No. 14/1941:

THE THERAPEUTIC SUBSTANCES (AMENDMENT) REGULATIONS, 1941.

THE THERAPEUTIC SUBSTANCES (AMENDMENT) REGULATIONS, 1941.

DEPARTMENT OF LOCAL GOVERNMENT AND PUBLIC HEALTH.

The Minister for Local Government and Public Health, in exercise of the powers conferred on him by the Therapeutic Substances Act, 1932 , does by this his Order, after consultation with the Therapeutic Substances Advisory Committee, order as follows, that is to say :—

1. —(1) This Order may be cited as the Therapeutic Substances (Amendment) Regulations, 1941, and shall be read and construed as one with the Therapeutic Substances Regulations, 1934 to 1939 and may be cited collectively together therewith as the Therapeutic Substances Regulations, 1934 to 1941.

(2) These Regulations shall come into operation on the 1st day of February, 1941.

(3) In this Order, the expression " the Principal Regulations " means the Therapeutic Substances (Saorstát Éireann) Regulations, 1934.

2. In Article 5 of the Principal Regulations paragraph (a) shall be renamed paragraph (a) (i) and the following paragraphs shall be inserted therein, that is to say :—

" (a) (ii) Without prejudice to the generality of the foregoing requirement, every licensee, who for any purpose engages in the culture or manipulation of pathogenic spore-bearing micro-organisms, shall provide to the satisfaction of the Minister separate laboratories and utensils and apparatus required for the culture or manipulation of such microorganisms. The separate laboratories and utensils and apparatus so provided shall not be used for the manufacture of any other therapeutic substance."

(a) (iii) The immediately preceding paragraph shall not apply to a licensee who manufactures therapeutic substances intended to be used solely for veterinary purposes and who does not manufacture therapeutic substances intended for human use.

3. The Principal Regulations shall be amended by the addition to the Second Schedule thereof of Parts I and II of the Schedule to these Regulations in manner following, that is to say :—

(a) Part I of the Schedule to these Regulations shall be appended to Part II (Toxins and Antigens) of the Second Schedule to the Principal Regulations : and

(b) Part II of the Schedule to these Regulations shall be appended to Part IV (Provisions applicable to particular Sera and Antitoxins) of the Second Schedule to the Principal Regulations.

4. Notwithstanding anything contained in Article 2 of the Therapeutic Substances (Amendment) Regulations, 1939, adrenalin of animal origin intended for injection shall cease to be a therapeutic substance to which the Therapeutic Substances Act, 1932 , applies, and the provisions of the Therapeutic Substances Regulations, 1934 to 1939, as amended by this Order, shall accordingly cease to apply to such substance.

SCHEDULE.

PART I.

(G)

PROVISIONS APPLICABLE TO TETANUS TOXOID.

DEFINITION AND PROPER NAME.

1. Tetanus Toxoid is tetanus toxin (the sterile filtrate from a culture in nutrient broth of Clostridium tetani) the specific toxicity of which has been completely removed by the action of Chemical substances in such a manner that it retains efficient properties as an immunising antigen. Its proper name is " Tetanus Toxoid."

LABELLING.

2. The label on the container shall indicate the dose, or doses, appropriate for administration at one injection to a human subject.

TESTS.

3. Tetanus Toxoid shall be submitted to the following tests and it shall not be issued unless it passes all of the tests :

(a) Tests for sterility.—Tetanus Toxoid shall be submitted to the tests for sterility as required under Part IV of the Therapeutic Substances Regulations, 1934, and in addition, it shall be tested on media and under conditions approved by the Minister as being specially favourable for the growth of Clostridium tetani.

(b) Tests to determine that the Specific toxicity of the toxin used in its preparation has been completely removed.—5 c.c. of the tetanus toxoid shall be injected into each of not less than five normal guinea-pigs, each weighing from 250 to 350 grammes. If this injection produces any evidence of tetanus in any of the animals injected within 21 days of injection the tetanus toxoid shall be held not to have passed the test.

(c) Tests for potency as an immunising antigen.—The tests shall be carried out on not less than nine normal guinea pigs, each weighing from 250 to 350 grammes. Each guinea-pig shall receive by injection the tetanus toxoid, either in a dose of 5 c.c. on one occasion, or in two doses each of 0·1 c.c. on each of two occasions separated by an interval of not more than four weeks. It shall be permissible to include in the test guinea-pigs injected by either of these two methods provided that the total number so included is not less than nine. At a date not later than six weeks after the single injection hereinbefore prescribed, or if they have received the two injections hereinbefore prescribed, at a date not later than two weeks after the second injection, the tetanus antitoxin present in the serum of each guinea-pig shall be determined.

If the serum of each of two-thirds or more of the guinea-pigs tested contains 0·1 international unit or more of tetanus antitoxin per c.c. of serum or alternatively, if the serum of each of one-third or more of the guinea-pigs tested contains 1 international unit or more of tetanus antitoxin per c.c. of serum, the tetanus toxoid shall be accepted as sufficiently potent.

