Korea Food and Drug Administration Public Announcement No. 2009-269

Public Notice for Proposed Partial Revision to ‘Medical Devices Standard ’

October, 2009

Korea Food and Drug Administration

Korea Food and Drug Administration Public Announcement No. 2009-269

We hereby announce, in accordance with provisions in the Article 46 of the ‘Administrative Procedures Act’, the intent, reason and the key elements of the partial revision to ‘Standard for Medical Devices’; to notify the citizens in advance and to collect the public’s opinions.

October 23, 2009

Commissioner,

Korea Food and Drug Administration

Public Notice for Proposed Partial Revision to ‘Medical Devices Standard ’

1. Reason for the revision

The reason for this revision is to reflect the changes made to some of item names in ‘Regulations for medical device items and the classification’, to revise the Medical Devices Standard to conform to the international standard, and to establish the standard for “Acrylic resin based bone cement”; in order to stipulate the needed standard to ensure the safety and effectiveness of the devices.

2. Key Elements

A. Revise the item name and standard for “Dental Noble Metal Alloy (Porcelain Fused to Alloy)” (Appendix).

(1) Changed the item name to “Metal Ceramic Alloy” in accordance with the ‘Regulations for medical device items and the classification’.

(2) Established a standard for the contents of hazardous elements (nickel, cadmium, and beryllium) in a product.

(3) Established physical, chemical and performance test specifications for melting range, coefficient of linear thermal expansion etc. to conform to the international standard.

B. Revise the item name and standard for “Dental Noble Metal Alloy (Brazing materials)” (Appendix).

(1) Changed the item name to “Alloy for brazing” in accordance with the ‘Regulations for medical device items and the classification’.

(2) Established a standard for the contents of hazardous elements (nickel, cadmium, beryllium, and lead) in a product.

(3) Established physical, chemical and performance test specifications for melting range, coefficient of linear thermal expansion etc. to conform to the international standard.

C. Establish the standard for “Acrylic resin based bone cement” (Appendix).(1) Established test methods and standards for compressive strength, flexural strength, and

component checking or content testing in that they conform to the international standard.

3. Presenting written opinions

Any individual or group who has opinion(s) about the Proposed Partial Revision to ‘Medical Devices Standard ’ (Attachment) is welcome to present opinions in writing to the Commissioner of the Korea Food and Drug Administration (CC: Medical Device Standardization Division, Address: 194 Tongilro, Eunpyeong-gu Seoul (Postal Code: 122-704), Phone: 02-350-4951 Fax: 02-350-4950) with the following information by November 16th, 2009:

A. Opinions about this announcement (Whether you are for or against it and the reasoning)B. Your name (for groups, name of the group and name of the representative), address and phone

number C. Other references

Attachment: Proposed Partial Revision to ‘Medical Devices Standard’

Korea Food and Drug Administration Public Notice No. 2009-

We hereby revise the ‘Medical Devices Standard’, which is under the provision of the Article 18 of ‘Medical Devices Act’, (Korea Food and Drug Administration, Public Notice No. 2009-134, Dated August 24, 2009), as follows.

2009

Commissioner, Korea Food and Drug Administration

Proposed Partial Revision to ‘Medical Devices Standard ’

‘Medical Devices Standard’ shall be revised as follows:

Change “Dental Noble Metal Alloy (Porcelain Fused to Alloy)”, “Dental Noble Metal Alloy (Brazing materials)” to “Metal Ceramic Alloy”, “Alloy for Brazing” respectively as per the enclosure, and newly add “Acrylic resin based bone cement” as per the enclosure.

ADDENDUM (2009. .)

Article 1 (Date of Enforcement) This regulation shall take effect from the date of the notice.

Article 2 (Transitional Measures) If any written requests for review of “Metal ceramic Alloy” and “Alloy for Brazing”, such as application for permission, permission for changes, or review of technical documents has already submitted at the time of the enforcement of this notice, they may follow the previous standard.

[Enclosure]

Metal Ceramic Alloy(Related Standards: ISO 22674 and ISO 9693)

1. Scope

1.1 Scope of application This standard applies to metal ceramic alloys that come under the classification C03000 of ‘Regulations for medical device items and the classification’ (Korea Food and Drug Administration Notice), and is limited to metallic materials that are suitable to use for dental restoration, which is combination of metal and ceramic.

1.2 ClassificationThe classification of alloys used for metal ceramic alloy shall follow the classifications of dental noble metal alloy, dental base-metal alloy I (Cobalt based), dental base metal alloy II (Nickel based) in this notice, or ISO 22674 classification system.

