[Federal Register Volume 77, Number 54 (Tuesday, March 20, 2012)]
[Rules and Regulations]
[Pages 16158-16163]
[FR Doc No: 2012-6502]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 211

[Docket No. FDA-1997-N-0518] (formerly 97N-0300)

Current Good Manufacturing Practice in Manufacturing, Processing,
Packing, or Holding of Drugs; Revision of Certain Labeling Controls

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is amending the
packaging and labeling control provisions of the current good
manufacturing practice (CGMP) regulations for human and veterinary drug
products by limiting the application of special control procedures for
the use of cut labeling to immediate container labels, individual unit
cartons, or multiunit cartons containing immediate containers that are
not packaged in individual unit cartons. FDA is also permitting the use
of any automated technique, including differentiation by labeling size
and shape, that physically prevents incorrect labeling from being
processed by labeling and packaging equipment when cut labeling is
used. This action is intended to protect consumers from labeling errors
more likely to cause adverse health consequences, while eliminating the
regulatory burden of applying the rule to labeling unlikely to reach or
adversely affect consumers. This action is also intended to permit
manufacturers to use a broader range of error prevention and labeling
control techniques than permitted by current CGMPs.

DATES: This final rule is effective on March 20, 2013, except for the
amendment adding Sec.  211.122(g)(4), which is effective April 19,
2012.

FOR FURTHER INFORMATION CONTACT: Brian Hasselbalch, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, rm. 4364, Silver Spring, MD 20993-0002, 301-
796-3279, email<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of July 29, 1997 (62 FR 40489) (the
proposed rule), FDA proposed to amend the packaging and labeling
control provisions of the CGMP regulations for human and veterinary
drug products by limiting the application of special control procedures
for the use of cut labeling to immediate container labels, individual
unit cartons, or multiunit cartons containing immediate containers that
are not packaged in individual unit cartons, and to permit the use of
any automated technique, including differentiation by labeling size and
shape, that physically prevents incorrect labeling from being processed
by labeling and packaging equipment when cut labeling--single labels
for individual drug products that are ``cut'' from a sheet or roll of
labels--is used.
    Persistent problems with drug product mislabeling and subsequent
recalls led FDA in 1987 and in 1990 to review labeling procedures and
product recalls. The review identified gang-printed and cut labeling as
a leading cause of labeling mixups. Gang-printed labeling is defined in
Sec.  210.3(b)(22) (21 CFR 210.3(b)(22)) as labeling derived from a
sheet of material on which more than one item of labeling is printed.
Each sheet includes labeling for a variety of products and, because of
this, labeling for individual drug products must be separated from the
labeling for other products. When labels are gang-printed, the labels
for different drug products or different strengths for the same drug
product are processed together, making them especially susceptible to
mixups. Similarly, cut labeling is commonly placed in separate stacks
before being transported to packaging and labeling lines for
application to appropriate products. FDA found that stacks of labeling
of similar size, shape, and color could easily be intermixed and, if
the printer or manufacturer did not detect the error, incorrect
labeling could be applied and a mislabeled drug product distributed. To
reduce the frequency and likelihood of such mislabeling, FDA, in the
Federal Register of August 3, 1993 (58 FR 41348), amended the packaging
and labeling control provisions of the CGMP regulations in part 211 (21
CFR part 211) to provide specific conditions for the use of all gang-
printed and cut labeling. Under Sec.  211.122(f), use of gang-printed
labeling for different drug products, or different strengths or net

contents of the same product, is prohibited unless the labeling from
gang-printed sheets is adequately differentiated by size, shape, or
color. Under Sec.  211.122(g), packaging and labeling operations must
use one of three special control features if cut labeling is used: (1)
Packaging and labeling lines must be dedicated to each different
strength of each different drug product; (2) appropriate electronic or
electromechanical equipment must be used to conduct a 100 percent
examination for correct labeling during or after completion of
finishing operations; or (3) where labeling is hand-applied, use of
visual inspection to conduct a 100 percent examination for correct
labeling during or after completion of finishing operations must be
performed by one person and independently verified by a second person.
    To further limit the potential for mislabeling, FDA also required
written procedures for the identification and handling of filled drug
product containers not immediately labeled (Sec.  211.130(b)). FDA also
amended Sec.  211.125(c) to exempt manufacturers that use automated 100
percent examination for correct labeling from the label reconciliation
requirements. FDA also defined gang-printed labeling at Sec.
210.3(b)(22). The final rule applied to all types of labeling,
including product inserts, multiunit containers packaged in individual
containers, and shipping containers.
    In May 1994, FDA received two citizen petitions from several trade
associations requesting, among other things, that FDA consider
additional comments on the application of Sec.  211.122(g) to items of
labeling other than the immediate container label, and requesting
additional time to obtain, install, or validate equipment necessary to
comply with the August 3, 1993 final rule. In response to these
requests, FDA extended the compliance date to August 3, 1995, for Sec.
211.122(g) as it applies to labeling other than immediate container
labels, and opened the administrative record for comments on the scope
of Sec.  211.122(g). All other provisions of the August 3, 1993, final
rule became effective on August 3, 1994. To adequately assess comments
received during the extended comment period and provide industry
additional time to comply with the regulation, FDA published several
notices extending the compliance date for Sec.  211.122(g), as it
applies to labeling other than immediate container labels, to August 2,
1996, to August 1, 1997, and, in the July 29, 1997, Federal Register
(62 FR 40447), until the effective date of this final rule.
    FDA evaluated the comments received during the extended comment
period, met with industry representatives, reviewed recall data to
determine the danger to consumers from errors in different types of
drug product labeling, and surveyed packaging and labeling control
technology. On July 29, 1997, FDA issued a proposed rule to narrow the
scope of Sec.  211.122(g) and to expand the permissible control
procedures. This rule finalizes the July 29, 1997, proposed rule. As
described in more detail in section II of this document, the final rule
adopts the proposed codified without change.

