XIX.  Comments on Returned Dietary Supplements

  (Final Subpart N)

A. Organization of Final Subpart N

     In the 2003 CGMP Proposal, the requirements for returned dietary
supplements were set forth in proposed § 111.85.  As shown in table
15, we are reorganizing proposed § 111.85 into a distinct subpart
(final subpart N – Returned Dietary Supplements).  Table 15 lists the
sections in final subpart N and identifies the proposed sections that
form the basis of the final rule. 

Table 15. - Derivation of Sections in Final Subpart N

Final Rule	2003 CGMP Proposal

§ 111.503 What are the Requirements Under This Subpart for Written
Procedures?	N/A

§ 111.510 What Requirements Apply When a Returned Dietary Supplement
is Received?	§ 111.85(a)

§ 111.515 When Must a Returned Dietary Supplement be Destroyed, or
Otherwise Suitably Dispose of?	§ 111.85(b) and (c)

§ 111.520 When may a returned dietary supplement be salvaged?
§ 111.37(b)(15)

§ 111.525 What Requirements Apply to a Returned Dietary Supplement
that the Quality Control Unit Approves for Reprocessing?	§ 111.50(g)



§ 111.530 When Must an Investigation be Conducted of Your
Manufacturing Processes and Other Batches?

	§ 111.85(d)

§ 111.535 Under this Subpart, What Records Must You Make and Keep?
§ 111.50(g)

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●	Revisions that reflect that the final rule applies to persons who
manufacture, package, label, or hold dietary supplements unless subject
to an exclusion in § 111.1.  

●	A provision (final § 111.520) that we are adding for consistency,
so that the final rule for returned dietary supplements clearly sets
forth the requirements for a positive outcome (i.e., when you may
salvage a returned dietary supplement) as well as a negative outcome
(i.e., when you must destroy or otherwise suitably dispose of a returned
dietary supplement); and

●	A provision (final § 111.525) we are adding for consistency, so
that the final rule for returned dietary supplements clearly sets forth
the requirements for reprocessed materials.

2.  Changes After Considering Comments

     The final rule:

●	Includes a new requirement to establish and follow written
procedures to fulfill the requirements for returned dietary supplements;

●	Includes a revised description of the conditions that preclude you
from salvaging a returned dietary supplement; and 

●	Provides flexibility for firms to salvage a returned dietary
supplement without conducting tests to demonstrate that the dietary
supplement meets all specifications, provided that the quality control
unit conducts a material review and makes a disposition decision to
approve the salvage. 

C.  General Comments on Proposed § 111.85

     (Comment 312) Several comments request we clarify the roles of the
various parties in the “pre-consumer supply chain” for dietary
supplements. 

     (Response) We have discussed, in section VI, who is subject to the
final rule in what the comment describes as the “pre-consumer supply
chain” and do not repeat that discussion here.  The requirements for
returned dietary supplements do not distinguish between those returned
to a person who manufactures a finished batch and those returned to a
person whose role in the manufacturing process is limited to operations
such as packaging, labeling, or holding.       

Any reprocessing operations, other than repackaging or relabeling, by a
packager or labeler who receives a product for packaging or labeling as
a dietary supplement would make that packager or labeler subject to all
relevant regulatory requirements under this final rule, as explained in
sections VI and .  A packager or labeler that only conducts repackaging
or relabeling operations may conclude that a product was returned for
reasons related to a problem with the manufacture of the product it
received for packaging or labeling, and therefore cannot be salvaged. 
In such a case, under final § 111.515 the packager or labeler would
have to destroy or otherwise suitably dispose of the dietary supplement.
 Under final § 111.515, the packager or labeler may contact the
manufacturer to determine if the packager or labeler could suitably
dispose of the dietary supplement by sending it back to the manufacturer
for possible reprocessing (see discussion of final § 111.515 in this
section).  A manufacturer who receives a dietary supplement returned by
a packager or labeler would be required to comply with the requirements
of final subpart N for returned dietary supplements, including
requirements for any reprocessing of the returned dietary supplements.

D. What Are the Requirements Under This Subpart

 for Written Procedures? 

 (Final § 111.503)

  

We received many comments that recommended written procedures for
various provisions.  We address the need for written procedures
generally in section IV.  We also respond to individual comments on
specific provisions in the same section.

	Final § 111.503 requires you to establish and follow written
procedures to fulfill the requirements of subpart N. Under final §
111.535(b)(1) we are requiring you to make and keep records of such
written procedures.  Such records would be available to us under the
requirements in subpart P.

 

E.  What Requirements Apply When a 

Returned Dietary Supplement is Received?