1.2.1 Class 0: A fixed dental restoration that stands against low load. For example, one surface inlay covered with small veneer and a veneer crown.* The metallic material for metal ceramic gold crown made by a way of electroforming or sintering also belongs to the Class 0.

1.2.2 Class 1: A fixed dental restoration that stands against low load. For example, one surface inlays with veneer and a veneer crown.

1.2.3 Class 2: A fixed dental restoration with ceramic veneer. For example, a veneer crown that has multiple surfaces.

1.2.4 Class 3: Multiple-unit fixed dental restoration with ceramic veneer, such as a bridge.

1.2.5 Class 4: An implant that supports the superstructure. It is applied to a thin layer, which receives a large force. For example, removable partial denture, clasp, thin veneer crown, wide and long briefs or bridge with narrow surface, bar, and attachment.

2. Test Standard

2.1 Physical and chemical test

2.1.1 Indication of elements

The elements in raw materials that take more than 1.0 wt. % of the total elements of alloy must be represented in ±0.1 wt. % precision. And elements that take between 0.1 wt. % and 1.0 wt. % of the total elements must be represented by its name or symbol.

2.1.2 Element content tolerance

2.1.2.1 The content of silver or each alloy component in the noble metal alloy shall be within ±0.5 wt. % tolerance range of the value provided by the manufacturer.

2.1.2.2 For base metal alloy, the content of elements that take more than 20 wt. % of the total elements shall be within ±2 wt. % of the value provided by the manufacturer, and the content of elements that take between 1 wt. % and 20 wt. % of the total elements shall be within ±1 wt. % of the value provided by the manufacturer.

2.1.2.3 Contents of hazardous elementsNickel, cadmium, beryllium are regarded as hazardous elements. The contents of cadmium and beryllium shall not exceed 0.02 wt. %. If the nickel content exceeds 0.1 wt. %, its amount shall be displayed on the package in 0.1 wt. % precision.

2.1.2.4 TitaniumThe standard specification data, in accordance with ASTM B 348-03, shall be applied to unalloyed titanium. And data identifying its grade shall be submitted.

2.1.3 CharacteristicsThe mechanical attributes, density, corrosion resistance, discolouration resistance shall compatible with the classifications of dental noble metal alloy, dental base metal alloy I (Cobalt based), dental base metal alloy II (Nickel based) in this notice, or ISO 22674. However, in case of Class 0 alloys, the specimen for tensile strength shall be prepared according to the ISO 22674.

2.1.4 Melting rangeIf the solidus temperature of the alloy is below 1,200 °C, both the solidus and liquidus temperature shall be within ±20°C of the represented value, and within ±50°C if the solidus temperature of the alloy is above 1,200 °C.

However, if the melting point of unalloyed metal is below 1,200 °C, the melting point shall be within ±20 ° C of the represented value and ±50 ° C if it is above 1,200 °C.

2.1.4.1 Test methodUsing cooling curve test, measure alloys of which the solidus temperature is below 1,200 °C and unalloyed metals of which the melting point is below 1,200 °C in ±10°C precision. For alloys of which the solidus temperature is above 1,200 °C and unalloyed metal of which the melting point is above 1,200 °C, measure in ±25°C precision.

2.2 Performance test

2.2.1 Coefficient of linear thermal expansion

2.2.1.1 StandardMeasured value for coefficient of linear thermal expansion shall be within ±0.5x10-6xK1 of the value provided by the manufacturer. But this value is not guaranteed to conform to all ceramics.

2.2.1.2 EquipmentUse a dilatometer that has been properly rectified for the test.

2.2.1.3 Test specimen preparationFollowing the manufacturer’s direction, prepare 2 metal specimens. Each specimen shall be in bar or rod shape with a cross section of less than 30mm2. Polish both ends of each specimen, and make sure they are at right angles to the major axis of the specimen.

2.2.1.4 Test methodApply heat treatment with the same method as the one used for mechanical attribute test specimen preparation. Measure the thermal expansion up to 550 °C for each of 2 specimens with the heating speed of 5±1°C/min. Calculate the coefficient of linear thermal expansion for each specimen from between 25°C and 500°C of the thermal expansion curve, which has been generated as the temperature increases. In the case of titanium and other unalloyed metals, relevant documents may be referred.

2.2.1.5 Analysing the resultFor metals, average the values taken from between 25°C and 500°C of the thermal expansion curve to get the linear thermal expansion coefficient α (25°C ~ 500°C), round this average value off to the degree of 0.1 x 10-6K-1 and record it as the average coefficient of thermal expansion.

