§ 108.11

Water supply.

The supply of hot and cold water at licensed establishments shall be ample and clean. Adequate facilities shall be provided for the distribution of water in each establishment and for the washing of all containers, machinery, instruments, other equipment, and animals used in the preparation, handling, or storing of any biological product.

§ 108.12 Rooms and equipment.

(a) All rooms, compartments, and other places used in connection with the preparation, handling, or storing of any biological product at licensed establishments shall be so constructed and arranged as to prevent cross contamination of biological products. Such rooms, compartments, and other places shall be of such material, construction, and design as can be readily and thoroughly cleaned.

(b) All containers, instruments and other apparatus and equipment used for preparing, handling, or storing biological products shall not be used for handling preparing, or storing other forms of biological products until such containers, instruments and other apparatus and equipment have been cleaned and sterilized and so handled thereafter as to prevent contamination.

[34 F.R. 18119, Nov. 11, 1969]

§ 108.13 Hands and clothing.

(a) All employees of licensed establishments who handle biological products shall keep their hands and clothing clean. The hands of such employees shall not come in contact with any biological product or with any part of sterilized containers, instruments, or other equipment which may come in contact with such products.

(b) Caps, gowns, and other outer clothing worn by persons while handling any biological product shall be of clean, white material whenever practicable. All persons, immediately before entering the operating or laboratory rooms of a licensed establishment, shall change their outer clothing or effectively cover the same with gowns or other satisfactory garments.

§ 108.14 Outer premises.

The outer premises of licensed establishments, embracing docks, driveways, approaches, yards, pens, chutes, and alleys, shall be drained properly and kept in a clean and orderly condition.

No nuisance shall be allowed in any licensed establishment or on its premises. § 108.15 Flies and other vermin.

Every practicable precaution shall be taken to keep licensed establishments free of flies, rats, mice, and other vermin. The accumulation, on the premises of an establishment, of any material in which flies or other vermin may breed is forbidden.

§ 108.16

Carcasses, refuse materials, and biological products.

All parts of the carcasses of animals producing viruses, all other dead animals and parts and refuse, all materials unsatisfactory for production purposes, all biological products unsatisfactory for marketing, and all worthless, contaminated, dangerous, or harmful biological products, shall be incinerated or otherwise disposed of by licensees as may be required by the Deputy Administrator. § 108.17 Smoking or expectorating, etc.

Such practices as smoking in laboratories or expectorating on the floors of any room, compartment, or place in which biological products are prepared, handled, or stored at licensed establishments are prohibited.

AUTHORITY: The provisions of this Part 109 issued under 87 Stat. 832-833; 21 U.S.C. 151-158.

SOURCE: The provisions of this Part 109 appear at 23 F.R. 10051, Dec. 23, 1958; 36 F.R. 24928, Dec. 24, 1971, unless otherwise noted. § 109.1 Equipment and the like.

(a) All containers, instruments, and other apparatus and equipment, before being used in preparing, handling, or storing biological products, at a licensed establishment, except as otherwise prescribed herein, shall be thoroughly sterilized by live steam at a temperature of at least 120° C. for not less than one-half hour, or by dry heat at a temperature of at least 160° C. for not less than one hour. If for any reason such methods of sterilization are impracticable, then a process

135 F.R. 16039, Oct. 13, 1970.

Pro

Steam and dry-heat sterilizers used in connection with the processing of biological products at licensed establishments shall be equipped with automatic temperature recording gauges: vided, That other record keeping systems may be used when approved by the Deputy Administrator. When gauges are used, they shall be periodically standardized to assure accuracy. Charts and other temperature records made during production shall be available at all times charts and records shall be kept in accordance with Part 116 of this chapter. [35 F.R. 16039, Oct. 13, 1970] § 109.3

Pasteurizers.

All pasteurizing equipment shall meet the requirements in paragraphs (a), (b), and (c) of this section and be acceptable to Veterinary Services.

(a) Metal serum containers shall be used in licensed establishments. During the heating process, each container shall be surrounded by a separate water jacket or equivalent so that the entire container, including its lid, is heated to the required temperature. Each serum container shall be equipped with a motor-driven agitator and a separate automatic recording thermometer.

