SANS 440-2008 Sterilized water for injections《注射用无菌水》.pdf

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1、 Collection of SANS standards in electronic format (PDF) 1. Copyright This standard is available to staff members of companies that have subscribed to the complete collection of SANS standards in accordance with a formal copyright agreement. This document may reside on a CENTRAL FILE SERVER or INTRA

2、NET SYSTEM only. Unless specific permission has been granted, this document MAY NOT be sent or given to staff members from other companies or organizations. Doing so would constitute a VIOLATION of SABS copyright rules. 2. Indemnity The South African Bureau of Standards accepts no liability for any

3、damage whatsoever than may result from the use of this material or the information contain therein, irrespective of the cause and quantum thereof. ISBN 978-0-626-20833-2 SANS 440:2008Edition 5SOUTH AFRICAN NATIONAL STANDARD Sterilized water for injections Published by Standards South Africa 1 dr lat

4、egan road groenkloof private bag x191 pretoria 0001 tel: 012 428 7911 fax: 012 344 1568 international code + 27 12 www.stansa.co.za Standards South Africa SANS 440:2008 Edition 5 Table of changes Change No. Date Scope Foreword This South African standard was approved by National Committee StanSA SC

5、5140.36A, Intravenous solutions, injectables and infusion sets Intravenous solutions and injectables, in accordance with procedures of Standards South Africa, in compliance with annex 3 of the WTO/TBT agreement. This document was published in February 2008. This document supersedes SABS 440:1987 (th

6、ird revision). A reference is made in 6.2.1(j) to labelling required by “the current relevant national legislation“. In South Africa this means the Medicines and Related Substances Control Act, 1965 (Act No. 101 of 1965). Annex A forms an integral part of this standard. Annex B is for information on

7、ly. SANS 440:2008 Edition 5 1 Contents Page Foreword 1 Scope . 3 2 Normative references 3 3 Definitions . 3 4 Requirements . 4 4.1 Freedom from visible suspended matter and sediment . 4 4.2 Fill volume 4 4.3 Conductivity 4 4.4 Acidity or alkalinity 4 4.5 Oxidizable substances . 4 4.6 Chlorides 4 4.7

8、 Nitrates. 4 4.8 Sulfates 54.9 Ammonium . 5 4.10 Calcium and magnesium 5 4.11 Heavy metals 5 4.12 Residue on evaporation . 5 4.13 Particulate matter (sub-visible particles) 5 4.14 Sterility 5 4.15 Bacterial endotoxins. 5 5 Inspection and methods of test . 5 5.1 General. 5 5.2 Inspection. 5 5.3 Fill

9、volume 6 5.4 Conductivity 6 5.5 Acidity or alkalinity 6 5.6 Oxidizable substances . 7 5.7 Chlorides 7 5.8 Nitrates. 8 5.9 Sulfates 9 5.10 Ammonium . 9 5.11 Calcium and magnesium 10 5.12 Heavy metals 11 5.13 Residue on evaporation . 12 5.14 Particulate matter (sub-visible particles) 12 5.15 Sterility

10、 12 5.16 Bacterial endotoxins. 12 6 Packing and marking. 12 Annex A (normative) Sampling and compliance with this standard 15 Annex B (informative) Quality verification of sterilized water for injections. 16 Bibilography. 16 SANS 440:2008 Edition 5 2 This page is intentionally left blank SANS 440:20

11、08 Edition 5 3 Sterilized water for injections 1 Scope This standard covers chemical and biological requirements for water for injections that has been dispensed into suitable containers, sealed and sterilized. It also specifies the required marking. 2 Normative references The following referenced d

12、ocuments are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. Information on currently valid national and international standards can be

13、obtained from Standards South Africa. 2.1 Standards SANS 1384, Plastics containers for parenteral solutions. SANS 3696/ISO 3696, Water for analytical laboratory use Specification and test methods. 2.2 Other publications British Pharmacopoeia (BP). United States Pharmacopoeia (USP). 3 Definitions For

