Document ID: FDA-1996-N-0028-0084
Agency: fda
Document Type: Supporting & Related Material
Title: 
Posted Date: 2007-08-01T04:00Z

XIV.  Comments on the Production and Process Control System: 

Requirements for the Batch Production Record 

(Final Subpart I)

A.  Organization of Final Subpart I

    In the 2003 CGMP Proposal, the proposed requirements for the batch
production record were set forth in § 111.50.  As shown in table 10, we
are setting forth the requirements for the batch production record in a
distinct subpart (final subpart I – Production and Process Control
System: Requirements for the Batch Production Record) that contains the
requirements that derive from proposed § 111.50.  In addition, we are
moving some proposed requirements from §§ 111.35 and 111.37 into final
subpart I.  Table 10 lists the sections in final Subpart I and
identifies the provisions that form the basis for the final rule.

Table 10.- Derivation of Sections in Final Subpart I

Final Rule	2003 CGMP Proposal

§ 111.255  What is the Requirement to Establish a Batch Production
Record?	§ 111.50(a), (b), and

(i) 

§ 111.260 What Must the Batch Record Include?	§ 111.35(i)(2) and (j)

§ 111.35(m) and (o)(2)

§ 111.37(b)(3), (b)(5), and (b)(9)

§ 111.50(c)(1)through (c)(11), (c)(13), (c)(14), (d)(2), (e), and (g)

§ 111.70(b)(6), (e), and (g)

     The requirements in final subpart I are set forth from the
perspective of the manufacture of a batch of a dietary supplement. 
However, you must comply with the requirement to prepare and follow a
“batch production record” or a “batch record” regardless of
whether you manufacture a batch or whether you package or label product
you receive from a supplier for packaging or labeling as a dietary
supplement (and for distribution rather than for return to the
supplier).  As discussed in section VI if you are a packager or labeler,
you only need to include those parts relevant to your process.  For
example, if you are a labeler under final § 111.260(e) you would not
need to include the identity and weight or measure of each component
used, because you would be starting from packages that already had been
filled.

B.  Highlights of Changes to the Proposed Requirements

for the Batch Production Record

1.  Revisions  

   The final rule:

●	Includes 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.  

●	Does not use the term “shipment lot” when referring to
components.

2.  Changes Associated With the Reorganization

●	Several provisions derive in whole or in part from proposed §§
111.35, 111.37, or 111.70.

●	Several requirements in proposed § 111.50 are redundant with
requirements set forth in other subparts and are not repeated in subpart
I.

●	Several proposed requirements for reprocessing are moved to final §
111.90 in final subpart E.

●	The proposed requirement to collect reserve samples of each batch of
dietary supplement is moved to final § 111.83 in subpart E, where we
clarify that the requirement relates to each lot of packaged and labeled
dietary supplement rather than to a finished batch awaiting packaging
and labeling.

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●	Provides flexibility for firms to document information about the
maintenance, cleaning, and sanitizing of equipment used in producing the
batch in either the batch production record or in individual equipment
logs that it cross-references in the batch production record.

●	Provides flexibility for firms to include in the batch production
record either the results of any testing or examination performed, or a
cross-reference to the results of any testing or examination.

C.  What is the Requirement to 

Establish a Batch Production Record? 

(Final § 111.255) 

     Final § 111.255(a) requires you to prepare a batch production
record every time you manufacture a batch of a dietary supplement. 
Final § 111.255(b) requires that the batch production record include
complete information relating to the production and control of each
batch.  Final § 111.255(a) and (b) derive from proposed § 111.50(a),
with a nonsubstantive revision that divides the proposed requirements
into two separate paragraphs.

     Final § 111.255(c) requires your batch production record to
accurately follow the appropriate master manufacturing record and you to
perform each step in the production of the batch.  Final § 111.255(c)
derives from proposed §111.50(b). 

     Final § 111.255(d) requires you to make and keep batch production
records in accordance with subpart P.  Final § 111.255(d) derives from
proposed § 111.50(i) with editorial changes associated with the
reorganization.

     We did not receive comments specific to proposed § 111.50(a), (b),
or (i).