2.2.2 Metal-ceramic combination (Schwickerath crack initiation test)

2.2.2.1 StandardThe debonding/crack initiation strength of the metallic materials and the ceramics shall be greater than 25 MPa for at least one ceramic.

2.2.2.2 EquipmentFlexural strength tester:It shall be 3-point flexural strength testing machine, which the distance between the supports is 20mm. The crosshead speed shall be 1.5 ± 0.5 mm/min, and the ends of the supports and the bending bar shall have hemispherical surfaces with radius of 1mm.

2.2.2.3 Test specimen preparationCast 6 of 25 ± 1 mm * 3 ± 0.1 mm * 0.5 ± 0.05 mm alloy/metal specimens, to be used as the base structures for metal ceramic dental prostheses, according to the manufacturer’s processing procedure. Examine the specimens by closely watching the surface finishing (for example, washing, sandblasting and oxidation etc.) as directed by the manufacturer.Before applying the ceramic as a specimen, fix the electric kiln for calcinations as recommended by the manufacturer. Perform test calcinations with raw ceramic to get the appropriate grade of

calcinations and surface grossing on opaque ceramic and body ceramic. Adjust the temperature and time when necessary.As shown in Figure 1, symmetrically apply opaque ceramic to the 3mm sides with 8 ± 0.1 mm distance as directed by the manufacturer. Add each specimen on top of the casted ceramic in that the total thickness of the ceramic to be 1.1 ± 0.1 mm after the calcinations.

<Figure 1> Arrangement of specimens (unit: mm)

The layers of ceramic shall be rectangular. Body ceramics can be added to calcinations to get needed thickness and shape, if necessary. Carefully polish the rectangular shape using a disk. If needs be, remove ceramics overflowed from the metal plate. Perform the second calcinations as directed by the manufacturer.

2.2.2.4 Test methodPlace the calcinated specimen on a ceramic flexural strength test fixture (distance between the supports: 20 mm, radius of the bending piston: 1 mm) that is located symmetrically on the opposite side of the load. Apply force at a constant speed of 1.5 ± 0.5 mm/min until the specimen fractures and record the force. The fracture force for each of 6 specimens Ffail (Newton) shall be measured from specimens failing, which ruptured due to debonding or cracking initiation at one end of the ceramic layer. If there is any fractured specimen due to the cracking in the middle of the ceramic layer, replace it to keep the number of appropriate specimens to 6.

2.2.2.5 Analysing the resultCoefficient k shall be multiplied by the fracture force Ffail. Coefficient k can be read from Figure 2. Coefficient k is the thickness factor of the 0.5 ± 0.05 mm metal plate dM and the value of the modulus of elasticity EM for the used metallic material. To see the k value for a certain thickness dM, select the corresponding curve for proper EM value, and then read the value of that thickness dM from the curve. Debonding/crack initiation strength Tb can be calculated using the following formula.

Tb = k * Ffail

If more than 4 out of 6 specimens satisfy the requirements, the metal-ceramic combination is considered as compatible. If 3 of them were satisfied, perform the test over again. When less

than 3 specimens satisfied the requirements after the retest, the metal-ceramic combination is considered as incompatible.

<Figure 2> Diagram for measuring coefficient k

2.2.2.6 Alternative procedureDebonding/crack initiation strength Tb also can be calculated based on the flowchart in Figure 3.

<Figure 3> Flowchart for debonding/crack initiation strength calculation

2.3 Biological safety testThe biocompatibility shall be evaluated. When the test standard on biological safety is needed, the standard shall conform to the ‘Common Standard for Biological Safety of Medical Devices’ (Korea Food and Drug Administration Notice), ISO 10993 and ISO 7405 etc.

3. Items to record

The test results shall be recorded in accordance with the items mentioned in the ‘Regulations for examining technical document etc. of medical devices’ (Korea Food and Drug Administration Notice) including following items. In addition, the material, manufacturer or supplier of ingot shall be clearly represented. Metals that are supplied in too small or irregular particles to express are excluded.

3.1 Chemical composition (wt. %)(In the case of titanium, indicate the class specified in ASTM Designation B 265-03 or B 348-03)

3.2 Classification of dental noble metal alloy, dental base metal alloy I (Cobalt based), dental base metal alloy II (Nickel based), or ISO 22674 classification.

