to in Article 1(2)(b), as
(Clinical Data) ALK-
specified by the manufacturer, taking account of the generally
CE-HCG
acknowledged state of the art. They must achieve the performances, in
System)
particular, where appropriate, in terms of analytical sensitivity,
diagnostic sensitivity, analytical specificity, diagnostic specificity,
accuracy, repeatability, reproducibility, including control of known
relevant interference, and limits of detection, stated by
(Packing
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Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
the manufacturer.
The traceability of values assigned to calibrators and/or control
materials must be assured through available reference measurement
procedures and/or available reference materials of a higher order.
4. The characteristics and performances referred to in sections 1 and 3
A
EN 540:1993
ALK-CE-HCG
must not be adversely affected to such a degree that the health or the
(Clinical Data) ALK-
safety of the patient or the user and, where applicable, of other persons,
CE-HCG
are compromised during the lifetime of the device as indicated by the
System)
(Packing
manufacturer, when the device is subjected to the stresses which can
occur during normal conditions of use. When no lifetime is stated, the
same applies for the lifetime reasonably to be expected of a device of
that kind, having regard to the intended purpose and the anticipated use
of the device.
5. The Device must be designed, manufactured and packed in such a way
A
EN 980: 2002
ALK-CE-HCG
that their characteristics and performances during their intended use will
(Packing
System)
not be adversely affected under storage and transport conditions
ALK-CE-HCG
(temperature, humidity, etc.) taking account of the instructions and
(Labeling)
information provided by the manufacturer.
B. Design and manufacturing requirements
1. Chemical and physical properties
.1. The Device must be designed and manufactured in such a way as to
achieve the characteristics and performances referred to in section A on
the ‘General requirements’. Particular attention must be paid to the
possibility
of
impairment
of
analytical
performance
due
to
incompatibility between the materials used and the specimens (such as
biological tissues, cells, body fluids and micro-organisms) intended to
be used with the device, taking account of its intended purpose.
A
EN 980:2002
ALK-CE-HCG
(Labeling)
Essential Requirement
1.2. The Device must be designed, manufactured and packed in such a way
A or
Reference
Conformity
N/A
Standards
Evidence
A
EN 980:2002
ALK-CE-HCG
(Labeling)
as to reduce as far as possible the risk posed by product leakage,
contaminants and residues to the persons involved in the transport,
storage and use of the Device, taking account of the intended purpose of
the products.
2. Infection and microbial contamination
2.1. The Device and their manufacturing processes must be designed in such
A
EN 980: 2002
ALK-CE-HCG
a way as to eliminate or reduce as far as possible the risk of infection to
(General
the user or other persons. The design must allow easy handling and,
Description)
where necessary, reduce as far as possible contamination of, and leakage
from, the device during use and, in the case of specimen receptacles, the
risk of contamination of the specimen. The manufacturing processes
must be appropriate for these purposes.
2.2. Where a device incorporates biological substances, the risks of infection
A
ALK-CE-HCG
must be reduced as far as possible by selecting appropriate donors and
Design
appropriate substances and by using appropriate, validated inactivation,
Document
conservation, test and control procedures.
2.3. Device labelled either as ‘STERILE’ or as having a special
NA
microbiological state must be designed, manufactured and packed in an
appropriate pack, according to procedures suitable for ensuring that they
remain in the appropriate microbiological state indicated on the label
when placed on the market, under the storage and transport conditions
specified by the manufacturer, until the protective packaging is damaged
or opened.
2.4. Device labelled either as ‘STERILE’ or as having a special
NA
microbiological state must have been processed by an appropriate,
validated method.
2.5. Packaging systems for Device other than those referred to
NA
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Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
in section 2.3 must keep the product without deterioration at the level of
cleanliness indicated by the manufacturer and, if the devices are to be
sterilised prior to use, reduce as far as possible the risk of microbial
contamination.
Steps must be taken to reduce as far as possible microbial contamination
during selection and handling of raw materials, manufacture, storage and
distribution where the performance of the Cassette can be adversely
affected by such contamination.
2.6. Device intended to be sterilized must be manufactured in appropriately
N/A
controlled (e.g. environmental) conditions.
2.7. Packaging systems for non-sterile device must keep the product
NA
without deterioration at the level of cleanliness stipulated and, if the
devices are to be sterilized prior to use, minimize the risk of microbial
contamination; the packaging system must be suitable taking account of
the method of sterilization indicated by the manufacturer.
3. Manufacturing and environmental properties
3.1. If the device is intended for use in combination with other device or
NA
equipment, the whole combination, including the connection system,
must be safe and must not impair the specified performances of the
device. Any restrictions on use must be indicated on the label and/or in
the instructions for use.
3.2. Devices must be designed and manufactured in such a way as to reduce
N/A
as far as possible the risks linked to their use in conjunction with
materials, substances and gases with which they may come into contact
during normal conditions of use.
