YY/T 0606.9-2007 English PDF (YYT0606.9-2007)

This Part of YY/T 0606 specifies the requirements, test methods, testing rules, marks, packaging, transportation and storage of the sodium hyaluronate used in surgical implants and tissue engineered medical products. This Part applies to the sodium hyaluronate which can be used for preparing the surgical implants and tissue engineered medical products.

YY/T 0606.9-2007
YY
PHARMACEUTICAL INDUSTRY STANDARD
OF THE PEOPLE’S REPUBLIC OF CHINA
ICS 11.040.40
C 45
Tissue engineered medical products –
Part 9. Sodium hyaluronate
组织工程医疗产品
ISSUED ON. JANUARY 31, 2007
IMPLEMENTED ON. JANUARY 1, 2008
Issued by. China Food and Drug Administration
Table of Contents
Foreword ... 3
1 Scope ... 4
2 Normative references ... 4
3 Terms and definitions ... 5
4 Classification ... 6
5 Requirements ... 6
6 Test methods ... 9
7 Inspection rules ... 12
8 Marks ... 13
9 Packaging, transportation and storage ... 14
Appendix A ... 15
Appendix B ... 18
Appendix C ... 22
Appendix D ... 25
References ... 28
Foreword
YY/T 0606 Tissue engineered medical products is divided into.
— Part 1. General requirements;
— Part 2. Terminology;
— Part 3. General classification;
— Part 4. Terminology and classification of skin substitute;
— Part 5. Characterization and testing of substrates and scaffolds;
— Part 6. Type I collagen;
— Part 7. Chitosan;
— Part 8. Alginate;
— Part 9. Sodium hyaluronate;
— Part 10. In vivo assessment of implantable devices intended to repair or regenerate articular cartilage;
— Part 12. Guide for processing cells, tissues, and organs;
— Part 13. Product conservation;
— Part 16. Guide for gel immobilization or microencapsulation of alginates in the living cells or tissues.
This Part is the Part 9 of YY/T 0606.
The Appendixes A, B and C of this Part are normative; while the Appendix D is informative.
This Part was proposed by China Food and Drug Administration.
This Part shall be under the jurisdiction of the National Institute for the Control of Pharmaceutical and Biological Products.
Drafting organizations of this Part. Shanghai Qisheng Institute of Biomaterial and Technology, and Medical Device Testing Center of the National Institute for the Control of Pharmaceutical and Biological Products.
Main drafters of this Part. Gu Qisheng, Huang Zhiben, and Xi Tingfei.
Tissue engineered medical products –
Part 9. Sodium hyaluronate
1 Scope
This Part of YY/T 0606 specifies the requirements, test methods, testing rules, marks, packaging, transportation and storage of the sodium hyaluronate used in surgical implants and tissue engineered medical products.
This Part applies to the sodium hyaluronate which can be used for preparing the surgical implants and tissue engineered medical products.
2 Normative references
The provisions in the following documents become the provisions of this Part through reference in this Part of YY/T 0606. For dated references, the
subsequent amendments (excluding corrections) or revisions do not apply to this Part. However, parties who reach an agreement based on this Part are encouraged to study if the latest versions of these documents are applicable. For undated references, the latest versions apply to this Part.
GB 191-2000 Packaging – Pictorial marking for handling of goods (eqv ISO 780.1997)
GB/T 14518-1993 Determination of the pH of adhesives (neq NFT 76-
103.1972)
GB/T 16886.1-2001 Biological evaluation of medical devices – Part 1.
Evaluation and testing (idt ISO 10993-1.1997)
GB/T 16886.3-1997 Biological evaluation of medical devices – Part 3. Tests for genotoxicity, carcinogenicity and reproductive toxicity (idt ISO 10993- 3.1992)
GB/T 16886.4-2003 Biological evaluation of medical devices – Part 4.
Selection of tests for interactions with blood (ISO 10993-4.2002, IDT)
GB/T 16886.5-2003 Biological evaluation of medical devices – Part 5. Test for in vitro cytotoxicity (ISO 10993-5.1999, IDT)
GB/T 16886.6-1997 Biological evaluation of medical devices – Part 6. Tests for local effects after implantation (idt ISO 10993-6.1994)
GB/T 16886.10-2005 Biological evaluation of medical devices – Part 10.