II. Description of the Final Rule

A. Scope of Sec.  211.122

    The first sentence of current states: ``If cut labeling is used,
packaging and labeling operations shall include one of the following
special control procedures.'' The final rule amends the first sentence
of Sec.  211.122(g) to state: ``If cut labeling is used for immediate
container labels, individual unit cartons, or multiunit cartons
containing immediate containers that are not packaged in individual
unit cartons, packaging and labeling operations shall include one of
the following special control procedures.'' Thus, instead of applying
to all types of labeling as required in the August 3, 1993, final rule,
the control procedures specified in revised Sec.  211.122(g) apply only
to cut labeling used for immediate container labels, individual unit
cartons, or multiunit cartons containing immediate containers that are
not packaged in individual unit cartons. This amendment is intended to
protect consumers from labeling errors that are more likely to cause
adverse health consequences, while eliminating the regulatory burden of
applying the rule to labeling unlikely to reach or adversely affect
consumers. As explained in the proposed rule, the immediate container
label is most likely to be read by consumers. The individual unit
carton labeling is the outermost container in which a drug product is
commonly marketed at retail, and many consumers read this labeling when
deciding whether to purchase a product. When using multiunit cartons
containing immediate containers that are not packaged in individual
unit cartons (for example, sterile dosage forms in tray packs in which
immediate containers lack unit cartons), consumers and health
professionals are more likely to rely on labeling on the outer
multiunit container than to examine the labeling on the individual drug
product immediate containers.

B. Special Control Procedures

    Currently, there are three control procedures delineated in Sec.
211.122(g)(1) through (g)(3): (1) Dedication of labeling and packaging
lines to each different strength of each different drug product; (2)
use of appropriate electronic or electromechanical equipment to conduct
a 100 percent examination for correct labeling during or after
completion of finishing operations; or (3) use of visual inspection to
conduct a 100 percent examination for correct labeling during or after
completion of finishing operations for hand-applied labeling. The
visual inspection must be performed by one person and independently
verified by a second person. The final rule amends Sec.  211.122(g) to
add a fourth alternative special control procedure for packaging and
labeling operations when cut labeling is used that provides for more
flexibility in determining adequate controls. The fourth control, added
at Sec.  211.122(g)(4), states: ``Use of any automated technique,
including differentiation by labeling size and shape, that physically
prevents incorrect labeling from being processed by labeling and
packaging equipment.'' As noted in the proposed rule (62 FR 40489 at
40491), this additional control procedure is being added because FDA
believes that this will provide manufacturers with the widest possible
latitude in selecting appropriate labeling control technologies. It
will permit the use of a number of automated techniques that will
physically prevent incorrect labeling from being processed by packaging
and labeling equipment. A labeling control method using size and shape
as part of an automated technique that prevents incorrect labeling from
being processed by labeling and packaging lines provides equivalent
labeling control protection, through prevention, as do the other
special control procedures through surveillance or dedication of
labeling and packaging lines. An acceptable automated technique will
allow labeling and packaging operations to operate only if correct
labeling unique to a given product (for example, a specific size) is
used.

III. Responses to Comments on the Proposed Rule

    FDA received three comments on the proposed rule which raised a
limited number of issues. The specific issues raised by the commenters
are described in this section III.
    (Comment 1) One comment said that the final rule should permit all
effective means of label control, whether they

