[Federal Register Volume 83, Number 192 (Wednesday, October 3, 2018)]
[Notices]
[Pages 49960-49962]
[FR Doc No: 2018-21486]

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

SECURITIES AND EXCHANGE COMMISSION

[Release No. 34-84299; File No. SR-CboeEDGX-2018-035]

Self-Regulatory Organizations; Cboe EDGX Exchange, Inc.; Order
Approving a Proposed Rule Change, as Modified by Amendment Nos. 1 and
3, To Permit the Listing and Trading of Options That Overlie the Mini-
SPX Index and the Russell 2000 Index

September 27, 2018.

I. Introduction

    On August 10, 2018, Cboe EDGX Exchange, Inc. (``Exchange'') filed
with the Securities and Exchange Commission (``Commission'' or
``SEC''), pursuant to Section 19(b)(1) of the Securities Exchange Act
of 1934 (``Act'') \1\ and Rule 19b-4 thereunder,\2\ a proposed rule
change to permit the listing and trading of options that overlie the
Mini-SPX Index (``XSP options''), the Russell 2000 Index (``RUT
options''), and the Dow Jones Industrial Average (``DJX options''). The
proposed rule change was published for comment in the Federal Register
on August 21, 2018.\3\ The Commission received no comments in response
to the Notice. On September 18, 2018, the Exchange filed Amendment No.
1 to the proposal.\4\ On September 25, 2018, the Exchange filed
Amendment No. 3 to the proposal.\5\ This order approves the proposed
rule change, as modified by Amendment Nos. 1 and 3 thereto.
---------------------------------------------------------------------------

    \1\ 15 U.S.C. 78s(b)(1).
    \2\ 17 CFR 240.19b-4.
    \3\ See Securities Exchange Act Release No. 83853 (August 15,
2018), 83 FR 42344 (``Notice'').
    \4\ Amendment No. 1 provides that the lowest strike price
interval that may be listed for XSP option series under the Short
Term Option Series Program is $0.50. The Exchange notes that this
provision was inadvertently omitted in the initial filing. Amendment
No. 1 is available at https://www.sec.gov/comments/sr-cboeedgx-2018-035/srcboeedgx2018035-4388446-175573.pdf. Because Amendment No. 1
does not materially alter the substance of the proposed rule change
or raise unique or novel regulatory issues, Amendment No. 1 is not
subject to notice and comment.
    \5\ The Exchange filed Amendment No. 2 to the proposal on
September 24, 2018. On September 25, 2018, the Exchange withdrew
Amendment No. 2 and replaced it with Amendment No. 3. Amendment No.
3 removes all aspects of the proposal related to the listing and
trading of DJX options. Amendment No. 3 is available at https://www.sec.gov/comments/sr-cboeedgx-2018-035/srcboeedgx2018035-4423273-175678.pdf. Because Amendment No. 3 removes all references specific
to the listing and trading of DJX options from the original proposal
and does not raise unique or novel regulatory issues, Amendment No.
3 is not subject to notice and comment.
---------------------------------------------------------------------------

II. Description of the Amended Proposal 6
---------------------------------------------------------------------------

    \6\ For a more complete description of the proposed rule change,
see Notice, supra note 3; Amendment No. 1, supra note 4; and
Amendment No. 3, supra note 5.
---------------------------------------------------------------------------

    The Exchange proposes to amend the Exchange's index options rules
to permit the listing and trading of XSP options and RUT options. As
more fully set forth in the Notice and Amendment Nos. 1 and 3 and
further described below, the proposed new rules and changes to existing
rules of the Exchange are based on the existing rules of other options
exchanges.\7\
---------------------------------------------------------------------------

    \7\ See, e.g., Cboe Options Rules 6.42, 24.7, and 24.9; C2 Rule
6.11(a)(2).
---------------------------------------------------------------------------

    XSP and RUT options will be A.M., cash-settled contracts with
European-style exercise.\8\ XSP options are options on the Mini-SPX
Index, the current value of which is 1/10th the value of the Standard &
Poor's 500 Stock Index reported by the reporting authority.\9\ RUT
options are options on the Russell 2000 Index.\10\ According to the
Exchange, the index underlying each of XSP and RUT options satisfies
the criteria of a broad-based index for the initial listing of options
on that index, as set forth in Rule 29.3(b). XSP and RUT options will
be subject to the maintenance listing standards set forth in Rule
29.3(c).\11\
---------------------------------------------------------------------------

    \8\ See proposed changes to Rule 29.11(a)(4) and Rule
29.11(a)(5)(B).
    \9\ See proposed Interpretation and Policy .01 to Rule 29.11,
which states that the current index value of XSP options will be 1/
10th the value of the Standard & Poor's 500 Stock Index reported by
the reporting authority. The Exchange states that the S&P Dow Jones
Indices is the reporting authority for the Mini-SPX Index. See
proposed Interpretation and Policy .01 to Rule 29.2.
    \10\ The Exchange states that the Frank Russell Company is the
reporting authority for the Russell 2000 Index. See proposed
Interpretation and Policy .01 to Rule 29.2.
    \11\ In the event XSP or RUT options fails to satisfy the
maintenance listing standards set forth in Rule 29.3(c), the
Exchange states that it will not open for trading any additional
series of options of that class unless the continued listing of that
class of index options has been approved by the Commission under
Section 19(b)(2) of the Act. See Notice, supra note 3, at 42345, n.
4.
---------------------------------------------------------------------------