3.3. Device must be designed and manufactured in such a way as to remove
or reduce as far as possible:
NA
Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
A
ISO 14971:2000
— the risk of injury linked to their physical features (in particular aspects
of volume x pressure, dimension and, where appropriate, ergonomic
features),
— risks linked to reasonably foreseeable external influences, such as
ALK-CE-HCG
magnetic fields, external electrical effects, electrostatic discharge,
(Risk
pressure, humidity, temperature or variations in pressure or acceleration
Management
or accidental penetration of substances into the device.
Report)
Device must be designed and manufactured in such a way as to provide
N/A
an adequate level of intrinsic immunity of electromagnetic disturbance
to enable them to operate as intended.
3.4. Device must be designed and manufactured in such a way as to reduce
N/A
as far as possible the risks of fire or explosion during normal use and in
single fault condition. Particular attention must be paid to device whose
intended use includes exposure to or use in association with flammable
substances or substances which could cause combustion.
3.5. Device must be designed and manufactured in such a way as to
NA
facilitate the management of safe waste disposal.
3.6. The measuring, monitoring or display scale (including colour change
A
ISO 14971:2000
ALK-CE-HCG
and other visual indicators) must be designed and manufactured in line
(Risk
with ergonomic principles, taking account of the intended purpose of the
Management
device.
Report)
4. Device which are instruments or apparatus with a measuring
function
4.1 Devices which are instruments or apparatus having a primary
analytical measuring function must be designed and manufactured in
such a way as to provide adequate stability and
N/A
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Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
accuracy of measurement within appropriate accuracy limits, taking into
account the intended purpose of the device and of available and
appropriated reference measurement procedures and materials. The
accuracy limits have to be specified by the manufacturer.
4.2 When values are expressed numerically they must be given in legal
units conforming to the provisions of council Directive 80/181/EEC of
20 December 1979 on the approximation of the laws of the member
states relating to units of measurement.
5. Protection against radiation
N/A
5.1 Device shall be designed manufactured and packaged in such a way
that exposure of users and other persons to the emitted radiation is
minimized.
5.2 When devices are intended to emit potentially hazardous, visible and/or
invisible radiation, they must as far as possible be.
Designed and manufactured in such a way as to ensure that the
characteristics and quantity of radiation emitted can be controlled and/or
adjusted.
Fitted with visual displays and/or audible warnings of such emissions.
5.3 The operating instructions for device emitting radiation must give
detailed information as to the nature of the emitted radiation, means of
protecting the user, and on way of avoiding misuse and of eliminating
the risks inherent in installation.
6. Requirements for medical Device connected to or equipped
with an energy source
6.1 Device incorporating electronic programmable systems including
software, must be designed to ensure the repeatability, reliability and
performance of these systems according to the intended use.
N/A
T
CE Technical File
Document No
ALK-CE-HCG
One Step HCG Urine Pregnancy Test
Page
38/65
A or
Reference
Conformity
N/A
Standards
Evidence
Essential Requirement
6.2 Device must be designed and manufactured in such a way as to
minimize the risks of creating electromagnetic perturbation which could
impair the operation of other device or equipment in the usual
environment.
6.3 Device must be designed and manufactured in such a way as to avoid, as
far as possible the risk of accidental electric shocks during normal use
and in single fault condition provided the device are installed and
maintained correctly.
6.4 Protection against mechanical and thermal risks
Devices must be designed and manufactured in such a way as to protect
the user against mechanical risks. Device must be sufficiently stable
under the foreseen operating conditions. They must be suitable to
withstand stresses inherent in the foreseen working environment, and to
retain this resistance during the expected life of the device, subject to
any inspection and maintenance requirements as indicated by the
manufacture.
Where there are risks due to the presence of moving parts, risks due
to break-up or detachment, or leakage of substances, then appropriated
protection means must be incorporated.
Any guards or other means included with the device to protection, in
particular against moving parts, must be secure and must not interfere
with access for the normal operation of the device, or restrict routine
maintenance of the device as intended by the manufacturer.
Device must be designed and manufactured in such a way as to reduce to
the lowest possible level the risks arising from vibration generated by
the device, taking account of technical progress and of the means
available for progress and of the means available for limiting vibrations,
particularly at source, unless the librations
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Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
EN 980:2002
ALK-CE-HCG
are part of the specified performance.
Device must be designed and manufactured in such a way as to reduce
as far as possible the risks arising from the noise emitted, taking account
of technical progress and of the means available to reduce noise emitted
is part of the specified performance.
Terminals and connectors to electricity, gas or hydraulic and pneumatic
energy supplies which the user has to handle must be designed and
manufactured in such a way as to minimize all possible risks.
Accessible parts of the device (excluding the parts of areas intended to
supply hear or reach given temperatures) and their surroundings must
not attain potentially dangerous temperatures under normal use.
7. Requirements for Device for self-testing
Device for self-testing must be designed and manufactured in such a
A
way that they perform appropriately for their intended purpose taking
ISO13485:2003
into account the skills and the means available to users and the influence
(Labels and
Instructions for use)
resulting from variation that can reasonably be anticipated in users’
technique and environment. The information and instructions provided
by the manufacturer should be easily understood and applied by the
user.