involve automated systems or nonautomated systems. The comment said
that FDA has indicated that both automated and nonautomated systems of
label control are equally effective in preventing label mixups. The
comment cited the June 23, 1989, proposed rule and the August 3, 1993,
final rule, and noted that FDA said that three label control practices
were not involved in any of the recalls attributed to label mixups
(i.e., the use of labels differentiated by size, shape, or color; the
use of dedicated packaging lines; and the use of electronic label
verification systems that validate the labeling of each product during
finishing operations (100 percent label inspection)). The comment said
that these label control practices include both automated (the use of
electronic label verification systems that validate the labeling of
each product during finishing operations) and nonautomated (use of
labels differentiated by size, shape, or color and the use of dedicated
packaging lines) methods.
    The comment also said that industry's experiences with certain
electronic and electromechanical control systems have shown
inconsistent results, and 50-60 percent of the electronic systems that
were installed during the recent past (the comment was submitted in
1997) could not be used because of lack of reliability against the
zero-defect standard. The comment said that some automated systems are
not robust enough to identify ``bad'' labels 100 percent of the time,
at certain line speeds and under certain conditions, and the systems
erred with unacceptable levels of false positives (that is, flagging
``good'' labels as ``bad'').
    The comment said the special control procedures under proposed
Sec.  211.122(g) should be modified to allow companies to document a
system of control that best fits the unique abilities of each
particular company, without requiring any one particular control system
(for example, electronic or electromechanical controls) to be used
across the entire industry. The comment said this approach would allow
the implementation of technology appropriate for the individual plants
involved.
    The comment noted that many companies currently use multiple layers
of control in their labeling operations that have yielded very robust
systems of total control, and they should not be required to add
another special layer of control that may not improve their total
system. The comment stated that FDA should permit additional automated
and nonautomated methods of control for items of labeling within the
scope of Sec.  211.122(g). Differentiation by size, shape, or color or
by any other effective, validated means should be permitted, whether
automated or not. The comment described other types of layers of
control that should be permitted, including labeling design to minimize
mixups, using labeling suppliers that have excellent internal control,
using label control rooms, proper purging of labeling lines, using
computerized material requirements planning systems, online checks of
operations, and reconciliation of labeling.
    Another comment said that the proposed rule would limit industry's
choice of control measures, and too great an emphasis was placed on
``high tech'' electronic verification systems. The comment stated that
traditional methods of label control have proven to be just as
effective. The comment said that industry is largely operating using
traditional label control measures along with some high tech electronic
verification systems as part of an overall system of label control.
These traditional systems consist of multilevel control measures that
work together to ensure that label mixups are avoided. The comment said
that the use of electronic systems alone will not provide this level of
assurance, because electronic systems are not 100 percent effective and
often give false alarms in labeling operations that can lead to
operator complacency and/or inefficient line operation. The comment
expressed doubt that the use of electronic verification systems would
improve systems currently in place at its company. The comment
recommended other control measures as part of an overall system for
label control that should be considered by FDA, including: (1) An
ongoing program to assess the label supplier's operations and controls;
(2) labeling designed to avoid mixups such as differentiation by size,
shape, and color; (3) procedures addressing art/label approval; (4) a
multilevel control system that incorporates personnel training, label
inspection, line clearance, and other control procedures designed to
avoid mixups; and (5) a validation of such systems that gives assurance
that label controls are acceptable.
    (Response) First, the Agency believes that it is important to
emphasize that one of the special controls listed in Sec.  211.122(g)
must be used only when cut labeling is used for the types of labeling
described in Sec.  211.122(g). Manufacturers have significant
additional flexibility to use different labeling controls for other
types of labeling.
    When cut labeling is used for the identified types of labeling, at
least one of the special controls in Sec.  211.122(g) must be used. The
final rule permits the choice of a special control from one of four
options specified in Sec.  211.122(g)(1) through (g)(4). Two are
nonautomated controls: dedication of lines (paragraph (g)(1)) and
visual inspection for hand applied labels (paragraph (g)(3)). Two are
automated controls: Electronic or electromechanical examination to
conduct a 100-percent examination for correct labeling during or after
completion of finishing operations (paragraph (g)(2)), and use of any
automated technique that physically prevents incorrect labeling from
being processed by labeling and packaging equipment (paragraph (g)(4)).
This provides industry with a number of options, including manual,
electronic, electromechanical, and automated systems. It also permits
broad discretion to industry to select appropriate electronic or
automated systems for this purpose, and to ``layer'' different
controls, if desired, as long as at least one of the options listed in
paragraph (g) is used as one of the layers.
    However, FDA disagrees that additional nonautomated special
controls, in addition to dedicated lines or visual inspection, should
be added to paragraph (g). As we noted in the proposed rule (62 FR
40489 at 40491), nonautomated (i.e., manual) differentiation of size
and shape as a labeling control does not provide adequate protection
from labeling mixups when cut labeling is used. It is the increased
opportunity for human error afforded by the process of cutting,
sorting, and subsequent handling of different items of labeling that
has caused labeling mixups and recalls. One of the goals of this
rulemaking is to reduce the likelihood for such human error through the
increased use of automated labeling control systems and through the
elimination of manual label differentiation by size and shape. In
addition, in response to the commenter's concern that electronic
systems are not sufficiently reliable, we believe that development and
use of advanced code scanning equipment has made many current
electronic verification systems accurate and reliable. For example, all
prescription drug products (with limited exceptions), biological
products, and certain over-the-counter (OTC) drug products are now
required by 21 CFR 201.25 to bear on the label a bar code containing,
at a minimum, the drug's NDC (National Drug Code). Electronic systems
can use these codes to scan the labels as part of

