[Code of Federal Regulations]
[Title 21, Volume 2]
[Revised as of April 1, 2008]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR111.75]

[Page 238-240]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 111_CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS--Table of Contents
 
  Subpart E_Requirement to Establish a Production and Process Control 
                                 System
 
Sec.  111.75  What must you do to determine whether specifications are met?

    (a) Before you use a component, you must:
    (1)(i) Conduct at least one appropriate test or examination to 
verify the identity of any component that is a dietary ingredient, 
unless you petition the agency under paragraph (a)(1)(ii) of this 
section and the agency exempts you from such testing;
    (ii) You may submit a petition, under 21 CFR 10.30, to request an 
exemption from the testing requirements in paragraph (a)(1)(i) of this 
section. The petition must set forth the scientific rationale, and must 
be accompanied by the supporting data and information, for proposed 
alternative testing that will demonstrate that there is no material 
diminution of assurance, compared to the assurance provided by 100 
percent identity testing, of the identity of the dietary ingredient 
before use when the dietary ingredient is obtained from one or more 
suppliers identified in the petition. If FDA grants the petition, you 
must conduct the tests and examinations for the dietary ingredient, 
otherwise required under Sec.  111.75(a)(1)(i), under the terms 
specified by FDA when the petition is granted; and
    (2) Confirm the identity of other components and determine whether 
other applicable component specifications established in accordance with 
Sec.  111.70(b) are met. To do so, you must either:
    (i) Conduct appropriate tests or examinations; or
    (ii) Rely on a certificate of analysis from the supplier of the 
component that you receive, provided that:
    (A) You first qualify the supplier by establishing the reliability 
of the supplier's certificate of analysis through confirmation of the 
results of the supplier's tests or examinations;
    (B) The certificate of analysis includes a description of the test 
or examination method(s) used, limits of the test or examinations, and 
actual results of the tests or examinations;
    (C) You maintain documentation of how you qualified the supplier;
    (D) You periodically re-confirm the supplier's certificate of 
analysis; and

[[Page 239]]

    (E) Your quality control personnel review and approve the 
documentation setting forth the basis for qualification (and re-
qualification) of any supplier.
    (b) You must monitor the in-process points, steps, or stages where 
control is necessary to ensure the quality of the finished batch of 
dietary supplement to:
    (1) Determine whether the in-process specifications are met; and
    (2) Detect any deviation or unanticipated occurrence that may result 
in a failure to meet specifications.
    (c) For a subset of finished dietary supplement batches that you 
identify through a sound statistical sampling plan (or for every 
finished batch), you must verify that your finished batch of the dietary 
supplement meets product specifications for identity, purity, strength, 
composition, and for limits on those types of contamination that may 
adulterate or that may lead to adulteration of the finished batch of the 
dietary supplement. To do so:
    (1) You must select one or more established specifications for 
identity, purity, strength, composition, and the limits on those types 
of contamination that may adulterate or that may lead to adulteration of 
the dietary supplement that, if tested or examined on the finished 
batches of the dietary supplement, would verify that the production and 
process control system is producing a dietary supplement that meets all 
product specifications (or only those product specifications not 
otherwise exempted from this provision by quality control personnel 
under paragraph (d) of this section);
    (2) You must conduct appropriate tests or examinations to determine 
compliance with the specifications selected in paragraph (c)(1) of this 
section;
    (3) You must provide adequate documentation of your basis for 
determining compliance with the specification(s) selected under 
paragraph (c)(1) of this section, through the use of appropriate tests 
or examinations conducted under paragraph (c)(2) of this section, will 
ensure that your finished batch of the dietary supplement meets all 
product specifications for identity, purity, strength, and composition, 
and the limits on those types of contamination that may adulterate, or 
that may lead to the adulteration of, the dietary supplement; and
    (4) Your quality control personnel must review and approve the 
documentation that you provide under paragraph (c)(3) of this section.
    (d)(1) You may exempt one or more product specifications from 
verification requirements in paragraph (c)(1) of this section if you 
determine and document that the specifications you select under 
paragraph (c)(1) of this section for determination of compliance with 
specifications are not able to verify that the production and process 
control system is producing a dietary supplement that meets the exempted 
product specification and there is no scientifically valid method for 
testing or examining such exempted product specification at the finished 
batch stage. In such a case, you must document why, for example, any 
component and in-process testing, examination, or monitoring, and any 
other information, will ensure that such exempted product specification 
is met without verification through periodic testing of the finished 
batch; and
    (2) Your quality control personnel must review and approve the 
documentation that you provide under paragraph (d)(1) of this section.
    (e) Before you package or label a product that you receive for 
packaging or labeling as a dietary supplement (and for distribution 
rather than for return to the supplier), you must visually examine the 
product and have documentation to determine whether the specifications 
that you established under Sec.  111.70 (f) are met.
    (f)(1) Before you use packaging, you must, at a minimum, conduct a 
visual identification of the containers and closures and review the 
supplier's invoice, guarantee, or certification to determine whether the 
packaging specifications are met; and
    (2) Before you use labels, you must, at a minimum, conduct a visual 
examination of the label and review the supplier's invoice, guarantee, 
or certification to determine whether label specifications are met.
    (g) You must, at a minimum, conduct a visual examination of the 
packaging and labeling of the finished packaged

[[Page 240]]

and labeled dietary supplements to determine whether you used the 
specified packaging and applied the specified label.
    (h)(1) You must ensure that the tests and examinations that you use 
to determine whether the specifications are met are appropriate, 
scientifically valid methods.
    (2) The tests and examinations that you use must include at least 
one of the following:
    (i) Gross organoleptic analysis;
    (ii) Macroscopic analysis;
    (iii) Microscopic analysis;
    (iv) Chemical analysis; or
    (v) Other scientifically valid methods.
    (i) You must establish corrective action plans for use when an 
established specification is not met.

[72 FR 34942, June 25, 2007, as amended at 72 FR 34968, June 25, 2007]