XX.  Comments on Product Complaints (Final Subpart O)

A.  Organization of Final Subpart O

     In the 2003 CGMP Proposal, the requirements for consumer complaints
were set forth in § 111.95.  As shown in table 16, we are reorganizing
proposed § 111.95 into three provisions in a new subpart (Subpart O
– Product Complaints).  Table 16 lists the sections in final subpart O
and identifies the provisions that form the basis for the final rule.

Table 16. - Derivation of Sections in Final Subpart O

Final Rule	2003 CGMP Proposal

 § 111.553 What Are the Requirements Under this Subpart for Written
Procedures?	N/A

§ 111.560 What requirements Apply to the Review and Investigation of a
Product complaint? 	§ 111.95(a), (b), (c), and (d)

§ 111.570 Under this Subpart,
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●	Includes changes that reflect the final rule applies to persons who
manufacture, package, label, or hold dietary supplements unless subject
to an exclusion in § 111.1. 

● 	Uses the term “product complaint” rather than “consumer
complaint,” and the definition of “product complaint” does not
include an explanation about the types of complaints that may or may not
be covered by the CGMP regulations.  The definition does, however,
include examples of product complaints.

2.  Changes After Considering Comments

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●	A qualified person investigates any product complaint that involves
a possible failure of a dietary supplement to meet any requirements of
part 111, without an intermediate step of having the quality control
personnelunit first determine whether the complaint should be
investigated;

●	The qQuality control personnelunit reviews and approves all
decisions made by athe qualified person about whether to investigate a
product complaint and the findings and follow-up action of any
investigation performed rather than conduct the investigation and follow
up itself; and

●	The review and investigation of the product complaint extends to all
relevant batches and records, without identifying specific records, and
specific batches, that must be included in the review and investigation.
 

C.  General Comments on Proposed § 111.95

(Final Subpart O)

     (Comment 314) Some comments express general support for the
proposed procedures for consumer complaints.  Other comments request
proposed § 111.95 be deleted.  Most of these comments point out that
we had announced the development of CFSAN’s Adverse Event Reporting
System (CAERS) for reporting to FDA adverse events attributed to food
products and suggest that this new system would be the appropriate
mechanism for handling complaints about dietary supplements. 

     (Response)  We disagree with these comments.  Because the problem
giving rise to the complaint may be associated with a failure in
manufacturing, packaging, labeling, or holding, it is CGMP for a firm
that receives a product complaint to review it and investigate, if
necessary, regardless of whether we are notified about the complaint. 
An important goal of the firm’s review and investigation is to
determine whether there is a problem with the production and process
control system for the manufacture, packaging, labeling, or holding of
the dietary supplement.  That goal would not be achieved merely by
notifying us.  A firm subject to any of the requirements of this final
rule, whether such firm is a manufacturer, packager, labeler, or holder,
is responsible for the requirements in subpart O for a product complaint
it receives.

     (Comment 315)  Some comments assert that the proposed requirements
for consumer complaints do not go far enough and urge that any final
rule require any complaints that involve an adverse event be referred to
us.  The comments stress accurate reporting of adverse events is
essential to long-term evaluations of a product’s safety.

     (Response)  Mandatory reporting requirements to us regarding
adverse events related to dietary supplements are outside the scope of
this rulemaking.  This final rule addresses the internal processes and
controls that persons who manufacture, package, label, or hold dietary
supplements must follow.  Mandatory reporting to FDA of serious adverse
events, however, is now required as a result of the enactment of the
“Dietary Supplement and Non-Prescription Drug Consumer Protection
Act” (Pub. L. 109-462) signed into law on December 22, 2006.  The new
law requires manufacturers, packers, or distributors of such products to
submit reports to FDA about serious adverse events involving such
products based on specific information that they receive from the
public.  Serious adverse events are defined in the law as those events
that result in death, a life-threatening situation, an inpatient
hospitalization, a persistent or significant disability or incapacity,
or a congenital anomaly or birth defect or one that requires medical or
surgical intervention to prevent such serious outcomes (based on
reasonable medical judgment).  

	As discussed in the preamble to the 2003 CGMP Proposal (68 FR 12157 at
12217), however, we continue to strongly recommend that firms that
receive such product complaints, that are not “serious adverse
events,” notify us about any illness or injury, because, for example,
we may have additional expertise or data that may be helpful in
investigating the complaint or determining whether the problem applies
to more than one product.  In light of the requirement in the final rule
to establish and follow written procedures for handling product
complaints, we encourage you to include our recommendations in the
written procedures that you develop for handling product complaints (see
discussion of final § 111.553 in this section).

