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REGISTERED No. D-(D)-72

The Gazette of India

EXTRAORDINARY

PART II—Section 3—Sub-section (i)

PUBLISHED BY AUTHORITY

No. 59] NEW DELHI, WEDNESDAY, FEBRUARY 18, 1976 MAGHA 39, 1897

Separate paging is given to this Part in order that it may be filed

as a separate compilation

MINISTRY OF HEALTH AND FAMILY PLANNING

(Department of Health)

NOTIFICATION

New Delhi, the 18th February 1976

G.S.R. 86(E).—The following draft of rules further to amend the Drugs and Cosmetics Rules, 1945, which the Central Government proposes to make after consultation with the Drugs Technical Advisory Board, in exercise of the powers conferred by section 12 and 33 of the Drugs and Cosmetics Act, 1940 (23 of 1940), is hereby published, as required by the said sections, for the information of all persons likely to be affected thereby; and notice is hereby given that the said draft rules will be taken into considera- tion after the expiry of the period of three months from the date on which the copies of the Official Gazette in which this notification is published are made available to the public.

Any objections or suggestions which may be received from any person with respect to the said draft rules before the expiry of the period so specified will be taken into consideration by the Central Government,

DRAFT RULES

1. These rules may be called the Drugs and Cosmetics (Amendment) Rules, 1976.

2. In the Drugs and Cosmetics Rules, 1945 (hereinafter referred to as the said rules), In rule 67-A, after sub-rule (2), the following sub-rule shall be inserted, namely:—

"(3) If the original licence is either defaced, damaged or lost, a duplicate copy thereof may be issued on payment of a fee of one rupee and twenty-five paise".

( 3 3 1)

3 In the said rules, in rule 96, in sub-rule (L), to clause (v), the following shall be, added, namely:—

"NOTES.—([) In the case of drugs manufactured by a continuous process, like manufacture of magnesium sulphate, pharmaceutical chemicals, etc., the production resulting in one homogeneous mix of the finished products shall be considered as one "Batch",

(2) In the case of powders, liquid orals, ointments, etc., one "Batch Number"

shall be assigned to all the containers, filled from one homogeneous. bulk.

(3) In the case of tablets, capsules, lozenges, troches, etc,, one, "Batch. Number" shall be assigned to the products manufactured from one homogeneous mix ready for compression or filling.

(4) In the case of parenteral preparations sterilized by steam under pressure, one "Batch Number" shall be assigned to all containers, filled from the homo- geneous solution and sterilized in one sterilizer load.

(5) In the case of containers of parenteral, preparations, filled from one. homo- geneous solution and sterilized in more than one sterilizer load, the "Batch; Number" assigned to the containers in the different Sterilizer loads shall be the same "Batch Number" as is assigned to the homogeneous bulk solu- tion, provided the samples taken from all the sterilizer loads pass the sterility test, and are kept separate from one another until, the report of the sterility test is available.

Explanation.—For the purpose of chemical and other tests, representative samples from all containers filled, from the homogeneous bulk solution should be taken.

(6) In the case of parenteral and other sterile products filled aspecially, a "Batch Number" shall be assigned to all containers filled from one homogeneous mix during one filling operation, the filling operation being from completed in a period of not more than a day and during which no scheduled change in the filling assembly is made.

When containers arc filled from one homogeneous mix, in a number of filling operations, the "Batch Number" assigned to the containers filled" in indivi- dual filling operations shall be the same "Batch Number"* • s is assigned to the homogeneous mix, provided the samples taken from atl the different filling operations pass the sterility tests, and are kept separate from one another until the report of the sterility test is available.

Explanation.—-For the purpose of chemical and other tests, representative samples from all containers filled from the homogeneous mix should be laken,

(7) In the case of medicinal gases produced by a continuous process of operation

a week's production from one tank load shall be considered as "Batch".

4. In Schedule A of the said rules,

(i) in Form 20-C, under the heading 'Conditions of licence', after item 4, the following item shall be inserted, namely:—

"(5) Where any change in the constitution of the firm takes place, a licensee shall inform the Licensing Authority in writing about the same and the current licence shall be valid only for a period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution",

(ii) In Form 20-D, under the heading 'Conditions of Licence' after item 3, the following item shall be inserted namely:—

"(4) The licensee shall inform the Licensing Authority in writing in the event of any change in the constitution of the firm operating under the licence and the current licence shall be valid only for a period of three months from the date on which the change takes place unless, in the meantime, a fresh licence has been taken from the Licensing Authority in the name of the firm with the changed constitution".

