PART 600—BIOLOGICAL PRODUCTS: GENERAL

600.20 Inspectors.

600.21 Time of inspection. 600.22 Duties of inspector.

AUTHORITY: Secs. 201, 501, 502, 503, 505, 510, 519, 701, 704 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 355, 360, 360i, 371, 374); secs. 215, 351, 352, 353, 361 of the Public Health Service Act (42 U.S.C. 216, 262, 263, 263a, 264).

SOURCE: 38 FR 32048, Nov. 20, 1973, unless otherwise noted.

CROSS REFERENCES: For U.S. Customs Service regulations relating to viruses, serums, and toxins, see 19 CFR 12.21-12.23. For U.S. Postal Service regulations relating to the admissibility to the United States mails see Parts 124 and 125 of the Domestic Mail Manual, that is incorporated by reference in 39 CFR Part 111.

As used in this subchapter:

(a) "Act" means the Public Health Service Act (58 Stat. 682), approved July 1, 1944.

(b) "Secretary” means the Secretary of Health and Human Services and any other officer or employee of the Department of Health and Human Services to whom the authority involved has been delegated.

(c) "Commissioner of Food and Drugs" means the Commissioner of the Food and Drug Administration.

(d) "Center for Biologics Evaluation and Research" means Center for Bio

logics Evaluation and Research of the Food and Drug Administration.

(e) "State" means a State or the District of Columbia, Puerto Rico, or the Virgin Islands.

(f)

"Possession" includes among other possessions, Puerto Rico and the Virgin Islands.

(g) "Products" includes biological products and trivalent organic arsenicals.

(h) "Biological product" means any virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment or cure of diseases or injuries of man:

(1) A virus is interpreted to be a product containing the minute living cause of an infectious disease and includes but is not limited to filterable viruses, bacteria, rickettsia, fungi, and protozoa.

(2) A therapeutic serum is a product obtained from blood by removing the clot or clot components and the blood cells.

(3) A toxin is a product containing a soluble substance poisonous to laboratory animals or to man in doses of 1 milliliter or less (or equivalent in weight) of the product, and having the property, following the injection of non-fatal doses into an animal, of causing to be produced therein another soluble substance which specifically neutralizes the poisonous substance and which is demonstrable in the serum of the animal thus immunized.

(4) An antitoxin is a product containing the soluble substance in serum or other body fluid of an immunized animal which specifically neutralizes the toxin against which the animal is immune.

(5) A product is analogous:

(i) To a virus if prepared from or with a virus or agent actually or potentially infectious, without regard to the degree of virulence or toxicogenicity of the specific strain used.

(ii) To a therapeutic serum, if composed of whole blood or plasma or containing some organic constituent or product other than a hormone or an

amino acid, derived from whole blood, plasma, or serum.

(iii) To a toxin or antitoxin, if intended, irrespective of its source of origin, to be applicable to the prevention, treatment, or cure of disease or injuries of man through a specific immune process.

(i) "Trivalent organic arsenicals" means arsphenamine and its derivatives (or any other trivalent organic arsenic compound) applicable to the prevention, treatment, or cure of diseases or injuries of man.

(j) A product is deemed “applicable to the prevention, treatment, or cure of diseases or injuries of man" irrespective of the mode of administration or application recommended, including use when intended through administration or application to a person as an aid in diagnosis, or in evaluating the degree of susceptibility or immunity possessed by a person, and including also any other use for purposes of diagnosis if the diagnostic substance so used is prepared from or with the aid of a biological product.

(k) "Proper name", as applied to a product, means the name designated in the license for use upon each package of the product.

(1) "Dating period" means the period beyond which the product cannot be expected beyond reasonable doubt to yield its specific results.

(m) "Expiration date" means the calendar month and year, and where applicable, the day and hour, that the dating period ends.

(n) The word "standards" means specifications and procedures applicable to an establishment or to the manufacture or release of products, which are prescribed in this subchapter and which are designed to insure the continued safety, purity and potency of such products.

(0) The word "continued" as applied to the safety, purity and potency of products is interpreted to apply to the dating period.

(p) The word "safety" means the relative freedom from harmful effect to persons affected, directly or indirectly, by a product when prudently administered, taking into consideration the character of the product in relation to

the condition of the recipient at the time.

(q) The word "sterility" is interpreted to mean freedom from viable contaminating microorganisms, as determined by the tests prescribed in § 610.12 of this chapter.