D.  What must the batch record include?  

(Final § 111.260) 

1.  Final § 111.260(a) 

     Final § 111.260(a) requires the batch production record to include
the batch, lot, or control number: (1) Of the finished batch of dietary
supplement; and (2) that you assign in accordance with § 111.415(f)
for: (i) Each lot of packaged and labeled dietary supplement from the
finished batch of dietary supplement; and (ii) each lot of dietary
supplement, from the finished batch of dietary supplement, that you
distribute to another person for packaging or labeling.

 	Final § 111.260(a) derives, in part, from proposed § 111.50(c)(1),
which would require the batch, lot, or control number in the batch
production record.  Consistent with comments that requested that we
clarify responsibilities when more than one party is involved with the
manufacturing, packaging, labeling, or holding of a dietary supplement
(see section VI), we have added the requirements of final §
111.260(a)(1) and (a)(2)(i) and (a)(2)(ii) to ensure you are able to
determine the manufacturing history and control of the packaged and
labeled dietary supplement from all stages of manufacturing through
distribution and to be consistent with other provisions of this final
rule.  In subpart L, section XVI, we explain in detail final
§ 111.410(d), which requires you to be able to determine the complete
manufacturing history and control of the packaged and labeled dietary
supplement through distribution.  In that same section, we explain final
§ 111.415(f) which requires you to assign a batch, lot, or control
number to each lot of packaged and labeled dietary supplement from a
finished batch and each lot of dietary supplement from a finished batch
that you distribute to another person for packaging and labeling.  In
that way, these batch, lot, or control numbers can be used to determine
the manufacturing history and control of the batch.  However, you can
determine how you track the batch, lot, or control number of the
packaged and labeled dietary supplement, or dietary supplement you send
to another person for packaging and labeling, to a distributed dietary
supplement.

	We did not receive comments specific to proposed § 111.50(c)(1).  We
respond to comments relevant to final subpart L in section XVI.

2. Final § 111.260(b)

     Final § 111.260(b) requires that the batch production record
include the identity of equipment and processing lines used in producing
the batch and derives from proposed § 111.50(c)(3).

     We did not receive comments specific to proposed § 111.50(c)(3).

3.  Final § 111.260(c)

     Final § 111.260(c) requires that the batch production record
include the date and time of the maintenance, cleaning, and sanitizing
of the equipment and processing lines used in producing the batch, or a
cross-reference to records, such as individual equipment logs, where
this information is retained. Final § 111.260(c) derives from proposed
§ 111.50(c)(4).

     (Comment 263) Many comments argue that it is not necessary or
appropriate to retain the records of maintenance, cleaning, and
sanitizing equipment and processing lines in the batch production
record.  These comments request that the final rule provide flexibility
to retain such records in individual equipment files or log books for
easy access.  One comment recommends the requirement to retain such
records be set forth within Subpart D. 

      (Response) As discussed in section IX (final § 111.35(b)(2)), we
agree with these comments.  Consistent with final § 111.35(b)(2), final
§ 111.260(c) provides flexibility to retain the records of maintenance,
cleaning, and sanitizing equipment and processing lines in either the
batch production record or another record you cross-reference in the
batch production record. 

4.  Final § 111.260(d)

     Final § 111.260(d) requires that the batch production record
include the unique identifier you assigned to each component (or, when
applicable, to a product you receive from a supplier for packaging or
labeling as a dietary supplement), packaging, and label used.  Final §
111.260(d) derives from proposed § 111.50(c)(5), which would require
that the batch record include the shipment lot unique identifier of each
component, dietary supplement, packaging, and label used.  Consistent
with the convention we are establishing under final §§ 111.80(a),
111.155, and 111.160, final § 111.260(d) does not use the term
“shipment lot.”

     We did not receive comments specific to proposed § 111.50(c)(5).

5.  Final § 111.260(e) and (f)

     Final § 111.260(e) requires that the batch production record
include the identity and weight or measure of each component used and
derives from proposed § 111.50(c)(6).

     Final § 111.260(f) requires that the batch record include a
statement of the actual yield and a statement of the percentage of
theoretical yield at appropriate phases of processing.  Final §
111.260(f) derives from proposed § 111.50(c)(9).

     (Comment 264) A few comments argue that the requirements in
proposed § 111.50(c)(6) are not applicable to continuous operations and
that yield information required in proposed § 111.50(c)(9) is
irrelevant for quality control in continuous operations used for
producing dietary ingredients.  One of these comments also discusses
“continuous operations,” such as a continuous operation built
adjacent to a soy crushing or vegetable oil refinery to receive a
continuous side stream flow from that operation (see the discussion of
final § 111.155(c) in section XII).  This comment explains that in such
operations, quarantine and quality control approval occurs after the
material has been isolated and concentrated in a stable matrix suitable
for holding.

