21 U.S.C. § 356a : US Code - Section 356A: Manufacturing changes

Search 21 U.S.C. § 356a : US Code - Section 356A: Manufacturing changes

(a) In general
With respect to a drug for which there is in effect an approved
application under section 355 or 360b of this title or a license
under section 262 of title 42, a change from the manufacturing
process approved pursuant to such application or license may be
made, and the drug as made with the change may be distributed, if -

(1) the holder of the approved application or license (referred
to in this section as a "holder") has validated the effects of
the change in accordance with subsection (b) of this section; and
(2)(A) in the case of a major manufacturing change, the holder
has complied with the requirements of subsection (c) of this
section; or
(B) in the case of a change that is not a major manufacturing
change, the holder complies with the applicable requirements of
subsection (d) of this section.
(b) Validation of effects of changes
For purposes of subsection (a)(1) of this section, a drug made
with a manufacturing change (whether a major manufacturing change
or otherwise) may be distributed only if, before distribution of
the drug as so made, the holder involved validates the effects of
the change on the identity, strength, quality, purity, and potency
of the drug as the identity, strength, quality, purity, and potency
may relate to the safety or effectiveness of the drug.
(c) Major manufacturing changes
(1) Requirement of supplemental application
For purposes of subsection (a)(2)(A) of this section, a drug
made with a major manufacturing change may be distributed only
if, before the distribution of the drug as so made, the holder
involved submits to the Secretary a supplemental application for
such change and the Secretary approves the application. The
application shall contain such information as the Secretary
determines to be appropriate, and shall include the information
developed under subsection (b) of this section by the holder in
validating the effects of the change.
(2) Changes qualifying as major changes
For purposes of subsection (a)(2)(A) of this section, a major
manufacturing change is a manufacturing change that is determined
by the Secretary to have substantial potential to adversely
affect the identity, strength, quality, purity, or potency of the
drug as they may relate to the safety or effectiveness of a drug.
Such a change includes a change that -
(A) is made in the qualitative or quantitative formulation of
the drug involved or in the specifications in the approved
application or license referred to in subsection (a) of this
section for the drug (unless exempted by the Secretary by
regulation or guidance from the requirements of this
subsection);
(B) is determined by the Secretary by regulation or guidance
to require completion of an appropriate clinical study
demonstrating equivalence of the drug to the drug as
manufactured without the change; or
(C) is another type of change determined by the Secretary by
regulation or guidance to have a substantial potential to
adversely affect the safety or effectiveness of the drug.
(d) Other manufacturing changes
(1) In general
For purposes of subsection (a)(2)(B) of this section, the
Secretary may regulate drugs made with manufacturing changes that
are not major manufacturing changes as follows:
(A) The Secretary may in accordance with paragraph (2)
authorize holders to distribute such drugs without submitting a
supplemental application for such changes.
(B) The Secretary may in accordance with paragraph (3)
require that, prior to the distribution of such drugs, holders
submit to the Secretary supplemental applications for such
changes.
(C) The Secretary may establish categories of such changes
and designate categories to which subparagraph (A) applies and
categories to which subparagraph (B) applies.
(2) Changes not requiring supplemental application
(A) Submission of report
A holder making a manufacturing change to which paragraph
(1)(A) applies shall submit to the Secretary a report on the
change, which shall contain such information as the Secretary
determines to be appropriate, and which shall include the
information developed under subsection (b) of this section by
the holder in validating the effects of the change. The report
shall be submitted by such date as the Secretary may specify.
(B) Authority regarding annual reports
In the case of a holder that during a single year makes more
than one manufacturing change to which paragraph (1)(A)
applies, the Secretary may in carrying out subparagraph (A)
authorize the holder to comply with such subparagraph by
submitting a single report for the year that provides the
information required in such subparagraph for all the changes
made by the holder during the year.
(3) Changes requiring supplemental application
(A) Submission of supplemental application
The supplemental application required under paragraph (1)(B)
for a manufacturing change shall contain such information as
the Secretary determines to be appropriate, which shall include
the information developed under subsection (b) of this section
by the holder in validating the effects of the change.
(B) Authority for distribution
In the case of a manufacturing change to which paragraph
(1)(B) applies:
(i) The holder involved may commence distribution of the
drug involved 30 days after the Secretary receives the
supplemental application under such paragraph, unless the
Secretary notifies the holder within such 30-day period that
prior approval of the application is required before
distribution may be commenced.
(ii) The Secretary may designate a category of such changes
for the purpose of providing that, in the case of a change
that is in such category, the holder involved may commence
distribution of the drug involved upon the receipt by the
Secretary of a supplemental application for the change.
(iii) If the Secretary disapproves the supplemental
application, the Secretary may order the manufacturer to
cease the distribution of the drugs that have been made with
the manufacturing change.