the label controls. These and other advanced scanning techniques have
made current electronic systems reliable to the 100 percent standard.
    If cut labeling is used, the choice of one of the four special
control procedures listed above should allow manufacturers to document
a system of control that best fits the unique abilities of each
particular manufacturer without requiring any one particular control
system to be used. The final rule permits manufacturers considerable
latitude under Sec.  211.122(g)(1) through (g)(4) in establishing
control procedures over cut labeling, and is sufficiently flexible to
permit technological innovation in automated labeling inspection
systems. For example, under the final rule, a labeling control method
designed by an individual manufacturer could incorporate electronic or
electromechanical equipment or the use of a visual inspection to
conduct a 100 percent examination for correct labeling. Moreover,
manufacturers are free to use one of the specifically enumerated
special controls in Sec.  211.122(g) in combination with any other
special or general labeling controls. The rule merely establishes that,
at a minimum, one of the four enumerated special controls must be used
when the identified types of cut labeling are used. Accordingly, many
of the alternative special and general controls discussed by the
commenters could also be used in conjunction with one of the enumerated
special controls.
    The comments suggest that this rule will mandate that manufacturers
who currently have effective label control systems but are not
currently using one of the controls enumerated in Sec.  211.122(g)(1)
through (g)(4) must change their system to include one of the four
special controls. FDA points out that this would only be true for
situations where cut labeling is currently being used for those labels
subject to the enforcement discretion period (labels other than
immediate container labels) if the manufacturer is not currently
voluntarily using one of the enumerated special controls. Processes
using cut labeling for immediate containers labels (the bulk of the
labels covered by this change) were not subject to enforcement
discretion and would already be required to use one of the three
special controls in current Sec.  211.122(g)(1) through (g)(3). The
only change made by this rule for those labeling processes would be the
addition of a new option to meet the requirement of subsection (g).
Those lines would not be required to make any change by this final
rule.
    (Comment 2) One comment said that the controls for cut labeling
used for multiunit cartons containing immediate containers that are not
packaged in individual unit cartons (Sec.  211.122(g)) should not apply
to OTC drug product shelf-packs. The comment explained that OTC drug
products are sometimes packaged in what could be called multiunit
cartons containing immediate containers that are not packaged in
individual unit cartons. These are often called ``shelf-packs'' or
``trays.'' The comment gave the following examples: antacid tablets
packaged in individual rolls and placed in a tray near the checkout of
a drugstore or supermarket; bottles of sunscreen products displayed in
an end-unit in a store for convenience and added display space; and
analgesic powders in printed envelopes placed in a tray to keep them
upright on the store shelf. The comment noted that for these products
the immediate containers are not packaged in individual unit cartons.
However, complete labeling is on the individual packages, and neither
consumers nor health professionals rely on the information on the tray
or end-unit to purchase or use the product. The comment said that the
proposed rule could be interpreted to apply to OTC shelf-packs, trays,
or end units, but that special control procedures are not needed for
these products because their labeling is not relied on to purchase the
products. In addition, because the labeling on the shelf pack, tray, or
end unit itself does not accompany the product to its point of use, it
is not relied on by the consumer to use the product. Therefore, the
comment said, no significant additional protection to the public health
and safety would result from special control procedures for these
products. The comment recommended that proposed Sec.  211.122(g) be
revised to read: ``* * * multiunit cartons containing immediate
containers of prescription drugs that are not packaged in individual
unit cartons * * *.''
    (Response) FDA does not agree that the final rule should
specifically exclude OTC shelf-packs. First, FDA disagrees with the
assertion that consumers and health professionals do not rely on the
information on the tray or end-unit to purchase or use the product.
Although mislabeling of immediate containers poses the most obvious
threat to public health and safety, a considerable danger is also posed
by errors in the labeling that influences consumer selection of the
product at the time of purchase. Indeed, we believe that, in the
context of shelf-packs, these requirements are more important for OTC
drugs for which there is not necessarily a health care professional
involved to help ensure proper product selection. FDA does not agree
that the rule would significantly affect the use of shelf-packs because
shelf-packs rely on other packaging and labeling operations and
infrequently use cut labeling. To the extent that OTC shelf-packs do
use cut labeling, the special control procedures allow manufacturers
considerable latitude in establishing appropriate controls.
    (Comment 3) One comment said the rule should not apply to drug
products in preprinted immediate containers such as tubes, vials, cans,
bottles, pouches, and blister packages. The comment requested that the
final rule be revised to specifically exclude preprinted immediate
containers.
    (Response) FDA agrees that the rule does not apply to drug products
in preprinted immediate containers because the likelihood of labeling
mixups appears to be remote and because preprinted drug product
containers are still subject to existing general labeling controls to
prevent mixups. Preprinted immediate containers include tubes, vials,
cans, bottles, pouches, and blister packages where the labeling is
directly ``inked'' into the package. FDA does not agree that it is
necessary to amend Sec.  211.122 to expressly exclude drug products in
preprinted immediate containers because, as adopted in this final rule,
Sec.  211.122 does not apply to preprinted containers.
    (Comment 4) One comment requested that the rule be finalized only
as currently applied to immediate container labels in Sec.  211.122(g)
and not expanded to individual unit cartons or multiunit cartons
containing immediate containers that are not packaged in individual
unit cartons.
    (Response) As explained earlier in this preamble, the control
procedures specified in Sec.  211.122(g) apply to cut labeling used for
immediate container labels, individual unit cartons, or multiunit
cartons containing immediate containers that are not packaged in
individual unit cartons. This is intended to protect consumers from
labeling errors that are more likely to cause adverse health
consequences, while eliminating the regulatory burden of applying the
rule to labeling unlikely to reach or adversely affect consumers. The
immediate container label is most likely to be read by consumers. The
individual unit carton labeling is the outermost container in which a
drug product is commonly marketed at retail, and many consumers read
this labeling when deciding whether to purchase a