    As described more fully in the Notice and Amendment Nos. 1 and 3,
the Exchange has proposed rules related to the listing and trading of
XSP and RUT, including the minimum increments applicable to XSP \12\
and strike intervals applicable to both XSP and RUT.\13\ In addition,
the Exchange has proposed changes to its long-term index options

rules, including proposing to extend the maximum term to 180 months (15
years) \14\ and adding RUT to the list of indices on which the Exchange
may list reduced-value long-term options series.\15\ The proposed rule
change also modifies the Exchange's rules to describe the opening
process for index options,\16\ which the Exchange states will be the
same as the opening process for index options on C2 Exchange, Inc.
(``C2'').\17\ The Exchange also proposed rule changes to clarify the
applicability of certain provisions of its rules.\18\ Additionally, the
Exchange has proposed changes to its rules relating to trading
halts,\19\ the obvious error process,\20\ and listing additional
expiration months \21\ that are consistent with the rules of another
options exchange.\22\
---------------------------------------------------------------------------

    \12\ See proposed Rule 21.5, Interpretation and Policy .02. The
minimum increment for RUT will be as set forth in current Rule 21.5:
Five cents if the series is trading below $3.00, and ten cents if
the series is trading at or above $3.00. See Notice, supra note 3,
at 42345.
    \13\ See proposed changes to Rule 29.11(c)(1) and (c)(5).
    \14\ See proposed change to Rule 29.11(b)(1). The Exchange
represents that it has confirmed with the Options Clearing
Corporation (``OCC'') that OCC can configure its systems to support
long-term options contracts that have a maximum term of 180 months
(15 years). See Notice, supra note 3, at 42346.
    \15\ See proposed change to Rule 29.11(b)(2). The Exchange
represents that the reduced-value long-term RUT series will be
subject to the same trading rules as long-term RUT series, except
the minimum strike price interval will be $2.50 for all series
regardless of the strike price. See Notice, supra note 3, at 42346.
The Exchange also states that for reduced-value long-term RUT
series, the underlying value will be computed at 10% of the value of
the Russell 2000 Index. See id.
    \16\ See proposed changes to Rule 21.7.
    \17\ See Notice, supra note 3, at 42348.
    \18\ See proposed changes to Rules 29.11(b)(1)(A), 29.13(b);
proposed Rule 29.15.
    \19\ See proposed changes to Rule 29.10(b).
    \20\ See proposed changes to Rule 20.6(g) and (h).
    \21\ See proposed Rule 29.11(i).
    \22\ See Cboe Options Rule 6.42, Interpretation and Policy .03;
Cboe Options Rule 6.25(g) and (h); and Cboe Options Rule 24.9,
Interpretation and Policy .01(b).
---------------------------------------------------------------------------

    The Exchange represents it has an adequate surveillance program in
place for index options, and that it is a member of the Intermarket
Surveillance Group (``ISG'').\23\ Additionally, the Exchange represents
that has analyzed its capacity and believes that it and the Options
Price Reporting Authority (``OPRA'') have the necessary systems
capacity to handle the additional traffic associated with the listing
of XSP and RUT options up to the proposed number of possible
expirations and strike prices.\24\ The Exchange believes that any
additional traffic that would be generated from the introduction of XSP
and RUT options will be manageable, and that its Members will not have
a capacity issue as a result of this proposed rule change.\25\ The
Exchange also represents that it does not believe this expansion will
cause fragmentation of liquidity.\26\ The Exchange states that it will
monitor the trading volume associated with the additional options
series listed as a result of this proposed rule change and the effect
(if any) of these additional series on market fragmentation and on the
capacity of the Exchange's automated systems.\27\
---------------------------------------------------------------------------

    \23\ See Notice, supra note 3, at 42349-50.
    \24\ Id. at 42350.
    \25\ Id.
    \26\ Id.
    \27\ Id.
---------------------------------------------------------------------------

    The Exchange states that XSP and RUT options will be subject to the
margin requirements set forth in Chapter 28 and the position limits set
forth in Rule 29.5. Chapter 28 imposes the margin requirements of
either Cboe Options or the New York Stock Exchange on Exchange Options
Members. Similarly, Rule 29.5 imposes position (and exercise) limits
for broad-based index options of Cboe Options on Exchange Options
Members. XSP and RUT options are currently listed and traded on Cboe
Options, and the Exchange proposes that the same margin requirements
and position and exercise limits that apply to these products as traded
on Cboe Options will apply to these products when listed and traded on
the Exchange.\28\
---------------------------------------------------------------------------

    \28\ Id.
---------------------------------------------------------------------------

III. Discussion and Commission's Findings

    The Commission finds that the proposed rule change is consistent
with the requirements of the Act and the rules and regulations
thereunder applicable to a national securities exchange.\29\
Specifically, the Commission finds that the proposal is consistent with
Section 6(b)(5) of the Act,\30\ which requires, among other things,
that the rules of a national securities exchange be designed to promote
just and equitable principles of trade, to remove impediments to and
perfect the mechanism of a free and open market and a national market
system, and, in general, to protect investors and the public interest.
---------------------------------------------------------------------------

