§ 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—
(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);
(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.
(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.