TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 
 
                                                  DRAFT TANZANIA STANDARD  
 
 
 
      Sterilized sodium chloride intravenous infusion  
 
 
 
 
 
 
 
 
 
 
 
 
 
TANZANIA BUREAU OF STANDARDS  
 
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 0 Foreword  
 
This Draft Tanzania Standard is being prepared by the Pharmaceuti cals Technical Committee, under the 
supervision of Chemicals Divisional Standards Committee and it is in accordance with the procedures of the 
Bureau.  
 
This Draft Tanzania Standard has been prepared with assistance drawn from ; 
 
                      South Africa Standard SANS 595 :2009  Sterilized sodium chloride intravenous infusion , published  
                      by South Africa Bureau of Standards.   
  
For the purpose of deciding whether a particular requirement of this draft Tanzania Standard is complied  with, 
the final value observed or calculated, expressing the result of a test or analysis, shall be rounded off in 
accordance with TZS 4.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
  
 
1 Scope  
 
This Draft Tanzania  standard covers  chem ical and biolog ical requ irement s for a solution of sod ium chlor ide in water for 
injections that has been manufactured and packed into su itable conta iners, sealed and ster ilized. It also specifies the 
required marking .  
2 Normative references  
The follow ing referenced documents are indis pensable for the appl ication of th is document . For dated references , only the 
edition cited appl ies. For undated references , the latest edition of the referenced document (includ ing any amendments) 
applies.  
2.1 Standards  
ISO 15747, Plastics containers fo r intravenous injection.   
TZS 59 , Water for analytic al laborator y use - Spec ification and test methods . 
TZS 773 , Marking and labeling of pharmaceutical products -Specification  
2.2 Other publications  
British Pharmacopoeia (SP ).  
United States Pharmacope ia (USP).  
3 Definitions  
For the purposes of th is document , the follow ing def initions apply.  
3.1  
acceptable  
acceptable to the author ity admin istering th is standa rd, or to the part ies concludi ng the purchase contract , as relevant  
3.2  
batch  
that quant ity of the prod uct that is homogenous , filled and sealed into con tainers, and ste rilized in the same cycle of 
operations  
3.3  
certified  
reagent for which a certificate of analys is stat ing the percentage pur ity is ava ilable  
3.4  
product  
sodium chloride intra venous infusion that is fi lled, sealed and ster ilized in the f inal conta iner  
 
 3.5 
Clean 
free from dirt, marks, stains and any other contaminants  
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
  TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 4 Requirements  
4.1 Freedom from visible suspended matter and sediment  
When examined in accordance with 5 .2, the product s hall be clear and colorless , without odour or taste ,  
4.2 Fill volume  
4.2.1  The maximum nominal fill volume of a container shall not exceed 1 L .  
4.2.2 When determ ined in accordance with 5 .3, the volume of the contents of each containe r shall not be less than the 
nominal volume and not more than 110 % of the nom inal volume .  
4.3 pH value  
When determ ined in accordance with 5.4 , the pH value of the product shall be between 4 .5 and 7.0.  
4.4 Identification  
4.4.1 Sodium  
When tested in accor dance with 5 .5.1, the precip itate fo rmed shall comply w ith the solubil ity tests in 5.5.1.2 that indicate the 
presence of sodium .  
4.4.2 Chlorides  
When tested in accordance w ith 5.5 .2, the product shall give a positive react ion for chlo rides.  
4.5 Sodium c hloride content  
When determin ed in acco rdance with 5 .6, the sodium chloride (NaCI ) conten t of the produ ct shall 
be between 95 .0 % and 105 .0 % of the concent ration stated on the container or on the label .  
4.6 Particulate matter (sub -visible particles)  
When tested in accordance w ith 5.7, the number of part icles w ith a d iameter ≥ 10 µm and  ≥ 25 µm, respectively , shall 
comply with the limits for small vol ume inject ions and large volume inject ions, as relevant .  
4.7 Sterility  
When tested in accordance with 5 .8, there shall be no signs of microbial g rowth .  
4.8 Bacterial endotoxins  
When tested in accordance w ith 5.9 , the product shall not conta in more than 0 .5 USP Endotoxin Units per millilitre where 
the labelled amount of sodium chlo ride in the infusion is between 0 .5 % and 0 .9 %, and not more than 3 .6 USP Endotoxin 
Units per m illilitre where the labelled amount of sodium chlor ide in the infusion is between 3 .0 % and 24 ,3 %.  
 
