Foreword
Codeofchina.com is in charge of this English translation. In case of any doubt about the English translation, the Chinese original shall be considered authoritative.
This standard is developed in accordance with the rules given in GB/T 1.1-2009.
This standard replaces YY 0308-2004 Medical sodium hyaluronate gel. The following main technical changes have been made with respect to YY 0308-2004:
——The terms, definitions and requirements of shear viscosity, elasticity, viscoelastic and weight average molecular weight have been added (see 3.2 ~ 3.5, 5.8, 5.9 and 5.10.2);
——The terms, definitions and requirements of kinematic viscosity have been deleted (see 3.2 and 5.8 of Edition 2004);
——The requirements of effective usage have been modified (see 5.2; 5.2 of Edition 2004);
——The requirements of transmittance have been modified (see 5.5; 5.5 of Edition 2004);
——The requirements of protein content have been modified (see 5.11; 5.10 of Edition 2004);
——The requirements of refractive index have been added (see 5.13);
——The index of ethanol residue has been modified (see 5.15; 5.13 of Edition 2004);
——The index of bacterial endotoxin content has been modified (see 5.17; 5.15 of Edition 2004);
——The description of biological test methods has been deleted (see 5.17.2~5.17.7 of Edition 2004);
——The determination method of sodium hyaluronate content has been modified (see Annex A; Annex A of Edition 2004).
Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. The issuing body of this document shall not be held responsible for identifying any or all such patent rights.
This standard was proposed by the China Food and Drug Administration.
This standard is under the jurisdiction of Jinan Medical Apparatus Supervision and Inspection Center of China Food and Drug Administration.
This standard was first issued in October 1998, first revised in November 2004, and this is the second revision.
Introduction
Sodium hyaluronate is a kind of naturally linear polysaccharide, which is composed of disaccharide structure unit composed of (1→4)-β-D-glucuronic acid and (1→3)-2-acetylamino-β-D-glucose. According to the characteristics of sodium hyaluronate, the medical sodium hyaluronate gel made by deep processing is non-toxic and water-soluble new biomaterial with good biocompatibility, which can be used in ophthalmic surgery, articular cavity lubrication and surgical operation to prevent postoperative tissue adhesion.
For articular injection, medical sodium hyaluronate gel needs a molecular weight closer to that of sodium hyaluronate in normal synovial fluid; for ophthalmic surgery, high shear viscosity is particularly important for surgical operation; however, for prevention of postoperative tissue adhesion, it mainly depends on the biological barrier caused by high viscoelasticity. Since the shear viscosity is closely related to the determination temperature and shear rate, the shear viscosity value at low shear rate (that is the surgical instrument is operated in viscoelastic solution in the anterior chamber) is selected in this standard. Meanwhile, the elasticity is also closely related to clinical application, in consideration of ophthalmic viscoelastic solutions and products for intra-articular injection.
Sodium hyaluronate, as a medical biomaterial implanted into the body, must be strictly controlled of the content of various foreign materials to ensure the safety and effectiveness. In consideration that sodium hyaluronate shall be mixed with organic solvents in the purification and drying process, and it is a high polymer material that is difficult to dry, making it difficult for organic solvents to volatilize completely, the trace amount of organic solvents in sodium hyaluronate will stimulate patients to varying degrees during the usage. Therefore, in order to minimize the adverse effects of products on patients, and in consideration of the current production process level, it is necessary to limit the ethanol residual to a reasonable extent. Since some manufacturers may use organic solvents other than ethanol, it is necessary to establish corresponding technical requirements and test methods.
Some sodium hyaluronate is extracted from animal tissues or organs, so it may carry viruses and infectious factors. Manufacturers shall take effective control measures to remove or inactivate viruses and infectious factors in animal tissues or organs.
Note: For control measures of viruses and infectious factors in animal tissues, please refer to YY/T 0771 standards series.
Some sodium hyaluronate is prepared by microbial fermentation, during which metabolites may be produced by strains. So manufacturers shall take effective measures to control harmful streptococcal secretions.
Medical sodium hyaluronate gel is sterile product produced by sterile operation technology or other sterilization technologies. Therefore, manufacturers should take corresponding measures to minimize microbial and particulate pollution during production and packaging, and organize production according to YY/T 0287, YY 0033 and YY/T 0567.
For ease of use, the packaging of medical sodium hyaluronate gel often has the functional requirements for clinical use, so as to control the amount of gel used clinically and minimize the secondary pollution during use. The functional requirements of packaging shall be an important part of product performance. However, due to the diversity of packaging and in order not to limit technological innovation, this standard does not include packaging requirements.
Medical sodium hyaluronate gel
1 Scope
This standard specifies the classification, requirements, inspection rules, marking and packaging of medical sodium hyaluronate gel.
This standard is applicable to medical sodium hyaluronate gel. Medical sodium hyaluronate gel is applicable to viscoelastic solutions for ophthalmic surgery, lubricants for intra-articular injection and barrier agents for surgical operations.
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition (including any amendments) applies.
GB/T 16886.1 Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
Pharmacopoeia of the People’s Republic of China (Volume II) Edition 2010
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
medical sodium hyaluronate gel
gelatinous solution prepared with sodium hyaluronate used in human body
3.2
shear viscosity
ability of a fluid to resist the deformation rate under shear force
Note 1: Quantitatively, the shear viscosity is the quotient of shear stress divided by shear rate at a constant shear rate.
Note 2: The shear viscosity is expressed in Pa·s, which is usually also expressed in mPa·s.
Note 3: The shear rate is the velocity gradient of the fluid, expressed in s-1.
Note 4: The kinematic viscosity is the quotient of shear viscosity divided by the density of fluid, which is a measure of the viscosity of fluid affected by inertia (e.g. gravity).
3.3
elasticity
property of deforming material restored to its original shape after getting rid of external force
Note: Elasticity can be quantitatively expressed as stress (force per unit area) divided by strain (relative change in size of an object).
3.4
viscoelastic
characteristics of fluid with viscosity and elasticity
Note: The viscosity modulus G″ is commonly referred to as the loss modulus, and the elastic modulus G′ is commonly referred to as the storage modulus, both of which are expressed in Pascal (Pa). Both can express the elasticity of viscoelastic solution together.
3.5
weight average molecular weight
average molecular weight with mass as the statistical weight ( )
Note: The average molecular weight with the amount of substance as the statistical weight is referred to as number average molecular weight ( ).
4 Classification
4.1 Medical sodium hyaluronate gel can be divided by clinical applicability into ophthalmic gel, surgical gel and intra-articular injection gel.
4.2 Medical sodium hyaluronate gel is generally divided by packaging specification into 0.5mL, 0.8mL, 1mL, 2mL, 2.5mL, 3mL, 5mL, etc.
Foreword i
Introduction iii
1 Scope
2 Normative references
3 Terms and definitions
4 Classification
5 Requirements
6 Inspection rules
7 Marking
8 Packaging
Annex A (Normative) Determination of sodium hyaluronate content
Annex B (Normative) Determination of weight average molecular weight and molecular weight distribution coefficient
Annex C (Normative) Determination of protein content
Annex D (Normative) Determination of ethanol residue (gas chromatography)
Bibliography