14、 the purposes of this document, the following definitions apply. 3.1 acceptable acceptable to the authority administering this standard, or to the parties concluding the purchase contract, as relevant 3.2 batch that quantity of the product that is homogenous, filled and sealed into containers, and s

15、terilized in the same cycle of operations 3.3 certified reagent for which a certificate of analysis stating the percentage purity, is available SANS 440:2008 Edition 5 4 3.4 product water for injections that is filled, sealed and sterilized in the final container 3.5 test solution aliquot of the pro

16、duct used for testing to which one or more chemicals have been added 4 Requirements 4.1 Freedom from visible suspended matter and sediment When examined in accordance with 5.2, the product shall be clear and colourless, without odour or taste, and shall not contain antimicrobial agents nor any other

17、 added substances. 4.2 Fill volume 4.2.1 The maximum nominal fill volume of a container shall not exceed 1 L. 4.2.2 When determined in accordance with 5.3, the volume of the contents of each container shall not be less than the nominal volume and not more than 110 % of the nominal volume. 4.3 Conduc

18、tivity When determined in accordance with 5.4, the conductivity of the contents of containers with a nominal volume of a) 10 mL shall not exceed 25 Scm-1, and b) 10 mL shall not exceed 5 Scm-1. 4.4 Acidity or alkalinity When tested in accordance with 5.5, the product shall pass the test. 4.5 Oxidiza

19、ble substances When tested in accordance with 5.6, the solution shall remain faintly pink. 4.6 Chlorides 4.6.1 Containers with a nominal volume of 100 mL When tested in accordance with 5.7.2.1, the product shall not contain 0,5 g/mL of chlorides. 4.6.2 Containers with a nominal volume of 100 mL When

20、 tested in accordance with 5.7.2.2, the test solution shall show no change in appearance for 15 min. 4.7 Nitrates When tested in accordance with 5.8, the product shall not contain 0,2 g/mL of nitrates. SANS 440:2008 Edition 5 5 4.8 Sulfates When tested in accordance with 5.9, the test solution shall

21、 show no change in appearance for at least 1 h. 4.9 Ammonium When tested in accordance with 5.10, the product shall not contain 0,2 g/mL of ammonium. 4.10 Calcium and magnesium When tested in accordance with 5.11, a pure blue colour shall be produced. 4.11 Heavy metals When determined in accordance

22、with 5.12, the product shall not contain 0,1 g/mL of lead. 4.12 Residue on evaporation When determined in accordance with 5.13, the residue on evaporation of the test solution of a product with a nominal volume of a) 10 mL shall not exceed 0,004 g/100 mL, and b) 10 mL shall not exceed 0,003 g/100 mL

23、. 4.13 Particulate matter (sub-visible particles) When tested in accordance with 5.14, the number of particles with a diameter 10 m and 25 m, respectively, shall comply with the limits for small volume injections and large volume injections, as relevant. 4.14 Sterility When tested in accordance with

24、 5.15, there shall be no signs of microbial growth. 4.15 Bacterial endotoxins When tested in accordance with 5.16, the product shall not contain more than 0,25 USP Endotoxin Units per millilitre. 5 Inspection and methods of test 5.1 General Unless otherwise specified, only use water that complies wi

25、th the requirements for grade 3 water as given in SANS 3696, and reagents of analytical reagent grade or of the purest grade available. NOTE Commercially available volumetric solutions can also be used where appropriate. 5.2 Inspection 5.2.1 Gently invert the container and examine, without magnifica

26、tion, for any visible signs of suspended matter or sediment (see A.3). SANS 440:2008 Edition 5 6 5.2.2 Check for compliance with 4.1. 5.3 Fill volume 5.3.1 Containers with a nominal volume of 10 mL 5.3.1.1 Transfer, as completely as possible, the contents of no less than three containers into a grad

27、uated measuring cylinder of a size able to contain at least 110 % of the nominal volume of three containers. 5.3.1.2 Record the volume of liquid in the measuring cylinder. 5.3.1.3 Determine the average fill volume per container. 5.3.1.4 Check for compliance with 4.2. 5.3.2 Containers with a nominal