product. When using multiunit cartons containing immediate containers
that are not packaged in individual unit cartons (for example, sterile
dosage forms in tray packs in which immediate containers lack unit
cartons), consumers and health professionals are likely to rely both on
labeling on the outer multiunit container as well as the labeling on
the individual drug product immediate containers.
    (Comment 5) One comment questioned the use of the term ``gang-
printed materials'' in the following paragraph of the proposed rule:
``FDA notes, however, that nonautomated (i.e., manual) differentiation
of size and shape as a labeling control does not provide adequate
protection from labeling mixups. It is the increased opportunity for
human error afforded by the process of cutting, sorting, and subsequent
handling of different items of labeling from gang-printed materials
that has caused labeling mixups and recalls. One of the goals of this
proposed rulemaking is to reduce the likelihood for such human error
through the use of automated labeling control systems'' (62 FR 40489 at
40491 and 40492).
    The comment said that this paragraph appears to equate cut labeling
with gang-printing. The comment noted that gang-printing is prohibited
under Sec.  211.122(f): ``Use of gang-printed labeling for different
drug products, or different strengths or net contents of the same
product, is prohibited unless the labeling from gang-printed sheets is
adequately differentiated by size, shape, or color.'' In addition,
gang-printed labeling is defined in Sec.  210.3(b)(22) as ``labeling
derived from a sheet of material on which more than one item of
labeling is printed.'' The comment noted that the printing of
repetitions of the same item of labeling on the same sheet results in
cut labeling, as the individual repetitions of the item are cut from
the sheet for use. The comment said that this is not gang-printing and
does not present the same opportunity ``for human error afforded by the
process of cutting, sorting, and subsequent handling of different items
of labeling'' as does gang-printing, because the labeling is all
identical.
    (Response) FDA acknowledges that the distinction between ``gang-
printed labeling'' and ``cut labeling'' in the July 29, 1997, proposed
rule (62 FR 40490) may have caused confusion among some readers. Gang-
printed labeling, as explained earlier in this preamble, is defined in
Sec.  210.3(b)(22) (21 CFR 210.3(b)(22)) as labeling derived from a
sheet of material on which more than one item of labeling is printed.
For example, a sheet of material that contains labeling for different
strengths of a drug product is considered to be gang-printed. In
contrast, cut labeling, as described in the August 3, 1993, final rule
(58 FR at 41350), refers to items of labeling that have been detached
or ``cut'' from printed stock material. This stock material may or may
not be gang-printed; it may contain labeling for different drug
products or different strengths of the same drug product or it may
contain identical labeling for the same drug product. The printing
method of the stock material has no bearing on whether labeling is
considered to be cut labeling. The defining feature of cut labeling is
simply that it is ``cut.'' After being cut, such labeling is commonly
sorted by type or strength of drug product (if it is not identical),
placed into separate, corresponding stacks, and then transported to the
packaging and labeling lines for application to the appropriate
product. Cut labeling is problematic because the items, when cut and
placed into individual stacks for application to different drug
products, are easily mixed up. FDA found that stacks of labeling of
similar size, shape, and color could easily be intermixed and, if the
manufacturer did not detect the error, incorrect labeling could be
applied and a mislabeled drug product distributed.
    (Comment 6) One comment said that Sec.  211.122(g)(3) should be
revised to include the sentence: ``Such a 100 percent examination must
be conducted by one person and independently verified by a second
person.'' The comment said by omitting this phrase the public might be
led to the presumption that the ``verification by a second person'' is
no longer required.
    (Response) FDA notes that it did not propose to amend Sec.
211.122(g)(3), nor is that section being amended by this final rule.
Moreover, because the first sentence of Sec.  211.122(g)(3) already
states that ``a 100-percent examination'' for correct labeling is
required, repeating the phrase ``100-percent'' in the second sentence
of paragraph (3), as proposed by the commenter, would be redundant.
Therefore, the final rule does not adopt the change suggested by the
commenter.
    (Comment 7) One comment said that the proposed compliance date of 6
months after publication of the final rule should be extended to 1 year
to adequately implement any new controls.
    (Response) As requested by the comment, we are providing an
effective date of 1 year from the date of publication of this final
rule as it applies to labels that had not previously been covered by
this regulation. The application of Sec.  211.122(g) to labeling other
than labeling used for immediate container labels has been stayed since
August 3, 1994. Although it lifts the stay, the final rule also narrows
the applicability of Sec.  211.122(g) so that, in addition to immediate
container labeling, the only other labeling that is subject to final
Sec.  211.122(g) is cut labeling used for individual unit cartons, or
multiunit cartons containing immediate containers that are not packaged
in individual unit cartons. We believe 1 year will be sufficient to
permit companies to adopt an appropriate control from Sec.
211.122(g)(1) through (g)(4) for those limited additional categories of
cut labeling.
    The shorter implementation period applicable to cut labeling used
for immediate container labels (which make up the majority of cut
labeling used) reflects the fact that sections 211.122(g)(1) through
(g)(3) as they apply to such labels have been effective since August 3,
1994. As to those labels, this final rule merely adds an additional
control option for the appropriate use of cut labeling (i.e., Sec.
211.122(g)(4)). Accordingly, as to those labels, we are making this
rule effective 30 days after its publication in the Federal Register.
If they wish, labelers may continue to use one of the appropriate
controls listed in Sec.  211.122(g)(1) through (g)(3) that have been
applicable to those labels since 1994. Adoption of the additional
control option in Sec.  211.122(g)(4) added by this final rule is
purely voluntary but, since the regulation provides an alternative
method of compliance, there is no reason to delay its applicability
beyond the statutory 30-day period.

