Food And Drug Regulations ( CRC , C. 870) - Laws.justice.

PART CDrugs (continued)

DIVISION 4 (continued)

Smallpox Vaccine (continued)

C.04.111 Every fabricator and packager/labeller shall fabricate and package/label smallpox vaccine only in an independent unit that is isolated from all other laboratory activities, and in or about which no extraneous materials are permitted or stored.

• SOR/97-12, s. 43

C.04.112 A fabricator shall exclude the personnel who care for the vaccine animals from horse stables and paddocks and from contact with horses while smallpox vaccine is being propagated.

• SOR/97-12, s. 61

C.04.113 Every fabricator and packager/labeller shall dispense smallpox vaccine only in sterile glass containers that are sealed under aseptic conditions.

• SOR/97-12, s. 63

C.04.114 Every fabricator and packager/labeller shall test smallpox vaccine to establish that it is free from

• (a) spore-forming anaerobic micro-organisms;

• (b) coagulase positive staphylococci;

• (c) haemolytic streptococci; and

• (d) any other contaminating pathogenic micro-organisms.

• SOR/97-12, s. 63

C.04.115 Smallpox vaccine, when tested by acceptable methods,

• (a) shall be free from extraneous micro-organisms, in the case of vaccine prepared for use by jet gun; and

• (b) shall contain not more than 500 viable non-pathogenic bacteria per millilitre, in the case of vaccine prepared for use by the multiple pressure technique or by scarification.

C.04.116 Smallpox vaccine must demonstrate evidence of disease prevention that is at least equivalent to that of a vaccine that

• (a) is known to prevent human to human transmission of smallpox; and

• (b) meets the potency of equal to or greater than 108 pockforming units per millilitre, as determined using chick embryo chorioallantoic membranes.

• SOR/2006-2, s. 2

C.04.117 No person shall sell smallpox vaccine unless

• (a) in the case of fluid vaccine, it has been stored at a temperature below -10°C;

• (b) in the case of dried vaccine, it has been stored at a temperature below 10°C; and

• (c) the outer label carries a statement that it shall be stored at a temperature of not more than 5°C.

• SOR/97-12, s. 44

C.04.118 Notwithstanding the provisions of section C.04.003, the date of issue of smallpox vaccine shall be not later than

• (a) in the case of fluid vaccine, nine months after the date of manufacture; and

• (b) in the case of dried vaccine, 24 months after the date of manufacture.

C.04.119 The expiration date of smallpox vaccine shall not exceed the following, unless supported by evidence of stability satisfactory to the Minister:

• (a) in the case of fluid vaccine, 3 months after the date of issue; or

• (b) in the case of dried vaccine, 12 months after the date of issue.

• SOR/2006-2, s. 3

C.04.120 No inner label shall be required for smallpox vaccine in single-dose containers or when dispensed in capillary tubes.

C.04.121 No person shall sell smallpox vaccine to which an antibiotic has been added.

Poliomyelitis Vaccine

C.04.122 Poliomyelitis vaccine shall be an aqueous suspension of killed poliomyelitis viruses, Types I, II, and III.

C.04.123 Poliomyelitis vaccine shall be prepared in acceptable tissue culture medium from strains of poliomyelitis virus proven capable of producing vaccine of acceptable potency.

C.04.124 Poliomyelitis vaccine in its final form shall contain not more than 0.35 milligram per millilitre of total nitrogen, nor more than one part per million of animal serum.

C.04.125 No person shall sell poliomyelitis vaccine unless it has been tested by an acceptable method for potency and safety and when so tested it shall be safe and of acceptable potency.

C.04.126 The outer label shall carry a statement of any antibiotic present in the vaccine.

C.04.127 The expiration date of the poliomyelitis vaccine shall be not later than 12 months after the date of the last satisfactory potency test unless evidence, satisfactory to the Minister, is presented that a longer period is appropriate.

• SOR/85-715, s. 6
• SOR/2018-69, s. 27

Previous Version

Poliovirus Vaccine, Live, Oral

C.04.128 Poliovirus Vaccine, Live, Oral or Poliovirus Vaccine, Live, Oral (Naming the strains) shall be prepared from living poliomyelitis virus types I, II and III that

• (a) have been obtained directly from a source acceptable to the Minister;

• (b) are shown to be genetically stable by an acceptable method;

• (c) are shown to be non-pathogenic when given orally to humans;

• (d) are proved to be capable of multiplying in the human alimentary tract and of producing type specific neutralizing antibodies when administered orally; and

• (e) have a history of successful use in the production of polio-virus vaccine, live, oral.

