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

• C.04.595 (1) A fabricator shall not sell Protamine Zinc Insulin unless he

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

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

  • (c) has received from the Minister 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 insulin or zinc-insulin crystals employed in the manufacture of Protamine Zinc Insulin,

    • (i) protocols of assay of its potency in International Units per cubic centimetre in the case of insulin and in International Units per milligram in the case of zinc-insulin crystals,

    • (ii) a report on its moisture content in percentage determined by drying to constant weight at 100°C in the case of zinc-insulin crystals, 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 components used in the preparation of the trial mixture of Protamine Zinc Insulin, a report on the quantity of

    • (i) insulin in grams or in International Units,

    • (ii) zinc in grams or in milligrams, per 1,000 International Units of insulin,

    • (iii) protamine in grams or in milligrams, per 1,000 International Units of insulin, and

    • (iv) the volume of the preparation in cubic centimetres or litres;

  • (c) for the trial mixture of Protamine Zinc 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 per 1,000 International Units of insulin,

    • (iii) protocols of its biological reaction showing retardation of the insulin effect, and

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

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

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

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

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

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

    • (iv) [Repealed, SOR/95-203, s. 8]

C.04.596 The expiration date printed on the inner and outer labels of every package of Protamine Zinc Insulin shall be a date not later than two years after the date of filling of the immediate container.

Sulphated Insulin

C.04.597 The insulin preparation “Sulphated Insulin” shall be a clear or slightly turbid, colourless or almost colourless, sterile, isotonic preparation of zinc-insulin crystals chemically modified by treatment with sulphuric acid, shall have a pH of not less than 6.0 and not more than 7.0, and shall contain,

• (a) weight by volume,

  • (i) not less than 0.6 per cent and not more than 1.0 per cent sodium chloride, and

  • (ii) not less than 0.2 per cent and not more than 0.3 per cent phenol; and

• (b) as determined by an acceptable method,

  • (i) not more than 200 milligrams protein for each 1,000 International Units of insulin, and

  • (ii) not less than 5.5 and not more than 6.5 sulphate groups per insulin molecule.

C.04.598 The neutralization ratio means the amount of anti-beef-insulin serum required to neutralize one unit of Sulphated Insulin divided by the amount required to neutralize one unit of beef insulin, and shall be determined by an acceptable method.

C.04.599 The neutralization ratio of Sulphated Insulin shall be not less than 4 to 1.

C.04.600 No person shall sell Sulphated 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 100 International Units of insulin as determined by an acceptable method.

• C.04.601 (1) A fabricator shall not sell Sulphated Insulin unless he

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

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

  • (c) has received from the Minister 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 Sulphated Insulin,

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

    • (ii) a report of its moisture content in percentage 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; and

  • (b) for each lot of Sulphated Insulin prepared from each master lot of zinc-insulin crystals,

    • (i) a report of the amount of each component,

    • (ii) a report of the protein content in milligrams per 1,000 International Units of insulin,

    • (iii) a report on the determination of the neutralization ratio,

    • (iv) a report on the determination of the number of sulphate groups per insulin molecule,

    • (v) protocols of assay of its potency expressed as International Units per cubic centimetre, and

    • (vi) a report on the determination of its pH.

    • (vii) [Repealed, SOR/95-203, s. 9]

C.04.602 The expiration date printed on the inner and outer labels of every package of Sulphated Insulin shall be a date not later than two years after the date of filling of the immediate container.