3.3 Yield strength (MPa) and fracture elongation (%), density (g/cm2)

3.4 Casting temperature range and melting temperature range (°C)

3.5 Coefficient of linear thermal expansion (10-6K-1)

3.6 The name and content of hazardous element, if exists.

3.7 The message of warning and caution for hazardous element, if exists.

3.8 The colour of the metallic material (“white” or “yellow”)

3.9 Recommended combination technique or method.

4. Other ReferencesThe distributor of metallic material shall provide a detailed guide to the metallic material including the directions on brazing or welding, and the surface finishing needed to get a satisfactory combination for at least one particular (name of) ceramic raw material. In relation to titanium, the distributor of related processing system(s) shall provide the above mentioned guide. The manufacturer’s recommendations for at least one (name of) metallic material to provide satisfactory combination with the ceramic material, and guide to applying the ceramic material and detailed direction of calcinations schedule shall be provided by the distributor of the ceramic. Detailed direction with regard to matters that require attention shall be written on the package or attached document.

Alloy for Brazing(Related Standards: ISO 9333)

1. ScopeThis standard applies to alloy for brazing used to connect dental alloys and come under the classification C04000 of ‘Regulations for medical device items and the classification’ (Korea Food and Drug Administration Notice).

2. Test Standard

2.1 Physical and chemical Test

2.1.1 Indication of elements

2.1.1.1 StandardThe elements in raw material that take more than 1.0 wt. % of the total elements must be represented in ±0.1 wt. % precision. And elements that take between 0.1 wt.% and 1.0 wt.% of the total elements must be represented by its name or symbol.

2.1.2 Element content tolerance

2.1.2.1 StandardThe content of silver or each alloy component in a noble metal alloy shall be within ±0.5 wt. % tolerance range of the value provided by the manufacturer.For base metal alloy, the content of elements that take more than 20 wt.% of the total elements shall be within ±2 wt.% of the value provided by the manufacturer, and the content of elements that take between 1 wt.% and 20 wt.% of the total elements shall be within ±1 wt.% of the value provided by the manufacturer.Nickel, cadmium, beryllium, and lead are regarded as hazardous elements. The contents of cadmium, beryllium and lead shall not exceed 0.02 wt.%. If the content of nickel exceeds 0.1 wt. %, its amount shall be displayed in 0.1 wt. % precision on the package.

2.1.2.2 Test methodTest with one of commonly used quantitative analysis methods by which greater than 0.1 wt. % precision is guaranteed.

2.1.3 Melting range

2.1.3.1 StandardBoth the solidus and liquidus temperatures of alloy shall be within ±20°C of the value represented by the manufacturer.

2.1.3.2 Test methodUsing cooling curve test, measure the solidus and liquidus temperatures in ±10°C precision.

2.1.4 Corrosion resistance (static immersion test)

2.1.4.1 StandardWhen the tested and untested specimens were compared with naked eyes, any differences due to chemical reaction shall not be observed.

2.1.4.2 Test specimen preparationPrepare 4 of approximately 10 mm * 10 mm * 1 mm specimens and wash the surfaces. Cut the specimens in halves so that the size becomes 5 mm * 10 mm * 1 mm, and then braze two of these halves. If two different kinds of metallic materials are being brazed, make sure one of each half is being used. Keep the gap between the halved specimens to be 0.2 ± 0.1 mm. Use recommended fluxing agent and follow brazing process provided by the manufacturer. Perform surface polishing according to the standardized metal surface polishing procedure so that minimum 0.1 mm of all the surfaces is ground and all foreign substances can be completely removed. At the final phase of the surface polishing, finish with wet silicon carbide papers that conform to ASTM 600 or FEPA P 1200 standard. The same kind of carbide paper should be used for all specimens, so that every specimen will have the same components.

2.1.4.3 ReagentsLactic acid (90%) (C3H6O3) For analysisSodium chloride (NaCl) For analysisDistilled water Grade 2 (see ISO 696 for reference)Ethanol (C2H5OH) or methanol (CH3OH)

2.1.4.4 Etching solution preparationUse new etching solution for each test. Dissolve 10.0 ± 0.1 g of lactic acid and 5.85 ± 0.05 g of sodium chloride in approximately 300 ml of distilled water to prepare the etching solution. The pH of the etching solution shall be 2.3 ± 1.0.

2.1.4.5 Test methodMeasure the surface of prepared specimen in 0.1cm2 precision.Steep the specimen in ethanol or methanol for ultrasonic cleaning for 2 minutes. Next, wash with distilled water and then dry it completely. Put each specimen into an individual borosilicate glass container (approximately 16 mm in diameter, 160 mm in depth); measure the Potential Hydrogen (pH) of the test solution; fill the glass container with this test solution to completely submerge the specimen(about 10 ml). Record the amount of the test solution used for corrosion test in 0.1 ml precision. Make the glass container airtight to prevent the etching solution from evaporation; keep it for 7 ± 0.1 days at 37 ±1 °C. Remove the specimen from the glass container; measure and record the pH of the remaining etching solution.