5. In Schedule F of the said rules, after Part XIT-B the following Part shall be Inserted,

namely:—

"Part VII-C.—Test for disintegration to be compiled with by the manufacturers of patent or proprietary medicines in the form of lttkfel$.

J. A patent or proprietary medicine, marketed in the form of a tablet and intend- ed to be swallowed as a whole, when subjected to a test as prescribed in the current edition of the Indian Pharmacopoeia for the time being in force, shall disintegrate in not more than thirty minutes.

2. In case the tablet referred to in paragraph one has an enteric coating or a coating designed to have a similar purpose, it shall not disintegrate when immersed in simulated gastric juice for sixty minutes, but shall disintegrate in simul- ated intestinal juice in another sixty minutes;

Provided that in case any manufacturer wants to manufacture tablets whose disinte- gration time may be longer than that prescribed above, he shall apply to the Licensing Authority giving sufficient reasons in support of disintegration time being longer before permission to market such tablets can be granted:

Provided further that the patent or proprietary medicines marketed as sustained release tablets, vaginal tablets or tablets meant to be sucked or chewed or tablets meant for veterinary use, shall not be required to conform to the test for disintegration mentioned above".

6. In Schedule K of the said rules, in the first column under the heading "Class of Drugs", in entry 10(ii) the word "Lactose¹, shall be omitted.

7. For Schedule O of the said rules, the following Schedule shall be substituted, Jiamely;—•

SCHEDULE O

(See Rule 126)

STANDARDS FOR DISINFECTANT FLUIDS I. Provision applicable to Bluck Fluids, White Fluids, Modied Black Fluids and Modified White Fluids.

1. Classification.—The disinfectants shall be classified as follows —

(A) Black Fluids. (B) White Fluids. (C) Modified Black Fluids. CD) Modified White Fluids.

(A) Black Fluids.—These are dark brown in colour and consist of homogeneous solu- tions of coaltar acids of similar acids derived from petroleum or the mixture of both Tvith or without hydrocarbons and a suitable emulsifler.

(B) While Fluids.—These are white or brownish in colour and consist of finely dis- persed homogeneous emulsions of coaltar acids or similar acids derived from petroleum or th: mixture of both, with or without hydrocarbons.

(C) Modified Black F/"W.s.—Modified Black Fluids are Black Fluids containing also any other active ingredients. The exact nature and quantity of such ingredients shall be •stated on the label.

(D) Modified White Fluids—Modified White Fluids are While Fluids containing also any other active ingredients. The exact nature and quantity of such ingredients shall be stated on the label.

2. Gradation.—Each of the above classes of disinfectant fluids shall be graded on the 'basis of the minimum requirements in respect of:—.

Rideal Wilker (RW) Coefficient as follows;—

(See Table I below)

Table I

Grade

Rideal Walkar {RW) Coefficient (Min-'mum)

1.

2. 3.

18 10 5

3. Type—E=ich of the above grades of Disinfectant Fluids shall be stable in the range ••of temperatures indented against each type :

Type

Stable in the range of

(D Normal. (II) Winter .

. K°C to AI'C 5'C to 3o°C

4. Retirements.—All classes and grades of Disinfectant Fluids shall comply with the following requirements, namely:-—

(1) Stability after dilution.—Wbeir tested by the method described hereinafter, the Disinfectant Fluid shall bo misciblc with artificial hard water (for Black Fluids and Modified Black Fluids) or with artificial sea water (for White Fluids and Modified White Fluids) in all proportion from 1 per cent to 5 per cent by volume, to give emulsion which shall not break or show more than traces of separation of either top or bottom oil when kept for 6 hours at 15°C to 45°C for Type (1) (Normal) and 5°C to 30°C for Type (II) (Winter).

(2) Germicide! Value:—

(a) Rideal Walker Coefficient.—-Black Fluids, White Fluids, Modified Black Fluids- and Modified White Fluids shall be tested for the determination of Rideal Walker Co- efficient (R.W. Coefficient) by the method described hereinafter.

(b) Staphylococcal coefficient.—Modified Black Fluids and Modified White Fluids- shall, in addition to complying with the requirements in respect of the Rideal Walker Coefficient as specified in the preceding paragraph (a), be tested tor the Staphylococcal' coefficient by the method described hereinafter. The staphylococcal coefficient shall con- form to label declaration which shall not be less than 2.5.

(3) Storage.—Disinfectant Fluids of all classes shall be stored in mild steel, tinned mild steel or other suitable containers. These shall not be stored in containers made of galvanised iron.