    \29\ In approving this proposed rule change, the Commission has
considered the proposed rule's impact on efficiency, competition,
and capital formation. See 15 U.S.C. 78c(f).
    \30\ 15 U.S.C. 78f(b).
---------------------------------------------------------------------------

    The Commission believes that the Exchange's proposal gives options
investors the ability to make an additional investment choice in a
manner consistent with the requirements of Section 6(b)(5) of the
Act.\31\ The Commission notes that the Exchange represents that the
index underlying each of XSP and RUT options satisfies the criteria of
a broad-based index for the initial listing of options on that index in
Rule 29.3(b), which rule has previously been approved by the
Commission.\32\ In considering the proposed changes to the Exchange
rules related to the listing and trading of XSP and RUT, including the
rules related to minimum increments \33\ and strike price
intervals,\34\ the Commission notes that the proposed rules are
consistent with the rules of another exchange.\35\ In addition, the
Commission notes that the proposed rule changes related to long-term
options series,\36\ trading halts,\37\ the obvious error process,\38\
the opening process \39\ and listing additional expiration months \40\
are also consistent with the rules of other exchanges.\41\ The
Commission believes that the Exchange's proposal does not raise any
novel regulatory issues, as it is consistent with the rules of other
national securities exchanges previously approved by the Commission.
Finally, the Commission notes that certain of the Exchange's proposed
rule changes are intended to promote clarity about the applicability of
the Exchange's rules,\42\ thereby reducing any potential investor
confusion.
---------------------------------------------------------------------------

    \31\ 15 U.S.C. 78f(b)(5).
    \32\ See Securities Exchange Act Release No. 75650 (August 7,
2015), 80 FR 48600 (August 13, 2015). Additionally, the Commission
notes that options on XSP and RUT will be subject to the maintenance
listing standards of Rule 29.3(c). The Exchange represents that in
the event XSP or RUT options fails to satisfy the maintenance
listing standards set forth herein, the Exchange will not open for
trading any additional series of options of that class unless the
continued listing of that class of index options has been approved
by the Commission under Section 19(b)(2) of the Exchange Act. See
Notice, supra note 3, at 42345, n. 4.
    \33\ See proposed Rule 21.5, Interpretation and Policy .02.
    \34\ See proposed Rule 29.11(c)(1) and (c)(5).
    \35\ See Cboe Options Rule 6.42, Interpretation and Policy .03;
Cboe Options Rule 24.9. Interpretations and Policies .01(a), .11.
    \36\ See proposed changes to Rule 29.11(b).
    \37\ See proposed changes to Rule 29.10(b).
    \38\ See proposed changes to Rule 20.6(g) and (h).
    \39\ See proposed changes to Rule 21.7.
    \40\ See proposed Rule 29.11(i).
    \41\ See, e.g., Cboe Options Rule 24.9(b)(1); Cboe Options Rule
24.9, Interpretation and Policy .13; Cboe Options Rule 24,7(a); Phlx
Rule 1047A(c); Cboe Options Rule 6.25(g) and (h); C2 Rule
6.11(a)(2).
    \42\ See, e.g., proposed changes to Rule 29.11(b)(1)(A); Rule
29.13; Rule 29.15.
---------------------------------------------------------------------------

    The Commission further believes that the Exchange's proposed
position and exercise limits, margin requirements and other aspects of
the proposed rule change related to the listing and trading of XSP and
RUT options are appropriate and consistent with the Act. In particular,
the Commission notes that the Exchange rules regarding position and
exercise limits and margin requirements incorporate by reference the
corresponding Cboe Options rules

which were previously approved by the Commission. The Commission notes
that the Exchange represents that it has an adequate surveillance
program in place for index options.\43\ Further, the Exchange is a
member of the ISG, which provides for the sharing of information and
the coordination of regulatory efforts among exchanges trading
securities and related products to address potential intermarket
manipulations and trading abuses.
---------------------------------------------------------------------------

    \43\ See Notice, supra note 3, at 42349-50.
---------------------------------------------------------------------------

    In approving the proposed rule change, the Commission has also
relied upon the Exchange's representation that it and OPRA have the
necessary systems capacity to support the new options series that will
result from this proposal, and that the Exchange will monitor the
trading volume associated with the additional options series listed as
a result of this proposed rule change and the effect (if any) of these
additional series on market fragmentation and on the capacity of the
Exchange's automated systems.\44\
---------------------------------------------------------------------------

    \44\ See id. at 42350.
---------------------------------------------------------------------------

IV. Conclusion

    It is therefore ordered, pursuant to Section 19(b)(2) of the
Act,\45\ that the proposed rule change (SR-CboeEDGX-2018-035), as
modified by Amendment Nos. 1 and 3, be approved.
---------------------------------------------------------------------------

    \45\ 15 U.S.C. 78s(b)(2).