7.1 Device for self-resting must be designed and manufactured in such a
A
way as to :
EN 980:2002
ISO13485:2003
-ensure that the device is easy to use by the intended lay user at all
ALK-CE-HCG
-reduce as far as practicable the risk of user error in the handling of the
(General
device and in the interpretation of the results.
control, i.e. a procedure by which the user can verity that, at the time of
use, the product with perform as
(Labels and
Instructions for use)
stages of the procedure, and
7.2 Device for self-testing must, where reasonable possible, include user
ALK-CE-HCG
Description)
A
EN 980:2002
ISO13485:2003
ALK-CE-HCG
(Labels and
Instructions for
Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
intended.
use)
ALK-CE-HCG
(General
Description)
8. Information supplied by the manufacturer
8.1. Each device must be accompanied by the information needed to use it
A
safely and properly, taking account of the training and knowledge of the
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
potential users, and to identify the manufacturer. This information
Instructions for use)
comprises the data on the label and in the instructions for use.
As far as practicable and appropriate, the information needed to use the
A
device safely and properly must be set out on the device itself and/or,
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
where appropriate, on the sales packaging. If individual full labeling of
Instructions for use)
each unit is not practicable, the information must be set out on the
packaging and/or in the instructions for use supplied with one or more
device.
Instructions for use must accompany or be included in the packaging of
A
one or more device.
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
In duly justified and exceptional cases no such instructions for use are
needed for a device if it can be used properly and safely without them.
8.2. Where appropriate, the information to be supplied should take the form
A
of symbols. Any symboland identification colour used must conform to
the harmonized standards. In areas for which no standards exist, the
supplied with the device.
considered as being dangerous, taking account of
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
symbols and colour used must be described in the documentation
8.3. In the case of device containing or a preparation which may be
EN 980:2002
NA
t: 01 835 2411 f: 01 835 2461
email: service@medguard.ie
Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
the nature and quantity of its constituents and the form under which they
are present, relevant danger symbols and labeling requirements of
Directive 67/548/EEC and Directive 88/379/EEC shall apply. Where
there is insufficient space to put all the information on the device itself
or on its label, the relevant danger symbols shall be put on the label and
the other information required by those Directives shall be given in the
instructions for use.
The provisions of the aforementioned Directives on the safety data sheet
NA
shall apply, unless all relevant information as appropriate is already
made available by the instructions for use.
8.4. The label must bear the following particulars which may take
A
the form of symbols as appropriate:
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
(a) the name or trade name and address of the manufacturer. For Device
imported into the Community with a view to their distribution in the
Community, the label, the outer packaging, or the instructions for use
shall contain in addition the name and address of the authorized
representative of the manufacturer;
(b) the details strictly necessary for the user to uniquely identify the device
A
and the contents of the packaging;
EN 980:2002
ALK-CE-HCG
IS013485:2003
(Labels and
Instructions for use)
(c) where appropriate, the word ‘STERILE’ or a statement indicating any
NA
special microbiological state or state of cleanliness;
(d) the batch code, preceded by the word ‘LOT’, or the serial number;
A
EN 980:2002
ALK-CE-HCG
IS013485:2003
(Labels and
Instructions for use)
Essential Requirement
(e) if necessary, an indication of the date by which the device or part of
A or
Reference
Conformity
N/A
Standards
Evidence
A
it should be used, in safety, without degradation of performance,
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
expressed as the year, the month and, where relevant, the day, in that
Instructions for use)
order;
(f) in case of Device for performance evaluation, the words ‘for
NA
performance evaluation only’;
(g) where appropriate, a statement indicating the in vitro use of the
A
device;
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
(h) any particular storage and/or handling conditions;
A
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
(i) where applicable, any particular operating instructions;
(j) appropriate warnings and/or precautions to take;
NA
A
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
(k) if the device is intended for self-testing, that fact must be clearly
A
stated.
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
8.5. If the intended purpose of the device is not obvious to the user, the
A
manufacturer must clearly state the intended purpose in the instructions
for use and, if appropriate, on the label.
8.6. Wherever reasonable and practicable, the device and separate
components must be identified, where appropriate in terms of batches, to
allow all appropriate action to detect any potential risk posed by the
Device and detachable components.