Tests for irritation and delayed-type hypersensitivity (ISO 10993-10.2002, IDT)
GB/T 16886.11-1997 Biological evaluation of medical devices – Part 11.
Tests for systemic toxicity (idt ISO 10993-11.1993)
GB/T 16886.12-2005 Biological evaluation of medical devices – Part 12.
Sample preparation and reference materials (ISO 10993-12.2002, IDT)
YY/T 0313-1998 Package, label, transport and storage for medical polymer products
YY 0466-2003 Medical devices – Symbols to be used with medical device
labels, labelling and information to be supplied (ISO 15233.2000, IDT)
Pharmacopoeia of People’s Republic of China (2005 Edition, Volume 2)
3 Terms and definitions
The following terms and definitions apply to this Part of YY/T 0606.
3.1 Hyaluronic acid
It refers to the linear polysaccharide that is composed of disaccharide repeating structural units generated by connecting D-glucuronic acid and N-acetyl-D- glucosamine together via β-(1-3) glucosidic bond. Each disaccharide unit is connected with another unit via β-(1-4) glucosidic bond.
3.2 Sodium hyaluronate
It refers to the sodium salt form of the hyaluronic acid. The molecular weight of its structural unit is 401. The molecular structural formula is shown in the figure below.
Note. SEE Appendix D for the additional information about the hyaluronic acid. 5.15 Safety of raw materials
5.15.1 The sodium hyaluronate prepared by using the bio-fermentation
method shall be conducted with the hemolysis test for hemolytic streptococcus. The test results shall have no hemolytic.
5.15.2 The sodium hyaluronate prepared by using the tissue extraction
method shall be conducted with relevant inspection and quarantine. The test results shall be qualified.
5.16 Biological properties
5.16.1 General rules
The sodium hyaluronate shall be conducted with biological evaluation
according to the requirements specified in the GB/T 16886.1. It shall not release any substances that have adverse effects on the human bodies.
5.16.2 Cytotoxicity test
The cytotoxic reaction shall not be greater than Level 1.
5.16.3 Intradermal reaction test
The primary irritation index (PII) shall not be greater than 0.4.
5.16.4 Acute systemic toxicity
There shall be no acute systemic toxicity.
5.16.5 Hemolysis test
There shall be no hemolytic reaction.
5.16.6 Sensitization test
There shall be no skin sensitization.
5.16.7 Subcutaneous implant test
There shall be no significant differences between tissue reaction and negative control, 14 days after implantation.
5.16.8 Genotoxicity test
There shall be no genotoxicity.
GB/T 16886.5. It shall conform to the provisions specified in the Article 5.16.2. 6.16.3 Intradermal reaction test
The determination shall be conducted according to the methods specified in the GB/T 16886.10. It shall conform to the provisions specified in the Article 5.16.3. 6.13.4 Acute systemic toxicity
The determination shall be conducted according to the intraperitoneal injection method specified in the GB/T 16886.11. It shall conform to the provisions specified in the Article 5.16.4.
6.16.5 Hemolysis test
The determination shall be conducted according to the hemolysis test method specified in the GB/T 16886.4. It shall conform to the provisions specified in the Article 5.16.5.
6.16.6 Sensitization test
The determination shall be conducted according to the maximum dose method specified in the GB/T 16886.10. It shall conform to the provisions specified in the Article 5.16.6.
6.16.7 Subcutaneous implant test
PREPARE the hyaluronic acid solution according to the instructions for use. USE 3 New Zealand rabbits. Respectively SELECT 2 implant points on both sides of the rabbit’s spine. CONDUCT the subcutaneous injection of 0.5mL of hyaluronic acid to each point. TAKE samples for observation after 14 days. Other test procedures shall be conducted according to the methods specified in the GB/T 16886.6. The test procedures shall conform to the provisions specified in the Article 5.16.7.
6.16.8 Genotoxicity test
The determination shall be conducted according to the methods for Ames test, micronucleus test, and chromosome aberration test (mouse sperm test)
specified in the GB/T 16886.3. It shall conform to the provisions specified in the Article 5.16.8.
7 Inspection rules
7.1 General rules
8.3 The storage and transportation marks shall conform to the provisions specified in the GB/T 191.
9 Packaging, transportation and storage
9.1 USE appropriate packaging to ensure the safety and effectiveness of the sodium hyaluronate products.
9.2 The packaging, transportation and storage of produ...