IV. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L.
104-4). Executive Orders 12866 and 13563 direct Agencies to assess all
costs and benefits of available regulatory alternatives and, when
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety, and other advantages; distributive impacts; and
equity). The Agency believes that this final rule is not a significant
regulatory action under Executive Order 12866.
    The Regulatory Flexibility Act requires Agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because this rule reduces the scope of the 1993
final rule and

provides manufacturers greater flexibility to meet regulatory
requirements, the Agency certifies that the final rule will not have a
significant economic impact on a substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that Agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $136 million, using the most current (2010) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
final rule to result in any 1-year expenditure that would meet or
exceed this amount.
    The purpose of this final rule is to protect consumers from those
labeling errors that are more likely to cause adverse health
consequences, while eliminating the regulatory burden of applying the
rule to labeling unlikely to reach or adversely affect consumers. This
rule amends the 1993 final rule by limiting the scope to cut labeling
for immediate container labels, individual unit cartons, and multiunit
cartons containing immediate containers that are not packaged in
individual unit cartons. This rule also increases flexibility for firms
selecting special labeling control procedures by adding a provision for
the use of any automated technique, including differentiation by size
and shape, that physically prevents incorrect labeling from being
processed by labeling and packaging equipment. Therefore, this rule is
expected to have a positive economic impact on drug manufacturers that
would otherwise be subject to the more stringent requirements under
current regulations.

V. Paperwork Reduction Act of 1995

    This final rule contains no collections of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.

VI. Environmental Impact

    The Agency has determined under 21 CFR 25.30(h) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.

List of Subjects in 21 CFR Part 211

    Drugs, Labeling, Laboratories, Packaging and containers,
Prescription drugs, Reporting and recordkeeping requirements,
Warehouses.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
211 is amended as follows:

PART 211--CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED
PHARMACEUTICALS

0
1. The authority citation for 21 CFR part 211 continues to read as
follows:

    Authority: 21 U.S.C. 321, 351, 352, 355, 360b, 371, 374; 42
U.S.C. 216, 262, 263a, 264.

0
2. Section 211.122 is amended by revising the introductory text of
paragraph (g) and by adding paragraph (g)(4) to read as follows:

Sec.  211.122  Materials examination and usage criteria.

* * * * *
    (g) If cut labeling is used for immediate container labels,
individual unit cartons, or multiunit cartons containing immediate
containers that are not packaged in individual unit cartons, packaging
and labeling operations shall include one of the following special
control procedures:
* * * * *
    (4) Use of any automated technique, including differentiation by
labeling size and shape, that physically prevents incorrect labeling
from being processed by labeling and packaging equipment.
* * * * *

    Dated: March 13, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-6502 Filed 3-19-12; 8:45 am]
BILLING CODE 4160-01-P


[Federal Register Volume 82, Number 141 (Tuesday, July 25, 2017)]
[Notices]
[Page 34518]
[FR Doc No: 2017-15549]

-----------------------------------------------------------------------

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings #2

    Take notice that the Commission received the following electric
rate filings:

    Docket Numbers: ER17-1167-002.
    Applicants: New York Independent System Operator, Inc.
    Description: Compliance filing: Compliance Effective Date Notice
for BoP TCC Auctions to be effective 8/1/2017.
    Filed Date: 7/18/17.
    Accession Number: 20170718-5114.
    Comments Due: 5 p.m. ET 8/8/17.

    Docket Numbers: ER17-2107-000.
    Applicants: Southwestern Public Service Company.
    Description: Sec.  205(d) Rate Filing: SPS-GSEC-SPEC-IA-T-L-
Milwaukee-684-0.0.0 to be effective 9/18/2017.
    Filed Date: 7/19/17.
    Accession Number: 20170719-5053.
    Comments Due: 5 p.m. ET 8/9/17.

    Docket Numbers: ER17-2108-000.
    Applicants: New York Independent System Operator, Inc.
    Description: Sec.  205(d) Rate Filing: NYISO 205 filing re: Remove
Bond Funds from Cash Collateral Investment Options to be effective 9/
18/2017.
    Filed Date: 7/19/17.
    Accession Number: 20170719-5078.
    Comments Due: 5 p.m. ET 8/9/17.

    Docket Numbers: ER17-2109-000.
    Applicants: PJM Interconnection, L.L.C., Old Dominion Electric
Cooperative.
    Description: Sec.  205(d) Rate Filing: Third Revised Service
Agreement No. 3746--NITSA among PJM and ODEC to be effective 7/1/2017.
    Filed Date: 7/19/17.
    Accession Number: 20170719-5091.
    Comments Due: 5 p.m. ET 8/9/17.

    Docket Numbers: ER17-2110-000.
    Applicants: ISO New England Inc.
    Description: Permanent De-List Bids and Retirement De-List Bids
Submitted for 2021-22 Forward Capacity of ISO New England Inc.
    Filed Date: 7/19/17.
    Accession Number: 20170719-5102.
    Comments Due: 5 p.m. ET 8/9/17.

