Food and Drug Regulations (C.R.C., c. 870)

Regulations are current to 2017-04-12 and last amended on 2017-03-14. Previous Versions

 The expiration date printed on the inner and outer labels of every package of Globin Insulin with Zinc shall be a date not later than two years after the date of filling of the immediate container.

  • SOR/82-769, s. 4.

NPH Insulin or Isophane Insulin

 The insulin preparation “NPH Insulin” or “Isophane Insulin” shall be a sterile preparation of rod-shaped crystals containing insulin, protamine and zinc, suspended in a buffered aqueous medium, shall have a pH of not less than 7.0 and not more than 7.8 and shall contain

  • (a) weight by volume, not less than 0.15 per cent and not more than 0.25 per cent anhydrous disodium phosphate, and either

    • (i) not less than 1.4 per cent and not more than 1.8 per cent glycerin and not less than 0.15 per cent and not more than 0.17 per cent metacresol and not less than 0.06 and not more than 0.07 per cent phenol, or

    • (ii) not less than 0.40 per cent and not more than 0.45 per cent sodium chloride and not less than 0.7 per cent and not more than 0.9 per cent glycerin and not less than 0.18 per cent and not more than 0.22 per cent metacresol; and

  • (b) as determined by an acceptable method, for each 1,000 International Units of insulin,

    • (i) not more than 8.5 milligrams of nitrogen,

    • (ii) not less than 3.0 milligrams and not more than 6.0 milligrams of protamine except that the ratio of the protamine to the insulin shall be not less than the isophane ratio and shall not exceed the isophane ratio by more than 10 per cent,

    • (iii) not less than 0.16 milligram and not more than 0.40 milligram of zinc, and

    • (iv) no protease activity significant for the stability of NPH insulin.

  • SOR/82-769, s. 4;
  • SOR/85-715, s. 11.

 The protamine used in preparing NPH Insulin shall be obtained from the sperm or from the mature testes of fish belonging to the family Salmonidae, genera Oncorhynchus Suckley, or Salmo Linne.

  • SOR/82-769, s. 4.

 The isophane ratio means the minimum number of milligrams of protamine required to precipitate 100 International Units of insulin and shall be determined by an acceptable method.

  • SOR/82-769, s. 4.

 The insulin used in the preparation of NPH Insulin shall be obtained from one or more master lots and shall be present in an amount sufficient to provide either 40, 80 or 100 International Units of insulin in each cubic centimetre of the preparation when the precipitate is suspended uniformly.

  • SOR/82-769, s. 4.

 The clear supernatant liquid obtained from NPH insulin shall contain not more than 0.4 International Units of insulin per cubic centimetre when the potency of the insulin preparation is 40 units per cubic centimetre, not more than 0.6 International Units of insulin per cubic centimetre when the potency of the insulin preparation is 80 units per cubic centimetre and not more than 0.7 International Units of insulin per cubic centimetre when the potency of the insulin preparation is 100 units per cubic centimetre, as determined by an acceptable method.

  • SOR/82-769, s. 4.

 No person shall sell NPH Insulin unless

  • (a) it is dispensed in a vial of approximately 10 cubic centimetre capacity that contains an excess volume sufficient to permit withdrawal of 10 cubic centimetres; and

  • (b) each cubic centimetre thereof provides,

    • (i) 40 International Units of insulin,

    • (ii) 80 International Units of insulin, or

    • (iii) 100 International Units of insulin.

  • SOR/82-769, s. 4.
  •  (1) A fabricator shall not sell NPH Insulin unless he

    • (a) has filed with the Director, in accordance with subsection (2), a submission relating to that preparation, in a form and having a content satisfactory to the Director;

    • (b) has furnished the Director with such additional information as the Director may require; and

    • (c) has received from the Director a notice that the information contained in the submission is in accordance with the requirements of this section.

  • (2) A submission filed pursuant to subsection (1) shall include at least,

    • (a) for each master lot of zinc-insulin crystals employed in the manufacture of NPH Insulin,

      • (i) protocols of assay of its potency in International Units per milligram,

      • (ii) a report of its moisture content in per cent determined by drying to constant weight at 100°C, and

      • (iii) reports of assay of its nitrogen content in milligrams and its zinc content in milligrams per 1,000 International Units of insulin;

    • (b) for the master lot of protamine, a report of the isophane ratio for the insulin used in the preparation of the NPH Insulin;

    • (c) for the trial mixture of NPH Insulin,

      • (i) a report of assay of its nitrogen content in milligrams per cubic centimetre or per 1,000 International Units of insulin,

      • (ii) a report of assay of its zinc content in milligrams per cubic centimetre or per 1,000 International Units of insulin,

      • (iii) a report of the insulin content in International Units per cubic centimetre of the supernatant liquid after removal of the suspended precipitate,

      • (iv) a report on the determination of its pH, and

      • (v) a report on the microscopic examination of the precipitate;

    • (d) for the first finished lot of NPH Insulin from each trial mixture of NPH Insulin, a report on the amount of each component in the preparation; and

    • (e) for the first filling of the first finished lot of NPH Insulin from each trial mixture of NPH Insulin,

      • (i) a report of assay of its nitrogen content in milligrams per cubic centimetre or per 1,000 International Units of insulin,

      • (ii) a report of assay of its zinc content in milligrams per cubic centimetre or per 1,000 International Units of insulin,

      • (iii) a report on the determination of its pH,

      • (iv) a report on the microscopic examination of the precipitate, and

      • (v) a report of its identification as determined by an acceptable method.

      • (vi) [Repealed, SOR/95-203, s. 7]

  • SOR/82-769, s. 4;
  • SOR/95-203, s. 7;
  • SOR/97-12, s. 61.

 The expiration date printed on the inner and outer labels of NPH Insulin shall be a date not later than two years after the date of filling of the immediate container.

  • SOR/82-769, s. 4.

Protamine Zinc Insulin

 The insulin preparation “Protamine Zinc Insulin” shall be a sterile white suspension in a buffered aqueous medium, containing insulin modified by the addition of protamine and zinc, shall have a pH of not less than 7.1 and not more than 7.4, and shall contain,

  • (a) weight by volume,

    • (i) not less than 0.15 per cent and not more than 0.25 per cent anhydrous disodium phosphate,

    • (ii) not less than 1.4 per cent and not more than 1.8 per cent glycerin, and

    • (iii) either not less than 0.18 per cent and not more than 0.22 per cent cresol, or not less than 0.22 per cent and not more than 0.28 per cent phenol; and

  • (b) as determined by an acceptable method, for each 1,000 International Units of insulin,

    • (i) not more than 12.5 milligrams of total nitrogen,

    • (ii) not less than 10.0 milligrams and not more than 15.0 milligrams of protamine,

    • (iii) not less than 1.7 milligrams and not more than 2.5 milligrams of zinc.

  • SOR/82-769, s. 4.
 
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