0338 21cfr601 2 2007

§ 600.81

21 CFR Ch. I (4–1–05 Edition)

that the report or information submitted under this section constitutes
an admission that the biological product caused or contributed to an adverse
effect. For purposes of this provision,
this paragraph also includes any person
reporting under paragraph (c)(1)(iii) of
this section.

§ 600.90

[59 FR 54042, Oct. 27, 1994, as amended at 62
FR 34168, June 25, 1997; 62 FR 52252, Oct. 7,
1997; 63 FR 14612, Mar. 26, 1998; 64 FR 56449,
Oct. 20, 1999; 70 FR 14982, Mar. 24, 2005]

§ 600.81

Waivers.

(a) A licensed manufacturer may ask
the Food and Drug Administration to
waive under this section any requirement that applies to the licensed manufacturer under §§ 600.80 and 600.81. A
waiver request under this section is required to be submitted with supporting
documentation. The waiver request is
required to contain one of the following:
(1) An explanation why the licensed
manufacturer’s compliance with the requirement is unnecessary or cannot be
achieved,
(2) A description of an alternative
submission that satisfies the purpose of
the requirement, or
(3) Other information justifying a
waiver.
(b) FDA may grant a waiver if it
finds one of the following:
(1) The licensed manufacturer’s compliance with the requirement is unnecessary or cannot be achieved,
(2) The licensed manufacturer’s alternative submission satisfies the requirement, or
(3) The licensed manufacturer’s submission otherwise justifies a waiver.

Distribution reports.

The licensed manufacturer shall submit to the Center for Biologics Evaluation and Research or the Center for
Drug Evaluation and Research (see
mailing addresses in § 600.2), information about the quantity of the product
distributed under the biologics license,
including the quantity distributed to
distributors. The interval between distribution reports shall be 6 months.
Upon written notice, FDA may require
that the licensed manufacturer submit
distribution reports under this section
at times other than every 6 months.
The distribution report shall consist of
the bulk lot number (from which the
final container was filled), the fill lot
numbers for the total number of dosage
units of each strength or potency distributed (e.g., fifty thousand per 10milliliter vials), the label lot number
(if different from fill lot number), labeled date of expiration, number of
doses in fill lot/label lot, date of release
of fill lot/label lot for distribution at
that time. If any significant amount of
a fill lot/label lot is returned, include
this information. Disclosure of financial or pricing data is not required. As
needed, FDA may require submission of
more detailed product distribution information. Upon written notice, FDA
may require that the licensed manufacturer submit reports under this section
at times other than those stated. Requests by a licensed manufacturer to
submit reports at times other than
those stated should be made as a request for a waiver under § 600.90.

PART 601—LICENSING
Subpart A—General Provisions
Sec.
601.2 Applications for biologics licenses;
procedures for filing.
601.4 Issuance and denial of license.
601.5 Revocation of license.
601.6 Suspension of license.
601.7 Procedure for hearings.
601.8 Publication of revocation.
601.9 Licenses; reissuance.

Subpart B [Reserved]
Subpart C—Biologics Licensing
601.12 Changes to an approved application.
601.14 Regulatory submissions in electronic
format.
601.15 Foreign establishments and products:
Samples for each importation.
601.20 Biologics licenses; issuance and conditions.
601.21 Products under development.
601.22 Products in short supply; initial manufacturing at other than licensed location.

[59 FR 54042, Oct. 27, 1994, as amended at 64
FR 56449, Oct. 20, 1999; 70 FR 14983, Mar. 24,
2005]

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Food and Drug Administration, HHS

§ 601.2

601.25 Review procedures to determine that
licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or suggested conditions of use.
601.26 Reclassification procedures to determine that licensed biological products
are safe, effective, and not misbranded
under prescribed, recommended, or suggested conditions of use.
601.27 Pediatric studies.
601.28 Annual reports of postmarketing pediatric studies.
601.29 Guidance documents.

AUTHORITY: 15 U.S.C. 1451–1561; 21 U.S.C.
321, 351, 352, 353, 355, 356b, 360, 360c–360f, 360h–
360j, 371, 374, 379e, 381; 42 U.S.C. 216, 241, 262,
263, 264; sec 122, Pub. L. 105–115, 111 Stat. 2322
(21 U.S.C. 355 note).
SOURCE: 38 FR 32052, 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.

Subpart D—Diagnostic
Radiopharmaceuticals

Subpart A—General Provisions

601.30 Scope.
601.31 Definition.
601.32 General factors relevant to safety and
effectiveness.
601.33 Indications.
601.34 Evaluation of effectiveness.
601.35 Evaluation of safety.