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
NA
t: 01 835 2411 f: 01 835 2461
email: service@medguard.ie
Essential Requirement
8.7. Where appropriate, the instructions for use must contain the
A or
Reference
Conformity
N/A
Standards
Evidence
A
following particulars:
EN 980:2002
ALK-CE-HCG
IS013485:2003
(Labels and
Instructions for use)
(a) the details referred to in section 8.4 with the exception of points (d)
and (e);
(b) composition of the reagent product by nature and amount or
NA
concentration of the active ingredient(s) of the reagent(s) or kit as well
as a statement, where appropriate, that the device contains other
ingredients which might influence the measurement;
(c) the storage conditions and shelf life following the first opening of the
NA
primary container, together with the storage conditions and stability of
working reagents;
(d) the performances referred to in section 3 of part A;
(e) an indication of any special equipment required including
NA
NA
information necessary for the identification of that special equipment for
proper use;
(f) the type of specimen to be used, any special conditions of collection,
NA
pre-treatment and, if necessary, storage conditions and instructions for
the preparation of the patient;
(g) a detailed description of the procedure to be followed in using the
NA
device;
(h) the measurement procedure to be followed with the device including
as appropriate:
— the principle of the method,
— the specific analytical performance characteristics (e.g. sensitivity,
and measurement range, including information needed for the control of
known relevant interferences), limitations of the method and information
NA
Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
about the use of available reference measurement procedures and
materials by the user,
— the details of any further procedure or handling needed before the
device can be used (for example, reconstitution, incubation, dilution,
instrument checks, etc.),
— the indication whether any particular training is required;
(i) the mathematical approach upon which the calculation of the
NA
NA
analytical result is made;
(j) measures to be taken in the event of changes in the analytical
performance of the device;
(k) information appropriate to users on:
NA
NA
— internal quality control including specific validation procedures,
— the traceability of the calibration of the device;
(l) the reference intervals for the quantities being determined, including
A
a description of the appropriate reference population;
EN 980:2002
ALK-CE-HCG
ISO13485:2003
(Labels and
Instructions for use)
(m) if the device must be used in combination with or installed with or
NA
connected to other medical Device or equipment in order to operate as
required for its intended purpose, sufficient details of its characteristics
to identify the correct Device or equipment to use in order to obtain a
safe and proper combination;
(n) all the information needed to verify whether the device is properly
installed and can operate correctly and safely, plus details of the nature
and frequency of the maintenance and calibration needed to ensure that
the
NA
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Essential Requirement
A or
Reference
Conformity
N/A
Standards
Evidence
device operates properly and safely; information about safe waste
disposal;
(o) details of any further treatment or handling needed before the device
NA
can be used (for example, sterilization, final assembly, etc.);
(p) the necessary instructions in the event of damage to the protective
NA
packaging and details of appropriate methods of resterilisation or
decontamination;
(q) if the device is reusable, information on the appropriate processes to
allow
reuse,
including
cleaning,
disinfection,
packaging
NA
and
resterilisation or decontamination, and any restriction on the number of
reuses;
(r) precautions to be taken as regards exposure, in reasonably foreseeable
NA
environmental conditions, to magnetic fields, external electrical
influences, electrostatic discharge, pressure or variations in pressure,
acceleration, thermal ignition sources, etc.;
(s) precautions to be taken against any special, unusual risks related to the
A
EN 980:2002
ALK-CE-HCG
use or disposal of the device including special protective measures;
(Labels and
where the device includes substances of human or animal origin,
Instruction for use)
attention must be drawn to their potential infectious nature;
(t) specifications for Device for self-testing: (omit)
A
EN 980:2002
ALK-CE-HCG
(Labels and
Instruction for use)
(u) date of issue or latest revision of the instructions for use.
A
EN 980:2002
ALK-CE-HCG
(Labels and
Instruction for use)
VII
Principle, Test Method and Limitation
1.
Principle and Physical Description of the Test
2.
Test Method
3.
Limitation of the Method
1. Principle and Physical Description of the test
The HCG assay is a rapid one-step test, based on an immunochromato graphic technology. A membrane with an absorbent
pad overlapping a strip of fiber glass paper that is impregnated with a lyophilized colloidal conjugate of gold particles and
monoclonal solid phase antibodies to HCG. Other absorbent pads at the end of the assay absorb excess sample fluid. The
urine sample is introduced into the device, and moves along the absorbent pad, then laterally onto a chromatographic
membrane. As it contacts the membrane, the sample dissolves the lyophilized conjugate. In a reactive sample, the HCG
antigen will attach to the antibodies in the colloidal solution. As the conjugate moves forward on the membrane, anti-HCG
monoclonal antibody affixed on the test zone (“T”) will bind the HCG-gold conjugate complex, forming a pink line (“T”).
Any sample will cause a pink colored line to appear in the control zone (“C”).
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This line is formed by the binding of the polyclonal antibodies (Anti-mouse IgG) affixed onto the control zone to the
sample-colloidal gold conjugate. Presence of this line indicates that the test has been carried out correctly. In less than 5
minutes, levels of HCG as low as 25mlU/ml can be detected.
The One Step HCG Urine Pregnancy Test contains a membrane strip, which is pre-coated with capture antibody (goat
anti-HCG) on test band region and goat anti-mouse IgG on the control band region. During testing, the specimen is
allowed to react with colored conjugate (mouse anti-beta HCG monoclonal antibody-colloidal gold conjugate) which
was pre-dried on conjugate pad. The mixture (mouse anti-beta HCG monoclonal antibody colloidal gold + HCG in
specimen) then move upward on the membrane chromatographically by capillary action. For a positive result, a purplecolored band with the HCG in specimen-mouse anti-beta HCG monoclonal antibody-colloid conjugate complex will
form in the test band region of result window. Absence of this purple-colored band in the test band region suggests a
negative result. Regardless of the presence of HCG, as the mixture continues to move across the membrane to
immobilized goat anti-mouse IgG, a purple colored band at the control band region of result window will always appear.