 
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 5 Inspection and methods of test  
5.1 General   
Unless otherwise specified , only u se water that complies with the requirements for grade 3 water as given in TZS 59 , and 
reagents of analytical reagent grade or of the purest grade available .  
5.2 Inspection  
5.2.1  Gently invert the container and examine , without magnificat ion, for any v isible signs of suspended matter or sediment 
(see A.3 ).  
5.2.2  Check for compl iance w ith 4.1.  
5.3 Fill volume  
5.3.1 Containers with a nominal volume of  500 mL  
5.3.1.1  Transfer , as completely as possible , the contents of no t less than three containers into a graduated  measuring 
cylinder of a size able to contain at least 110 % of the nom inal volume of three containers .  
5.3.1.2  Record the volume of l iquid in the measur ing cylinder.  
5.3.1.3  Determine the average f ill volume pe r conta iner.  
5.3.1.4  Check for  comp liance with 4 .2.  
5.3.2 Containers with a nominal volume of   1000 mL  
5.3.2.1 Transfer , as completely as possible , the contents of a container into a graduated measuring cylinder of a s ize able 
to contain at least 1 10 % of the nom inal volume of the co ntainer .  
5.3.2.2  Record the volume of liqu id in the measur ing cyl inder.  
5.3.2.3  Determine the average fill volume of at least three containers .  
5.3.2 .4 Check for compliance with 4 .2.  
5.4 pH value  
5.4.1  Determ ine the pH value in accordance with the rel evant procedure descr ibed in the current BP .  
5.4.2  Check for compliance with 4 .3.  
5.5 Identification  
5.5.1 Sodium  
5.5.1.1 Reagents  
5.5.1.1.1 Absolute ethanol  
Analytical reagent grade of commerce that contains not less than 99 .5 % of ethanol (C 2HsO) (volume fraction ).  
 
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 5.5.1.1.2 Methoxyphenylacetic reagent  
Dissolve 2 .7 g of methoxyphenylacet ic acid in 6 mL of tet ramethylammon ium hydroxide so lution and add 20 mL of absolute 
ethanol. Sto re in a polyethylene conta iner.  
5.5.1.1.3 Ammonia solution , 5 M  
Dilute 37 .5 mL of concentrated ammon ia (about 13.5 M) to 100 .0 mL w ith water .  
5.5.1.1.4  Ammonium carbonate solution , 15.8 g/100 mL  
Dissolve 7.9 g of ammonium carbonate in wate r and d ilute to 50 .0 mL with water .  
5.5.1.2 Procedure  
5.5.1.2.1  Add 1 .5 mL o f the metho xyphenylacet ic reagent to 0 .5 mL of the p roduct in a test tube and cool in ice wate r for 
30 min . A volu minous white precipitate is formed.  
5.5.1.2.2  Place the test tube in wate r at 20 °C and st ir for 5 min. The precipitate does not disappear .  
5.5.1.2.3 Add 1 mL of the ammonia solut ion. The precip itate d issolves complete ly.  
5.5.1.2.4  Add 1 mL of the ammonium ca rbonate solut ion. No precip itate is formed.  
5.5.1.2.5  Check for compl iance w ith 4.4 .1.  
NOTE Al ternative test methods for the identification of sodium can also b e used prov ided the y give equivalent results.  
5.5.2 Chlorides  
5.5.2.1 Reagents  
5.5.2.1.1  Nitric acid solution , concentration HN0 3 2 mol /L  
Dilute 12 .6 mL of co ncentrated nitric acid (density  at 25°C = 1.42) to 100.0 mL with water.  
5.5.2.1.2  Silver nitrate solution , 4.25 g/100 mL  
Dissolve 4 .25 g of silver n itrate (AgN0 3) in water and d ilute to 100.0 mL w ith water. Ensure that the silver n itrate 
solut ion is clear before use , and filter if necessa ry. Store protec ted from light.  
5.5.2.2 Procedure  
5.5.2.2.1  Transfer 2 mL of the product into a 50 mL centr ifuge tube .  
5.5.2.2.2  Add one drop of the nitric acid solution and 0 .4 mL of the silver nitrate solut ion. Shake and allow to stand. A 
curdled white precip itate is formed.  
5.5.2.2. 3 Centrifuge the tube with the contents . Wash the prec ipitate three t imes w ith 1 mL of water . Carry out this 
operation rapidly in subdued light , disregard ing the fact that the supernatant might not become perfectly clear .  
5.5.2.2.4  Suspend the precipitate  in 2 mL of water and add 1 .5 mL of concentrated ammonia . The precipitate dissolves 
easily w ith the except ion of a few large particles , which dissolve slowly .  
5.5.2.2.5  Check for compliance with 4 .4.2.  
 
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 5.6 Sodium chloride content  
5.6.1 Reagents  
5.6.1 .1 Silver nitrate solution , concentration  0.1 mol/L  
Dissolve 17 .0 g of silver nitrate (AgN0 3) in water and dilute to 1 L with water . Standardize aga inst certified 
sodium chloride and store protected from light .  
NOTE 1 Comme rcially available con centrated  volumetr ic solut ions can also b e used prov ided t hey are  
standard ized after d ilution.  
NOTE 2 The met hods fo r standard ization given in the USP o r in the BP can be used .  
5.6.1.2 Potassium chromate solution , 5 g/100 mL  
Dissolve 5 g of potassium chromate (K 2Cr0 4) in water and dilute to 100 .0 mL w ith water . Potassium chromate produces a 
red precipitate with silver nitrate in neutral solutions.  
5.6.2 Procedure  
5.6.2.1  Transfer a volume of the product that conta ins approximately 0 .1 g of sodium chloride into a conical flask and add 
about 1 mL of the potass ium chromate solution .  
5.6.2.2  Titrate w ith the standa rdized silver n itrate solut ion to a redd ish-brown endpo int.  
5.6.2.3  Calculate the sodium chloride content (S) in the product , in g/100 mL , using the fol lowing  
formula  
 