2.1.4.6 Analysing the resultObserve the brazed gap of specimen with a microscope of 10 magnifications.

2.2 Performance test

2.2.1 Tensile strength

2.2.1.1 StandardThe tensile strength at the brazed joint shall be higher than 250 MPa. If the 0.2% offset yield strength of one or both of metals to be soldered by brazing material is lower than 250 MPa, the tensile strength of the brazing material shall be higher than the 0.2% offset yield strength of the one that has lower yield strength of the two metals.

2.2.1.2 Specimen preparationThe specimen consists of metallic materials to be combined with the brazing material, which is provided by the manufacturer. Produce the specimen using an investment casting that is also known as “lost wax process”, the commonly used metal casting method. For metallic material to be tested with brazing material, another method provided by the manufacturer can be used and can be prepared as follows.Prepare 6 test specimens as shown in Figure 1 or Figure 2. If any visible fault is detected in a specimen, replace it with another. Cut each specimen, using a sharp saw, at the centre of gauge length perpendicular to the major axis; remove the rough edge. Polish the cutting plane to be flat and perpendicular to the major axis of specimen. Align two of halved specimens using any device or a jig. When brazing with different metallic materials, use each half of the two specimens. Make the gap distance to be 0.2 ± 0.1 mm. Braze according to the direction provided by the manufacturer with the recommended fluxing agent. The diameter of each tensile test specimen after the brazing shall be within the tolerance range as shown in Figure 1 and Figure 2, and any partial disposition shall not be observed when rotated. If the yield strength of the base alloy is lower than 250 MPa, prepare additional 6 specimens of the base alloy to get 0.2% offset yield strength.

<Figure 1> Rodlike Tensile Strength I (unit: mm)

<Figure 2> Rodlike Tensile Strength II (unit: mm)2.2.1.3 Test methodPerform tensile test on brazed specimen with 1.5 ± 0.5 mm per minute cross-head speed until the specimen ruptured. If the rupture occurred outside of the gauge length, ignore the specimen and the result value; replace the specimen with another and repeat the test. Calculate the tensile strength for initial cross section of each specimen from the load-displacement record.

Record the measured value from the test and the average value in 1 MPa and 5 MPa respectively.

2.2.1.4 Analysing the resultIf 4 out of 6 specimens satisfied the standard value, it will be deemed as compatible. If satisfied specimens are less than 2, it will be deemed as incompatible. When satisfied specimens were 3, retest with 6 specimens on another lot. It will be deemed as compatible only if more than 5 specimens satisfied the standard value from the retest.

2.3 Biological safety testThe biocompatibility shall be evaluated. When the test standard on biological safety is needed, the standard shall conform to the ‘Common Standard for Biological Safety of Medical Devices’ (Korea Food and Drug Administration Notice), ISO 10993 and ISO 7405 etc.

3. Items to recordThe test results shall be recorded in accordance with the mentioned items in the ‘Regulations for examining technical document etc. of medical devices’ (Korea Food and Drug Administration Notice) including following items.

3.1 Chemical composition (wt.%), density (g/cm2)

3.2 Tensile strength

3.3 Recommended fluxing agent and metallic material etc.

3.4 Detailed direction on brazing for the recommended metallic material

3.5 The name and content of hazardous element, if it exists.

3.6 The message of warning and caution for hazardous element, if it exists.

Acrylic Resin based Bone Cement(Related Standard: ISO 5833)

1. Scope

1.1 Scope of application This standard applies to bone cement that come under the classification B03190.01 of ‘Regulations for medical device items and the classification’ (Korea Food and Drug Administration Notice); is limited to acrylic resin based bone cement intended to use for the fixation of polymer or metallic implant, such as artificial hipbone joint and artificial kneecap joint, to living bone.

1.2 TypesAcrylic resin based bone cement has two types; intended for use with a syringe or in dough state. These are supplied as units containing premeasured amounts of sterile powder and of sterile liquid in forms suitable for mixing at the time of implantation. Powder contains polymer particles and initiator, and radio-opacifier when necessary. In some cases, the radio-opacifier is supplied separately.

2. Test Standard

2.1 Physical and chemical Test

2.1.1AppearanceThere shall not be any other particles or pollutants, and the powder shall not have any lumps in it.

2.1.2 CapacityWhen the volume of liquid and the weight of powder in 5 bone cements were measured with ±0.1 ml and ±0.1g precision respectively, the tolerance range shall be within 5% of the claimed value.