(b) Each water bath shall have an automatic temperature control to limit the temperature of the water to a maximum of 62° C., an automatic recording thermometer, an indicating thermometer set in a fixed position, and circulating mechanism adequate to insure equal temperatures throughout the bath. The heating unit for the bath shall be separated from the serum container and the water jacket.

(c) Accurate

thermometers at licensed establishments shall be used at frequent intervals to check temperatures of the serum as registered by recording thermometers.

[35 F.R. 16039, Oct. 13, 1970]

(a) Each immediate or true container of biological products prepared at a licensed establishment or imported by a permittee, in compliance with the regulations for the purpose of sale, barter, exchange, or commercial distribution, and found not to be worthless, contaminated, dangerous, or harmful, shall be labeled and packaged as provided in this part, before it is removed from the licensed establishment or presented for importation.

(b) No container of any biological product may be labeled until it has been tested and found to be not worthless, contaminated, dangerous, or harmful. The Deputy Administrator may permit labeling in advance if in his opinion adequate precautions to prevent marketing of untested products are taken by the licensee.

(c) No person shall apply or affix, or cause to be applied or affixed, any label, stamp, or mark to any biological product prepared or received in a licensed establishment or imported except in compliance with the regulations. Suitable tags or labels of a distinct design shall be used for identifying all biological products while in course of preparation at licensed establishments.

(d) When used in regulations Parts 101 through 117 of this subchapter

(1) The term "label" means all written, graphic, or printed matter upon or attached to a final container, and unless otherwise specified, any statement or other information required to be on the label, shall also appear on the outside of the immediate carton, box, or wrapper (sometimes herein referred to as "carton"), if any, used to package the final container.

(2) The term "labeling" means all labels and other written, graphic, or printed matter (1) upon the final container or packaging, or (ii) accompanying the final container.

[23 F.R. 10051, Dec. 23, 1958, as amended at 26 F.R. 7727, Aug. 18, 1981; 30 F.R. 920, Jan. 29, 1965; 34 F.R. 610, Jan. 16, 1969; 36 F.R. 21579, Nov. 11, 1971; 36 F.R. 24928, Dec. 24, 1971]

$112.2 Required and permitted infor

mation.

(a) Except as provided by the Deputy Administrator, each label of a biological product prepared at a licensed establishment or imported shall include the following:

(1) The true name of the product which name shall be identical with that shown in the license or permit under which the product is prepared or imported and shall be prominently lettered and placed giving equal emphasis to each word composing it;

(2) In case the product is manufactured in the United States, the name and address of the licensee, or of the subsidiary which manufactured the product, when named in the establishment license as provided in § 102.4(e) of this subchapter, and in the case of a foreign-manufactured biological product offered for importation, the name and address of the permittee and of the foreign manufacturer: Provided, That when the licensee has more than one premise, one street address only shall be given, although the general location of each premise in such case may be stated;

(3) The license or permit number assigned by the Department which shall be shown only in one of the following forms, respectively: "U.S. Veterinary License No. ----," or "U.S. Vet. License No. ----,' or "U.S. Veterinary Permit No. "U.S. Vet. Permit No.

11119

or

(4) A serial number by which the product can be identified with the manufacturer's records of preparation: Provided, That when a liquid antigenic fraction is to be used instead of a water diluent for one or more desiccated antigenic fractions in a combination package, a hyphenated serial number composed of the serial number of the desiccated fraction and that of the liquid fraction shall be on the final container carton;

(5) A permitted expiration date affixed before the product is removed from the manufacturer's establishment;

(6) A dosage table and full instructions for the proper use of the product or a statement in the case of very small labels as to where such information is to be found;

(7) The recoverable quantity of the content of each final container;

(8) Instructions to store the biological product at a temperature of not over 45° F.;

(9) In the case of a multiple-dose container, a warning that all of the product should be used at the time the container is first opened, except as provided in subparagraphs (13) and (14) of this paragraph;

