Title 9
SECTION 101.5
101.5 Testing terminology.
§ 101.5 Testing terminology.Terms used when evaluating biological products shall mean:
(a) Standard Requirement. Test methods, procedures, and criteria established by Animal and Plant Health Inspection Service for evaluating biological products to be pure, safe, potent, and efficacious, and not to be worthless, contaminated, dangerous, or harmful under the Act.
(b) Log. Logarithm computed to the base 10.
(c) Pure or purity. Quality of a biological product prepared to a final form relatively free of extraneous micro-organisms and extraneous material (organic or inorganic) as determined by test methods or procedures established by Animal and Plant Health Inspection Service in Standard Requirements or in the approved Outline of Production for such product, but free of extraneous microorganisms or material which in the opinion of the Administrator adversely affects the safety, potency, or efficacy of such product.
(d) Safe or safety. Freedom from properties causing undue local or systemic reactions when used as recommended or suggested by the manufacturer.
(e) Sterile or sterility. Freedom from viable contaminating microorganisms as demonstrated by procedures prescribed in part 113 of this subchapter, Standard Requirements, and approved Outlines of Production.
(f) Potent or potency. Relative strength of a biological product as determined by test methods or procedures as established by Animal and Plant Health Inspection Service in Standard Requirements or in the approved Outline of Production for such product.
(g) Efficacious or efficacy. Specific ability or capacity of the biological product to effect the result for which it is offered when used under the conditions recommended by the manufacturer.
(h) Dose. The amount of a biological product recommended on the label to be given to one animal at one time.
(i) Vaccinate. An animal which has been inoculated, injected, or otherwise administered a biological product being evaluated.
(j) Control animal. An animal, which may be referred to as a control, used in a test procedure for purposes of comparison or to add validity to the results.
(k) Day. Time elapsing between any regular working hour of one day and any regular working hour of the following day.
(l) Test results. Terms used to designate testing results are as follows:
(1) No Test. Designation used when a deficiency in the test system has rendered a test unsuitable for drawing a valid conclusion.
(2) Satisfactory. Designation is a final conclusion given to a valid test with results that meet the release criteria stated in the filed Outline of Production or Standard Requirement.
(3) Unsatisfactory. Designation is a final conclusion given to a valid test with results that do not meet the release criteria stated in the filed Outline of Production or Standard Requirement.
(4) Inconclusive. Designation used for an initial test when a sequential test design established in the filed Outline of Production or Standard Requirement allows further testing if a valid initial test is not satisfactory.
(m) Healthy. Apparently normal in all vital functions and free of signs of disease.
(n) Unfavorable reactions. Overt adverse changes which occur in healthy test animals subsequent to initiation of a test and manifested during the observation period prescribed in the test protocol which are attributable either to the biological product being tested or to factors unrelated to such product as determined by the responsible individual conducting the test.
(o) Master reference. A Master Reference is a reference whose potency is correlated, directly or indirectly, to host animal immunogenicity. The Master Reference may be used as the working reference in in vitro tests for relative potency. The Master Reference may also be used to establish the relative potency of a serial of product used in requalification studies and to establish the relative potency of working references. The preparation of a Master Reference as described in a filed Outline of Production may be:
(1) A completed serial of vaccine or bacterin prepared in accordance with a filed Outline of Production;
(2) A purified preparation of a protective immunogen or antigen; or
(3) A nonadjuvanted harvested culture of microorganisms.
(p) Working reference. A Working Reference is the reference preparation that is used in the in vitro test for the release of serials of product. Working References may be:
(1) Master References; or
(2) Serials of product that have been prepared and qualified, in a manner acceptable to Animal and Plant Health Inspection Service for use as reference preparations.
(q) Qualifying serial. (1) A serial of biological product used to test for immunogenicity when the Master or Working Reference is a purified antigen or nonadjuvanted harvest material. Qualifying serials shall be produced in accordance with the filed Outline of Production, tested for immunogenicity in accordance with methods deemed appropriate by the Animal and Plant Health Inspection Service, and have a geometric mean relative potency, when compared to the Master Reference, of not greater than 1.0 as established by: independent parallel line assays with five or more replicates; or other valid assay methods for determining relative antigen content which demonstrate linearity, specificity, and reproducibility at least equivalent to the parallel line assay and are acceptable to the Animal and Plant Health Inspection Service.
(2) Qualifying serials used to requalify or extend the dating period of a Master Reference shall be determined to be immunogenic in accordance with methods deemed appropriate by the Animal and Plant Health Inspection Service as provided in paragraph (a)(1) of this section, and, in addition, shall be within their permitted dating period and have been prepared in accordance with the production method described in the currently filed Outline of Production.
(r) Immunogenicity. The ability of a biological product to elicit an immune response in animals as determined by test methods or procedures acceptable to the Animal and Plant Health Inspection Service.
(s) Stability-indicating assay. A stability-indicating assay is a validated quantitative analytical procedure that can detect changes over time in a pertinent property of the product.
[38 FR 8426, Apr. 2, 1973, as amended at 40 FR 45419, Oct. 2, 1975; 41 FR 6751, Feb. 13, 1976; 43 FR 3701, Jan. 27, 1978; 56 FR 66782, 66783 Dec. 26, 1991; 62 FR 19037, Apr. 18, 1997; 79 FR 55969, Sept. 18, 2014; 83 FR 11143, Mar. 14, 2018]