• SOR/2018-69, s. 27

Previous Version

C.04.129 Poliovirus vaccine, live, oral, shall be fabricated, packaged/labelled and tested in premises separated from buildings where other products are fabricated, packaged/labelled or tested, and from buildings where control tests involving the use of cell lines or virus strains not employed in the fabrication, packaging/labelling and testing of poliovirus vaccine, live, oral, are carried out.

• SOR/97-12, s. 45

C.04.130 No fabricator shall permit the introduction of any bacterial or viral cultures other than those used in the manufacture of poliovirus vaccine, live, oral on any premises that are used for the manufacture of poliovirus vaccine, live, oral.

• SOR/97-12, s. 61

C.04.131 Notwithstanding sections C.04.129 and C.04.130, a fabricator may manufacture other drugs in an area in which polio-virus vaccine, live, oral is manufactured at times when that vaccine is not being manufactured, if

• (a) both prior to and following each manufacture the area is cleaned and disinfected by methods acceptable to the Minister; and

• (b) the fabricator has received written permission from the Minister to carry out such manufacture.

• SOR/97-12, s. 61
• SOR/2018-69, s. 27

Previous Version

C.04.132 Poliovirus vaccine, live, oral shall be prepared only

• (a) in a tissue culture,

• (b) in a medium, and

• (c) by methods

acceptable to the Minister.

• SOR/2018-69, s. 27

Previous Version

C.04.133 No fabricator shall sell poliovirus vaccine, live, oral, unless he has tested each lot for extraneous micro-organisms and the vaccine is free therefrom.

• SOR/97-12, s. 61

C.04.134 A fabricator of poliovirus vaccine, live, oral shall test, by a method acceptable to the Minister, each lot of vaccine for neurovirulence and for genetic markers and it shall meet the requirements established by the Minister.

• SOR/97-12, s. 61
• SOR/2018-69, s. 27

Previous Version

C.04.135 No fabricator shall employ any person in the manufacture of poliovirus vaccine, live, oral unless such person

• (a) is free from infectious disease;

• (b) has been vaccinated successfully against poliomyelitis by poliovirus vaccine, live, oral; and

• (c) has been proved by periodic tests to be a non-carrier of poliomyelitis virus.

• SOR/97-12, s. 61

C.04.136 A fabricator of poliovirus vaccine, live, oral shall not permit the entry to a building in which the vaccine is manufactured of any person who

• (a) is not directly concerned with the manufacturing processes; or

• (b) has been working on the same day with experimental animals or with infectious agents.

• SOR/97-12, s. 61

Bacteriophage

C.04.137 Bacteriophage shall be a virus preparation with specific lytic action against micro-organisms actually or potentially pathogenic.

C.04.138 The expiration date of bacteriophage shall be not later than 12 months after the date of manufacture or the date of issue.

Toxins, Toxoids

Schick Test Reagents

C.04.140 Schick test reagents for the diagnosis of susceptibility to diphtheria shall be

• (a) diphtheria toxin for Schick test;

• (b) Schick control; and

• (c) diphtheria toxin for Schick test with control.

C.04.141 Diphtheria toxin for Schick test shall be sterile diluted diphtheria toxin stabilized by an acceptable method.

C.04.142 Schick control shall be suitably diluted

• (a) diphtheria toxoid; or

• (b) sterile diphtheria toxin heated at a temperature of 95°C for five minutes.

C.04.143 The human test dose of diphtheria toxin for Schick test, when aged toxin containing a preservative is used, shall be determined by

• (a) intracutaneous injection into normal guinea pigs in mixtures with different proportions of diphtheria antitoxin, and one test dose mixed with 1/750 or more of a unit of antitoxin must cause no local reaction but mixed with 1/1,250 or less of a unit of antitoxin must cause a definite local reaction of the type known as the “positive Schick reaction”; and

• (b) intracutaneous injection into normal guinea pigs without admixture with antitoxin, and 1/50 of one test dose must not cause, and 1/25 of one test dose must cause, a definite local reaction of the type known as the “positive Schick reaction”.