 
S = t   x   M   x 58.44  x 100        
              V   x   1 000   
 
Where    
    T       is the volume of Silver nitrate used in the titration,in millilitres  
    M       is the molarity of the standardized silver nitrate solution  
    58.44 is the molecular mass of sodium chloride (NaCl)  
    V       is the volume of product used for the test,in millilitres  
5.6.2.4  Alternatively , the sodium chloride content in the product can be calculated using the following factor :  
1 ml of 0 .1 mol/L, silver nitrate solution is equivalent to 0 .005844 g of sodium chloride  
NOTE Alternative t itrimetric methods or potentiometric methods can also be used to determine the sodium chloride content 
of the product.  
 
5.6.2.5  Check for compliance with 4.5.  
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 5.7 Particulate matter  (sub-visible particles)   
5.7.1  Use the method under "Light obscuration particle count test" given in the USP.  
5.7.2  Check for compliance with 4 .6.  
5.8 Sterility  
5.8.1  Use the method under "Sterility tests" given in the USP .  
5.8.2  Check for compliance with 4 .7.  
5.9 Bacterial endotoxins  
5.9.1  Use the method under "Bacterial endotoxins test" given in the USP.  
5.9.2  Check for compliance with 4.8.   
6 Packing and marking  
6.1 Packing  
6.1.1 Containers  
6.1.1.1  The product shall be dispe nsed in acceptable, clean , single -dose , colorless containers that shall not affect 
or be affected by the contents.  
6.1.1.2  Glass containers shall be transparent and shall be of type I or type II glass as described under "Glass containers 
for pharmaceut ical use" in the BP . Plastics containers shall comply with the requirements of  ISO 15747   
6.1.1.3  Containers shall be hermetically closed by means of suitable closures that shall not affect or be affected by 
the contents of the container .  
6.1.2  Primary Packa ges  
An acceptable number of containers of the same batch identification shall be packed together in a package of  suitable 
design that is sufficiently robust to protect the contents during normal handling , transportation and storage.  
6.1.3 Secondary and t ertiary packages  
An acceptable number of packages of the same batch identification shall be packed in a bulk pack that is  sufficiently robust 
to protect the contents during normal handling, transportation and storage .  
6.2 Marking  
Marking shall be in acco rdance with TZS 773  
 
 
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 Annex A  
(normative)  
Sampling and compliance with this standard  
A.1 Sampling  
A.1.1 General  
The following sampling procedure shall be applied in determining whether a lot submitted for inspection and testing 
complies with the rele vant requ irements of th is standard. The sample so drawn shall be deemed to represent the  
lot.  
A.1.2 Definitions  
A.1.2.1  
defective  
sample that fa ils in one or more respects to comply with the relevant requirements of this standard  
A.1.2.2  
batch  
that q uantity of the prod uct that is homogenous , filled and sealed into con tainers, and ste rilized in the same cycle of 
operations  
A.2 Sample for testing  
A.2.1 Chemical tests  
From the Batch/ lot draw , at random , enough containers to obta in a volume of at least 200 mL .  
A.2.2 Sterility test  
From the batch/ lot draw , at random , 20 conta iners.  
A.2.3 Bacterial endotoxin test  
From the lot draw , at random , enough containers to obtain a volume of at least 100 mL.  
A.3 Compliance with this standard  
The lot shall be d eemed to comply w ith the requirements of this standa rd if, after inspect ion (see 5 .2) and test ing of 
the sa mples taken in accordance w ith A.2, no defect ive is found.
                                                                     
 
 
 
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
                                                                        Annex B  
                                        (Normative ) 
Quality verification of sterilized sodium chloride intravenous  infusion  
When a purchase r requires ongo ing verification of the qua lity of ster ilized sod ium chlor ide intravenous infusion , it is 
suggested that , instead of concent rating solely on evalua tion of the f inal p roduct , he also directs his attent ion to the 
manufact urer's qual ity system . In th is connection it should be noted that TZS 501  and TZS 1967  cover the  
provisions of an integrated qual ity system .  
 
 
 
 
 
 
 
 TBS/CDC 16(6641 ) P3 
 
 
 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
 Bibliography  
TZS 501 /1S0 9001 , Quality mana gement systems - Requ irements.  
TZS 1967/I S0 13485 , Medical de vices - Quality managemen t systems - Requirements for regula tory pu rposes .  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
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 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
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 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
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 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
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 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
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 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020  
 
 
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 ©TBS 20 20 – All rights reserved                                                                                   First Edition 2020