     (Comment 316) Some comments raise questions about who would be
subject to the proposed requirements regarding consumer complaints. 
Some comments state the section should apply only to manufacturers of
dietary supplements, not to manufacturers of dietary ingredients.  Other
comments are concerned that distributors who merely put their label on
the finished product may be held responsible for keeping records of
adverse events caused by failures to follow CGMPs during the manufacture
of the supplements.

     (Response) The final rule only applies to persons who manufacture,
package, label, or hold a dietary supplement.  We discuss the scope of
this final rule in detail in section VI.

     In most cases, the person who receives a product complaint from a
consumer will be the manufacturer, packager, or distributor of the
dietary supplement.  A distributor (also a “holder” under this final
rule) who receives a product complaint must review and investigate that
complaint to determine whether the complaint relates to a failure of the
processes under the control of the distributor, such as conditions of
temperature, humidity, and light that could affect the identity, purity,
strength, or composition of the dietary supplement.  If the distributor
concludes the problem is unrelated to any process under the control of
the distributor, the distributor should contact the manufacturer.  Under
the final rule, any person in the manufacturing chain who receives a
product complaint - regardless of the source - must comply with the
requirements in this subpart O.

     (Comment 317) One comment suggests proposed § 111.95, which
describes requirements for consumer complaints, could be combined with
proposed § 111.85 which describes requirements for returned dietary
supplements.

     (Response) We decline to adopt this suggestion.  In this final
rule, we are incorporating the requirements for returned dietary
supplements into a distinct subpart (final subpart N) that sets forth
requirements for returned dietary supplements. The procedures described
in final subpart O, which relate solely to the handling of product
complaints rather than returned dietary supplement products, are quite
different from those described in final subpart N, which addresses the
handling, review, and possible reprocessing of returned product.

     (Comment 318) Some comments assert the proposed requirements for
complaints are different from those for food CGMPs.

     (Response) We are making no changes to the requirements after
considering these comments.  We responded to similar comments asserting
that certain aspects of the proposed regulations are different from
those for other food CGMP requirements in section V.  

D.  What Are the Requirements under this Subpart 

for Written Procedures?

(Final § 111.553)

     We received many comments which 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 § 111.553 requires that you establish and follow written
procedures to fulfill the requirements of this subpart O.   Under final
§ 111.570(b)(1) we require you to make and keep records of such
procedures.  Such records would be required to be made available to us
under the requirements in subpart P.

	We encourage you to include in your written procedures the
recommendation made in the 2003 CGMP Proposal for you to consult with a
health care provider if you receive complaints that involve serious
illness or injury.  and for you to notify us about complaints of illness
or injury associated with the quality of the dietary supplementEven if
the complaints are not required to be submitted to FDA under the newly
enacted “Dietary Supplement and Non-Prescription Drug Consumer
Protection Act” (Pub. L. 109-462), we encourage your company to notify
us about the product complaints.  nder this newly enacted law, which
requires reporting to FDA of “serious adverse events,”
Mmanufacturers and distributors should be aware that this newly enacted
law, which requires reporting to FDA of “serious adverse events,”
contains the new mandatory provisions that require record retention of
adverse event reports that are separate from the requirements in this
CGMP final rule concerning product complaints.  

E.  What Requirements Apply to the Review and Investigation of a Product
Complaint? 

(Final § 111.560)

1.  Final § 111.560(a)(1)

     Final § 111.560(a)(1) requires a qualified person to review all
product complaints to determine whether the product complaint involves a
possible failure of a dietary supplement to meet any of its
specifications, or any other requirements of part 111, including those
specifications and other requirements that, if not met, may result in a
risk of illness or injury.  Final § 111.560(a)(1) derives from
proposed § 111.95(a).

     We did not receive comments specific to proposed § 111.95(a).

2.  Final § 111.560(a)(2), (b), and (c)

     Final § 111.560(a)(2) requires a qualified person to investigate
any product complaint that involves a possible failure of a dietary
supplement to meet any of its specifications, or any other requirements
of part 111, including those specifications and other requirements that,
if not met, may result in a risk of illness or injury.  Final
§ 111.560(b) requires that the quality control personnel unit review
and approve decisions by the qualified person about whether or not to
investigate a product complaint and the findings and follow-up action of
any investigation performed.  Final § 111.560(c) requires that the
review and investigation extend to all relevant batches and records.