     (Response) Based on the limited information provided by these
comments, it appears that they are describing the manufacture of a
“dietary ingredient” or other component that will subsequently be
used in the manufacture of a dietary supplement.  Therefore, in this
scenario, the identity and weight or measure of the stable matrix must
be taken.  The statement of the actual yield and the theoretical yield
refers to the batch in which the stable matrix is added as a component. 

6.  Final § 111.260(g)

    Final § 111.260(g) requires that the batch production record
include the actual results obtained during any monitoring operation. 
Final § 111.260(g) derives from proposed § 111.35(o)(2) which would
require you to make and retain records of the actual results obtained
during monitoring of the in-process production.  Consistent with the
reorganization we are specifying that the records of monitoring be
located in the batch production record, because the monitoring is
associated with the batch production.

     We did not receive comments specific to proposed § 111.35(o)(2).

7.  Final § 111.260(h)

     Final § 111.260(h) requires that the batch production record
include the results of any testing or examination performed during the
batch production, or a cross-reference to such results.  Final §
111.260(h) derives from proposed § 111.50(c)(10) which would require
you to record the actual results of any testing performed during
production of the batch.

     (Comment 265) A few comments object to the requirement in proposed
§ 111.50(c)(10) that actual test results be included in the batch
production record.  These comments state test results are typically
retained in other records, such as laboratory records, and that it would
be duplicative to include such results in the batch production record. 
One comment states the “actual” (original record of) test results
may not be available to the manufacturer when the testing is performed
electronically or an outside laboratory does the testing.  This comment
adds for test results obtained in-house, original records are typically
kept as part of the master laboratory records and cross-referenced in
batch records.

     (Response) After considering these comments, we are providing
flexibility to either include the results of tests or examinations in
the batch production record, or provide a cross-reference to such
results.  We note that final § 111.260(h) does not require that you
have the original documentation of the test results.  If an outside
laboratory has performed testing for you, you must obtain a copy of the
test results and include these in your batch production record or in
another appropriate record that you can cross-reference and make readily
available for inspection.

8.  Final § 111.260(i)

     Final § 111.260(i) requires that the batch production record
include documentation that the finished dietary supplement meets
specifications established in accordance with § 111.70(e) and (g). 
Final § 111.260(i) derives from proposed § 111.50(c)(11).  We have
made a change to identify which required specifications the dietary
supplement must meet.

	We did not receive comments specific to proposed § 111.50(c)(11).

9.  Final § 111.260(j)

     Final § 111.260(j) sets forth the requirements for documentation
you must make and include in the batch production record, at the time of
performance, of the manufacture of the batch.  Final § 111.260(j)
derives from proposed § 111.50(c)(2) and (c)(7).

     a.  Final §111.260(j)(1).  Final § 111.260(j)(1) requires
documentation, at the time of performance, of the date on which each
step of the master manufacturing record was performed.  Final
§111.260(j)(1) derives from proposed § 111.50(c)(2).  We did not
receive comments specific to proposed § 111.50(c)(2).

     b.  Final §111.260(j)(2).  Final § 111.260(j)(2) requires
documentation, at the time of performance, of the initials of the
persons performing each step in the master manufacturing record.  Final
§ 111.260(j)(2) derives from the second part of proposed §
111.50(c)(2),(c)(7) and (c)(8).

     (Comment 266)  One comment asks whether the persons responsible for
batch production must be identified by name or by position.  

     (Response)  The requirement is for the initials of the name of the
person rather than for identification of the position.  Requiring that
the record include the initials of the person(s) performing each step in
the master manufacturing record means that the person performing the
step is the person who physically initials the batch record at the time
the person performs the step.  The intent is for the person to
acknowledge that he or she performed the requirement rather than to
merely provide information that would identify that person.

     (Comment 267) One comment asks whether we will allow electronic
signatures for batch production records, laboratory test results, and
quality control unit documentation.  The comment notes that many
companies have fully computerized, automated production and quality
control management systems that utilize password-protected (or otherwise
secure) means of entering data at key quality control steps.  