    Docket Numbers: ER17-2111-000.
    Applicants: Otter Tail Power Company.
    Description: Sec.  205(d) Rate Filing: Amendment and Restatement of
Otter Tail Rate Schedule No. 110 to be effective 7/30/2010.
    Filed Date: 7/19/17.
    Accession Number: 20170719-5108.
    Comments Due: 5 p.m. ET 8/9/17.

    The filings are accessible in the Commission's eLibrary system by
clicking on the links or querying the docket number.
    Any person desiring to intervene or protest in any of the above
proceedings must file in accordance with Rules 211 and 214 of the
Commission's Regulations (18 CFR 385.211 and 385.214) on or before 5:00
p.m. Eastern time on the specified comment date. Protests may be
considered, but intervention is necessary to become a party to the
proceeding.
    eFiling is encouraged. More detailed information relating to filing
requirements, interventions, protests, service, and qualifying
facilities filings can be found at: http://www.ferc.gov/docs-filing/efiling/filing-req.pdf. For other information, call<PHONE_NUMBER>
(toll free). For TTY, call<PHONE_NUMBER>.

    Dated: July 19, 2017.
Kimberly D. Bose,
Secretary.
[FR Doc. 2017-15549 Filed 7-24-17; 8:45 am]
 BILLING CODE 6717-01-P


[Federal Register Volume 79, Number 212 (Monday, November 3, 2014)]
[Notices]
[Pages 65270-65271]
[FR Doc No: 2014-26005]

-----------------------------------------------------------------------

SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-73444; File No. SR-ICC-2014-18]

Self-Regulatory Organizations; ICE Clear Credit LLC; Notice of
Filing of Proposed Rule Change To Revise the ICC Risk Management
Framework

October 28, 2014.
    Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934
(``Act'') \1\ and Rule 19b-4 thereunder \2\ notice is hereby given that
on October 22, 2014, ICE Clear Credit LLC (``ICC'') filed with the
Securities and Exchange Commission (``Commission'') the proposed rule
change as described in Items I, II, and III below, which Items have
been prepared primarily by ICC. The Commission is publishing this
notice to solicit comments on the proposed rule change from interested
persons.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
---------------------------------------------------------------------------

I. Self-Regulatory Organization's Statement of the Terms of Substance
of the Proposed Rule Change

    The principal purpose of the proposed rule change is to revise the
ICC Risk Management Framework to incorporate certain risk model
enhancements. These revisions do not require any changes to the ICC
Clearing Rules (``Rules'').

II. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

    In its filing with the Commission, ICC included statements
concerning the purpose of and basis for the proposed rule change and
discussed any comments it received on the proposed rule change. The
text of these statements may be examined at the places specified in
Item IV below. ICC has prepared summaries, set forth in sections A, B,
and C below, of the most significant aspects of these statements.

A. Self-Regulatory Organization's Statement of the Purpose of, and
Statutory Basis for, the Proposed Rule Change

    ICC proposes revising the ICC Risk Management Framework to
incorporate risk model enhancements related to anti-procyclicality,
devolatilization, liquidity charges, and concentration charges. ICC
believes such revisions will facilitate the prompt and accurate
clearance and settlement of securities transactions and derivative
agreements, contracts, and transactions for which it is responsible.
The proposed revisions are described in detail as follows.
    ICC proposes revising the ICC Risk Management Framework to
facilitate compliance with requirements under the European Market
Infrastructure Regulations, specifically anti-procyclicality conditions
described in Article 28 of the Regulatory Technical Standards.\3\
Currently, ICC considers three levels of volatility in its Risk
Management Framework to account for stable but prudent margin
requirements. ICC proposes adding a fourth volatility scale that
assigns a 25% weight to a stress period (currently the stress period is
set to January 14, 2008 to December 31, 2008) and the remaining 75% to
the immediate most recent 250 observations, consistent with Article
28(b) of the Regulatory Technical Standards. The revised initial margin
requirements are expected to result in more conservative initial margin
figures for some risk factors. In addition, ICC proposes introducing
devolatilization enhancements to describe spread log-return time series
that span market periods associated with different volatility regimes.
---------------------------------------------------------------------------

    \3\ Commission Delegated Regulation (EU) No. 153/2013 of 19
December 2012 Supplementing Regulation (EU) No. 648/2012 of the
European Parliament and of the Council with regard to Regulatory
Technical Standards on Requirements for Central Counterparties (the
``Regulatory Technical Standards'').
---------------------------------------------------------------------------

