0458 21cfr600 14 2-2007

Food and Drug Administration, HHS

§ 600.14
one final container as a final package,
or package-equivalent of such filling of
each lot of the product as intended for
distribution. Such sample material
shall be stored at temperatures and
under conditions which will maintain
the identity and integrity of the product. Samples retained as required in
this section shall be in addition to
samples of specific products required to
be submitted to the Center for Biologics Evaluation and Research or the
Center for Drug Evaluation and Research (see mailing addresses in § 600.2).
Exceptions may be authorized by the
Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research,
when the lot yields relatively few final
containers and when such lots are prepared by the same method in large
number and in close succession.

temperature and other conditions relating to each sterilization of equipment and supplies used in the processing of products shall be made by
means of automatic recording devices
or by means of a system of recording
which gives equivalent assurance of the
accuracy and reliability of the record.
Such records shall be maintained in a
manner that permits an identification
of the product with the particular manufacturing process to which the sterilization relates.
(d) Animal necropsy records. A necropsy record shall be kept on each
animal from which a biological product
has been obtained and which dies or is
sacrificed while being so used.
(e) Records in case of divided manufacturing responsibility. If two or more establishments participate in the manufacture of a product, the records of
each such establishment must show
plainly the degree of its responsibility.
In addition, each participating manufacturer shall furnish to the manufacturer who prepares the product in final
form for sale, barter or exchange, a
copy of all records relating to the manufacturing operations performed by
such participating manufacturer insofar as they concern the safety, purity
and potency of the lots of the product
involved, and the manufacturer who
prepares the product in final form shall
retain a complete record of all the
manufacturing operations relating to
the product.

[41 FR 10428, Mar. 11, 1976, as amended at 49
FR 23833, June 8, 1984; 50 FR 4133, Jan. 29,
1985; 55 FR 11013, Mar. 26, 1990; 70 FR 14982,
Mar. 24, 2005]

§ 600.14 Reporting of biological product deviations by licensed manufacturers.
(a) Who must report under this section?
(1) You, the manufacturer who holds
the biological product license and who
had control over the product when the
deviation occurred, must report under
this section. If you arrange for another
person to perform a manufacturing,
holding, or distribution step, while the
product is in your control, that step is
performed under your control. You
must establish, maintain, and follow a
procedure for receiving information
from that person on all deviations,
complaints, and adverse events concerning the affected product.
(2) Exceptions:
(i) Persons who manufacture only in
vitro diagnostic products that are not
subject to licensing under section 351 of
the Public Health Service Act do not
report biological product deviations for
those products under this section but
must report in accordance with part
803 of this chapter;
(ii) Persons who manufacture blood
and blood components, including licensed manufacturers, unlicensed registered blood establishments, and

[38 FR 32048, Nov. 20, 1973, as amended at 49
FR 23833, June 8, 1984; 55 FR 11013, Mar. 26,
1990; 70 FR 14982, Mar. 24, 2005]

§ 600.13 Retention samples.
Manufacturers shall retain for a period of at least 6 months after the expiration date, unless a different time period is specified in additional standards, a quantity of representative material of each lot of each product, sufficient for examination and testing for
safety and potency, except Whole
Blood, Cryoprecipitated AHF, Platelets, Red Blood Cells, Plasma, and
Source Plasma and Allergenic Products
prepared to a physician’s prescription.
Samples so retained shall be selected
at random from either final container
material, or from bulk and final containers, provided they include at least

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§ 600.15

21 CFR Ch. I (4–1–06 Edition)

transfusion services, do not report biological product deviations for those
products under this section but must
report under § 606.171 of this chapter;
(iii) Persons who manufacture Source
Plasma or any other blood component
and use that Source Plasma or any
other blood component in the further
manufacture of another licensed biological product must report:
(A) Under § 606.171 of this chapter, if a
biological product deviation occurs
during the manufacture of that Source
Plasma or any other blood component;
or
(B) Under this section, if a biological
product deviation occurs after the
manufacture of that Source Plasma or
any other blood component, and during
manufacture of the licensed biological
product.
(b) What do I report under this section?
You must report any event, and information relevant to the event, associated with the manufacturing, to include testing, processing, packing, labeling, or storage, or with the holding
or distribution, of a licensed biological
product, if that event meets all the following criteria:
(1) Either:
(i) Represents a deviation from current good manufacturing practice, applicable regulations, applicable standards, or established specifications that
may affect the safety, purity, or potency of that product; or
(ii) Represents an unexpected or unforeseeable event that may affect the
safety, purity, or potency of that product; and
(2) Occurs in your facility or another
facility under contract with you; and
(3) Involves a distributed biological
product.
(c) When do I report under this section?
You should report a biological product
deviation as soon as possible but you
must report at a date not to exceed 45calendar days from the date you, your
agent, or another person who performs
a manufacturing, holding, or distribution step under your control, acquire
information
reasonably
suggesting
that a reportable event has occurred.
(d) How do I report under this section
You must report on Form FDA–3486.
(e) Where do I report under this section?
(1) For biological products regulated by

the Center for Biologics Evaluation
and Research (CBER), send the completed Form FDA–3486 to the Director,
Office of Compliance and Biologics
Quality (HFM–600) (see mailing addresses in § 600.2), or an electronic filing through CBER’s Web site at http://
www.fda.gov/cber/biodev/biodev.htm.
(2) For biological products regulated
by the Center for Drug Evaluation and
Research (CDER), send the completed
Form FDA–3486 to the Division of Compliance Risk Management and Surveillance (HFD–330) (see mailing addresses
in § 600.2). CDER does not currently accept electronic filings.
(3) If you make a paper filing, you
should identify on the envelope that a
biological product deviation report
(BPDR) is enclosed.
(f) How does this regulation affect other
FDA regulations? This part supplements
and does not supersede other provisions
of the regulations in this chapter. All
biological product deviations, whether
or not they are required to be reported
under this section, should be investigated in accordance with the applicable provisions of parts 211 and 820 of
this chapter.
[65 FR 66634, Nov. 7, 2000, as amended at 70
FR 14982, Mar. 24, 2005]

§ 600.15 Temperatures
ment.

during

The following products shall be maintained during shipment at the specified
temperatures:
(a) Products.
Product
Cryoprecipitated AHF ............
Measles and Rubella Virus
Vaccine Live.
Measles Live and Smallpox
Vaccine.
Measles, Mumps, and Rubella Virus Vaccine Live.
Measles and Mumps Virus
Vaccine Live.
Measles Virus Vaccine Live ..
Mumps Virus Vaccine Live ....
Fresh Frozen Plasma ............
Liquid Plasma ........................
Plasma ...................................

Temperature
¥18 °C or colder.
10 °C or colder.
Do.
Do.
Do.
Do.
Do.
¥18 °C or colder.
1 to 10 °C.
¥18 °C or colder.

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