2.1.3 Heavy metal testMix and harden the bone cement and elute it at 37 ± 1 °C for 72 ± 2 hours; put in the test solution and test according to Method 1, Heavy Metal Test Methods, General Test Methods of the Korean Pharmacopoeia; the colour of the test solution shall not be darker than the comparative solution (comparative solution : standard lead solution 2.0 ml).

2.1.4 Component checking or Content testingPerform the component checking for powder and liquid components as listed in the Table 1 using the following methods; GC (Gas Chromatography), FTIR (Fourier Transform Infra-Red), HPLC (High-Performance Liquid Chromatography), MS (Mass Spectroscopy), X-ray, Titration

and other test methods that are equivalent to these. Examine if all the components of each product are presented as they were claimed to be. This component checking can be replaced with contents testing.

[Table 1. Example of Components]

Type Example of Components

Powder PMMA (Poly Methyl Methacrylate, Barium Sulphate (BaSO4), DiBenzoyl Peroxide (BPO), Antibiotics (only if they are contained in the product) etc.

Liquid MMA (Methyl Methacrylate), DMPT (N, N-Dimethyl Para Toluidine), Hydroquinone etc.

* The components may vary with products.

2.1.5 Stability of liquid component

2.1.5.1When tested with the method below, the viscosity of the liquid (streaming time) shall not increase more than 10%. Test with two liquid components.

2.1.5.2 Equipment and the test solution preparationKeep the viscometer and the liquid component of bone cement at 23 ± 1°C for at least 1 hour before the test. Process the test at this temperature.

2.1.5.3 Test methoda. Fill the viscometer with the liquidb. Measure the time taken for the liquid to be in equilibrium with the meniscus, and record the time as the streaming time ta (ta).c. Put the liquid in an airtight container in a dark place; heat it at 60 ± 2 °C for 48 ± 2 hours; cool it down to 23 ± 1°C and leave it for an hour at this temperature.d. Repeat the steps a and b, record the streaming time as tb (tb).

2.1.5.4 Analysing the resultCalculate the change in streaming times (∆t) of the liquid in percentage using the formula below.

∆t = tb - ta / ta * 100%

2.1.6 Kneading time

2.1.6.1 StandardWhen tested with the method below, the kneading time of dough state bone cement shall be under 5 minutes on average, and the acceptable kneading time tolerance between bone cements shall not exceed 1minute 30 seconds.

2.1.6.2 Equipment and test environment

Regulate the temperature of bone cements for kneading and related equipment to be 23± 1 °C ; keep at least for 2 hours in relative humidity of above 40% ; test under these temperature and humidity conditions.

2.1.6.3 Test methoda. Mix the bone cement as guided in the maker’s manual.b. Start to measure the time from the point when the liquid component is added to the powder component.c. Wait about a minute, wear powder-free and non-washed surgical latex gloves; carefully feel the surface of the mixture; observe whether there any fibres have formed between the bone cement and the glove when fingers are taken away. d. Continue kneading while the lower part of the bone cement is exposed to the air; observe frequently, at the maximum 15 seconds interval, as described in step c. New globes shall be used every time.e. Record the first time the gloved fingers were clearly separated from the bone cement; this will be the kneading time. f. Repeat step a through e for the second bone cement.g. If the difference of the two kneading times is more than 30 seconds, test again with two additional bone cements.h. Test 2 or 4 times and calculate the average kneading time. Round the values off to the closest 15 seconds to get the average.

2.1.7 The highest temperature and hardening time

2.1.7.1 StandardWhen tested using the mould depicted in Figure 1, the highest temperature and hardening time shall be the same as specified in the table below.

Highest Temperature (°C) Hardening Time (minute)Average Tolerance Average

For Syringe 90 ±5 6.5 ~ 15

For Dough 90 ±5 3 ~15

2.1.7.2 Equipment and test environmentRegulate the temperature of bone cements for kneading and related equipment to be 23± 1 °C ; keep at least for 2 hours in relative humidity of above 40% ; test under these temperature and humidity conditions.

2.1.7.3 Test methoda. Measure the ambient temperature from 0.5mm radius wire thermoelectric couple in the mould.b. Mix the bone cement as guided in the maker’s manual.c. Start to measure the time from the point when the liquid component is added to the powder component in ±0.1 second precision.

d. Knead the bone cement well, and then fill the mould with 25g of bone cement; install a plunger and remove the cement that brimmed over the mould. In the case of bone cement for syringe, fill the mould from the syringe.e. Measure temperatures until the point the temperature began to drop.f. Repeat the step a through e for the second bone cement.g. If the difference of the highest temperature and the hardening time is more than 10 °C and 1 minute respectively, test again with two additional bone cements.h. Draw a temperature/time curve for each bone cement as depicted in Figure 2. Record the highest temperature in terms of 1°C.