    For the Commission, by the Division of Trading and Markets,
pursuant to delegated authority.\46\
---------------------------------------------------------------------------

    \46\ 17 CFR 200.30-3(a)(12).
---------------------------------------------------------------------------

Eduardo A. Aleman,
Assistant Secretary.
[FR Doc. 2018-21486 Filed 10-2-18; 8:45 am]
 BILLING CODE 8011-01-P


Note to FDA Reviewers:  Document and assess the testing that is performed on
each cell bank.  Determine if the most relevant and critical testing for the
particular gene therapy product has been performed.  Appropriate tests should be
performed depending on the species of origin used to derive the cell bank.
1)
Master Cell Bank (MCB)/Packaging Cell Line
2
You should include in the IND information regarding MCB history, source,
derivation and characterization, including testing to adequately establish the
safety, identity, purity, and stability of the cells.  This section will likely
address:
x
Product microbiologic characteristics, including sterility, mycoplasma, in
vivo and in vitro testing for adventitious viral agents, as appropriate (see
Section IV below);
x
Freedom from the presence of specific pathogens, including, for human
1
If a feeder cell line of animal origin is used to propagate human cells (i.e., human and non-human animal cells are
co-cultivated), the final product falls within the definition of a xenotransplantation product (see both Refs. 9 and
10).
2
If an ecotropic cell line was used during the generation of a retroviral producer cell line, we recommend that
sponsors test for ecotropic retrovirus (see “Product testing”). Reviewers would assess and document the testing that
was performed.
7

Contains Nonbinding Recommendations
cells, testing for CMV, HIV-1 & 2, HTLV-1 & 2, EBV, B19, HBV, and
HCV, as appropriate.  For cell lines that are exposed to bovine or porcine
components (e.g., serum, serum components, trypsin), appropriate testing
would include testing for bovine and/or porcine adventitious agents.  See
further discussion of bovine components and reagents in Section III.A.2.a;
x
Identity of the cells, including tests to distinguish the specified cells
through physical or chemical characteristics of the cell line (i.e.,
phenotype, genotype, or other markers);
x
Purity of banked cells, including identification and quantification of any
contaminating cells;
x
Testing for activity of cells (e.g., activated lymphocytes, dopamine
secretion, insulin secretion) and cell maturation (e.g., dendritic cells).
This should be performed if activity is relevant to the therapeutic nature of
the product;
x
End of production cells (EOP).  This should be tested on a one time basis
to assess genetic stability of the MCB/packaging cell line; and
x
Processes critical to product safety, as applicable, including:
o
Culture conditions used, including documentation of all media, and
reagents/components used during production, with copies of
relevant certificates of analysis (COA);
o
Method of introduction of vector (transfection, transduction,
infection) into MCB/parental cells to establish vector producer
cell;
o
Analysis and selection of producer cell clone; and
o
Cryopreservation, storage, and recovery of the MCB, including
information pertaining to cell density, number of vials frozen,
storage temperature, and cell bank location; and
o
Genetic and phenotypic stability of the MCB after multiple
passages as well as viability of cells after cryopreservation.  We
recommend that, while the IND is in effect, you perform a stability
assessment EOP as a one-time test.  This testing is usually
performed later in product development and would be included as
part of the biologics license application (BLA).
2)
Master Viral Bank (MVB)
You should provide a description of the MVB and the testing that you have
performed to ensure safety, purity, and identity.  We recommend that you
address:
x
History and derivation of the MVB;
x
Culture conditions used during tissue culture scale up;
x
Testing of media and other reagents used during production, including
COAs;
8

Contains Nonbinding Recommendations
x
Product microbiologic characterization – including sterility, mycoplasma,
in vivo and in vitro testing for adventitious viral agents, as appropriate;
x
Freedom from the presence of specific pathogens, such as human viruses
if the cell line is of human origin, or pathogens specific to the origin of the
production cell line (e.g., murine, non-human primate,;
x
Tests to identify presence of replication competent virus;
x
Identity testing to establish the presence of gene therapy vector and
therapeutic transgene (e.g., Southern blot); and
x
Information pertaining to the cryopreservation of the MVB, including
condition and storage location(s).
3)
Working Cell Bank (WCB)/Working Viral Bank (WVB)
The WCB/WVB may have been derived from one or more vials of the
MCB/MVB.  As discussed in the guidance documents referenced in III.A2a,
the amount of information needed to document characterization of the
WCB/WVB (derived from the MCB, and MVB, respectively) is usually less
extensive than that needed to document characterization of the MCB/MVB.  If
there is a two tiered cell bank system in place (MCB, MVB), we recommend
that you test the WCB/WVB for:
x
In vitro adventitious viral agent testing;
x
Replication competent virus;
x
Bacterial and fungal sterility;
x
Mycoplasma; and
x
Limited identity testing (e.g., Southern blot, flow cytometry).
3. Reagents
You must list in your IND any reagents used in manufacturing the product (21 CFR
312.23(a)(7)(iv)(b)).  For the purpose of this guidance, reagents are those materials
that are used for cellular growth, differentiation, selection, purification, or other
critical manufacturing steps but are not intended to be part of the final product.
Examples include fetal bovine serum, trypsin, digestion enzymes (e.g., collagenase,
DNAse) growth factors, cytokines, monoclonal antibodies, antibiotics, cell
separation devices, and media and media components.  These reagents can affect the
safety, potency, and purity of the final product, especially by introducing
adventitious agents.  For monoclonal antibodies, refer to the guidance on “Points to
Consider in the Manufacture and Testing of Monoclonal Antibody Products for
Human Use” (Ref. 8) for further information.
a.
Tabulation of Reagents Used in Manufacture
We recommend that you provide the following information on all reagents used
during product manufacturing:
9