(4) Labelling. Subject to the other provisions in these rules, the label on the con^

tainer shall state:—

(i) The name of the product, (ii) The name and full address of the manufacturer, (iii) The name and quantity of any other active ingredient added in the case of Modified Black Fluids and Modified White Fluids,

(iv) Grade, type, R.W. coefficient of the product and In addition for modified fluids, the staphylococcal coefficient,

(v) Date of manufacture, (vi) Quantity present in the container, and

(vii) Indications and mode of use.

5. Method of testing :—

(1) Preparataion of Sample.—The sample of disinfectant fluid to be tested should be- mixed thoroughly taking care that no air is beaten into the fluid immediately beforer withdrawing any portion for testing. The test portion should be withdrawn from the.- middle of the sample.

(2) Method of testing stability after dilution:—

(a) Preparation of Artificial hard water.—40 ml, of IN Hydrochloric Acid (Analytical Reagent Quality) is neutralised with a slight excess of Calcium Carbonate and filtered. The filtrate is diluted to 1000 ml. with distilled water 10 parts of this solution is further diluted to 100 parts with distilled water.

(b) Preparation of Artificial Sea Water.—21 G of sodium chloride (Analytical Reagent Quality) and 5 O of Magnesium Sulphate (Analytical Reagent Quality) are dissolved' in Distilled water and diluted to 1000 ml. The solution is filtered before use.

(c) Procedure—Take 1 ml. and 5 ml. portions of the sample, in duplicate, in 100 ml. stoppered measuring cylinders (IS-878-1956) by means of pipettes. Dilute the samples with artificial hard water or Artificial Sea Water (as the case may be) upto 10 ml. mark. Mix thoroughly by inverting the cylinders 5 times. Keep the cylinders containing the- diluted filuids for 6 hours at the extremes of the temperature range specified for the parti- cular type. The sample complies with the test if the solution shows not more than a. trace of separation at its top and bottom.

(3) Method of determination of Rideal Walker Coefficient (R.fV.C):

Apparatus • A loop3 4 mm' in internal diameter is made at arid of a 28 Swg (0-376 mm) wire of platinum Or platinum lridium alloy, 38 mm long from the loop to'the holder. The loop is bent at such an angle to the length- of t he wire as will facilitate its removal vertically from the surface of the liquid, while keeping the plane- of the loop horizontal.

Incubator . . .. Set and maintained at 3 7 ° C ± i ° C-

.Pipettes . . .. Standard graduated pipettes of capacity 10 m l .3 5 m l.

and 1 m l.

dropping Pipette . . . Made to deliver 0 '2 m l.

Medication tubes • • .5 sterile plugged rimless test tubes 125 mm x 20 m m.

(5* x 3/4O made of hard neutral glass.

Broth tubes . . .. About 2 dozens of the same description as medication

tubes.

.Staniard measuring cylinders 500 ml.graduated in 10 ml.—one stoppered & graduated 100 ml.graduated I ml.—five.

All apparatus must be scrupulously clean and sterile

immediately before use.

Reagents . . . . (a) Broth.—Prepare a mixture of the following ingre-

dients:

Lab Lemco—20 gm.

Peptone (Oxo)—20 gm.

Sod-Chloride—10 gm.

(Reagent quality)

Distilled water—1000 ml.

Dissolve the solids in distilled water. Add sufficient Sodium Hydroxide to neutralise .the solution; then boil it to bring down Phosphates and filter while hot. The broth thus prepared is then adjusted to PH 7.6 with normal Hydrochloric Acid. The broth is then sterilised by autoclaving at 15 lbs. pressure for 20 minutes. It is then filtered and placed in 5 ml. quantities in sterilised broth tubes. The- tubes of media thus prepared are sterilised by autoclaving at 15 lbs. pressure for 10 minutes. The final PH of the medium should lie between 7.3 to 7.5. Further re-stcrilisation in bulk or in tubes is not permis- sible.

(b) Test organism.—The test organism used in Salmonella Typhi (NCTC 786) of -which suitable culture shall be obtained from the Director, Central Drugs Laboratory, Calcutta. This culture is maintained by weekly sub-culture on a Nutrient Agar Slope -(made by dissolving 2.5 per cent Agar Agar Difco in the broth prepared as above), incubating the sub-culture for 24 hours at 37°C and then storing in Refrigerator at a temperature below 22°C. For the purpose of the test a little of the growth from the inost recent sub-culture in Nutrient Agar slope is placed in tube of R.W. broth and incubated for 23 hours at 38°C. A standard loopful is then transferred to a second tube and incubated as before. This is done for at least three times before a test is carried out. Sub-culturing in broth is limited to 14 days.