     (Response) The use of electronic signatures is governed by our
regulations in part 11, which control whether electronic signatures are
permitted.  Our guidance entitled “Guidance for Industry Part 11,
Electronic Records; Electronic Signatures – Scope and Application”,
(Ref. 330) available at   HYPERLINK "http://www.fda.gov/cder/guidance/" 
www.fda.gov/cder/guidance/ 5667fnl.htm, discusses the use of electronic
signatures.  

c.  Final § 111.260(j)(2)(i) through § 111.260(j)(2)(iv).     Final §
111.260(j)(2)(i) requires you to document at the time of performance the
initials of the person responsible for weighing or measuring each
component used in the batch, and final § 111.260(j)(2)(ii) requires you
to document at the time of performance the initials of the person
responsible for verifying the weight or measure of each component used
in the batch.  Final § 111.260(j)(2)(i) and (j)(2)(ii) derive from
proposed § 111.50(c)(2)(i) and (c)(7), respectively.

     Final § 111.260(j)(2)(iii) requires you to document, at the time
of performance, the initials of the person responsible for adding the
component to the batch; and final § 111.260(j)(2)(iv) requires you to
document, at the time of performance, the initials of the person
responsible for verifying the addition of components to the batch. 
Final § 111.260(j)(2)(iii) derives from proposed § 111.50(c)(2)(ii)
and final § 111.260(j)(2)(iv) derives from proposed § 111.50(c)(8).

     We did not receive comments specific to proposed § 111.50(c)(2)(i)
and (c)(2)(ii) or § 111.50(c)(7) and (8).

10.  Final § 111.260(k)

     Final § 111.260(k) sets forth the requirements for documentation
you must make and include in the batch production record, at the time of
performance, of the packaging and labeling operations.  Final §
111.260(k) derives from proposed § 111.70(g) which we discuss below. 

     In final § 111.260(k)(3), we are eliminating proposed §
111.70(g)(4) which would require that the documentation include any
material reviews and disposition decisions for packaging and labels,
because it would be redundant with final § 111.180(b)(4)(ii)(D).

     a.  General comments on proposed § 111.70(g).

     (Comment 268) Some comments assert that the requirement of proposed
§ 111.70(g) that all packaging releases be placed in the batch
production record is unnecessary.  According to the comments, most
packaging material lots are used in multiple batches.  The comments
assert that a requirement for this disposition information to be copied
into each batch production record is unnecessary as long as lot
traceability exists and this information is kept in a central file. 

     (Response) These comments may have misinterpreted proposed §
111.70(g).  It would require that the documentation in the batch
production record for packaging and label operations include: (1) The
identity and quantity of the packaging and labels used and
reconciliation of any discrepancies between issuance and use; (2) the
examination conducted in accordance with proposed § 111.70(b)(7); (3)
the conclusions reached from retests conducted in accordance with
proposed § 111.70(e); and (4) any material reviews and disposition
decisions for packaging and labels.  None of these proposed requirements
would require that “packaging releases” be included in the batch
record.  

     The requirements for documentation for packaging you receive are
set forth in final § 111.180(b) in subpart G.

     b.  Final § 111.260(k)(1).  Final § 111.260(k)(1) requires the
documentation of packaging and labeling operations to include the unique
identifier you assigned to packaging and labels used, the quantity of
the packaging and labels used, and, when label reconciliation is
required, reconciliation of any discrepancies between issuance and use
of labels.  Final § 111.260(k)(1) derives from proposed § 111.70(g)(1)
which would require that the documentation include the identity and
quantity of the packaging and labels used and reconciliation of any
discrepancies between issuance and use.  For consistency with other
provisions of this final rule, such as final § 111.160(e)(1), final §
111.260(k)(1) requires “the unique identifier you assigned to
packaging and labels used,” rather than “the identity of packaging
and labels used.”  Final § 111.260(k)(1) also includes changes we are
making after considering comments. 

     (Comment 269) Some comments assert comprehensive label
reconciliation should not be required if appropriate electronic controls
are instituted to ensure that correct labels are used during labeling
operations.  The comments state this alternative is permitted for
labeling operations for drug products, which are generally identical or
similar in nature to labeling operations for dietary supplements.  As
such, the comments assert the same flexibility should be afforded to
dietary supplement manufacturers.  Some comments specifically suggest
changing the language of proposed § 111.70(g)(1) to read “The
identity and quantity of the packaging and labels used and either
reconciliation of any discrepancies between issuance and use or use of
appropriate electronic or electromechanical equipment to conduct a
100-percent examination for labeling during or after completion of
finishing operations.”

