GB 19192-2003Hygienic requirement for contact lens care solution [including MODIFICATION 1] (English PDF)

5.1.6 Physical compatibility with lenses

When tested according to the method of ISO/DIS 11981, it shall meet the corresponding requirements in Table 1.

5.2 Microbial indicators

5.2.1 Processing of solid sample

Accurately weigh 2.000 g of specimen. Put it into 20.0 mL of 0.03 mol/L phosphate buffer solution (PBS) (if the product contains antibacterial ingredients, use a neutralizer instead of PBS). Completely dissolve it. Take sample. Carry out testing, according to the following method.

5.2.2 Viable bacteria count

Take 1.0 mL of sample solution, to inoculate nutrient agar medium. Inoculate two plates in parallel in each tube. Incubate it at 35 °C ~ 37 °C for 48 h.

Calculate the average number of colonies on the plate, according to formula (2).

It shall meet the corresponding requirements in Table 1.

Viable bacteria count (cfu/g) = Average number of colonies on the plate x

10 ………………………... (2)

5.2.3 Pathogenic bacteria

Use the method in Appendix A of GB 15979-1995 "Hygienic standard for disposable sanitary products", to carry out testing for the Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli. It shall meet the corresponding requirements in Table 1.

Note 1: The neutralizer, which is used in this test, must pass the suspension quantitative neutralizer qualification test, which is specified in Appendix D (normative).

Note 2: If it can’t find a suitable neutralizer, it can process the sample solution, in accordance with the "Sterile inspection method" and "Membrane filtration method" of the Pharmacopoeia of the People's Republic of China (Part 2 of the 1995 edition). The film is directly inoculated with the corresponding culture medium for testing.

5.2.4 Sterility inspection

It is tested according to the "Sterile inspection method" of the Pharmacopoeia of the People's Republic of China (Part 2 of the 1995 edition) (if the product contains antibacterial ingredients, it must be treated with membrane filtration first). It shall meet the corresponding requirements in Table 1.

5.3 Disinfection effect index

See Appendix A (normative), which shall meet the corresponding requirements in Table 1.

5.4 Safety indicators

5.4.1 Acute oral toxicity test, mutagenicity test, skin irritation test, eye irritation

test, skin allergic reaction test

It is tested, according to the "Disinfectant Toxicology Experimental Technology", in the volume 1 "Experimental Technical Specifications" (1999), of the

"Disinfection Technical Specifications" (third edition) of the Ministry of Health of the People's Republic of China. It shall meet the corresponding requirements in Table 1.

5.4.2 Cytotoxicity test

See appendix B (normative), which shall meet the corresponding requirements in Table 1.

5.5 Stability Index

See appendix C (normative), which shall meet the corresponding requirements in Table 1.

5.6 Clinical tests

5.6.1 Products which must be subject to clinical tests:

a) Various care solutions containing new ingredients: It requires a 3-month clinical tests with 60 subjects;

b) Various care solutions whose active ingredients are higher than the concentration of the products on the market: It requires a 1-month clinical trial with 30 subjects;

c) Intraocular solutions whose active ingredients are lower than those of the marketed products AND care solutions which have cleaning, disinfection or neutralization effects: It requires a 1-month clinical trial with 30 subjects.

5.6.2 Test control: It must set paired control, which is equivalent to the subject.

5.6.3 Test method: When tested according to the method of ISO/DIS 11980, it

shall meet the corresponding requirements in Table 1.

7.1 Packaging

7.1.1 Packaging materials that are in direct contact with the contact lens care solution: It shall be safe and harmless; it shall not affect the hygienic quality of the product within the valid date.

7.1.2 The transportation and packaging of contact lens care products: It shall be able to protect the product from damage, during transportation and storage.

7.2 Marking

7.2.1 Sales packaging mark: In Chinese, it shall indicate the product name, main active ingredients, net content, production batch number, valid date or guarantee date, manufacturer's name and address, approval document number, implemented standard number, as well as necessary precautions. For imported products, it shall also be marked with the name and address of the distributor.

7.2.2 Transport packaging mark: In Chinese, it shall indicate the product name, specification and quantity, production batch number, valid date or guarantee date, manufacturer name and address, approval document number, implemented standard number, as well as necessary precautions. For imported products, it shall also be marked with the name and address of the distributor.

7.3 Instructions for use

7.3.1 Each sales package shall be accompanied by instructions for use.

7.3.2 Instructions for use must clearly indicate the following content, in Chinese:

product name and dosage form, main active ingredients and content, performance, scope of application and contraindications, detailed use methods and procedures, adverse reactions or side effects, storage conditions, valid date or guarantee date, as well as precautions.

7.3.3 For the instructions for use of the singledose product, it shall state “Use only once”. For the instructions for use of multidose products, it shall state “The container must be closed, immediately after each use”, as well as the discard date.

Appendix A (Normative)

Test method of disinfection effect

A1 Purpose

Used to determine whether the contact lens care solution has disinfection function.