    Additionally, ICC proposes a revised approach to computing index
liquidity charges. The enhancement consists of reducing the portfolio
liquidity benefits across different index series. As part of its
product offering, ICC clears credit default swap (``CDS'') index
series. A new series of CDS indices is issued every six months, and the
new series is referred to as being ``on-the-run,'' while previous
series is referred to as being ``off-the-run.'' The revised calculation
establishes series-specific liquidity charges by considering the
series-specific positions and establishing series-specific position
directionality based on the corresponding 5-year equivalent notional
amount directionality. Further, to capture the market behavior around
index rolls when the bid/offer width for index-roll transactions (i.e.,
trading the on-the-run vs. first off-the-run indices) is typically
smaller than the bid/offer width of each individual leg, ICC proposes
implementing time-dependent long/short liquidity charge portfolio
benefits for the on-the-run and the first off-the run series. The
proposed revisions to the liquidity charges are expected to result in
more conservative requirements than the ones associated with the
current approach.
    ICC also proposes enhancements to the calculation of its
concentration charges by introducing index series-specific
concentration charges. The revised calculation establishes series-
specific concentration charges for positions exceeding series-specific
concentration threshold limits based on the direction of the 5-year
equivalent notional amount or the net notional amount. Under the
revised calculation, ICC will estimate series-specific concentration
charge threshold limits based on the distribution of series-specific
open interest information at the Clearing House. The estimated series-
specific concentration charge threshold limits reflect the average open
interest over a 5-day period. The proposed revisions to the
concentration charge are expected to result in more conservative
requirements than the ones associated with the current approach.
    Section 17A(b)(3)(F) of the Act \4\ requires, among other things,
that the rules of a clearing agency be designed to promote the prompt
and accurate clearance and settlement of securities transactions, and
to the extent applicable, derivative agreements, contracts and
transactions and to comply with the provisions of the Act and the rules
and regulations thereunder. ICC believes that the proposed rule changes
are consistent with the requirements of the Act and the rules and
regulations thereunder applicable to ICC, in particular, to Section
17(A)(b)(3)(F),\5\ because ICC believes that the proposed rule changes
will promote the prompt and accurate clearance and settlement of
securities transactions, derivatives agreements, contracts, and
transactions, as the proposed risk model revisions enhance risk
policies and are expected to impose more conservative initial margin
requirements, which would enhance the financial resources available to
ICC and thereby facilitate its ability to promptly and accurately clear
and settle its

cleared CDS contracts. In addition, the proposed revisions are
consistent with the relevant requirements of Rule 17Ad-22. In
particular, the amendments to the Risk Management Framework will
enhance the financial resources available to the Clearing House by
imposing a more conservative initial margin requirement, and are
therefore reasonably designed to meet the margin and financial resource
requirements of Rule 17Ad-22(b)(2-3). As such, the proposed rule
changes are designed to promote the prompt and accurate clearance and
settlement of securities transactions, derivatives agreements,
contracts, and transactions within the meaning of Section 17A(b)(3)(F)
\6\ of the Act.
---------------------------------------------------------------------------

    \4\ 15 U.S.C. 78q-1(b)(3)(F).
    \5\ Id.
    \6\ Id.
---------------------------------------------------------------------------

B. Self-Regulatory Organization's Statement on Burden on Competition

    ICC does not believe the proposed rule changes would have any
impact, or impose any burden, on competition. The risk model
enhancements apply uniformly across all market participants. Therefore,
ICC does not believe the proposed rule changes impose any burden on
competition that is inappropriate in furtherance of the purposes of the
Act.

C. Self-Regulatory Organization's Statement on Comments on the Proposed
Rule Change Received From Members, Participants or Others

    Written comments relating to the proposed rule change have not been
solicited or received. ICC will notify the Commission of any written
comments received by ICC.

III. Date of Effectiveness of the Proposed Rule Change and Timing for
Commission Action

    Within 45 days of the date of publication of this notice in the
Federal Register or within such longer period up to 90 days (i) as the
Commission may designate if it finds such longer period to be
appropriate and publishes its reasons for so finding or (ii) as to
which the self-regulatory organization consents, the Commission will:
    (A) By order approve or disapprove such proposed rule change, or
    (B) institute proceedings to determine whether the proposed rule
change should be disapproved.

IV. Solicitation of Comments

    Interested persons are invited to submit written data, views, and
arguments concerning the foregoing, including whether the proposed rule
change is consistent with the Act. Comments may be submitted by any of
the following methods:

Electronic Comments

     Use the Commission's Internet comment form (http://www.sec.gov/rules/sro.shtml); or
     Send an email to<EMAIL_ADDRESS>Please include
File Number SR-ICC-2014-18 on the subject line.

Paper Comments

     Send paper comments in triplicate to Secretary, Securities
and Exchange Commission, 100 F Street NE., Washington, DC 20549-1090.

All submissions should refer to File Number SR-ICC-2014-18. This file
number should be included on the subject line if email is used. To help
the Commission process and review your comments more efficiently,
please use only one method. The Commission will post all comments on
the Commission's Internet Web site (http://www.sec.gov/rules/sro.shtml). Copies of the submission, all subsequent amendments, all
written statements with respect to the proposed rule change that are
filed with the Commission, and all written communications relating to
the proposed rule change between the Commission and any person, other
than those that may be withheld from the public in accordance with the
provisions of 5 U.S.C. 552, will be available for Web site viewing and
printing in the Commission's Public Reference Room, 100 F Street NE.,
Washington, DC 20549, on official business days between the hours of
10:00 a.m. and 3:00 p.m. Copies of such filings will also be available
for inspection and copying at the principal office of ICE Clear Credit
and on ICE Clear Credit's Web site at https://www.theice.com/clear-credit/regulation.
    All comments received will be posted without change; the Commission
does not edit personal identifying information from submissions. You
should submit only information that you wish to make available
publicly. All submissions should refer to File Number SR-ICC-2014-18
and should be submitted on or before November 24, 2014.

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\7\
---------------------------------------------------------------------------

    \7\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

Kevin M. O'Neill,
Deputy Secretary.
[FR Doc. 2014-26005 Filed 10-31-14; 8:45 am]
BILLING CODE 8011-01-P