§ 601.2 Applications for biologics licenses; procedures for filing.
(a) General. To obtain a biologics license under section 351 of the Public
Health Service Act for any biological
product, the manufacturer shall submit
an application to the Director, Center
for Biologics Evaluation and Research
or the Director, Center for Drug Evaluation and Research (see mailing addresses in § 600.2 of this chapter), on
forms prescribed for such purposes, and
shall submit data derived from nonclinical laboratory and clinical studies
which demonstrate that the manufactured product meets prescribed requirements of safety, purity, and potency; with respect to each nonclinical
laboratory study, either a statement
that the study was conducted in compliance with the requirements set forth
in part 58 of this chapter, or, if the
study was not conducted in compliance
with such regulations, a brief statement of the reason for the noncompliance; statements regarding each clinical investigation involving human
subjects contained in the application,
that it either was conducted in compliance with the requirements for institutional review set forth in part 56 of this
chapter; or was not subject to such requirements in accordance with § 56.104
or § 56.105, and was conducted in compliance with requirements for informed
consent set forth in part 50 of this
chapter. A full description of manufacturing methods; data establishing stability of the product through the dating period; sample(s) representative of
the product for introduction or delivery for introduction into interstate

Subpart E—Accelerated Approval of Biological Products for Serious or LifeThreatening Illnesses
601.40 Scope.
601.41 Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible
morbidity.
601.42 Approval with restrictions to assure
safe use.
601.43 Withdrawal procedures.
601.44 Postmarketing safety reporting.
601.45 Promotional materials.
601.46 Termination of requirements.

Subpart F—Confidentiality of Information
601.50 Confidentiality of data and information in an investigational new drug notice for a biological product.
601.51 Confidentiality of data and information in applications for biologics licenses.

Subpart G—Postmarketing Studies
601.70 Annual progress
marketing studies.

reports

of

post-

Subpart H—Approval of Biological Products When Human Efficacy Studies Are
Not Ethical or Feasible
601.90 Scope.
601.91 Approval based on evidence of effectiveness from studies in animals.
601.92 Withdrawal procedures.
601.93 Postmarketing safety reporting.
601.94 Promotional materials.
601.95 Termination of requirements.

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§ 601.4

21 CFR Ch. I (4–1–05 Edition)

commerce; summaries of results of
tests performed on the lot(s) represented by the submitted sample(s);
specimens of the labels, enclosures, and
containers, and if applicable, any Medication Guide required under part 208 of
this chapter proposed to be used for the
product; and the address of each location involved in the manufacture of the
biological product shall be listed in the
biologics license application. The applicant shall also include a financial
certification or disclosure statement(s)
or both for clinical investigators as required by part 54 of this chapter. An
application for a biologics license shall
not be considered as filed until all pertinent information and data have been
received by the Food and Drug Administration. The applicant shall also include either a claim for categorical exclusion under § 25.30 or § 25.31 of this
chapter or an environmental assessment under § 25.40 of this chapter. The
applicant, or the applicant’s attorney,
agent, or other authorized official shall
sign the application. An application for
any of the following specified categories of biological products subject
to licensure shall be handled as set
forth in paragraph (c) of this section:
(1) Therapeutic DNA plasmid products;
(2) Therapeutic synthetic peptide
products of 40 or fewer amino acids;
(3) Monoclonal antibody products for
in vivo use; and
(4) Therapeutic recombinant DNA-derived products.
(b) [Reserved]
(c)(1) To obtain marketing approval
for a biological product subject to licensure which is a therapeutic DNA
plasmid product, therapeutic synthetic
peptide product of 40 or fewer amino
acids, monoclonal antibody product for
in vivo use, or therapeutic recombinant
DNA-derived product, an applicant
shall submit a biologics license application in accordance with paragraph
(a) of this section except that the following sections in parts 600 through 680
of this chapter shall not be applicable
to such products: §§ 600.10(b) and (c),
600.11, 600.12, 600.13, 610.11, 610.53, and
610.62 of this chapter.
(2) To the extent that the requirements in this paragraph (c) conflict
with other requirements in this sub-

chapter, this paragraph (c) shall supersede other requirements.
(d) Approval of a biologics license application or issuance of a biologics license shall constitute a determination
that the establishment(s) and the product meet applicable requirements to
ensure the continued safety, purity,
and potency of such products. Applicable requirements for the maintenance
of establishments for the manufacture
of a product subject to this section
shall include but not be limited to the
good manufacturing practice requirements set forth in parts 210, 211, 600,
606, and 820 of this chapter.
(e) Any establishment and product license for a biological product issued
under section 351 of the Public Health
Service Act (42 U.S.C. 201 et seq.) that
has not been revoked or suspended as
of December 20, 1999, shall constitute
an approved biologics license application in effect under the same terms and
conditions set forth in such product license and such portions of the establishment license relating to such product.
[64 FR 56450, Oct. 20, 1999, as amended at 70
FR 14983, Mar. 24, 2005]

§ 601.4

Issuance and denial of license.

(a) A biologics license shall be issued
upon a determination by the Director,
Center for Biologics Evaluation and
Research or the Director, Center for
Drug Evaluation and Research that the
establishment(s) and the product meet
the applicable requirements established in this chapter. A biologics license shall be valid until suspended or
revoked.
(b) If the Commissioner determines
that the establishment or product does
not meet the requirements established
in this chapter, the biologics license
application shall be denied and the applicant shall be informed of the
grounds for, and of an opportunity for
a hearing on, the decision. If the applicant so requests, the Commissioner
shall issue a notice of opportunity for
hearing on the matter pursuant to
§ 12.21(b) of this chapter.
[42 FR 4718, Jan. 25, 1977, as amended at 42
FR 15676, Mar. 22, 1977; 42 FR 19142, Apr. 12,
1977; 64 FR 56450, Oct. 20, 1999; 70 FR 14983,
Mar. 24, 2005]

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