     (Response)  We agree that label reconciliation need not be required
for cut or rolled labels if a 100 percent examination for correct labels
is performed by appropriate electronic or electromechanical equipment
during or after completion of finishing operations.  Thus we have made
two changes in this final rule in addition to the changes in final §
111.260(k)(1) that provide there must be label reconciliation when such
reconciliation is required either to account for discrepancies or to
ensure the use of the label that is specified in the master
manufacturing record.  First, we have revised the final rule in subpart
L (for packaging and labeling operations) to provide that you need not
conduct label reconciliation if a 100 percent examination for correct
labels is performed by appropriate electronic or electromechanical
equipment during or after completion of finishing operations (see
discussion of final § 111.410(b) in subpart L, section XVI).  Second,
final § 111.260(k)(1), requires you to include documentation in the
batch production of reconciliation of any discrepancies between issuance
and use of labels only when label reconciliation is required. 

     c.  Final § 111.260(k)(2).  Final § 111.260(k)(2) requires the
documentation of packaging and labeling operations to include an actual
or representative label, or a cross-reference to the physical location
of the actual or representative label specified in the master
manufacturing record.  Final § 111.260(k)(2) derives from proposed §
111.50(c)(12) which would require that the batch production record
include copies of all container labels used and the results of
examinations conducted during the label operation to ensure that the
containers have the correct label.

     (Comment 270)  A few comments ask that we clarify the container
labels that proposed § 111.50(c)(12) is referring to.  Specifically,
these comments ask whether proposed § 111.50(c)(12) is referring to
finished product labels, bulk material labels, or in-process container
labels.  One comment asserts proposed § 111.50(c)(12) is unnecessary
for ensuring the dosage form of dietary supplements meets
specifications. 

     One comment finds proposed § 111.50(c)(12) confusing, because it
does not specify what is meant by “label operation.”  This comment
notes that during the course of manufacturing operations, containers
holding in-process materials are often labeled but the comment assumes
that proposed § 111.50(c)(12) does not require the retention of copies
of in-process container labels, which would not add significant value
toward the assurance of a quality product.  

     In general, these comments ask for clarification of proposed §
111.50(c)(12), and suggest it be deleted.

     (Response) Proposed § 111.50(c)(12) referred to the product label
that would be affixed to the containers that hold the packaged and
labeled dietary supplement.  We did not receive any comments that a
related requirement (in proposed § 111.45(b)(7) in the master
manufacturing record) was confusing or needed clarification.  We
therefore believe that the requirement that the batch production record
include a label will be clearer if we state the requirement in a way
that is similar to the requirement in proposed § 111.45(b)(7). 
However, because comments to proposed § 111.45(b)(7) persuaded us to
provide flexibility for (1) having a representative label rather than an
actual label, and (2) cross-referencing the physical location of the
actual or representative label that is specified in the master
manufacturing record, we are providing the same flexibility for having a
label in the batch production record.  Therefore, we are revising the
proposed requirement that the batch production record include “copies
of all container labels used” so that, under final § 111.260(k)(2),
the batch production record must include an actual or representative
label, or a cross-reference to the physical location for the actual or
representative label that is specified in the master manufacturing
record.

    However, we are not requiring in final § 111.260(k)(2) that the
batch production record include the results of examinations conducted
during the label operation to ensure that the containers have the
correct label that is specified in the master manufacturing record,
because this would be redundant with final § 111.260(k)(3).  

d.  Final § 111.260(k)(3).  Final § 111.260(k)(3) requires that the
documentation of packaging and labeling operations include the results
of any tests or examinations conducted on packaged and labeled dietary
supplements (including repackaged or relabeled dietary supplements), or
a cross-reference to such results.  Final § 111.260(k)(3) combines the
proposed requirements of proposed § 111.70(g)(2) which would require
that the documentation include the results of examinations conducted in
accordance with proposed § 111.70(b)(7), and proposed § 111.70(g)(3)
which would require that the documentation include the conclusions from
retests conducted in accordance with proposed § 111.70.  For
consistency with other requirements for documentation that must be in
the batch record, final § 111.260(k)(3) requires you to include “the
results of any tests or examinations,” rather than “the
examination” (proposed § 111.70(g)(2)) and “conclusions”
(proposed § 111.70(g)(3)).  Final § 111.260(k)(3) also includes
editorial revisions associated with combining proposed 

§ 111.70(g)(2) and (3).  