Contains Nonbinding Recommendations
x
concentration of the reagent at the manufacturing step at which it is used;
x
vendor/supplier;
x
source:
o
human:  If human albumin is used, you should have procedures in
place to ensure that no recalled lots were used during manufacture
or preparation of the product.  If using human AB serum, ensure
serum is obtained from an approved blood bank and meets all
blood donor criteria.  For all other reagents that are human derived
you should identify whether it is a licensed product, or clinical or
research grade, and provide a COA or information regarding
testing of the donor and/or reagent.
o
porcine:  If porcine products are used, a COA or other
documentation that the products are free of porcine parvovirus.
o
bovine:  If a reagent is derived from bovine material, you should
identify the bovine material, the source of the material, information
on the location where the herd was born, raised, and slaughtered,
and any other information relevant to the likelihood that the animal
may have ingested animal feed prohibited under 21 CFR 589.2000.
It may be that bovine material is introduced at different points in
production of a reagent; the information described above should be
provided for all bovine materials used.  For more information see,
“Proposed Rule: Use of Materials Derived from Cattle in Medical
Products Intended for Use in Humans and Drugs Intended for Use
in Ruminants,” (72 FR 1581; January 12, 2007); found at
http://www.fda.gov/cber/rules/catruminant.htm. In addition, you
should provide a COA to document that bovine materials are
compliant with the requirements for the ingredients of animal
origin used for production of biologics described in 9 CFR 113.53.
Note to FDA Reviewers: For all animal derived products, enter the following
information in the animal components database:  source organism,
supplier/vendor, country of origin, and stage of manufacture.  Additionally, the
information provided on bovine materials should be evaluated to determine
whether, for informed consent that is adequate under 21 CFR Part 50, the subject
should be informed of the potential risk that TSE agents have been introduced
into the final product.
x
Reagent quality:  We recommend that you use FDA-approved or cleared,
or clinical grade reagents whenever they are available.
Note to FDA Reviewers:  If the reagent is regulated as a biological product, drug,
or device, consider whether a consultative review should be obtained.  See
Section III.A.5.b below for further information about consultative review process.
10

Contains Nonbinding Recommendations
x
COA or cross-reference letters:  If you are using a research grade (not
FDA-approved or cleared) reagent as part of the manufacturing process,
we recommend that you provide information verifying the source, safety,
and performance of the reagent.  If the vendor of the reagent has a
regulatory file with the FDA, a cross-reference letter from the sponsor
may be provided in the IND.  If a COA from the reagent manufacturer is
used, you may assess whether the testing performed is adequate (see
“Qualification Program” below) and provide that information in the IND.
Note to FDA Reviewers:  For letters of cross-reference, include the regulatory file
number and consider the need for a consultative review to determine whether
there are any safety concerns or other outstanding issues.
b. Qualification Program
If the reagent is not FDA-approved or cleared, additional testing may be needed
to ensure the safety and quality of the reagent.  We recommend that you establish
a qualification program that includes safety testing (sterility, endotoxin,
mycoplasma, and adventitious agents), functional analysis, purity testing, and
assays (e.g., residual solvent testing) to demonstrate absence of potentially
harmful substances.  The extent of testing will depend on how the specific reagent
is used in the manufacturing process.
c.
Determination of Removal of Reagents from Final Product
You should test the final product for residual manufacturing reagents with known
or potential toxicities and describe the test procedures you use to detect residual
levels of these reagents in the final product.  We recommend that you determine
whether a qualification study is sufficient to document their removal, or whether
lot release testing is appropriate prior to initiation of clinical trials.
d. Other Concerns
Because some patients may be sensitive to penicillin, we recommend that you do
not use beta-lactam antibiotics during the manufacturing of a therapeutic product
for humans.  If beta-lactam antibiotics are used, we recommend that you provide a
rationale for their use and describe precautions to prevent hypersensitivity
reactions.
Note to FDA Reviewers:  If beta-lactam antibiotics are used during
manufacturing, consult with the clinical reviewer concerning appropriate
exclusion criteria for the study and proper informed consent to address potential
patient sensitivity.  Discuss with the sponsor the rationale for using beta-lactam
antibiotics and whether an alternative to beta-lactam antibiotics can be used as an
appropriate substitute.
11

