
From the U.S. Code Online via GPO Access
[wais.access.gpo.gov]
[Laws in effect as of January 2, 2001]
[Document not affected by Public Laws enacted between
  January 2, 2001 and January 28, 2002]
[CITE: 21USC356a]

 
                        TITLE 21--FOOD AND DRUGS
 
             CHAPTER 9--FEDERAL FOOD, DRUG, AND COSMETIC ACT
 
                     SUBCHAPTER V--DRUGS AND DEVICES
 
                        Part A--Drugs and Devices
 
Sec. 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.

(June 25, 1938, ch. 675, Sec. 506A, as added Pub. L. 105-115, title I, 
Sec. 116(a), Nov. 21, 1997, 111 Stat. 2313.)


                             Effective Date

    Section 116(b) of Pub. L. 105-115 provided that: ``The amendment 
made by subsection (a) [enacting this section] takes effect upon the 
effective date of regulations promulgated by the Secretary of Health and 
Human Services to implement such amendment, or upon the expiration of 
the 24-month period beginning on the date of the enactment of this Act 
[Nov. 21, 1997], whichever occurs first.''