(10) In the case of a product composed of viable or dangerous organisms or viruses, the notice "Burn this container and all unused contents" prominently placed and lettered and affixed to the final container of such product;

(11) In the case of virus vaccine, the true name of the biological product shall be supplemented with: (i) The attenuation level as Live Virus, Modified Live Virus, Killed Virus, or Inactivated Virus; (ii) "Formalin Killed Virus" or "Chemically Inactivated" will be permitted. "Phenolized" will be permitted for Rabies Vaccine, Nerve Tissue Origin; (iii) The methods used to propagate the virus shall be designated on each label; and (iv) a designation of the animal of origin for all tissues used in production, shall be on each label. Commonly accepted designations such as Chick or Chicken, Duck, Turkey, Avian, Canine, Feline, Ovine, Equine, and Bovine shall be permitted. Abbreviations shall be permitted if defined on all labels and enclosures;

(12) In the case of a product which contains an antibiotic added during the production process, the statement "Contains as a preservative," or an equivalent statement indicating the antibiotic added, except that the label affixed to the final container is exempt from this requirement provided this statement appears on a carton label containing such final container:

(13) In the case of a desiccated biological product which is to be added to a diluent and never returned to the original container, all labels for such desiccated biological product are exempt from the provisions of subparagraph (9) of this paragraph;

(14) In the case of diagnostic or desensitizing antigens which are pack

aged as multiple-dose containers, all labels are exempt from the provisions of subparagraph (9) of this paragraph;

(15) Biological products recommended for use in domestic animals, the edible portions of which may be used for food purposes, shall have a withholding statement "Do not vaccinate within

days before slaughter" on all labels showing the required number of days for the type of products specified in subdivisions (i), and (ii) of this subparagraph; Provided, That longer periods shall be stated when deemed necessary by the Director:

(i) The withholding statement shall be not less than 21 days for the products containing adjuvants or precipitating agents;

(ii) The withholding statement shall be not less than 14 days for the products containing live microorganisins; Provided, That when a longer withholding period for a biological product such as Anthrax Spore Vaccine is specified in regulations pertaining to livestock slaughter, the longer period shall be used.

(16) The statement "No U.S. Standard of Potency" if no standard requirement for evaluating potency of the biological product has been established by Veterinary Services and no test method acceptable to Veterinary Services for evaluating potency of the product is included in the licensee's outline: Provided, That in the case of a combination biological product for which a standard requirement has been established by Veterinary Services for evaluating the potency of one or more fractions of the product or test methods acceptable to Veterinary Services for evaluating potency of one or more fractions of such product have been included in the licensee's outline, the statement "U.S. Standard for (name fractions) Fraction(s) Only" shall be used: Provided further, That if the applicable statement appears on the carton label and enclosure, if any is used, the label affixed to the final container shall be exempt from this requirement.

(17) In the case of Autogenous Bacterins, all labels shall designate the animal of origin from which the organisms used for seed were isolated and include the statement: "No U.S. Standard of Potency. The product is to be used only in the herd or flock from which the organisms were isolated;" and

(18) All other similar information required by the Deputy Administrator.

(b) Labels of biological products prepared at licensed establishments or imported may also include any other statement which is not false or misleading.

(c) Labels of biological products prepared at licensed establishments or imported shall not include any statement, design, or device which overshadows the true name of the product as licensed or which is false or misleading in any particular or which may otherwise deceive the purchaser.

(d) Anti-hog-cholera serum consisting of concentrated antibodies shall be named "hog-cholera antibody-concentrate."

(e) Restricted sales to veterinarians may be so stated on the labels: Provided, That the entire production of the product by the licensee involved shall be so restricted. The phrase "For Veterinary Use Only" or an equivalent statement may be used to indicate a product is recommended specifically for animals and not for humans.

[23 F.R. 10051, Dec. 23, 1958, as amended at 34 F.R. 610, Jan. 16, 1969; 36 F.R. 24928, Dec. 24, 1971]

Except as provided by the Deputy Administrator, each immediate or true container of diluent packaged with desiccated biological products, in accordance with the requirements in § 112.6, shall bear a label that includes the following:

(a) Name or statement indicating the nature of the contents;

(b) True name of the biological product with which the diluent is packaged, except as provided in paragraph (g) of this section;

(c) The recoverable quantity of contents in cubic centimeters.

