0338 21cfr680 1 2007

Food and Drug Administration, HHS

§ 680.1

(2) Name, address (including zip
code), and license number of the manufacturer.
(3) Lot number, including any sublot
designations.
(4) Expiration date.
(5) Preservative(s) used and its concentration.
(6) Number of containers, if more
than one.
(7) Recommended storage temperature in degrees Celsius.
(8) Source of the product.
(9) Reference to enclosed package insert.
(10) The statement: ‘‘For In Vitro Diagnostic Use.’’
(11) The statement: ‘‘Meets FDA Potency Requirements.’’
(12) A statement of an observable indication of an alteration of the product, e.g., turbidity, color change, precipitate, that may indicate possible deterioration of the product.
(13) Appropriate cautions.
(c) Package insert. Each final container of Anti-Human Globulin shall be
accompanied by a package insert meeting the requirements of § 809.10 of this
chapter. If two or more final containers
requiring identical package inserts are
placed in a single package, only one
package insert per package is required.
(d) Names of antibodies.
Antibody designation
on container label
(1) Anti-IgG, -C3d;
Polyspecific.
(2) Anti-IgG ................

(3) Anti-IgG; heavy
chains.
(4) Anti-C3b ...............

(5) Anti-C3d ...............
(6) Anti-C4b ...............
(7) Anti-C4d ...............

Definition
Contains anti-IgG and anti-C3d (may
contain other anticomplement and
anti-immunoglobulin antibodies).
Contains anti-IgG with no anti-complement activity (not necessarily
gamma chain specific).
Contains only antibodies reactive
against human gamma chains.
Contains only C3b antibodies with no
anti-immunoglobulin activity. Note:
The antibody produced in response to immunization is usually
directed against the antigenic determinant which is located in the
C3c subunit; some persons have
called this antibody ‘‘anti-C3c.’’ In
product labeling, this antibody
should be designated anti-C3b.
Contains only C3d antibodies with no
anti-immunoglobulin activity.
Contains only C4b antibodies with no
anti-immunoglobulin activity.
Contains only C4d antibodies with no
anti-immunoglobulin activity.

Anti-Human Globulin preparations
may contain one or more of the antibody specificities listed in this para-

graph as described
(a)(2)(i) of this section.

in

paragraph

[50 FR 5579, Feb. 11, 1985; 50 FR 9800, Mar. 12,
1985, as amended at 50 FR 16474, Apr. 26, 1985;
55 FR 11014, Mar. 26, 1990; 67 FR 9587, Mar. 4,
2002; 70 FR 14986, Mar. 24, 2005]

PART 680—ADDITIONAL STANDARDS
FOR
MISCELLANEOUS
PRODUCTS
Sec.
680.1
680.2
680.3

Allergenic Products.
Manufacture of Allergenic Products.
Tests.

AUTHORITY: 21 U.S.C. 321, 351, 352, 353, 355,
360, 371; 42 U.S.C. 216, 262, 263, 263a, 264.
SOURCE: 38 FR 32100, 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.

§ 680.1 Allergenic Products.
(a) Definition. Allergenic Products are
products that are administered to man
for the diagnosis, prevention or treatment of allergies.
(b) Source materials—(1) Criteria for
source material. Only specifically identified allergenic source materials that
contain no more than a total of 1.0 percent of detectable foreign materials
shall be used in the manufacture of Allergenic Products, except that this requirement shall not apply to molds and
animals described under paragraphs (b)
(2) and (3) of this section, respectively.
Source materials such as pelts, feathers, hairs, and danders shall be collected in a manner that will minimize
contamination of the source material.
(2) Molds. (i) Molds (excluding rusts
and smuts) used as source material in
the manufacture of Allergenic Products shall meet the requirements of
§ 610.18 of this chapter and § 680.2 (a) and
(b).
(ii) Mold cultures shall be free of contaminating materials (including microorganisms) prior to harvest, and care
shall be taken to minimize contamination during harvest and subsequent
processing.

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§ 680.1

21 CFR Ch. I (4–1–05 Edition)

(iii) Mold manufacturers shall maintain written standard operating procedures, developed by a qualified individual, that will ensure the identity of
the seed culture, prescribe adequate
processing of the mold, and specify the
acceptable limits and kinds of contamination. These limits shall be based
on results of appropriate tests performed by the manufacturer on at least
three consecutive lots of a mold that is
a representative species of mold subject to the standard operating procedures. The tests shall be performed at
each manufacturing step during and
subsequent to harvest, as specified in
the standard operating procedures. Before use of the mold as a source material for Allergenic Products, in accordance with 21 CFR 601.2, the standard
operating procedures and test data
from the three representative lots described above shall be submitted to and
approved by the Director, Center for
Biologics Evaluation and Research (see
mailing addresses in § 600.2).
(3) Mammals and birds—(i) Care of animals. Animals intended as a source material for Allergenic Products shall be
maintained by competent personnel in
facilities or designated areas that will
ensure adequate care. Competent veterinary care shall be provided as needed.
(ii) Health of animals. Only animals in
good health and free from detectable
skin diseases shall be used as a source
material for Allergenic Products. The
determination of good health prior to
collection of the source material shall
be made by a licensed veterinarian or a
competent individual under the supervision and instruction of a licensed veterinarian provided that the licensed
veterinarian certifies in writing that
the individual is capable of determining the good health of the animals.
(iii) Immunization against tetanus.
Animals of the equine genus intended
as a source material for Allergenic
Products shall be treated to maintain
immunity to tetanus.
(iv) Reporting of certain diseases. In
cases of actual or suspected infection
with foot and mouth disease, glanders,
tetanus, anthrax, gas gangrene, equine
infectious
anemia,
equine
encephalomyelitis, or any of the pock
diseases among animals intended for