2.1.7.4 Analysing the resulta. Calculate the average of 2 or 4 highest temperatures and record it in terms of 1°C (Round off the values of 0.5 °C). The resulting value will be the highest temperature.b. Referring the table in Figure 2, get the hardening time (tset) with the formula below.

Tset = Tmax + T amb / 2(T amb : temperature recorded in xxx, Tmax : highest temperature)

c. Record Tset values in 5 seconds. Calculate the average of 2 or 4 bone cements. Round the values off to the closest 15 seconds to get the average. The resulting value will be the hardening time.

<Figure 1> Mould to test the highest temperature and the hardening time

1)Mould 2)Plunger

1. Outer ring 2. Floor 3. Passage for thermoelectric couple 4. Polymer screw of the proper size to easily remove the specimen 5. 4 holes that grow to a point. Used to discharge exceeding bone

cement. a the diameter of thermoelectric couple (unit: mm, tolerance: ±0.2 mm (only if this is not specified))

* material for the mould: Select one from Polytetrafluoroethylene, Poly(ehtyleneterephthalate), Polyoxymethylene, and DDPE.

<Figure 2> A typical curve to determine the highest temperature and hardening timeTemperature (°C) Time (minute)

2.2 Performance test

2.2.1 Compressive strength

2.2.1.1 StandardWhen tested as below, the compressive strength shall be higher than 70 MPa.

2.2.1.2 Equipment and test environmenta. Use a stainless steel mould like the one in Figure 3, or an appropriate form of mould to produce polished bone cement of 12 ± 0.1 mm in length and 6 ± 0.1 mm in diameter.b. Regulate the temperature of bone cements for kneading and related equipment to be 23± 1 °C ; keep at least for 2 hours in relative humidity of above 40% ; test under these temperature and humidity conditions

2.2.1.3 Test methoda. Mix the bone cement as guided in the maker’s manual.

b. For dough state bone cement, fill the mould with bone cement up to a little over the brim within 1 minute from the kneading time that had taken in 2.1.6, and then engage the opposite side plate. In case of the bone cement for use with a syringe, fill the mould with bone cement using a syringe. The rest are the same as for dough state bone cement.c. Lock up the mould with holes and the other side plate each other, and leave it in a clamp for 1 hour to let the bone cement become hard.d. Get the cylinder shape bone cement out from the mould with a removing bar.e. Leave the cylinder for 24 hours at 23 ± 1°C, and then measure the average diameter of each specimen. The diameter shall be measured from two directions that are perpendicular to at least two cutting planes. f. Put the specimen on the tester; measure with 19.8 mm/min ~ 25.6 mm/min crosshead speed to produce load-strain curve like Figure 4. If the specimen breaks, stop running the tester.g. Repeat steps a through f for each specimen.

2.2.1.4 Analysing the resultRecord the force value or 2% offset load or maximum load that caused cracking; divide the load value by the cross section of the specimen, and have the resulting value as the compressive strength of the product.

<Figure 3> Mould to test compressive strength

1)Mould with holes 2) other side plate 3) the mould is tightened in a clamp 4) removing bar(unit: mm, tolerance: ±0.2 mm (only if this is not specified))

<Figure 4> Ideal load-strain curve

Load, NStrain, mm

(inside the graph, from the top: maximum load, yield load, 2% offset)

2.2.2 Flexural strength and coefficient of flexion

2.2.2.1 StandardWhen tested as below, the flexural strength and the coefficient of flexion shall be higher than 50 MPa and 1,800 MPa respectively.

2.2.2.2 Equipment and test environmenta. Prepare the flexural strength testing device like Figure 5 and 5 moulds, approximately 75 mm * 10 mm * 3.3 mm (width * length * height), that are made of polytetrafluorethylene, poly(ethylene tetrephthalate), polyoxymethylene, high density polyethylene, and aluminum alloys.b. Prepare flat and smooth plates of which the material is proper to cover the top and bottom of the mould, polyester film, and a C-clamp per each mould.c. Regulate the temperature of bone cements for kneading and related equipment to be 23± 1 °C ; keep at least for 2 hours in relative humidity of above 40% ; test under these temperature and humidity conditions.