(d) A serial number by which the diluent can be identified with the manufacturer's records of preparation;

(e) Name and address of the licensee; (f) In the case of a diluent with which a desiccated biological product is to come in contact while the diluent is in its original container, additional information as follows:

(1) In the case of a multiple dose container, a warning that all of the product should be used at the time the container is first opened;

(2) In the case of a product composed of viable or dangerous organisms or vi

ruses, the notice "Burn this container and all unused contents" prominently placed and lettered; and

(g) When the firm packages all desiccated biological products with the same diluent, or two or more types of diluent are used, and the licensees' methods of identification and storage ensure that all products are packaged with the correct type of diluent, labels affixed to immediate or true containers of diluent are exempt from the provisions of paragraph (b) of this section.

[26 FR. 7727, Aug. 18, 1961, as amended at 34 F.R. 611, Jan. 16, 1969; 36 F.R. 24938, Dec. 24, 1971]

§ 112.4 Reference to distributors and permittees.

(a) Distributors. The name and address of a distributor of a biological product (who is not the licensed producer of such product) shall not be placed on the labels or containers of such product in such a manner as to indicate that he is the producer of such product or operating under the license number shown on the label. The name and address of such distributor may be placed on labels or containers if the term "distributor." or "distributors," or "distributed by." or an equivalent term, is prominently placed in connection therewith: Provided, The terms are not so used as to be false or misleading. Reference to such distributor shall be by name and address only.

(b) Permittees. The name and address of a permittee shall not be placed on the labels or containers of an imported biological product in such manner as to indicate that he is the manufacturer of such product. Reference to such permittee shall be made by name, address, and U.S. Veterinary Biological Product Permit number only.

[26 F.R. 7727, Aug. 18, 1961; as amended at 34 F.R. 611, Jan. 16, 1969; 36 F.R. 24928, Dec. 24, 1971]

§ 112.5 Review and approval of labels and other material.

(a) Except as otherwise provided in this section quadruplicate copies of all labels, circulars, and enclosures distributed with biological products prepared by licensed establishment or imported shall be submitted to the Deputy Administrator for review and approval before they are placed in use. For the convenience and guidance of licensees and permittees, sketches or proofs of new

labels and the like may be submitted in triplicate to the Deputy Administrator for review and approval, and in this case the preparation of finished labels and the like shall be deferred until copies of such sketches or proofs are returned to the licensee or permittee. Blank transmittal forms will be furnished upon request to Veterinary Services.

(b) Tags, stickers, and the like used to identify products or materials during process of production or testing, if not false or deceptive, may be used by licensees.

(c) Labels stamped or printed directly to the final container or glued thereto shall be permanently legible throughout the dating period. Biological products shall be withheld from the market if such labels have been altered, mutilated, destroyed, obliterated, or removed.

(d) When requested by the Deputy Administrator, licensees and permittees shall submit lists of labels, cartons, and required enclosures which they will continue in actual use. Each shall be properly identified by name of product, date of approval, the number assigned by Veterinary Services when approved.

[34 FR. 611, Jan. 16, 1969, as amended at 36 F.R. 24928, Dec. 24, 1971}

§ 112.6 Packaging desiccated products.

(a) Each immediate or true container of a desiccated biological product, produced by a licensee or presented for importation by a permittee, accompanied by recommendations for administration, to individual animals,

shall be packaged with an accompanying container of sterile diluent in a box or carton labeled in accordance with the applicable labeling provisions of the regulations in this part: Provided, That desiccated biological products prepared at licensed establishments may be exported without accompanying diluent if the true containers of such products bear labels prominently superimposed with the words "Export" or "For Export Only" or are printed in a foreign language, and such labels or accompanying circulars give adequate instructions for reconstituting the product prior to use.

(b) Except as provided in paragraph (d) of this section, only one multiple dose final container of a desiccated biological product and its accompanying container of diluent shall be packaged in an appropriately labeled box or carton.