A2 Test method

A2.1 Suspension quantitative sterilization test

A2.1.1 Test microorganisms a) Bacteria: Escherichia coli (ATCC 8739 or 8099)

Staphylococcus aureus (ATCC 6538)

Pseudomonas aeruginosa (ATCC 9027) b) Yeast: Candida albicans (ATCC 10231) c) Mold: Fusarium Solanaceae (ATCC 36031)

A2.1.2 Operating procedures

A2.1.2.1 Take a fresh slant culture (18 h ~ 24 h) of the nutrient agar of the 3 ~

14th generation of strains. Use 0.03 mol/L phosphate buffered saline (PBS) to rinse it. Dilute it to bacterial suspension, which has a bacterial content of 1x107 cfu/mL ~ 1x108 cfu/mL.

A2.1.2.2 Pipette 10.0 mL, respectively, from the three batches of specimens, into three sterile test tubes. Place in a water bath, at 20 °C ~ 25 °C, for 5 min.

A2.1.2.3 Add 0.1 mL of bacterial suspension, to the test tube, to make the final bacterial content at 1x105 cfu/mL ~ 1x106 cfu/mL. Mix well. Start timekeeping.

A2.1.2.4 At four different action times (25%, 50%, 75%, 100% of the recommended minimum disinfection time), respectively take 1.0 mL of the bacterial drug mixture; transfer it into 9.0 mL of the neutralizer. Mix well.

A2.1.2.5 After 10 minutes of neutralization, pipette 1.0 mL of the stock solution or 10-fold serial dilution. Respectively inoculate it with nutrient agar medium (bacteria), Sandburg's agar medium (yeast) or potato dextrose agar medium

Appendix B (Normative)

Test and evaluation method of cytotoxicity

B1 Purpose

A certain amount of test substance is added to cell culture medium, to culture cells. The potential toxicity of the care solution on mammalian cells is evaluated, by its influence on cell growth and proliferation.

B2 Reagents a) Positive control: 64 g/L phenol solution.

b) Negative control: The following medium.

c) Cell strain: It is recommended to use L-929 cells (mouse fibroblasts). The cells used for the test are cells that grow vigorously at regeneration for 48 h ~ 72 h.

d) Medium: Eagle's MEN is added with 10% calf serum;

e) Phosphate buffered saline (PBS).

Calcium-magnesium-free phosphate buffer: 100.0 mL

Phenol red solution: 10.0 mL

200 g/L magnesium chloride solution: 0.5 mL

100 g/L calcium chloride solution: 1.0 mL

Water: Add to 1000 mL

B3 Test procedure

B3.1 Preparation of cell suspension: Use the cell culture medium to prepare

40000 cells/mL cell suspension. Distribute it in test tubes (1 mL/tube), including

13 tubes for negative control group (1 spare tube) AND 10 tubes for material group (1 spare tube). If necessary, set up 3 tubes of the positive control group;

place them in a 37 °C constant temperature incubator, to culture it for 24 hours.

B3.2 Preparation of the test substance: Add 0.2 mL of the test substance, into the cell culture solution. Incubate it at 37 °C for 24 h.

B3.3 Test solution exchange: After 24 hours, discard the original culture solution in each tube. For the negative control group, 9 tubes are exchanged with fresh culture solution. For the positive control group, use cell culture solution which contains 64 g/L phenol for exchange. For the test substance group, use the fresh culture solution, which contains the test solution, at the volume fraction of

50%, for exchange. Count the cells in three negative control tubes. Keep the others at 37 °C, to continue the culture.

B3.4 Cell count and absorbance determination

B3.4.1 Perform cell count or absorbance determination, on each of the three tubes of the control group and the test group, at the 2nd, 4th, 7th days, to determine the degree of cell proliferation.

B3.4.2 Cell counting method: Use the crystal violet, which contains the sodium citrate, to stain it. Make counting for the hemocytometer, under a microscope.

The upper and lower limits shall not exceed 10%; otherwise, the count shall be repeated.

B3.4.3 Spectrophotometer absorbance method (arbitration method): Discard the original cell culture solution. Use PBS to rinse it. Use the formaldehyde solution, which has a volume fraction of 10%, to fix it for 10 min. Use water to wash it for (2 ~ 3) times. Add 1.5 mL of the 5 g/L crystal violet, to stain it for 3 min. Use water to wash it for (2 ~ 3) times. Add 3.5 mL of the 10 g/L sodium lauryl sulfate. Use a spectrophotometer, to measure the absorbance, at a wavelength of 588 nm.

B4 Result calculation

B4.1 Cell counting method: The upper limit, average, lower limit of the cell count are calculated, by mathematical statistics, at 95% reliability. The relative proliferation rate (RGR) is calculated by the cell count, as shown in formula (B1).

RGR = (Average value of test group/Average value of negative control group) x 100% ………………………. (B1)

B4.2 Absorbance determination method: The calculation of relative proliferation is as shown in formula (B2).

RGR = [(Absorbance of test group - Absorbance of blank control)/(Absorbance of negative control group - Absorbance of blank control)] x 100% ………… (B2)

B4.3 Toxicity assessment: According to Table B1, convert the RGR value into a six-level reaction, to assess the toxicity of the care solution.

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