C.04.144 The human test dose of diphtheria toxin for Schick test, when fresh toxin containing no preservative is used, shall be determined by

• (a) intracutaneous injection into normal guinea pigs in mixtures with different proportions of diphtheria antitoxin, and one test dose mixed with 1/750 or more of a unit of antitoxin must cause no local reaction, but mixed with 1/1,500 or less of a unit of antitoxin must cause a definite local reaction of the type known as the “positive Schick reaction”; and

• (b) intracutaneous injection into normal guinea pigs without admixture with antitoxin, and 1/100 of one test dose must not cause, and 1/50 of one test dose must cause, a definite local reaction of the type known as the “positive Schick reaction”.

C.04.145 The human test dose for the Schick control shall give a negative Schick reaction when injected intracutaneously into normal guinea pigs.

C.04.146 No person shall sell diphtheria toxin for Schick test unless both the inner and the outer labels carry a statement of the number of human test doses it contains together with the name of any stabilizer.

C.04.147 The expiration date of Schick test reagents for the diagnosis of susceptibility to diphtheria shall be not later than 12 months after the date of manufacture or the date of issue.

Diphtheria Toxoid

C.04.160 Liquid diphtheria toxoid shall be sterile, formalized, detoxified diphtheria toxin and shall not contain more than 0.02 per cent free formaldehyde.

C.04.161 Diphtheria toxoid alum precipitated shall be prepared from diphtheria toxoid, and shall not contain more than 15 milligrams of alum per human dose.

C.04.162 The alum used in the preparation of diphtheria toxoid alum precipitated shall contain not less than 99.5 per cent pure potassium alum, Al K(SO4)2,12H2O.

C.04.163 No fabricator shall use a culture medium for the production of diphtheria toxin that contains horse protein or Witte peptone or that has not been freed as far as possible from any other allergenic ingredient.

• SOR/97-12, s. 61

C.04.164 Diphtheria toxin from which diphtheria toxoid is prepared shall have a toxicity, as indicated by an L+dose, of not more than 0.20 millilitre or by an M.L.D. of not more than 0.0025 millilitre.

C.04.165 A fabricator shall test each bulk container of diphtheria toxoid, before being dispensed into the final containers, for toxicity by an acceptable method, and it shall be non-toxic.

• SOR/97-12, s. 61

C.04.166 No person shall sell any lot of diphtheria toxoid unless such lot has been shown to meet a test for antigenicity made by an acceptable method.

C.04.167 A fabricator shall fill diphtheria toxoid aseptically into clear glass containers and where preservative is not added shall seal the containers by fusion.

• SOR/97-12, s. 61

C.04.168 No person shall sell diphtheria toxoid that contains phenol.

C.04.169 No person shall sell diphtheria toxoid unless both the inner and the outer labels carry a statement of the appropriate dose for purposes of immunization.

C.04.170 The expiration date of diphtheria toxoid shall be not later than two years after the date of manufacture or the date of issue.

Tetanus Toxoid

C.04.180 Liquid tetanus toxoid shall be sterile, formalized, detoxified tetanus toxin, and shall not contain more than 0.02 per cent free formaldehyde.

C.04.181 Tetanus toxoid alum precipitated shall be prepared from tetanus toxoid, and shall not contain more than 15 milligrams of alum per human dose.

C.04.182 The alum used in the preparation of tetanus toxoid alum precipitated shall contain not less than 99.5 per cent pure potassium alum, Al K(SO4)2, 12H2O.

C.04.183 No fabricator shall use a culture medium for the production of tetanus toxin that contains horse protein or Witte peptone or that has not been freed as far as possible from any other allergenic ingredient.

• SOR/97-12, s. 61

C.04.184 Tetanus toxin from which tetanus toxoid is prepared shall have a toxicity as indicated by an M.L.D. for the guinea pig of not more than 0.0001 millilitre.

C.04.185 A packager/labeller shall test each bulk container of tetanus toxoid, before being dispensed into the final containers, for toxicity by an acceptable method, and it shall be non-toxic.

• SOR/97-12, s. 65