2.2.2.3 Test specimen preparationa. Cover the bottom of the mould with a polyester film, and then put the mould on a plate.b. Mix the bone cement as guided in the maker’s manual.c. For dough state bone cement, fill the mould with bone cement within 1 minute from the kneading time that had taken in 2.1.6; place a polyester film on it and then a plate; put it into a clamp. In case of the bone cement for use with a syringe, fill the mould with bone cement using a syringe. Prepare the rest as the same way as for dough state bone cement.

d. Wait about an hour; remove the specimen from the clamp; separate the polyester film from the specimen; remove the specimen from the mould.e. Wet polish the rim and the top of the specimen with grade 400 sandpaper to make required size (75 mm * 10 mm* 3.3 mm; tolerance: ±0.1 mm). Be careful to not break the specimen when polishing. Mark the bottom side that was not polished; this side will be used as a force receiving side during the flexural strength test. 2.2.2.4 Test methoda. Leave the above specimen for 24±2 hours at 23±1 °C before testing.b. Measure the size of at least 3 sections of the specimen (tolerance: 0.1 mm); place it symmetrically to 4-point flexural strength testing device.c. Apply force to central loading plunger starting from crosshead speed of 5±1 mm/min and then slowly increase the speed. Record the level of flexion caused by the force. Increase the force until the specimen breaks.d. Apply 15N and 50N of force; record the level of each flexion to the nearest 0.05mm; record the force value to the nearest 0.5N at the point when the specimen has broken.e. Repeat steps a through e for each of the rest 4 specimens.

2.2.2.5 Calculating the resultCalculate the flexural strength and the coefficient of flexion with the formula below; calculate the average and the standard deviation of the flexural strength and the coefficient of flexion in MPa for 5 specimens.

Flexural strength (B) = 3Fa / bh2

F: The force when the specimen was broken (N)b: Average vertical length of specimens (mm)h: Average height of specimens (mm)a: Distance between inner and outer loading points (20mm)

Coefficient of flexion (E) = ∆Fa / 4fbh3 * (3l2 – 4a2)

f: Difference in flexions when 15N and 50N of forces were applied (mm)b: Average vertical length of specimens (mm)h: Average height of specimens (mm)l: Distance between outer loading points (60mm)∆F: Load range (50N – 15N = 35 N)a: Distance between inner and outer loading points (20 mm)

1. Central loading plunger2. Inner loading points3. Test specimen4. Device for measuring deflection (dial gauge or other)5. Outer loading points

<Figure 5> 4-point flexural strength testing device

2.2.3 Overflow

2.2.3.1 StandardThis only applies to dough state bone cement. When tested with the method below, average overflow of at least one specimen shall be over 2 mm.

2.2.3.2 Test environmentRegulate the temperature of bone cements for kneading and related equipment to be 23± 1 °C ; keep at least for 2 hours in relative humidity of above 40% ; test under these temperature and humidity conditions.

2.2.3.3 Test methoda. Mix the bone cement as guided in the maker’s manual.b. For dough state bone cement, determine the kneading time that had taken in 2.1.6; put the dough into the mould as in Figure 6 and insert a plunger.c. After 1 minute ± 10 seconds after reached the kneading time, apply force of 49 ± 1 N to the plunger for 1 minute ± 2 seconds. Remove the force and leave the bone cement to harden.d. Separate the hardened bone cement from the mould; measure the bone cement overflowed through 4 holes.

e. Subtract the depth of the hole that was not filled with bone cement from the initial depth of the hole to get the amount of overflowed bone cement; measure the average of 4 holes to the nearest 0.5 mm.f. If the average overflow is less than 2 mm, repeat steps a through e to retest.

unit: mm tolerance: ±0.2 mm (only if this is not specified)

<Figure 6> Mould to test overflow (1. outer ring 2. Floor 3. Polymer screw in appropriate size to remove the specimen (optional))

2.3 Biological safety testTest according to the ‘Common Standard for Biological Safety of Medical Devices’ (Korea Food and Drug Administration Notice).

2.4 Sterility TestWhen tested according to Sterility Test Methods in General Test Methods of the Korean Pharmacopoeia, the result shall conform to its standard.

2.5 EO gas residue testIf sterilizing with EO gas, the amount of residue for both ethylene oxide (EO) and ethylene chlorohydrins (ECH) shall be less than 25 ppm when tested according to the ‘test method for amount of ethylene oxide (EO) residue after sterilization’ in the ‘Common Standard for Biological Safety of Medical Devices’ notified by the Commissioner of Korea Food and Drug Administration.

3. Items to record

The recording shall follow the ‘Regulations for examining technical document etc. of medical devices’ (Korea Food and Drug Administration Notice).