 (Final § 111.510)

     Final § 111.510 requires you to identify and quarantine returned
dietary supplements until the quality control unit conducts a material
review and makes a disposition decision. Final § 111.510 is similar to
proposed § 111.85(a).

     We did not receive comments specific to proposed § 111.85(a).  

F.  When Must a Returned Dietary Supplement Be 

Destroyed, or Otherwise Suitably Disposed of? 

(Final § 111.515)

     Final § 111.515(a) requires that you destroy, or otherwise
suitably dispose of, any returned dietary supplement, unless the outcome
of a material review and disposition decision is that the quality
control unit either: (1) Approves the salvage of the returned dietary
supplement for redistribution, or (2) approves the returned dietary
supplement for reprocessing.  Final § 111.515(a) derives from the
following proposed sections:

●	111.85(b) which would require that you not salvage returned dietary
supplements unless: (1) Evidence from their packaging (or, if possible,
an inspection of the premises where the dietary ingredients and dietary
supplements were held) indicates that the dietary ingredients and
dietary supplements were not subjected to improper storage conditions;
and (2) tests demonstrate that the dietary ingredients or dietary
supplements meet all specifications for identity, purity, quality,
strength, and composition; and

●	111.85(c) which would require that you destroy or suitably dispose
of the returned dietary ingredients or dietary supplements if such
dietary ingredients and dietary supplements do not meet specifications,
unless the quality control unit conducts a material review and makes a
disposition decision to allow reprocessing.  

     Final § 111.515(a) includes editorial changes and other changes
made after considering comments.

    (Comment 313) Several comments assert it is unnecessary to conduct
testing for all specifications for every returned product because
products may be returned for reasons unrelated to product quality.  For
example, products may be returned due to overstocking, ordering the
wrong quantity, going out of business, or failing to pay for the product
on time.  In addition, several comments assert that many returned
products are intact, show no signs of mishandling, and are within the
time limits for shelf life.  These comments assert that a material
review and disposition decision by the quality control unit to restock
the material without retesting may be acceptable in these types of
situations.  Some comments assert that proposed § 111.85(b) is more
restrictive than CGMP requirements for drug products, and suggest that
testing need be conducted only when some doubt has been cast upon the
identity, purity, quality, strength, or composition of the product, or
if the product was returned for some other GMP-related problem. 

     Some comments contend that proposed §§ 111.35(i)(3)(v) and
111.85 would make it difficult to salvage any returned product because
companies receiving returns often cannot verify the conditions under
which such products were held.  One comment refers to a stakeholder
meeting when we indicated that the extent of testing requirements would
depend upon the reason such products were returned.  The comments state
that the rule should allow flexibility as to when returned products must
be tested.

     Some comments specifically suggest the approach used in the USP
(revised in 2nd supplement USP 26).  These comments suggest that
proposed § 111.85(b) be revised as follows:

If the conditions under which returned products have been held, stored,
or shipped before or during their return, or if the condition of the
product, its container, carton or labeling, as a result of storage or
shipping, cast doubt on the safety, identity, strength, quality, or
purity of the product, the returned product should be destroyed unless
examination, testing or other investigations prove the product meets
appropriate standards of safety, identity, strength, quality, or purity.
 

These comments assert that inspection of the condition of the returned
product could be used to determine that a product can be returned to
inventory, and this inspection could be covered by internal procedures
and based on experience in testing product stored under conditions that
include extremes in heat and humidity without affecting the container or
closure system.

     (Response) As already discussed in this section, the final rule
includes a new requirement that you establish and follow written
procedures for handling returned dietary supplements.  The final rule
also retains the requirement that the quality control unit conduct a
material review and make a disposition decision regarding all returned
dietary supplements (see discussion of final § 111.113(a)(5) in
section XI).  We agree with the comments that it is not necessary to
conduct testing for all specifications for every returned product,
because products may be returned for reasons unrelated to the quality of
the dietary supplement.  Final § 111.130 provides for the quality
control unit to determine whether tests or examinations are necessary
for returned dietary supplements to determine compliance with product
specifications.  Therefore, final § 111.515 does not include a testing
requirement.  We believe the combination of written procedures and
oversight by the quality control unit is adequate to determine the
appropriate disposition of a returned dietary supplement, without
requiring a test in every case to demonstrate that the dietary
supplement meets specifications for identity, purity, strength, and
composition.  

     In final § 111.515(a) we generally accept the comments’
suggestions and reflect the approach of the USP for returned products. 
Thus you must destroy or otherwise suitably dispose of the returned
dietary supplement, unless the outcome of the material review and
disposition decision is that the quality control unit approves the
salvage of the returned dietary supplement for redistribution or
approves the reprocessing of the returned dietary supplement.  We
provide flexibility on how the quality control unit may conduct its
material review and make its disposition decision and do not require
testing in every case.  We respond to the comment asserting that the
proposed CGMPs exceed the drug CGMPs in section V.