(r) "Purity" means relative freedom from extraneous matter in the finished product, whether or not harmful to the recipient or deleterious to the product. "Purity" includes but is not limited to relative freedom from residual moisture or other volatile substances and pyrogenic substances.

(s) The word "potency" is interpreted to mean the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result.

(t) "Manufacturer" means any legal person or entity engaged in the manufacture of a product subject to license under the act.

(u) "Manufacture" means all steps in propagation or manufacture and preparation of products and includes but is not limited to filling, testing, labeling, packaging, and storage by the manufacturer.

(v) "Location" includes all buildings, appurtenances, equipment and animals used, and personnel engaged by a manufacturer within a particular area designated by an address adequate for identification.

(w) "Establishment" includes all locations.

(x) "Lot" means that quantity of uniform material identified by the manufacturer as having been thoroughly mixed in a single vessel.

(y) A “filling" refers to a group of final containers identical in all respects, which have been filled with the same product from the same bulk lot without any change that will affect the integrity of the filling assembly.

(z) "Process" refers to a manufacturing step that is performed on the product itself which may affect its safety, purity or potency, in contrast to such manufacturing steps which do not affect intrinsically the safety, purity or potency of the product.

(aa) "Selling agent" or "distributor" means any person engaged in the unrestricted distribution, other than by sale at retail, of products subject to li

cense.

(bb) "Container" (referred to also as "final container") is the immediate unit, bottle, vial, ampule, tube, or other receptacle containing the product as distributed for sale, barter, or exchange.

(cc) "Package" means the immediate carton, receptacle, or wrapper, including all labeling matter therein and thereon, and the contents of the one or more enclosed containers. If no package, as defined in the preceding sentence, is used, the container shall be deemed to be the package.

(dd) "Label" means any written, printed, or graphic matter on the container or package or any such matter clearly visible through the immediate carton, receptacle, or wrapper.

(ee) "Radioactive biological product" means a biological product which is labeled with a radionuclide or intended solely to be labeled with a radionuclide.

[38 FR 32048, Nov. 20, 1973, as amended at 40 FR 31313, July 25, 1975; 55 FR 11014, Mar. 26, 1990]

Subpart B-Establishment Standards § 600.10

Personnel.

(a) Responsible head. A person shall be designated as the responsible head who shall exercise control of the establishment in all matters relating to compliance with the provisions of this subchapter, with authority to represent the manufacturer in all pertinent matters with the Center for Biologics Evaluation and Research, and with authority to enforce or to direct the enforcement of discipline and the performance of assigned functions by employees engaged in the manufacture of products. The responsible head shall have an understanding of the scientific principles and the techniques involved in the manufacture of products. The responsible head shall have the responsibility for the training of employees in manufacturing methods and for their being informed concerning the application of the pertinent

provisions of this subchapter to their respective functions.

(b) Other personnel. Personnel shall have capabilities commensurate with their assigned functions, a thorough understanding of the manufacturing operations which they perform, the necessary training and experience relating to individual products, and adequate information concerning the application of the pertinent provisions of this subchapter to their respective functions. Personnel shall include such professionally trained persons as are necessary to insure the competent performance of all manufacturing

processes.

(c) Restrictions on personnel-(1) Specific duties. Persons whose presence can affect adversely the safety and purity of a product shall be excluded from the room where the manufacture of a product is in progress.

(2) Sterile operations. Personnel performing sterile operations shall wear clean or sterilized protective clothing and devices to the extent necessary to protect the product from contamination.

(3) Pathogenic viruses and sporebearing organisms. Persons working with viruses pathogenic for man or with spore-bearing microorganisms, and persons engaged in the care of animals or animal quarters, shall be excluded from areas where other products are manufactured, or such persons shall change outer clothing, including shoes, or wear protective covering prior to entering such areas.

(4) Live vaccine work areas. Persons may not enter a live vaccine processing area after having worked with other infectious agents in any other laboratory during the same working day. Only persons actually concerned with propagation of the culture, production of the vaccine, and unit maintenance, shall be allowed in live vaccine processing areas when active work is in progress. Casual visitors shall be excluded from such units at all times and all others having business in such areas shall be admitted only under supervision. Street clothing, including shoes, shall be replaced or covered by suitable laboratory clothing before entering a live vaccine processing unit. Persons caring for animals used in the