     (Comment 319) Some comments characterize the requirements of
proposed § 111.95 as a confusing and difficult scheme to review,
investigate, and resolve customer complaints.  These comments state the
2003 CGMP Proposal would require extensive human resources,
recordkeeping, and decision-making.

     (Response)  We disagree that the 2003 CGMP Proposal would require
extensive human resources, recordkeeping, or decision making.  The
comments provided no rationale for such assertions.  The 2003 CGMP
Proposal sets forth basic steps, i.e., review, evaluation, and
follow-up, that one would need to take to appropriately address a
product complaint.  For those product complaints for which there is a
reasonable possibility of a relationship to an adverse event, the 2003
CGMP Proposal would require that an investigation be done by the quality
control unit because we believe such an event would need more careful
review and follow-up.  

	To address the comments that found proposed § 111.90 confusing, we
have made the following changes in the final rule to simplify the
procedures for handling product complaints:

●	Replaced the proposed procedure in which a qualified person
determines whether a complaint should be investigated by the quality
control unit with a procedure in which a qualified person investigates
any product complaint that involves a possible failure of a dietary
supplement to meet any require敭瑮⁳景瀠牡⁴ㄱ⸱

●	Require an oversight function by the quality control personnelunit
for the review and evaluation of product complaints, but not require
that the quality control personnelunit do any investigations on its own.
 This is consistent with other changes that we are making in response to
comments that requested that the quality control unit focus on reviewing
tasks performed by others rather than on performing the tasks itself.

●	Refer to “any product complaint that involves a possible failure
of a dietary supplement to meet any of its specifications, or any other
requirements of this part [part 111], including those specifications and
other requirements that, if not met, may result in a risk of illness or
injury” rather than to “a reasonable possibility of a relationship
between the quality of a dietary supplement and an adverse event.” 
This is consistent with changes that we are making to the definition of
the term “product complaint” in final § 111.3 (see section VI).

●	Continue to require that the review and investigation of the product
complaint extend to all relevant batches and records but simplify the
language of the requirement by removing the details – i.e., that the
investigation must include the batch records associated with the dietary
supplement involved in the consumer complaint and not specifying that
the investigation must extend to other batches of dietary supplement. 
Rather, we require that the investigation must extend to all relevant
batches and records. 

     The final rule provides firms flexibility on how to use its human
resources.  Nothing in subpart O would preclude a qualified person
amongwithin the designated quality control personnelunit to be
designated to from actually reviewing product complaints and conducting
investigations of any product complaint.  If an individual is so
designated and  the quality control unit conducts the investigation,
reviews and approves the findings, and conducts follow up actions of any
investigation performed, final § 111.560(b) would not apply. 

    (Comment 320) Some comments object to the requirement in proposed §
111.95(c) that consumer complaints are to be investigated only when
there may be a relationship between product quality and an adverse
event.  These comments suggest this provision be extended to any
possible relationship between dietary supplements and adverse events,
including those that might be independent of whether the product is
produced under CGMPs.  These comments consider there should be
consistent procedures for handling product complaints, regardless of
whether the complaints relate to product quality.

     (Response) The action requested in these comments is outside the
scope of this rule, which specifically addresses CGMP requirements to
ensure the quality of the dietary supplement product.  However, we
encourage firms to investigate all product complaints in a consistent
way, regardless of whether the complaints relate to the quality of the
dietary supplement. 

     (Comment 321) Some comments request clarification of statements
made or terms used in the preamble to the 2003 CGMP Proposal regarding
the handling of product complaints.  In the  preamble discussion of
proposed § 111.95(c), we stated a consumer complaint about adverse
effects “after consuming several dietary supplements” is worthy of
quality control unit investigation.  One comment asks about the meaning
of “several” and whether this example means that a manufacturer is
responsible for consumers who take more than the recommended dosage. 

     (Response) In our discussion of proposed § 111.95(c) we addressed
a situation where a consumer had symptoms on more than one occasion
rather than a situation where a consumer took more than the recommended
dosage.  However, firms must investigate any complaint of illness or
injury even if a consumer reports that he/she has consumed more than the
amount recommended on the product label to determine if the complaint is
related to CGMP.

F.  Under this Subpart, What Records must You Make and Keep?  (Final
§ 111.570)

1.  Final § 111.570(a)

     Final § 111.570(a) requires you to make and keep the records
required under subpart O in accordance with subpart P.  Final
§ 111.570(a) derives from proposed § 111.95(f)(2) with changes
associated with the reorganization.  