28、volume of 10 mL 5.3.2.1 Transfer, as completely as possible, the contents of the container into a graduated measuring cylinder of a size able to contain at least 110 % of the nominal volume of the container. 5.3.2.2 Record the volume of liquid in the measuring cylinder. 5.3.2.3 Determine the average

29、 fill volume of at least three containers. 5.3.2.4 Check for compliance with 4.2. 5.4 Conductivity 5.4.1 Use the equipment and the calibration procedure under “Water for injections in bulk“ given in the BP. 5.4.2 Check for compliance with 4.3. 5.5 Acidity or alkalinity 5.5.1 Reagents 5.5.1.1 Phenol

30、red indicator solution Add 1,42 mL of a solution of 0,8 g/100 mL of sodium hydroxide and 5 mL of an aqueous 90 % solution of ethanol (volume fraction) to 0,1 g of phenol red. Warm until dissolved. Dilute with an aqueous 20 % solution of ethanol (volume fraction) to 250 mL. 5.5.1.2 Sodium hydroxide s

31、olution, c(NaOH) = 0,01 mol/L Dissolve 0,42 g of sodium hydroxide in water and dilute to 1 L with water. Standardize against certified potassium hydrogen phthalate, using the phenol red indicator solution. 5.5.1.3 Hydrochloric acid solution, c(HCl) = 0,01 mol/L Dilute 0,87 mL of concentrated hydroch

32、loric acid (d at 25 C = 1,18) to 1 L with water. Standardize against the 0,01 mol/L sodium hydroxide solution. NOTE The methods for standardization given in the USP or BP can be used. SANS 440:2008 Edition 5 7 5.5.2 Procedure 5.5.2.1 Add five drops of the phenol red indicator solution to 100 mL of t

33、he product. 5.5.2.2 The product shall be deemed to comply with 4.4 if not more than: 0,5 mL of the sodium hydroxide solution is required to change the colour of the test solution from yellow to red, or 0,75 mL of the hydrochloric acid solution is required to change the colour of the test solution fr

34、om red to yellow. 5.6 Oxidizable substances 5.6.1 Reagents 5.6.1.1 Sulfuric acid solution, c(H2SO4) = 1 mol/L While stirring, add 56 mL of concentrated sulfuric acid (d at 25 C = 1,84) to 500 mL of cooled water. Cool and dilute to 1 L with water. 5.6.1.2 Potassium permanganate solution, c(KMnO4) = 0

35、,02 mol/L Dissolve 3,2 g of potassium permanganate in 1 000 mL of water. Heat on a waterbath for 1 h, cool and filter through a sintered-glass filter. 5.6.2 Procedure 5.6.2.1 Add 10 mL of the sulfuric acid solution to 100 mL of the product and bring to the boil. 5.6.2.2 Add 0,2 mL of the 0,02 mol/L

36、potassium permanganate solution and boil for 5 min. 5.6.2.3 Check for compliance with 4.5. 5.7 Chlorides 5.7.1 Reagents 5.7.1.1 Chloride standard solution, 5 g/mL Cl Dissolve 0,0824 g of sodium chloride (NaCl) in water and dilute to 100,0 mL with water. Dilute 1,0 mL of this solution to 100,0 mL wit

37、h water. This diluted solution contains 5 g of chloride per millilitre. 5.7.1.2 Nitric acid solution, c(HNO3) = 2 mol/L Dilute 12,6 mL of concentrated nitric acid (d at 25 C = 1,42) to 100 mL with water. 5.7.1.3 Silver nitrate solution, c(AgNO3) = 0,1 mol/L Dissolve 17,0 g of silver nitrate in water

38、 and dilute to 1 L with water. Ensure that the silver nitrate solution is clear before use and filter if necessary. Store protected from light. SANS 440:2008 Edition 5 8 5.7.2 Procedure 5.7.2.1 Containers with a nominal volume of 100 mL 5.7.2.1.1 Add 1,5 mL of the chloride standard solution to 13,5