     We did not receive comments specific to proposed § 111.70(g)(2) or
(3).

11.  Final § 111.260(l)

     Final § 111.260(l) sets forth the requirements for documentation
the quality control personnelunit must make at the time of performance
and that must be included in the batch production record.  Final §
111.260(l) derives from proposed §§ 111.35(i)(2), (j), (m), (o)(2),
111.37(b)(3), (b)(5), (b)(9), 111.50(c)(1) to (c)(11), (c)(13),
111.50(c)(14), 111.50(d)(2), (e), (g), 111.70(b)(6) and 111.70(g).

     a.  Final § 111.260(l)(1).  Final § 111.260(l)(1) requires
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●	§ 111.50(d) which would require that the quality control unit
review in accordance with § 111.37(b)(5) the batch production record
established in paragraph (c) of this section; and 

●	§ 111.50(e) which would require that the quality control unit
document at the time of performance in accordance with § 111.37(c), the
review performed in accordance with paragraph (d) of this section. 

     Final § 111.260(l)(1) includes editorial changes associated with
the reorganization.  We did not receive comments specific to proposed §
111.50(d) or (e).

     b.  Final § 111.260(l)(1)(i).  Final § 111.260(l)(1)(i) requires
the documentation by the quality control personnel unit to include
review of any monitoring operation required under subpart E.  Final §
111.260(l)(1)(i) derives from proposed § 111.35(i)(2) which would
require that you review, among other things, the results of the
monitoring of the in-process control points, steps, or stages to ensure
specifications are met.  As discussed in section XI (final §
111.123(a)(3)), the final rule requires the quality control
personnelunit to review the required monitoring.

     We did not receive comments specific to proposed § 111.35(i)(2).

     c.  Final § 111.260(l)(1)(ii).  Final § 111.260(l)(1)(ii)
requires the documentation by the quality control personnelunit to
include the review by the quality control personnelunit of the results
of any tests or examinations, including tests or examinations conducted
on components, in-process materials, finished batches of dietary
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●	§ 111.50(e)(1) which would require that the documentation by the
quality control unit include review of component, dietary ingredient,
and dietary supplement receiving records, including review of testing
and examination results; and

●	§ 111.37(b)(9) which would require, in part, the quality control
unit to review all testing results.

     (Comment 271) A few comments assert that the proposed requirement
that the quality control unit review receiving records as part of its
review of the batch record is redundant and should be eliminated.  One
comment argues that it is unnecessarily burdensome to require the
quality control unit to re-review and cross reference all receiving
records, noting that the quality control unit already has performed a
review of these records when the components or dietary supplements were
received, approved, and released for use.  The comment asserts the
quality control unit should only have to repeat this review if it is
conducting an investigation or a material review.

     (Response)  We agree with the comments.  Therefore, final §
111.260(l)(1)(ii) retains the requirements of proposed §§ 111.50(e)(1)
and 111.37(b)(9) to review the results of testing and examination, but
does not require the quality control personnelunit to document, as part
of theits review of the batch record, receiving records for components
and dietary supplements.  

d.  Final § 111.260(l)(2).  Final § 111.260(l)(2) requires that the
documentation by the quality control personnelunit include that quality
control personnelit approved or rejected any reprocessing or
repackaging.  Final § 111.260(l)(2) derives from proposed §
111.50(c)(14) which would require that the batch production record
include the signature of the quality control unit to document its review
of the batch production record and any approval for reprocessing or
repackaging.  For consistency with other provisions in this final rule
(such as final § 111.90), final § 111.260(l)(2) includes a revision
that the quality control personnelunit must clearly choose between
approving - or rejecting - any reprocessing or repackaging.