     We did not receive comments specific to proposed § 111.95(f)(2).

2.  Final § 111.570(b)(1)

     As discussed in § 111.570(b)(1) the final rule includes a new
requirement, final § 111.553, which requires written procedures for
fulfilling the requirements of subpart O.  Those written procedures are
records.  Another new provision, final § 111.570(b)(1), requires you
to make and keep a record of the written procedures for fulfilling the
requirements of subpart O.

3.  Final § 111.570(b)(2)

     Final § 111.570(b)(2) requires you to make and keep a written
record of every product complaint that is related to CGMP.  Final
§ 111.570(b)(2) derives from proposed § 111.95(e) which would
require that you

. . . make and keep a written record of every consumer complaint that is
related to good manufacturing practices.  For the purposes of the
regulations in this part, a consumer complaint about product quality may
or may not include concerns about a possible hazard to health.  However,
a consumer complaint does not include an adverse event, illness, or
injury related to the safety of a particular dietary ingredient
independent of whether the product is produced under good manufacturing
practices.

	As a revision for consistency with the definition of “product
complaint” in final § 111.3, final § 111.570(b)(2) does not
include the two full sentences from proposed § 111.95(e), as quoted
above. 

4.  Final § 111.570(b)(2)(i)

     Final § 111.570(b)(2)(i) requires that the person who performs
the requirements of subpart O, at the time of performance, document and
record the performance.  Final § 111.570(b)(2)(i) is similar to
proposed § 111.95(f)(1) with changes associated with the
reorganization.

5.  Final § 111.570(b)(2)(ii)

     Final § 111.570(b)(2)(ii) requires that the written record of the
product complaint include: (1) The name and description of the dietary
supplement; (2) the batch, lot, or control number of the dietary
supplement, if available; (3) the date the complaint was received and
the name, address or telephone number of the complainant, if available;
(4) the nature of the complaint including, if known, how the product was
used; (5) the reply to the complainant, if any; and (6) findings of the
investigation and follow-up action taken when an investigation is
performed.  Final § 111.570(b)(2) is similar to proposed
§ 111.95(e)(1) through (e)(6) and includes a change we are making
after considering comments to proposed § 111.95(e)(4) (discussed
below) which would have required that the consumer complaint written
record include “The nature of the complaint including how the consumer
used the product.”  On our own initiative, we also made a change to
include the date the complaint was received.

     (Comment 322) One comment notes proposed § 111.95(e)(4) would
require the written record of consumer complaints to include “how the
consumer used the product.”  The comment notes this information may
not always be available and suggests the words “where known” should
be added.



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     (Comment 323) Some comments request clarification of statements
made or terms used in the preamble to the 2003 CGMP Proposal regarding
the handling of product complaints.  In our discussion of proposed
§ 111.95(e) we recommended that consumer complaints and investigations
be reported to us when consumption of a dietary supplement may be
related to “a serious adverse event.”  Some comments note that
“serious” is not defined.

     (Response) The term “serious adverse event” is widely used in
the industries we regulate.  Our current forms for reporting “serious
adverse events” via the MedWatch program do not define the term, but
instead list outcomes that were attributed to an adverse event.  These
outcomes include death, life-threatening, hospitalization (initial or
prolonged), disability, congenital anomaly, required intervention to
prevent (a serious adverse event), permanent impairment/damage, and
“other.”  As discussed in this section, however, there is a new
statutory requirement for mandatory reporting to FDA of serious adverse
events enacted in the “Dietary Supplement and Non-Prescription Drug
Consumer Protection Act” (Pub. L. 109-462).  The new law does define
“serious adverse events” as those events that result in death, a
life-threatening situation, an inpatient hospitalization, a persistent
or significant disability or incapacity, or a congenital anomaly or
birth defect or one that requires medical or surgical intervention to
prevent such serious outcomes (based on reasonable medical judgment). 
The law also has specific provisions for how these serious adverse
events are to be submitted to FDA and record retention for records
relating to these and other adverse event reports.  We anticipate
issuing guidance on implementation of the new statutory provisions.  We
encourage firms who are unsure as to whether the nature of a reported
adverse event should be merits reporteding to FDA to contact us for
assistance. 

FDA-Internal-Confidential-Deliberative

Final Subpart O 9-28-05, 6-26-06, 3-30-07, 5-04-07

Page   PAGE  920 