The presence of purple-colored band serve as 1) verification that sufficient volume is added, 2) that proper flow is
obtained, and 3) as a control for the reagents. One Step HCG Urine Pregnancy Test Cassette has a letter of “T” and “C”
as “Test line “and “Control line” in the result window. Both the test line and control line in result window are not visible
before applying any samples. Besides, One Step HCG Urine Pregnancy Test Cassette has a letter of “S” as “Sample
well” for dispensing sample.
2.
Test Method
2- 1 Specimen collection and storage
[Urine]
2-
1-1 First morning urine typically contains the highest concentration of HCG and is therefore the best sample for
performing the urine test. However, any urine specimen may be used.
2-
1-2 Collect the urine specimen in a clean glass or plastic container. Do not use preservatives.
2-
1-3 If the specimen is not used immediately following collection, but is to be used within 48 hours it should be
refrigerated (2 to 80), and brought back to room temperature (15 to 300) before testing. If specimen is not going to be
used for more than 48 hours, it should be frozen at -200. A frozen specimen must be completely thawed, thoroughly
mixed, and brought to room temperature.
2- 2 Procedure of the test
2-
2-1 Remove the test Cassette from the foil pouch, and place it on a flat, dry surface.
2-
2-2 Holding the urine dropper above the test Cassette, squeeze 3 to 4 drops of urine into the urine well (S).
2-
2-3 As the test begins to work, you will see purple color move across the result window in the center of the test
Cassette.
2-
2-4 Interpret test results at 3 minutes.
2-
2-5 Caution: The above interpreting time is based on reading the test results at room temperature of 15-300. If
your room temperature is significantly lower than 150, them the interpreting time should be properly increased.
2- 3
Interpretation of the test
2-
3-1 A color band will appear in the left section of the result window to show that the test is working properly.
This band is the Control Band.
2-
3-2 The right section of the result window indicates the test results. If another color band appears in the right
section of the result window, this band is the test band.
2-
3-3 Negative Result
The presence of only one purple color band (Control Band ) within the result window indicates that you are most
likely not pregnant and the test has been performed correctly.
2-
3-4 Positive Result
The presence of two purple color bands (“T” band and “C” band ) within the result window, regardless to which
one appears first, means that you are likely to be pregnant.
2-
3-5 Note: A positive result will not change once it has been established at 3 minutes. However, in order to
prevent any incorrect results, the test result should not be interpreted after 3 minutes.
2-
3-6 Invalid Result
If the purple color band is not visible within the result window after performing the test, the result is considered
invalid. Some causes of invalid results are : not following the directions correctly or the test may have deteriorated
beyond the expiration date. It is recommended that the specimen be re-tested using a new test kit.
3.
Limitation of the Method
3- 1
Precaution
The One Step HCG Urine Pregnancy Test should be stored at room temperature. The test is sensitive to humidity
as well as heat. Perform the test immediately after removing the test from the foil pouch. Do not use it beyond the
expiration.
3-1-1 For in vitro diagnostic use only.
3-1-2 Do not eat or smoke while handling specimens.
3-
1-3 Wear protective gloves while handling specimens. Wash hands thoroughly afterwards.
3-
1-4 Avoid splashing or aerosol formation.
3-
1-5 Clean up spills thoroughly using an appropriate disinfectant.
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3-
1-6 Decontaminate and dispose of all specimens, reaction kits and potentially contaminated materials, as if they
were infectious waste, in a biohazard container.
3-
1-7 Do not use the test kit if the pouch is damaged or the seal is broken.
3- 2 Limitation of the test
3-
2-1 One Step HCG Urine Pregnancy Test is not reusable.
3-
2-2 The test works only if the instruction are followed precisely.
3-
2-3 Unseal the foil pouch before using the test kit. In case of keeping under being refrigerated *2 to 8 degrees C),
it should be brought back to room temperature (15 to 30 degrees C ) for 20 minutes before testing.
3-
2-4 Do not reuse the used.
3-
2-5 A negative result obtained from a urine specimen collected from a mother in very early pregnancy may be due
to an extremely low concentration of HCG. In such cases, the test should be repeated on a fresh specimen obtained
two days later.
3-
2-6 In addition to pregnancy, HCG has been found in patients with both gestation and no-gestation trophoblast,
diseases. These conditions should be ruled out when interpreting HCG levels to establish a pregnancy diagnosis.
3-
2-7 After normal pregnancy, caesarean section, miscarriage, abortion. It can be detected the HCG for several
weeks.
3-
2-8 A normal pregnancy cannot be distinguished from an entopic pregnancy based solely on HCG levels. Also, a
spontaneous miscarriage may cause confusion in interpreting test results. In case of that, a suspected ectopic
pregnancy may be further evaluated using a quantities HCG assay.