Contains Nonbinding Recommendations
4. Excipients
For the purpose of this guidance, an excipient is any component that is intended to be
part of the final product, such as human serum albumin or Dimethyl Sulfoxide
(DMSO).  You must list in your IND all excipients used during manufacture of the
product that are intended to be present in the final product (21 CFR
312.23(a)(7)(iv)(b)).  You should include the concentration and source of the
excipients.  Also, you must provide information regarding the qualification of all
excipients that are present in the final product (21 CFR 211.84(a)).  For further
information, please see Section III.A.2 above on reagents.
5. Additional Considerations
a. Combination Products
This guidance also applies to combination products containing a human gene
therapy biological product in combination with a drug or device as part of the
final product.
3
When intended for a different use, the drug or device component
may already have FDA marketing approval or clearance (e.g., new drug
application (NDA), a premarket approval application (PMA), or a premarket
notification (510(k)), or it may be previously unstudied.
If information describing the drug or device component has already been
submitted to FDA (e.g., in another IND, IDE, or Master File), you may submit a
letter of authorization authorizing FDA to reference the previous submission for
CMC or other information related to the drug or device component of your
product.
Note to FDA Reviewers:  Determine the regulatory status of the drug or device
either by contacting the RPM from the center with jurisdiction for the drug or
device or the sponsor directly, if necessary.  If the drug or device has been
approved for any use, confirm and document this in your review.  In most cases,
request a consultative or collaborative review from the Center for Drug
Evaluation and Research (CDER) or the Center for Devices and Radiological
Health (CDRH) even if the drugs or device components were previously approved
for another use.  Confer with your supervisor if it is unclear whether a
consultative or collaborative review is needed.  Once an adequate letter of
authorization is submitted, verify
3
Regulations on combination products are found in 21 CFR Part 3, which describes how we will determine which
component of FDA has primary jurisdiction for the premarket review and regulation of a combination product.
Note to FDA Reviewers: If you have any concerns regarding the appropriateness of the jurisdictional assignment or
regulatory mechanism, you should contact the Office of Cellular, Tissues, and Gene Therapies’ jurisdictional
officer.
12

Contains Nonbinding Recommendations
that the referenced file contains the needed information.  Inform the consultative
or collaborative reviewer that the information referenced in the letter of
authorization should be reviewed as part of the application.
b. Consultative Reviews
Note to FDA Reviewers:  Follow the standard operating procedures and policies
(SOPP) on the “Intercenter Consultative/Collaborative Review Process” (Ref. 9).
Specify the questions the consultative reviewer should address, identify the
specific sections of the IND applicable to those questions, and request a date for
completion of the consultative review.  The requested date should be determined
by coordinating with the consulting review center and be based on timeframes
mandated by statute, the priority of the consultative review request, and the
workload of the designated reviewer.  The RPM will request the consultative or
collaborative review from the appropriate Center/Division using the form in
Appendix 1 of the SOPP.  Given the tight IND deadlines, work with the RPM to
contact the appropriate Center/Division before sending the consult request to
identify the appropriate reviewer and ensure that the review can be completed
within the time requirements.  Also, as described in the SOPP, the RPM should
send to the Office of Combination Products a copy of the
consultative/collaborative request for monitoring/tracking purposes.  The RPM
should follow up with the consultative reviewer to confirm that essential
documents are received along with the consultative review request.  If problems
that affect the timeliness of the consultative review occur during the consult
review period, discuss with your supervisor how to share these experiences with
the Office of Combination Products, which is responsible for monitoring the
efficiency and effectiveness of the intercenter consultative/collaborative review
process.
c.
Review of Device Components
Note to FDA Reviewers:  In the device consultative/collaborative review request,
describe the device component, and where to find relevant information in the
submission.  You should ask the consultative reviewer to identify concerns with
how the device component will be used, to determine whether appropriate types
of biocompatibility and other device testing were performed adequately, and to
assess testing of any hardware and software controlling the hardware.  In addition,
if the sponsor asserts barrier or performance claims, identify information relative
to these claims for the consultative reviewer to assess.  You should document in
the review basic information concerning the device, such as the device name,
vendor or source, purpose, regulatory status, and a brief description of the device.
When the consultative/collaborative review is completed, and signed off by the
appropriate CDRH supervisory chain, attach it to your review and communicate
any outstanding issues to the sponsor.
13

Contains Nonbinding Recommendations
d.
Review of Drug Components
Note to FDA Reviewers:  In the drug consultative/collaborative review request,
describe the drug component of the combination product and state where to find
relevant information on the component in the submission.  Ask the
consultative/collaborative reviewer to identify any concerns with how the drug
will be used and also to evaluate the methods of manufacturing and the adequacy
of results from testing of the drug substance and/or drug product.  You should
document in your review basic information concerning the drug component, such
as the drug name, vendor or source, purpose, regulatory status, and a brief
description of the use of the drug.  When the consultative/collaborative review is
completed and signed off by appropriate CDER supervisory chain, attach it to
your review and communicate any outstanding issues to the sponsor.
e.
Summarize Any Areas of Concern to be Addressed
Note to FDA Reviewers:  Summarize any areas of concern identified during the
review of the product components.  Discuss these concerns with the sponsor
and/or communicate them in a letter to the sponsor, as described in Section XI,
“Comments to Sponsor Generated by FDA Reviewers”.
B.
Product Manufacturing – Procedures
You should include a detailed description (list or summary) of all procedures used during
the collection, production, and purification of the gene therapy product.  We believe that
a schematic of the production and purification process, and in-process and final product
testing, helps to provide more clearly this information.
Note to FDA Reviewers:  If provided by the sponsor, append a copy of the process
schematic to the IND review.  If a schematic is not included, briefly summarize the
processing steps used during product manufacturing.  In addition, summarize any areas of
concern identified during the review of any submitted product manufacturing procedures.
Discuss these concerns with the sponsor and/or communicate to the sponsor in a letter, as
described in Section XI, “Comments to Sponsor Generated by FDA Reviewers”.
1.
Vector Production/Purification
You should include the following in your procedures:
x
all purification steps in order of processing, for example:  centrifugation,
column purification, and density gradients;
x
reagents/components used during vector manufacture;
x
describe cell lines used during production of vector product including; cell
passage number and cell plating density; and
x
culturing procedures, and media components used, including serum,
growth factors, and antibiotics used during cell propagation.
14