39、mL of water in a Nessler tube. 5.7.2.1.2 Transfer 15,0 mL of the product into a matched Nessler tube. 5.7.2.1.3 To each of the Nessler tubes add: 1 mL of the nitric acid solution; and 1 mL of the silver nitrate solution. 5.7.2.1.4 Swirl to mix and examine the solutions down the vertical axes of the

40、tubes. 5.7.2.1.5 The product shall be deemed to comply with 4.6.1 if, after 15 min, the intensity of opalescence produced in the test solution does not exceed that produced in the diluted chloride standard solution. 5.7.2.2 Containers with a nominal volume of 100 mL 5.7.2.2.1 Transfer 10,0 mL of the

41、 product into each of two matched Nessler tubes. 5.7.2.2.2 Add 1 mL of the nitric acid solution to each of the Nessler tubes. 5.7.2.2.3 Add 0,2 mL of water to one Nessler tube (control solution) and 0,2 mL of the silver nitrate solution to the other Nessler tube. Swirl to mix. 5.7.2.2.4 The product

42、shall be deemed to comply with 4.6.2 if, after 15 min, there is no change or turbidity in the product solution when compared to the control solution. 5.8 Nitrates 5.8.1 Reagents 5.8.1.1 Nitrate standard solution, 2 g/mL NO3Dissolve 0,163 g of potassium nitrate (KNO3) in water and dilute to 100,0 mL

43、with water. Immediately before use dilute 10,0 mL of this solution to 100,0 mL with water, then dilute 2,0 mL of this diluted solution to 100,0 mL with water. This final solution contains 2 g of nitrate per millilitre. 5.8.1.2 Nitrate-free water Add a few milligrams of potassium permanganate (KMnO4)

44、 to 100 mL of water and distil. Reject the first 10 mL of the distillate and collect the following 50 mL. 5.8.1.3 Potassium chloride solution, 10 g/100 mL Dissolve 5,0 g of potassium chloride (KCl) in water and dilute to 50,0 mL with water. Prepare fresh before use. 5.8.1.4 Diphenylamine solution Di

45、ssolve 0,5 g of diphenylamine in 10 mL of water. Add 16,5 mL of sulfuric acid slowly with constant stirring, and shake well. Then add an additional 32,5 mL of sulfuric acid to the solution. Use only if the solution is colourless. Store protected from light. SANS 440:2008 Edition 5 9 5.8.1.5 Sulfuric

46、 acid, concentrated (d at 25 C = 1,84) 5.8.2 Procedure 5.8.2.1 Transfer 5,0 mL of the product into a Nessler tube. 5.8.2.2 Transfer 0,5 mL of the nitrate standard solution and 4,5 mL of nitrate-free water into a matched Nessler tube. Immerse the tubes in ice water. 5.8.2.3 To each of the Nessler tub

47、es add: 0,4 mL of the potassium chloride solution; 0,1 mL of the diphenylamine solution; and 5,0 mL of the sulfuric acid, dropwise with swirling. 5.8.2.4 Transfer the Nessler tubes into a waterbath maintained at (50 1) C and heat in the waterbath for 15 min. 5.8.2.5 The product shall be deemed to co

48、mply with 4.7 if the intensity of colour produced in the test solution after 15 min does not exceed that produced in the nitrate standard solution. 5.9 Sulfates 5.9.1 Reagents 5.9.1.1 Hydrochloric acid solution, c(HCl) = approximately 2 mol/L Dilute 17,8 mL of concentrated hydrochloric acid (d at 25

49、 C = 1,18) to 100 mL with water. 5.9.1.2 Barium chloride solution, 6,1 g/100 mL Dissolve 6,1 g of barium chloride (BaCl2) in water and dilute to 100,0 mL with water. 5.9.2 Procedure 5.9.2.1 Transfer 10,0 mL of the product into each of the two matched Nessler tubes. 5.9.2.2 Add 0,1 mL of the hydrochloric acid solution to each of the Nessler tubes. 5.9.2.3 Add 0,1 mL of water to one Nessler tube (control solution) and 0,1 mL of the barium chloride solution to the other Nessler tube. Swirl to mix. 5.9.2.4 The product shall be deemed to com