3-
2-9 A third of all pregnancy has a miscarriage naturally; so then, there is a positive result during the early
pregnancy. And there are a negative result after the natural miscarriage. In the cases of a weak positive result, the test
should be repeated on a fresh specimen obtained two days later.
3-
2-10 According to persons. It can be appeared as a negative result due to the low concentration of HCG even if
there are the negative test result, don not take medicine, avoid strenuous exercise to be hazardous for a baby’s health.
3-
2-11 If there are no scheduled menstruation under the negative test result. Retest after 7 days. If the test result is
just the same, meet the physician obstetrician.
VIII
1.
Expected Values
2.
Sensitivity
3.
Specificity
4.
Storage
5.
Expiration Dating
6.
Method of Manufacture
7.
Clinical Trials
8.
Conclusion
Performance Evaluation Data
1. Expected values
The One Step HCG Urine Pregnancy Test rapid kit is capable of testing HCG levels of 25mIU/ml based capable of
correlation with WHO 3rd International Standards.
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Sensitivity
25 mIU/mL hCG in urine sample.
2. Specificity
3.1Cross Reactivity
The cross reactivity of hCG test kits was evaluated with hCG homologous hormones. Homologous hormones FSH, LH and
TSH were added to urine samples containing hCG at concentration of 0, 20 or 100 mIU/mL. No cross reactivity was
observed in the study (shown in Table 1).
2.2 Non-specific interference
One-Step hCG test was checked for possible interference from visibly hemolyzed, lipemic and icteric samples. Human
hemoglobin, bilirubin or albumin was spiked into samples with different concentration of hCG and tested using un-spiked
samples as controls. No significant interference was observed in 20 samples with results that were either positive or
negative for hCG. The results are shown in Table 2.
Table 1 - Cross-reactivity study of One-Step hCG test kit
hCG conc.
Unspiked
in
sample serum or urine
(mIU/mL)
samples
0
20
100
Urine samples spiked with homologous hormones
FSH
LH
1000 mIU/ml 1000 mIU/ml
-
TSH
1000 mIU/ml
-
-
-
-
-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
- Non-specificity study of One-Step hCG test kits
Sample No
Unspiked
samples
1
2
3
-
Urine samples spiked with (mg/mL)
Bilirubin
Albumin
0.06
100
-
Hemoglobin
10 1
----
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
3. Storage
4 to 30oC
4. Expiration Dating:
24 months from date of manufacture
5. Method of Manufacture:
6.1 Nitrocellulose Membrane Manufacture
6.1.1 The purified monoclonal antibody, diluted in phosphate buffer saline, is coated on the test region. Simultaneously,
goat anti- mouse IgG polyclonal antibody, diluted in phosphate buffer saline, is coated on the control region.
6.1.2 The coated membrane is dried for a minimum of 24 hours then sealed in an aluminum bag which contains silica gel
desiccant.
6.2 Anti-hCG colloidal gold conjugate pad manufacture
6.2.1 A buffer solution containing mouse Anti-hCG monoclonal antibody/colloidal gold conjugate is coated onto nonwoven cloth sheets.
6.2.2 The coated non-woven cloth is dried for minimum 24 hours then sealed in an aluminum bag which contains desiccant.
6.3 Test Device Assembly
6.3.1The coated membrane S1, the conjugate pad S4, and an absorbent pad is applied to an adhesive-coated backing.
6.3.2 A 2-part waterproof label is applied over the conjugate pad and the absorbent pad, the assembled sheet of
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material is cut into strips. The test strips are then vacuum-dried for a minimum of 4 hours.
6.3.3 The assembled test strip is sealed in an aluminum pouch along with a desiccant packet.
6. Clinical Trials
7.1 To establish the sensitivity and specificity of Atals link One-Step hCG urine pregnancy test kit relative to other rates of
qualitative urine hCG tests, 425 samples from women suspected of being pregnant were studied. The overall accuracy of
Atlas link One-Step hCG urine pregnancy test kit in this study was 100%, i.e., 425 samples got the expected results when
confirmed with results from clinical follow ups.
7.2 A commercially available qualitative test kits (ICON hCG) was used to compare with Atlas link One-Step hCG urine
pregnancy test test kit for relative sensitivity and specificity in 803 urine samples. In total, 8 samples were discordant. In
turn, the agreement is 99.0%. The results are shown in Table 3.
Table 3 - Comparison of One-step hCG with ICON product for 803 cases
Results of Atlas link
One-Step hCG urine
Subtotal
pregnancy test kit
Results of
ICON kits
Subtotal
+
484
7
491
+
-
1
311
312
485
318
803
Based on quantitative test results on those discrepant samples (n = 8), IND Diagnostic’s hCG test kits have better
sensitivity and specificity. The results are shown in Table 4. All of these 8 discrepant samples were confirmed with
clinical follow up 2 weeks later.
Table 4 - Quantitative results of discrepant samples
Sample
No.