(c) Standard Phenol.—A 5 per cent w/v solution in sterile distilled water of chemi- cally purs Phenol having a crystalising point of not Jess than 40.5*C is prepared. Test dilutions are prepared from this stock solution containing l.g of Phenol in each 95i 100, 105, 110, 115 ml. of the solution made. These dilutions shall be used within a week of preparation.

(d) *~Text dilutions of Disinfectant (sample).—The sample is prepared as described under "Preparation of samples", A test portion of 5 mil, is withdrawn and discharged into abofft 480 ml of sterile distilled water in a 7'" distilled water, the cylinder is stopped and the contents thoroughly mixed by inverting the cylinder several times. Suitable test dilutions in sterile distilled water are then immediately prepared from this stock solution.

Procedure.—5 ml. of 4 chosen dilutions of the disinfectant urc placed in 4 medication., tubes which are then placed in a rack, provided with a water-bath maintained at a constant temperature between 17°C and 18°C, with the strongest dilution on the left. The fifth, medication tube containing 5 ml. of the particular phenol dilution is placed on the right. When the content on the medication rtuta^S; a n d . J ^ t^ culture of the test organise have reached the temperature of the waterrh^tii^ipJafftinBiat zero time, 0.2 ml. of the culture is added to the left hand medication,-..^tupo-. and ttie tube is shaken gently. After 30 seconds the next tube is inoculated similarly and the process is repeated with each succes- sive tube at intervals of 30 seconds until the phenol control has been inoculated. 30 seconds after this last addition (that is 2J minutes from zero) a loopful of the well shaken contents of the tube at the extreme left is withdrawn and placed in tube contain- ing 5 ml. of the broth medium, 30 seconds after this, similar operation is performed on the second medication tube. The procedure is repeated at an interval of 3T) seconds with each of the 5 medication tubes working from left to right until 4 sets of cultures have been made i.e. at 2-}, 5, 7J and 10 minutes respectively after exposure. Tn each withdrawal care should be taken to ensure that loop Is removed vertically from the surface: of the liquid with its plans horizontally and without touching the side of the test tubes. The loop shall be sterilized by flaming between each operation, care being taken that the loop is cooled before being again used. The inoculated broth tubes are incubated for not less than 48 hours and not more than 72 hours at 37°C, when the tubes showing growth of the test organisms will be recognised by turbidity of the broth.

Calculation of Coefficient.—The R.W. coefficient is obtained by dividing that dilution- of the disinfectant which shows life of test organism in 2J and 5 minutes but not life thereafter by that dilution of the Phenol which gives the same response. A typical set of sample is given below:—

Time of exposures in minutes

Sample disinfectants Dilutions

*i .5 1$ 10

_

R.W. Coeff.

i :IOOO i : i i oo

•—

+

— —

1200

T : 1200

+

+

— —

TOO

= 12 i : 1300

+

+

+

—

— =

+ + —

Phert'l control ¹ : ¹⁰⁰

__ =no growth)

(+ =growth

(4) Method of determination of Staphylococcus Coefficient (S./i.)— General.—This method is a modification of the R.W. test described above, the same- apparatus and the procedure being used but with a different test organism and culturer medium.

Apparatus . . • • Same as for R.W. test.

Reagents • • • • (a) Broth.—Prepare a mixture of the following:—

Lab Lemco—5 g. Peptone (Oxo)—10 g. Sodium Chloride—5 g.

(Reagent quality) Distilled Water—1000 ml.

Dissolve the solids in distilled water and add sufficient IN Sodium hydroxide softitioir to bring the pH to 7. Sterilize the broth in bulk by autoclaving for 20 minutes at 16 lbs.. pressure. Filter the sterilized broth and place quantities of 10 m. in sterilized test tubes. Sterilize the broth tubes by autoclaving for 10 minutes at 16 lbs. pressure. Re-steriliza- tion in bulk or in tubes is not permisable.

(b) lest organism.—The test organism is staphylococcus Aureus (NCTC 3750) of which a suitable culture is to be obtained from the Director, Central Drugs Laboratory, Calcutta. The details for maintaining and preparing the test organism are thc same as for RW. teat.

(c) Standard Phenol.-—This is same as for R.W. test with the exception that the test dilutions arc made in the proportions of 1 g. of pure phenol in 85, 90, 95, 100, 105 ml. respectively of solutiains,

(d) Testing dilutiaas of Disinfectant Sample.—This is same as for R.W. test.

Procedure.—This is same as for R.W. lest.

Calculation of Coefficient.—The Staphylococeus Coefficient (SA) is obtained by divid- ing that dilution of disinfectant which shows life of the test organism in 2i and 5 minutes but no life thereafter by fhat dilution of phenol (1:85, 1:90, 1:95, 1:100 or 1:105) which gives' the same response.