Contains Nonbinding Recommendations
2.
Preparation of ex Vivo Gene-Modified Autologous or Allogeneic Cells
Autologous or allogeneic cells can be modified by using viral or plasmid vectors.
We recommend that you describe the following procedures:
a.
Method of Cell Collection/Processing/Culture Conditions
You should describe the cells used for ex vivo modification (i.e., cell lines,
tumor cells, donor derived cells).  If non-banked autologous or allogeneic cells
are used, describe the volume and number of cells collected.  You should
include any mechanical or enzymatic digestion steps used.  You should describe
the use of any cell selection device or separation device, including density
gradients, magnetic beads, or fluorescence activated cell sorting (FACS).  You
should include a description of culture systems (flasks, bags, etc.), and state
whether the system is closed or open.  Also, you should describe any in-process
testing that will be performed during these procedures.
b.
Ex Vivo gene modification
You should describe in detail the modification procedure, such as, transfection,
or infection.  You should describe in detail the selection of cells (methods,
devices, reagents) as well as any other cell modification steps such as
irradiation.  If the cells are cultured after the genetic modification occurs, you
should include the culture conditions used and time in culture.
c.
Irradiation of ex vivo gene modified cells
If the autologous or genetically modified allogeneic cell product is irradiated
before injection, you should provide data to demonstrate that the genetically
modified cells are rendered replication-incompetent, but still maintain their
desired characteristics after irradiation.  You should describe the documentation
of calibration of the cell irradiator source.
d. Final Harvest
You should provide a detailed description of the final harvest.  You should
inform FDA whether the final cell harvest is centrifuged prior to final
formulation, and if so, describe the wash conditions and media used.  You
should also inform FDA in your IND submission whether the cells are
cryopreserved after formulation or formulated immediately and given to the
patient.  If the final harvest is stored, you should describe the storage
conditions and the length of storage, and provide appropriate supporting data
(see Section VI below).
15

Contains Nonbinding Recommendations
3.
Process Timing and Intermediate Storage
Report the approximate time elapsed for each step in vector production including
vector purification, intermediate holding steps (i.e., storage of bulk harvest) and
cryopreservation of final vector product.  In addition, if the final product is ex vivo
genetically modified cells, you should report the approximate time elapsed for each
step from cell collection, to transduction, to final harvest.  It is important to know the
time limit of each step in production to determine what, if any, in-process testing to
perform. If the final product is cryopreserved before injection into patients, you
should include this information along with any stability studies initiated (see Section
VI.A.1 below).  Also, you should describe the time and conditions of storage prior to
patient administration.
Note to FDA Reviewers:  Describe and assess the procedures in place to ensure the
stability of the bulk harvest while in storage.
4. Final Formulation
You must describe the formulation of the final product, including excipients such as
growth factors or human serum albumin (21 CFR 312.23(a)(7)(iv)(a)).  You should
state the source of these components (see Section II.A.3 above).  You should identify
the vendor and final concentration of these excipients used in the final product.  If the
final product is delivered to the clinical site frozen, you should include a description
of how the product will be shipped and data to show that the product can be thawed
with consistent results.  In addition, if the product is shipped, you should provide data
on product stability during shipping (see Section VI.A.2 below).
IV.
PRODUCT TESTING
We recommend that product testing for gene therapies include, but not be limited to,
microbiological testing (including sterility, mycoplasma, and adventitious viral agent testing) to
ensure safety and assessments of other product characteristics such as identity, purity (including
endotoxin), viability, and potency.  We recommend that you perform this testing throughout the
manufacturing process, including on the manufacture of cell banks, to evaluate the
manufacturing process itself and to ensure the quality and consistency of the product.  You
should describe the specifications used for intermediate acceptance criteria and final product
release criteria.  Specifications are the quality standards (i.e., tests, analytical procedures, and
acceptance criteria) that confirm the quality of products and other materials used in the
production of a product.  Acceptance criteria mean numerical limits, ranges, or other attributes or
variables for the tests described.  Specifications should be appropriate to the stage of product
development, because release criteria should be refined and tightened as product development
progresses toward licensure (see Appendix B).  You should submit test results related to lot
release, characterization testing, MCB/MVBs, and WCB/WVBs in tabular form including the lot
number or identifier, date of manufacture, test, test method, the sensitivity and specificity of test
methods and, when appropriate, release criteria.