1
2
3
4
5
6
Quantitative
results (mIU/mL)
25
100
28
25
40
26
ICON
kits
Atlas link One-Step hCG
urine pregnancy test kit
+
-
+
+
+
+
+
7
8
50
28
-
+
+
7. Conclusion
This study shows that One Step HCG Urine Pregnancy Test kit has its advantages. Using One Step HCG Urine Pregnancy
Test kit is very simple, quick and it does not need any special equipments and with high degree of accuracy and specificity.
Therefore, One Step HCG Urine Pregnancy Test will be suitable to be adopted in clinical laboratory of basic hospital for
screening of pregnancy.
IX
1.
Label Design
2.
Label Language
3.
Special Requirements
4.
5.
Instructions for use
Attachment (Sample)
Labels and Instructions for use
10 Label design
There are three kinds of labels: small labels (the one on the tube), medium label (the one on the pack), outer labelB the
one on the carton 0 A label must include the following content:
1.1
Name and address of manufacturer and Importer (authorized representative in Europe);
1.2
Product name, type, specification, quantity;
1.3
Symbol for ‘ ‘DO NOT REUSE” or ‘ ‘SINGLE USE”, ‘ ‘USE ONLY ONCE”
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1.4
Validated date and symbol (USE BY):
1.4.1
Symbol:
1.4.2
Symbol followed by date. 4 digits for year, 2 digits for month.
1.4.3
No stipulation for size and location of symbol and date.
1.4.4
The symbol and date shows that to use before this date.
1.5
Batch code and symbol
1.5.1
Symbol
1.5.2
Symbol followed by batch code.
1.5.3
No stipulation for size and location of symbol and date.
1.5
Date of manufacture and symbol (DATE OF MANUFACTURE):
1.6.1
Symbol
8 digits to show.
1.6.2
Symbol followed by date, the first 4 for year, the next two for month
1.6.3
No stipulation for the size and location of symbol and digit.
1.6.4
No stipulation for their size and location.
1.7
Please look up in the directions for the symbols and content
1.7.1
Symbol:
1.7.2
The background color is yellow, foreground color is black; the symbol size is not stipulated as long as it can be noticed.
1.7.3
Some content drawing user’s attention should go under the symbol:
1.7.3.1 Method of use (special operation instructions);
1.7.3.2 Storage condition;
1.7.3.3 “DO NOT USE IF PACKING BROKEN”
1.8
Mark with CE after certification
1.8.1
Drawings
C<E
0123
1.8.2
The diameter of the drawing >5mm.
1.8.3
At the lower right corner of the CE mark, label the registration number of the certification body.
1.8.4
CE-mark should be distinct, clear and wear well.
2. Label language
2.1 Language confirmation through following method: l Notify Body. l CE Representative l Forwarder
l Samples provided by customers.
2.2 Instruction on all labels should be with at least one legal language of the country to which the goods are to be sold.
Austria
Belgium
Denmark
Finland
Norway
Portugal
Spain
ffl
ffl
ffl
ffl
ffl
ffl
ffl
ffl
ffl ffl
ffl
ffl
ffl
Slovenia
Slovak
ar
n
u
Polish
an
ii
Latvian
n
ot
s
Es
Russian
Czech
Swedish
Spanish
Portuguese
Italian
Icelandic
ffl
Italy
Luxembourg
Greek
German
ffl
Germany
Iceland
Ireland
French
ffl
ffl ffl
ffl
France
Greece
Holland
Finnish
English
Dutch
Danish
Country^
Norwegian
a
ii
^\Language
Lithuanian
2.3 List
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ffl
Sweden
ffl ffl
Swiss
ffl
UK
Cyprus
ffl
ffl
Czech
ffl
ffl
Estonia
Latvia
ffl ffl
ffl
ffl
ffl
Lithuanian
ffl
Malta
Poland
ffl
ffl
Slovakia
Slovenia
ffl
ffl
Hungary
30 Special requirements
For that label (or mark) which has special requirements from the customer, design as above mentioned except the content
that should meat customer’s requirements.
4. Instructions for use
A urine specimen must be collected in a clean and dry container. The first morning urine specimen is preferred since it
generally contains the highest concentration of HCG; however, urine specimens collected at any time of the day may be
used. Urine specimens exhibiting visible precipitates should be settled to obtain a clear specimen for testing. Urine cup
should be used to collect specimens (for strip/ cassette format).
Please see Appendix III
5.
Attachment (Sample)
5-1 Cassette format (pouches)
1 piKK'ptKkigk^
C^0f
M
M
_|_
■
'
ONE STEP
(Caw<Hc)
HCG URINE PREGNANCY TEST
1 fm to rttt C«a« •••!>. IIh Btly | lt»*»
,.r'A ® Mi
WUH M t-Pt ' 1
L
U
For Self-Testing
Dimension:
I
120*60 mm
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5-2 Strip format (pouch)
5-3 HCG Midstream, (pouch)
Dimension: 190*55 inm
5-4 Strip box (sample)
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5-5 Cassette box (sample)
(Cassette)L21 ()mm*W 12
5mm*H65mra
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X
Results of Stability Studies
1. Preservation and Storage
2. Stability Studies
1. Preservation and Storage
1- 1 Introduction
The components of the kit are together treated to prolong its shelf life. Listed below the substances, which are
used for preservation. Also listed are the methods of conservation of kit components.