(5) Method of Phenol Coefficient tests for Modified Black and Modified White Dis~

infectant fluids containing Quarternary Ammonium Compounds or Mercurials.

(a) Nutrient broth •

Lab. Lamco . . . 5 g.

Peptone (Oxo) . . . l o g.

Sodium Chloride . . 5 g. (Reagent Quality) Distilled Water to 1000 ml. pH 6-8.

(b) Letheen broth.—Dissolve the following in 400 ml. hot Ht O and boil until clear:

L-cithin . . .. 0-7 G.

Tweer. 80 . . . 5 G.

AdcJ 600 ml. of broth (a), boil for 10 minutes adjust pH to TO±O-2 and filter.

(c) Fluid Thioglycollate medium (USP-XVIT): L-cystirie . . . . 0-5 G. Pancreatic digest of casein . 15 G.

Yeast Extract . . . 5 G.

(Water soluble)

Sodium Chloride . - . 2-5 G. Dextrose . . . - 5-5 G. Sodium Thioglycollate . . 0-5 G. A.gar 0-75 G. Freshly prepared Resazurin solution 1% 1 ml. Distilled Water to 1000 ml.

pH 7-Ozt⁰'¹

Distribute the medium in each case in 10 ml. quantity in cotton wool plugged test tubes and sterilise in autoclave at 121 °C (15 lb. steam pressure) for 20 minutes.

Medium (b) is used for testing samples containing Quarternary Ammonium Compounds. Medium (c) is used for testing samples containing mercurial compounds and other heavy metals.

(B) The Culture—

(1) S. Typhi (Hopkins Strain 26, A TCC 6539).

(2) Staph. Aureus (FDA 209, A TCC 6538). They are maintained on nutrient agar slopes by weekly sub-culture, and for use In the test are grown for at least four consecutive daily transfers at 37°C In nutrient broth (a). They must be between 22 and 26 hours old.

(C) Disinfectant dilutions.—Prepare a stock 5 per cent (w/v) solution of pure phenol in sterile distilled water, and for the tests with salm. typhi, prepare from this stock solution two dilutions of 1 in 90 and 1 in 100; for the test with Staph. Aureus the dilu- tions required are 1 in 60 and 1 in 70.

For the disinfectant, prepare a 1 per cent dilution in sterile distilled water, and from this a further series of dilutions, each in 5 ml. amounts, in sterile medication tubes, which should-cover ki'.ling limits of disinfectants in 5—15 minutes and should a,t the same time be close enough for accuracy.

'~,(D) Procedure.—Place the tubes of phenol and disinfectant dilutions and that con- tailfiing the test culture in a water bath at 20°C. At half-minute intervals inoculate 0.5 ml. of the culture by means of a graduated pipette into each of the dilutions. At the end of 5, 10 and 15 minutes disinfection time transfer one Standard 4 mm loopful to a 10 ml. tube of the chosen culture medium, and read the results after 48 hours' incubation at 37°C.

_(E) Calculation of Results.—The results are assessed in terms of phenol coefficient number, or highest dilution killing test organisms in 10 minutes but not in 5 minutes whichever most accurately reflects the germicidal value of disinfectant.

The tests are only valid if the responses obtained are:—

Phenol 5 min. io min- 15 min.

1 in 90

For Salm. Typhi .

1 in 100

or —

or — + +

For staph. Aureus

1 in 60 1 in 70

+ + + + +

or — — + — + Interpolation of results is permitted where none of the disinfectant dilutions show growth in 5 minutes and killing in 10 minutes, and coefficients are quoted to the nearest first decimal piece.

II. Provisions applicable to other Disinfectant Fluids.—

Disinfectant Fluids which are mad6 with chemicals other than those specified under Part I of this Schedule shall conform to the formula or list of ingredients shown on the label.

Labelling.—-Subject to the provisions of rules on labelling the label of a container shall state:—

(i) the name of the product, (ii) the name and full address of the manufacturer, (iii) the fur.I formula or list of Ingredients of the preparation,

(iv) date of manufacture, (v) date upto which the product can be used, (vi) quantity present In the container, and (vii) Indications and mode of use".

[No. X. 11014/1/75-D&MS]

SHRAVAN KUMAR, Jt. Secy,

PRINTED BY THE GENERAL MANAGER, GOVERNMENT OF INDIA PRESS, MINTO ROAD,

NEW DELHI AND PUBLISHED BY THE CONTROLLER OF PUBLICATIONS. DELHI, 1 9 76