G.  When May a Returned Dietary Supplement be Salvaged? 

(Final § 111.520)

     Final § 111.520 permits the salvage of a returned dietary
supplement only if the quality control unit conducts a material review
and makes a disposition decision to allow the salvage.  Final
§ 111.520 is a conforming provision we are adding for consistency, so
that the final requirement for returned dietary supplements clearly sets
forth a positive outcome (i.e., when you may salvage a returned dietary
supplement) as well as a negative outcome (i.e., when you must destroy
or otherwise suitably dispose of a returned dietary supplement).  Final
§ 111.520 is consistent with final § 111.130 (proposed
§ 111.37(b)(15)) which requires the quality control unit to approve
the distribution of returned dietary supplements. 

H.  What Requirements Apply to a Returned Dietary Supplement That the
Quality Control Unit Approves for Reprocessing?  

(Final § 111.525)

      Final § 111.525(a) requires you to ensure that any returned
dietary supplements that are reprocessed meet all product specifications
established in accordance with final § 111.70(e).  Final § 111.525(b)
requires the quality control unit to approve or reject the release for
distribution of any returned dietary supplement that is reprocessed.  As
with final § 111.520, final § 111.525 is a provision we are adding
for consistency.  Final § 111.525 is consistent with final
§ 111.90(c). 

I.  When Must an Investigation Be Conducted of Your Manufacturing
Processes and Other Batches?

(Final § 111.530)

	Final § 111.530 requires that, if the reason for a dietary supplement
being returned implicates other batches, you must conduct an
investigation of your manufacturing processes and each of those other
batches to determine compliance with specifications.  Final § 111.530
derives from proposed § 111.85(d) which would require that if the
reason for a dietary supplement being returned implicates associated
batches, you must conduct an investigation of your manufacturing
processes and those other batches to determine compliance with
specifications.  Final § 111.530 includes a non-substantive editorial
change of “associated” to “each of those other batches” for
clarity.

     We did not receive comments specific to proposed § 111.85(d).

J.  Under This Subpart, What Records Must You Make and Keep? 

(Final § 111.535)

     Final § 111.535 sets forth the requirements to make and keep
records for returned dietary supplements.  Final § 111.180 derives
from proposed § 111.85(e) and (f).

     We did not receive comments specific to proposed § 111.85(e) or
(f).

1.  Final § 111.535(a)

     Final § 111.535(a) requires you to make and keep records required
under subpart N in accordance with subpart P.  Final § 111.535(a)
derives from proposed §111.85(f) and includes changes associated with
the reorganization.  

2.  Final § 111.535(b)(1)

     As discussed in this section, the final rule includes a new
requirement (final § 111.503) that you establish and follow written
procedures to fulfill the requirements of subpart N.  Those written
procedures are records.  Therefore, final § 111.535(b)(1) requires you
to make and keep a record of the written procedures for fulfilling the
requirements of subpart N. 

3.  Final § 111.535(b)(2)

     Final § 111.535(b)(2) requires you to make and keep a record of
any material review and disposition decision on a returned dietary
supplement.  Final § 111.535(b) derives from proposed § 111.85(e),
with revisions associated with the reorganization.

4.  Final § 111.535(b)(3)

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.establish and keep records on any testing conducted to determine
compliance with established specifications in the master manufacturing
record for the type of dietary supplement that was returned.  Final
§ 111.535(b)(3) includes the following revisions:

•    Consistent with final § 111.70(e), final § 111.535(b)(3)
substitutes “product specifications established under § 111.70(e)”
for “established specifications in the master manufacturing record for
the type of dietary ingredient or dietary supplement that was
returned.”  

•    Consistent with final § 111.75(c), final § 111.535(b)(3)
provides flexibility to use either tests or examinations to determine
whether specifications are met. 

5.  Final § 111.535(b)(4)

     Final § 111.535(b)(4) requires you to make and keep a record of
documentation of the reevaluation by the quality control unit of any
dietary supplement that is reprocessed and the determination by the
quality control unit of whether the reprocessed dietary supplement meets
product specifications established in accordance with § 111.70(e). 
Final § 111.535(b)(4) is related to final § 111.525.  Under final
§ 111.525, you must ensure that any returned dietary supplements that
are reprocessed meet all product specifications you established under
§ 111.70(e) and the quality control unit must approve or reject the
release for distribution of any returned dietary supplement that is
reprocessed.   

HHS/FDA-Internal-Confidential-Deliberative

Final Subpart N 9-28-05

Page   PAGE  893 