1- 1 Preservatives used in kit components
Preservatives
Kit Component HCG Cassette
HCG strip HCG Midstream 1-2 Conservation
No Preservatives
Methods for kit components Kit Component HCG No Preservatives
Cassette HCG strip HCG Midstream
No Preservatives
Storage Condition
2-300 sealed
2-300 sealed
2-300 sealed
2. Stability Studies
2-1 Introduction
The stability of One Step HCG Urine Pregnancy Test kit was evaluated using closed original kit, at room temperature (2300).
2-2 Materials
Materials used in this study are QC approved and optimized components.
2-3 Procedure
2-3-1 Three kits of our HCG products were used, one each from Batch 901, Batch 902 and Batch 903. Assay was
performed as per instruction manual.
2-3-2 All kit components are stored in the closed original condition at room temperature (22-300).
2-3-3 Evaluation of kits was performed at Month 0,6,12,18,24,26 from the date from the date of manufacturer. 2-3-4
Intensity of the overall intensity of the test lines for in-house reference panels are scored as follows:
- Strong Positive Intensity: 3+
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- Medium Positive Intensity: 2+
- Weak Positive Intensity: 1+
- No test lines/Intensity: - 2-4
Results
2-4-1 The stability data of Lot 901 kit at room temperature (2-300) are summarized Table 1. 2-4-2
The stability data of Lot 902 kit at room temperature (2-300) are summarized Table 2. 2-4-3 The
stability data of Lot 903 kit at room temperature (2-300) are summarized Table 3.
Table 1. Summary of intensity score of Lot 901 for QC panels
HCG Concentration
Test Intervals (month)
Concentration
0
6
12
18
24
26
25mIU/ml
1+
1+
1+
1+
1+
1+
0 mIU HCG/ml
50mIU/ml
3+
3+
3+
3+
3+
3+
200mIUhLH/ml
250mIU/ml
2+
2+
2+
2+
2+
2+
500mIU/ml
3+
3+
3+
3+
3+
3+
Test Intervals (month)
0
6
12
18
24
26
Table 2. Summary of intensity score of Lot 902 for QC panels
HCG Concentration
Test Intervals (month)
Concentration
0
6
12
18
24
26
25mIU/ml
1+
1+
1+
1+
1+
1+
0 mIU HCG/ml
50mIU/ml
3+
3+
3+
3+
3+
3+
200mIUhLH/ml
250mIU/ml
2+
2+
2+
2+
2+
2+
500mIU/ml
3+
3+
3+
3+
3+
3+
Test Intervals (month)
0
6
12
18
24
26
Table 3. Summary of intensity score of Lot 903 for QC panels
HCG Concentration
25mIU/ml
Test Intervals (month)
Concentration
0
6
12
18
24
26
1+
1+
1+
1+
1+
1+
Test Intervals (month)
0
0 mIU HCG/ml
6
12
18
24
26
50mIU/ml
3+
3+
3+
3+
3+
3+
250mIU/ml
2+
2+
2+
2+
2+
2+
500mIU/ml
3+
3+
3+
3+
3+
3+
200mIUhLH/ml
2-5 Comments
2-5-1 The 3 batches of closed original kits stored at room temperature is stable with no lessening of intensities of
the test lines for in-house reference panels till 26 month, when the studies were completed.
2-
5-2 All 3 batches of kits, Lot 901, 902 and 903, showed similar stability till the completion of the studies.
2- 6 Conclusion
Stability studies of the test kits at room temperature (2-300) indicated that the kits are stable for at least 24
months from the date of manufacture when stored unopened, in its original conditions.
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XI
Declaration of Conformity
Manufacturer:
Atlas Link (Beijing) Technology Co., Ltd.
Address:
Room 811 Zeyang Plaza, No.166 Fushi Road, Shijingshan Dist., Beijing, China
Tel: +86-10-8890 9112 Fax: +86-10-8890 9115
European Representative: Ciriano Global s.l.
B50927532 C/BLANCAS 4-6 1 B OFICINA 1 50001 ZARAGOZA, SPAIN Tel:
+34-97622 8974 Fax: +34-97636 0886
Product:
One Step HCG Urine Pregnancy Test
Classification:
IVD
Declaration of conformity:
We herewith declare that the above mentioned products meet the provisions of the following EC
Council Directives and Standards. All supporting documentations are retained under the premises of the
manufacturer and the notified body.
DIRECTIVES
Directive of medical Cassette: IVD Directive 98/79/EC
This declaration of conformity is based on the European In vitro Diagnostic Medical Cassette Directive 98/79/EC, Annex III.
Notified Body: TUV Product Service GMBH NO. 0123 EC Certificate:
Expiry date of the Certificate:
General Manager:
Date: