YY Translated English of Chinese Standard: YY

Transcription

1 Translated English of Chinese Standard: YY YY ICS C 31 Pharmaceutical National Standard of the People s Republic of China YY Sterile Insulin Syringe for Single Use 一次性使用无菌胰岛素注射器 (ISO 8537: A1:2000, Sterile single-use syringes, with or without needle, for insulin, NEQ) Issued on: December 7, 2005 Implemented on: December 1, 2006 Issued by: China Food and Drug Administration Page 1 of 32

2 Table of Contents Foreword Scope Normative references Terms and definitions Types of syringe Requirements Test methods Packaging Marks, operation instructions, and product certificate Storage Annex A Annex B Annex C Annex D Annex E Annex F Annex G Annex H Page 2 of 32

3 Foreword This Standard non-equivalently adopts International Standard ISO 8537:1991 Sterile Single-use Syringes, with or without Needle, for Insulin and its Amendment 1:2000. Main technical differences between this Standard and ISO 8537:1991 as well as its Amendment 1 are as follows: This Standard adds easily oxidized substance, hemolysis, acute systemic toxicity, cytotoxicity, subcutaneous stimulation or sensitization response performance indexes; adopts the test methods in GB/T Test Methods for Infusion, Transfusion, Injection Equipment for Medical Use - Part 1: Chemical Analysis Methods for chemical properties; and adopts the test methods in GB/T Test Methods for Infusion, Transfusion, Injection Equipment for Medical Use - Part 2: Biological Test Methods and GB/T Biological Evaluation of Medical Devices - Part 1: Evaluation and Test for biological properties. This Standard adds performance indexes of plungers, which shall comply with YY/T Plunger of Sterile Syringes for Single Use. This Standard cites GB Sterile hypodermic syringes for single use and specifies push-and-pull acting forces during whole process of test activities after fitting of syringe coat and plunger. This Standard adopts GB/T Sampling Procedures and Tables for Batch Inspection Apply to Inspection of Continuous Batches) and GB/T Sampling Procedures and Tables for Periodic Inspection by Attributes (Apply to Inspection of Process Stability). Annex A, Annex B, Annex C, and Annex D to this Standard are normative, while Annex E, Annex F, Annex G, and Annex H are informative. This Standard was proposed by National Technical Committee on Standardization of Injectors (Needles) for Medical Purposes. This Standard is responsibly drafted by Shanghai Misawa Medical Industry Co., Ltd. This Standard shall be under the jurisdiction of National Technical Committee on Standardization of Injectors (Needles) for Medical Purposes. Drafters of this Standard: Wang Hongbin, Sang Weidong, and He Bin. Page 3 of 32

4 Sterile Insulin Syringe for Single Use 1 Scope This Standard specifies classification, requirements, test methods, inspection rules, marks, operation instructions, packaging, transportation, storage, etc. for insulin syringe for single-use. It covers syringes for use with 40 units of insulin/ml (U-40) and 100 units of insulin/ml (U-100). This Standard applies to the insulin syringe for single-use that injects into human body soon after extracting insulin liquid (hereinafter refereed to as syringe). This Standard does not apply to sterile syringe for single-use, glass syringe for single-use, and prefilled syringe. 2 Normative references The provisions in following documents become the provisions of this Standard through reference in this Standard. For dated references, the subsequent amendments (excluding corrigendum) or revisions do not apply to this Standard, however, parties who reach an agreement based on this Standard are encouraged to study if the latest versions of these documents are applicable. For undated references, the latest edition of the referenced document applies. GB/T Conical fittings with a 6% (Luer) taper for syringes, needles and certain other medical equipment (idt ISO 594-1:1996) GB/T Sampling procedures and tables for lot-by-lot inspection by attributes (Apply to inspection of successive lots or batches) GB/T Sampling procedures and tables for periodic inspection by attributes (Apply to inspection of stability for productive process) GB Water for laboratory use; Specifications GB/T Infusion, transfusion, injection equipment for medical use - Part 1: Chemical analysis methods GB/T Test methods for infusion, transfusion, injection equipment for medical use - Part 2: Biological test methods GB Sterile hypodermic syringes for single-use (eqv ISO :1993) Page 4 of 32

5 13 - Nominal capacity lines; 14 - Graduated capacity lines; 15 - Conical head. NOTE: This figure is intended to be illustrative of components of a syringe only. It does not show a detachable needle or a permanently attached needle tube, and does not form part of the specification. The piston/plunger assembly may or may not be of integral construction and may incorporate more than one seal. Figure 1 Schematic diagram of insulin syringe 4.2 The types of syringe shall be designated as follows: Type 1: Syringe having a 6:100 (Luer) male conical fitting, supplied without a needle, and packaged in a unit container. Type 2: Syringe having a 6:100 (Luer) male conical fitting, supplied without a needle, and fitted with protective end caps. Type 3: Syringe having a 6:100 (Luer) male conical fitting, supplied with a detached or detachable needle, and packaged in a unit container. Type 4: Syringe having a 6:100 (Luer) male conical fitting, supplied with a detachable needle, and fitted with protective end caps. Type 5: Syringe having a fitting other than a 6:100 (Luer) taper, supplied with a needle not intended to be detached, and packaged in a unit container. Type 6: Syringe having a fitting other than a 6:100 (Luer) taper, supplied with a needle not intended to be detached, and fitted with protective end caps. Type 7: Syringe with fixed needle tube and packaged in a unit container. Type 8: Syringe with fixed needle tube and fitted with protective end caps. 4.3 See Annex D for requirements of syringe material. 5 Requirements 5.1 Syringe coat Requirements for syringe appearance Syringe coat shall be free of rough edges, burrs, plastic flow, defects, and other molding defects Syringe coat shall have sufficient transparency and fiducialine can be clearly Page 7 of 32

6 solution of the same batch; ph difference must not exceed Easily oxidized substance Syringe leach solution (see Annex B) is contrasted with blank contrast solution of the same batch with an equal volume; consumption difference of potassium permanganate solution at mol/l shall not exceed 0.5 ml Residue of ethylene oxide Residue of ethylene oxide shall not be greater than 10 μg/g Biological performance requirements Syringe shall be sterile Syringe endotoxin shall be less than 0.5 EU/mL Syringe shall have no hemolytic reaction; hemolysis rate shall not exceed 5% Syringe shall have no acute systemic toxicity. 6 Test methods 6.1 Appearance OBSERVE it by vision, which shall conform to the provisions of 5.1.1, , , 5.3, , 5.4.2, 5.4.3, 5.5, 5.6, and Dimensions MEASURE with general or special measuring tools, which shall conform to the provisions of 5.1.2, 5.2, , and Dimensions of conical head CONDUCT the test according to the method specified in GB , which shall conform to the provisions of Edge curl USE a bevel plate with a 10 angle to the level; place syringe on ramp in parallel, which shall conform to the provisions of Physical performance test of syringe Fitting of plunger and coat (slip resistance test) Page 13 of 32

7 6.6 Chemical performance test Extractable metal content test Test solution prepared based on Annex B is tested according to the method in 5.6 of GB/T , which shall conform to the provisions of PH test Test solution prepared according to Annex B is tested according to the method in of GB/T , which shall conform to the provisions of Easily oxidized substance Test solution prepared according to Annex B is tested according method II in 5.2 of GB/T , which shall conform to the provisions of Residue of ethylene oxide Preparation of test solution: WEIGH accurately after removing package of syringe; INJECT water of grade 3 in GB/T to a nominal volume (V); MAKE the temperature constant at 37 C±1 C; TAKE a certain amount of leaching solution and test according to gas chromatographic method in chapter 9 of GB/T ; OBTAIN corresponding concentration (c) in standard curve; CALCULATE ethylene oxide content W of syringe according to formula; W shall conform to the provisions of Where, W Content of ethylene oxide in product, in micrograms per gram (μg/g); c Corresponding concentration of test solution found in standard curve, in grams per liter (g/l); V Corresponding volume of test solution found in standard curve, in milliliters (ml); m 0 Mass of product, in grams (g). 6.7 Biological performance test Sterility test CONDUCT the test according to the method prescribed in GB/T sterility test, which shall conform to the provisions of Page 15 of 32

8 certificate 8.1 Marking If colour coding is used for indication of the insulin strength, the colour red shall be used for U-40 syringes, and the colour orange shall be used for U-100 syringes The colours red and orange shall not be used for marking except for marking of the strength of insulin Colour coding, if used, can be given on the syringe, protective end caps and/or all packaging. 8.2 Marks on syringe Marks on syringe coat: The barrels of syringes shall be marked with the following information: a) appropriate graduated scale in accordance with clauses 5.4.1, 5.4.2, and 5.4.3; b) the text "U-40 insulin" or "U-100 insulin" whichever is applicable; c) the word "units" or "U"; d) total graduated capacity in milliliters Additional marking for self-contained syringe units (syringes of types 2, 4, 6, and 8) The syringe or unit shall additionally be marked with the following information; a) the mark "for single-use" or " do not re-use (see Annex G); b) name and/or trademark of the manufacturer. 8.3 Marks on package Unit containers (syringes of types 1, 3, 5 and 7) Marks shall be sealed in a single package bag, which shall be marked as follows: a) Description of interiors, including nominal capacity; b) Manufacturer s name and trademark; c) Words of sterilization, non-pyrogen ; d) Batch number starts from the word batch ; Page 18 of 32

9 e) Single-use or do not re-use mark (see Annex G); f) Year and month of expiry date; g) License number as required by laws and regulations; h) If there is needle, specifications shall be indicated; i) Inspect the complete warnings of each single package Multi-unit packages (syringe type 2, 4, 6, and 8) Syringe unit shall be sealed in a packaging bag, which shall be marked as follows; a) Description of interiors, including nominal capacity and quantity; b) Manufacturer s name, address and trademark; c) Batch number starts from the word batch ; d) Year and month of expiry date; e) Single-use or do not re-use mark (see Annex G); f) interior sterilization of syringe, non-pyrogen or equivalent words; g) Inspect warning description on seal integrity of self-sealed syringe unit, unless the warning description has been indicated in syringe unit; h) License number as required by laws and regulations; i) If there is needle, specifications shall be indicated Medium packages Medium packages shall have following marks: a) Description of interiors, including nominal capacity and quantity; b) Manufacturer s name, address and trademark; c) Words of sterility, non-pyrogen ; d) Marks of single-use or do not re-use (see Annex G); e) Batch number starts from the word of batch ; f) Year and month of expiry date; g) If there is injection needle, specification shall be indicated; Page 19 of 32

10 A.4 stylet diameter of lumen patency of test-needle shall be in accordance with Table A.4. Table A.4 Size of stylet to test patency of lumen Nominal outer diameter Diameter of stylet Unit in millimeters A.5 The resistance to breakage shall be assessed in accordance with Table A.5, when tested as described in GB Nominal outer diameter Table A.5 Resistance to breakage Unit in millimeters Distance between rigid supports and application of bending force ± Page 22 of 32

11 Annex C (Normative) Positive-Pressure Test Method C.1 Test sample preparation C.1.1 Syringes of type 1 and type 2 CONNECT conical head of syringe with standard steel internal cone joint that conforms to GB/T C.1.2 Syringes of type 3 and type 4 REMOVE the needle (if any) and connect with standard steel internal cone joint according to C.1.1. C.1.3 Syringes of type 5 and type 6 ENSURE that connection conical head of syringe and needle bed is firm and has no leakage; INSERT pin tubing and install needle tubing to plunger or bulkhead of 6:100 conical head. C.1.4 Syringes of type 7 and type 8 INSERT pin tubing and install to plunger or bulkhead of 6:100 conical head. C.2 Procedures C.2.1 TEST according to the requirements in of GB C.2.2 CHECK syringe and record all plunger movements during pressing process. C.2.3 CHECK the syringe and observe whether there is any leakage when liquid passes through plunger seal. C.2.4 INSPECT the connection between conical head of syringe and steel standard cone joint or needle bead or the connection between syringe and needle tubing (as the case may be), and observe whether there is any leakage. C.3 Test report Test report shall provide following information: a) Specification of syringe; Page 24 of 32

12 RQL All qualified Sampling plan 8 [0 1] 12 [1 2] E.1.5 For syringes of type 3 and type 4, the sampling plan and discrimination method for inspection of injection needle referred to in 5.9 shall follow the provisions of GB E.2 Lot-by-lot inspection (exit-factory inspection) E.2.1 Lot-by-lot inspection shall be carried out according to relevant provisions of GB/T E.2.2 Sampling plan adopts single sampling; the stringency of sampling plan starts from normal sampling plan; the non-conformance classification, inspection items, acceptable quality level, and inspection level shall follow the provisions of Table E.2. Table E.2 Lot-by-lot inspection Non-conformance Classification (Based on Number of Class A Class B Class C Non-conformance Products) Non-conformance classification group I I I Inspection item , , 5.3, 5.4.1, , 5.8.2, 5.8.3, 5.4.2, 5.5, 5.6, 5.7, , 5.8.4, 5.9 Inspection level S-2 Acceptable quality level All qualified E.2.3 For syringes of type 3 and type 4 and the sampling plan of syringes in 5.9, non-conformance classification, inspection item, acceptable quality level, and inspection level are based on the provisions of GB Page 28 of 32

13 Annex G (Informative) Symbol for "do not re-use" G.1 General The standard number of the symbol that is used to denote equipment intended for single-use is ISO 7000/1051, as published in ISO 7000:1989 Graphical symbols for use on equipment - Index and synopsis. Further information on design, dimensions, and application of ISO symbols is given in ISO 3461:1987 General principles for the creation of graphical symbols - Part 2: Graphical symbols for use in technical product documentation. G.2 Original design Symbol in ISO 7000/1051 is shown in Figure E.1. The four visual centering lines are an aid for positioning the symbol and for relating it to its surroundings, but do not form part of the symbol. The thickness of the lines is 2 mm. Dimension a is the nominal size of the original design of all ISO symbols and is normally made equal to 50 mm. In many cases, including ISO 7000/1051, the actual dimension differs slightly, and the outer diameter of the circle (dimension h) of the original design is 1.16a, i.e. 58 mm. No colour is specified in ISO 7000/1051. G.3 Reduction and enlargement of original design For symbol application, it may be necessary to reduce or enlarge the size of the original to a suitable size at which it will actually appear. Practice has shown that dimension a may be reduced to 3 mm without the symbol losing its legibility. However, symbol legibility shall be checked when reducing the size. Page 30 of 32

14 Annex H (Informative) Technical Differences between This Standard and ISO 8537, and the Reasons Table H.1 shows technical differences between this Standard and ISO 8537, and the reasons. Table H.1 Technical differences between this Standard and ISO 8537, and the reasons Clause No. of this Standard Technical Differences Reasons 2 CITE standard of China that adopts international To suit national standard rather than national standard 5.2 ADD the distance from inner surface of coat edge curl To facilitate use of to outer surface of pressing-hand when core pin is standard pushed to coat back cover ADD performance index of plunger To suit national ADD performance index of easily oxidized substance To suit national 5.11 ADD biological performance index To suit national ADOPT corresponding standard of China for Test To suit national Method of Leakage between Barrel and Plunger ADOPT corresponding standard of China for capacity To suit national tolerance test ADOPT corresponding standard of China for residual To suit national amount test ADOPT corresponding standard of China for test of To suit national conical head leakage Annex E ADD this normative annex To suit national Annex F ADD this normative annex To suit national END Page 32 of 32