     We did not receive comments specific to proposed § 111.50(c)(14).

e.  Final § 111.260(l)(3).  Final § 111.260(l)(3) requires the
documentation by the quality control personnelunit to include that it
approved and released, or rejected, the batch for distribution,
including any reprocessed batch.  Final § 111.260(l)(3) derives from
the following proposed regulations:

●	§ 111.37(b)(5) which would require, in part, the quality control
unit to review the batch production record to approve the batch for
release for distribution;

●	§ 111.50(d)(2) which would require the quality control unit not to
approve and release for distribution any batch of dietary ingredients or
dietary supplement that does not meet all specifications; and

●	§ 111.50(g) which would require, in part, the results of the
reevaluation by the quality control unit to be documented in the batch
production record.  

     For consistency with other provisions of this final rule (such as
final § 111.90), final § 111.260(l)(3) requires that the quality
control personnelunit must clearly choose between approving - or
rejecting - the batch for distribution.  We did not receive comments
specific to those parts of proposed §§ 111.37(b)(5) or 111.50(d)(2)
that we are setting forth in final § 111.260(l)(3).

     f.  Final § 111.260(l)(4).  Final § 111.260(l)(4) requires the
batch production record to include documentation, at the time of
performance, that the quality control personnelunit approved and
released, or rejected, the packaged and labeled dietary supplement,
including any repackaged or relabeled dietary supplement.  Final §
111.260(l)(4) derives from the following proposed regulations:

●	§ 111.37(b)(3) which would require, in part, that the quality
control unit approve or reject all dietary supplements; and

●	§ 111.70(e) which would require, in part, that any repackaged or
relabeled dietary supplement meet all specifications and that the
quality control unit must approve or reject their release for
distribution.

	We did not receive comments specific to those parts of proposed §§
111.37(b)(3) or 111.70(e) that we are setting forth in final §
111.260(l)(4).

12.  Final § 111.260(m)

	Final § 111.260(m) requires the batch production record to include
documentation, at the time of performance, of any required material
review and disposition decision.  Final § 111.260(m) derives from the
following proposed provisions:

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●	§ 111.50(c)(13) which would require that the batch production
record include any documented review and disposition decision; and

●	§ 111.35(j) which would require that the person who conducts the
material review and makes the disposition decision document that
activity, at the time of performance, in the batch  production record.

	We did not receive comments specific to proposed §§ 111.35(j) or
111.50(c)(13).

13. Final § 111.260(n)

	Final § 111.260(n) requires that the batch production record include
documentation, at the time of performance, of any reprocessing.  We have
added this requirement in conjunction with the requirement for written
procedures for the quality control operations for approving or rejecting
any reprocessing, discussed generally in section IV. 

 

E. Review of Batch Production Record Deviations

(Proposed § 111.50(d)(1) and 111.50(e)(2), (e)(3), and (e)(4))

     Proposed §111.50(d)(1) would require, if a batch deviates from the
master manufacturing record, including any deviation from
specifications, the quality control unit to conduct a material review
and make a disposition decision and record any decision in the batch
production record.  Under final § 111.87 the quality control
personnelunit must conduct any required material review and make any
required disposition decision; under final § 111.113(a)(2) the quality
control personnelunit must conduct a material review and make a
disposition decision if a batch deviates from the master manufacturing
record, including any deviation from specifications.  Given the
requirements of final §§ 111.87 and 111.113, it would be redundant to
include proposed § 111.50(d)(1) in final subpart I. 

     Proposed § 111.50(e)(2) would require that the review of the batch
production record and documentation by the quality control unit include
identification of any deviation from the master manufacturing record
that may have caused a batch or any of its components to fail to meet
specifications identified in the master production record.  Proposed §
111.50(e)(3) would require that the review of the batch production
record and documentation by the quality control unit include records of
investigations, conclusions, and corrective actions performed in
accordance with proposed § 111.50(d).  Proposed § 111.50(e)(4) would
require that the review of the batch production record and documentation
by the quality control unit include the identity of the person qualified
by training and experience who performed the investigation in accordance
with paragraph (d) of this section.  

	Each of these requirements is already included in final §
111.140(b)(3) which sets forth the requirements for the documentation
that the quality control personnelunit must include for any required
material review and disposition decision.  In addition, under final §
111.260(m), the batch production record must include documentation of
any required material review and disposition decision.  Given the
requirements of final §§ 111.140(b)(3) and 111.260(m), it would be
redundant to include proposed § 111.50(e)(2), (e)(3), and (3)(4) in
final subpart I, and we are not including them. 

FDA-Internal-Deliberative-Confidential

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

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