use or used as source material in the
manufacture of allergenic Products,
the manufacturer shall immediately
notify the Director, Center for Biologics Evaluation and Research (see
mailing addresses in § 600.2).
(v) Dead animals. Dead animals may
be used as source material in the manufacture of Allergenic Products: Provided, That (a) the carcasses shall be
frozen or kept cold until the allergen
can be collected, or shall be stored
under other acceptable conditions so
that the postmortal decomposition
processes do not adversely affect the
allergen, and (b) when alive, the animal
met the applicable requirements prescribed in paragraphs (b)(3) (i), (ii), and
(iii) of this section.
(vi) Mammals and birds inspected by
the U.S. Department of Agriculture.
Mammals and birds, subject to inspection by the U.S. Department of Agriculture at the time of slaughter and
found suitable as food, may be used as
a source material, and the requirements of paragraph (b)(3) (i) through
(iv) of this section do not apply in such
a case. Notwithstanding U.S. Department of Agriculture inspection, the
carcasses of such inspected animals
shall be frozen or kept cold until the
allergen is collected, or shall be stored
under other acceptable conditions so
that the postmortal decomposition
processes do not adversely affect the
allergen.
(c) Listing of source materials and suppliers. Each licensed manufacturer
shall initially list with the Director,
Center for Biologics Evaluation and
Research (see mailing addresses in
§ 600.2), the name and address of each of
the manufacturer’s source material
suppliers. The listing shall identify
each source material obtained from
each source material supplier. The licensed manufacturers shall update the
listing annually to include new source
material suppliers or to delete those no
longer supplying source materials.
(d) Exemptions. (1) Exemptions or
modifications from the requirements
under paragraph (b) of this section
shall be made only upon written approval by the Director, Center for Biologics Evaluation and Research.

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Food and Drug Administration, HHS

§ 680.3

(2) Nonlicensed source material suppliers are exempt from drug registration.
[38 FR 32100, Nov. 20, 1973, as amended at 49
FR 25432, June 21, 1984; 49 FR 31395, Aug. 7,
1984; 55 FR 11014, Mar. 26, 1990; 67 FR 9587,
Mar. 4, 2002; 70 FR 14986, Mar. 24, 2005]

§ 680.2 Manufacture
of
Allergenic
Products.
(a) Extraneous allergenic substances.
All manufacturing steps shall be performed so as to insure that the product
will contain only the allergenic and
other substances intended to be included in the final product.
(b) Cultures derived from microorganisms. Culture media into which organisms are inoculated for the manufacture of Allergenic Products shall contain no allergenic substances other
than those necessary as a growth requirement. Neither horse protein nor
any allergenic derivative of horse protein shall be used in culture media.
(c) Liquid products for oral administration. Liquid products intended for oral
administration that are filled in multiple dose final containers shall contain a preservative in a concentration
adequate to inhibit microbial growth.
(d) Residual pyridine. Products for
which pyridine is used in manufacturing shall have no more residual pyridine in the final product than 25
micrograms per milliliter.
(e) [Reserved]
(f) Records. A record of the history of
the manufacture or propagation of
each lot of source material intended
for manufacture of final Allergenic
Products shall be available at the establishment of the manufacturer of the
source material, as required by § 211.188
of this chapter. A summary of the history of the manufacture or propagation
of the source material shall be available at the establishment of the manufacturer of the final product.
[38 FR 32100, Nov. 20, 1973, as amended at 49
FR 25433, June 21, 1984; 67 FR 9587, Mar. 4,
2002]

§ 680.3 Tests.
(a) Identity. When a specific identity
test meeting the provisions of § 610.14 of
this chapter cannot be performed, the
manufacture of each lot shall be separated from the manufacture of other

products in a manner that will preclude adulteration, and records made
in the course of manufacture shall be
in sufficient detail to verify the identity of the product.
(b) Safety. A safety test shall be performed on the contents of a final container of each lot of each product as
prescribed in § 610.11 of this chapter, except for the following:
(1) For lots consisting of no more
than 20 final containers or 20 sets of individual dilutions, or where the final
container contains no more than one
intended human dose, the safety test
need not be performed on the contents
of a final container provided the safety
test is performed on each lot of stock
concentrate and on each lot of diluent
contained in the final product. Only
stock concentrates and diluents which
have passed the general safety test
shall be kept in the work areas used for
the manufacture of Allergenic Products. A stock concentrate is an extract
derived from a single allergenic source
and used in the manufacture of more
than one lot of product, and from
which final dilutions or mixtures, are
prepared directly.
(2) For powders for scratch tests, a
sample shall be suspended in a suitable
diluent and injected into each animal,
and the sample size shall be the single
human dose recommended.
(c) Sterility. A sterility test shall be
performed on each lot of each Allergenic Product as prescribed in § 610.12
of this chapter, with the following exceptions:
(1) When bulk material is not prepared, the sterility test prescribed for
bulk material shall be performed on
each container of each stock concentrate at the time a stock concentrate is prepared, and the test sample shall be no less than 1 ml. from
each stock concentrate container.
(2) For lots consisting of no more
than 5 final containers, the final container test shall be performed in accordance with § 610.12(g)(6) of this chapter using the sample therein prescribed
or using a sample of no less than 0.25
ml. of product from each final container, divided in approximately equal
proportions for testing in Fluid
Thioglycollate and Soybean-Casein Digest Media. The test sample in the

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