PROVISIONS APPLICABLE TO TETANUS TOXOID PREPARED FOR ISSUE IN FORMS OTHER THAN SIMPLE SOLUTION.

PROPER NAME.

4. The proper name of any form of tetanus toxoid other than that of simple solution shall be " Tetanus Toxoid " together with a phrase indicating the nature of the additional process to which it has been subjected, e.g., " Tetanus Toxoid, Alum Precipitated," or " Alum Precipitated Tetanus Toxoid."

LABELLING.

5. The label on the container shall indicate the dose or doses, appropriate for administration at one injection to a human subject.

TESTS.

6. (a) When tetanus toxoid is prepared for administration in forms other than simple solution, such as Alum Precipitated Tetanus Toxoid, the tetanus toxoid, from which such forms are prepared shall be submitted to, and shall pass, the tests for sterility and for absence of specific toxicity hereinbefore prescribed.

(b) The product, after precipitation or other process used for its final preparation, shall again be subjected to the sterility tests hereinbefore prescribed, with such modifications as the nature of the product may require to make the test effective.

(c) The product, after the precipitation or other process used for its final preparation, shall be subjected to the tests for absence of specific toxicity and for potency as an immunising antigen hereinbefore prescribed, with the modification that the dose injected in the test for absence of specific toxicity and in the test for potency as an immunising antigen when a single dose is administered, shall be 1 c.c.

PART II

(K)

PROVISIONS APPLICABLE TO GAS-GANGRENE ANTITOXIN (HISTOLYTICUS).

PROPER NAME.

1. Gas Gangrene Antitoxin (Histolyticus) is the serum, or the antitoxic globulins, separated from the blood of animals which have been immunised against the specific toxin prepared by the growth of Clostridium histolyticum in a fluid medium. The proper name of the substance is " Gas-Gangrene Antitoxin (histolyticus)."

STANDARD PREPARATION.

2. The standard preparation is a quantity of dried gas-gangrene antitoxin (histolyticus) kept in an institution approved by the Minister.

QUALITY.

3.—(1) Gas-Gangrene Antitoxin (histolyticus) shall be issued for therapeutic use in the form of either—

(a) the serum separated from the blood or plasma of the immunised animals, or

(b) the solution of the globulins containing the specific immune substances, or

(c) the dried solid prepared from (1) natural serum or (ii) the globulins containing the specific immune substances.

(2) If issued in fluid form the liquid shall, at the time of issue, be clear or show, at most, a very slight opalescence or precipitate. Preparations of the natural serum (the liquid product of decantation of the coagulated blood or plasma without any addition, other than antiseptic, or substraction) shall not contain more than 10 per cent. of solid matter. A solution of the separated antitoxic globulins shall not contain more than 20 per cent. of solid matter.

STRENGTH.

4.—(1) The potency in units of gas-gangrene antitoxin (histolyticus) shall be determined, in accordance with a method approved by the Minister, by the injection into animals of a mixture of the antitoxin under test with a gas-gangrene (histolyticus) toxin which has been standardised in relation to the standard preparation of gas-gangrene antitoxin (histolyticus).

(2) Each container of gas-gangrene antitoxin (histolyticus) shall contain a sufficient number of units in excess of the minimum total number of units indicated on the label to ensure that the said minimum total number of units will still be present in the container at the date appearing on the label pursuant to article 8 (3) (e) of these regulations as the date up to which the preparation may be expected to retain its potency.

UNIT OF STANDARDISATION.

5. The unit of gas-gangrene antitoxin (histolyticus) for the purposes of these regulations is the specific neutralising activity for gas-gangrene (histolyticus) toxin contained in such an amount of the standard preparation as the Minister may from time to time indicate as the quantity exactly equivalent to the unit accepted for international use.

LABELLING.

6.—(1) The label on the container shall indicate :—

(a) the minimum total number of units in the container ; and

(b) either (i) the potency of the preparation expressed as the minimum number of units of antitoxin per c.c. in the case of liquid products, or as the minimum number of units of antitoxin per gramme in the case of dry products ; or (ii) the total number of c.c. in the container.

(2) The label on the container or the label or wrapper on the package shall indicate the nature of the particular product, that is to say, whether natural serum, a solution of antitoxin globulins, dried natural serum or dried antitoxin globulins.

MIXED ANTITOXINS.

7. A mixed antitoxin containing antitoxins against other toxins than that of Clostridium histolyticum shall, with respect to its content in units of gas-gangrene antitoxin (histolyticus) conform with paragraphs 4, 5 and 6 immediately preceding.

Given under the Official Seal of the Minister for Local Government and Public Health this 21st day of January, One Thousand Nine Hundred and Forty One.

PATRICK RUTTLEDGE,

Minister for Local Government and Public Health.