24
                                      44
                                     1,056
                                     52.8
                                     105.6
                                                                   $145,803.50
New Sources

Data Collection
                                      1.5
                                       2
                                       3
                                       0
                                       0
                                       0
                                       0
                                                                            $0
Records of Performance Tests
                                      0.1
                                       2
                                      0.2
                                       0
                                       0
                                       0
                                       0
                                                                            $0
F. Time to Train Personnel
                                      80
                                       1
                                      80
                                       0
                                       0
                                       0
                                       0
                                                                            $0
G. Time for Audits
                                      NA

Subtotal for Recordkeeping Requirements

                                     2,884

                                                                      $346,283
Total Labor Burden and Cost (rounded) [e]

                                     6,200
                                                                      $740,000
Total Capital and O&M Cost (rounded) [e]

                                                                       $43,600
Grand TOTAL (rounded) [e]

                                                                      $800,000

[a]  We have assumed that there are approximately 44 respondents operating furnaces and that 10% of the existing facilities will have new construction/reconstruction.
[b]  This ICR uses the following labor rates: $157.61 per hour for Executive, Administrative, and Managerial labor; $123.94 per hour for Technical labor, and $62.51 per hour for Clerical labor.  These rates are from the United States Department of Labor, Bureau of Labor Statistics, June 2021, "Table 2. Civilian Workers, by Occupational and Industry group."  The rates are from column 1, "Total Compensation."  The rates have been increased by 110% to account for the benefit packages available to those employed by private industry.
[c]  New furnaces test for NOx. We have assumed that 5 percent of respondents would repeat initial performance test due to failure.
[d]  The rule requires existing furnaces re-test semi-annually for NOx.  Existing furnaces are assumed to not have existing CEMS installed.
e  Totals have been rounded to 3 significant figures.  Figures may not add exactly due to rounding.

Table 9: Annual Respondent Burden and Cost  -  Basic Chemical Manufacturing, Petroleum and Coal Products Manufacturing, Pulp, Paper, and Paperboard Manufacturing, Year 1

                                  Burden Item
                           (A)
Hours per Occurrence
                       (B)
Occurrences/ Respondent/ Year
                     (C)
Hours/ Respondent/ Year
(A x B)
                           (D)
Respondents/
Year[a]
                       (E)
Technical Hours/Year
(C x D)
                     (F) Managerial Hours/Year
(E x 0.05)
                     (G)
Clerical Hours/Year
(E x 0.10)
                               (H)
Cost/ Year[b]
1. APPLICATIONS
                                      NA

2. SURVEY AND STUDIES
                                      NA

3.ACQUISITION, INSTALLATION, AND UTILIZATION OF TECHNOLOGY AND SYSTEMS
                                      16
                                       1
                                      16
                                       0
                                       0
                                       0
                                       0
                                                                            $0
4. REPORT REQUIREMENTS

A. Familiarize with regulatory requirement
                                      20
                                       1
                                      20
                                      55
                                     1100
                                      55
                                      110
                                                                   $151,878.65
B. Required Activities

New, Reconstructed, Modified Sources - Testing [c]

Initial NOx Performance Test (boiler)
                                      24
                                       2
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Repeat NOx Performance Test
                                      24
                                       2
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Existing Sources - Initial Testing [d]

Initial NOx Performance Test (boiler)
                                      24
                                       2
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Repeat NOx Performance Test
                                      24
                                       2
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
New and Existing Sources - Monitoring [e]

Daily Calibration Drift Tests - NOx CEMS
                                      0.3
                                      330
                                      99
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
C. Create Information (Included in 4B)

D. Gather Existing Information (Included in 4E)

E. Write Report

New, Reconstructed, Modified Sources

Notification of Demonstration of CEMS
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Notification of Initial Performance Test
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Report of Performance Tests
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Submit Quarterly Electronic Reports to Administrator of NOx Emission Rates data, Excess Emissions, Missing and Excluded Data, "F" factor, and other CEMS data.
                                      24
                                       4
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                            $0
Existing Sources

Notification of Demonstration of CEMS
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Notification of Initial Performance Test
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Report of Initial Performance Test Results
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Submit Quarterly Electronic Reports to Administrator of NOx Emission Rates data, Excess Emissions, Missing and Excluded Data, "F" factor, and other CEMS data.
                                       2
                                       4
                                       8
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Subtotal for Reporting Requirements

                                     1,265

                                                                      $151,879
5. RECORDKEEPING REQUIREMENTS

A. Familiarize with regulatory requirement

B. Plan Activities

C. Implement Activities

D. Record Data
                                      NA

E. Time to Transmit or Disclose Information

Existing Sources

Data Collection
                                      0.4
                                      12
                                      4.8
                                      55
                                      264
                                     13.2
                                     26.4
                                                                    $36,450.88
Records of Monthly Fuel Use
                                      0.4
                                      12
                                      4.8
                                      55
                                      264
                                     13.2
                                     26.4
                                                                    $36,450.88
New Sources

Data Collection
                                      1.5
                                      330
                                      495
                                       0
                                       0
                                       0
                                       0
                                                                            $0
Records of Monthly Fuel Use
                                      0.1
                                      330
                                      33
                                       0
                                       0
                                       0
                                       0
                                                                            $0
F. Time to Train Personnel
                                      80
                                       1
                                      80
                                       0
                                       0
                                       0
                                       0
                                                                            $0
G. Time for Audits
                                      NA

Subtotal for Recordkeeping Requirements

                                      607

                                                                       $72,902
Total Labor Burden and Cost (rounded) [f]

                                     1,900
                                                                      $220,000
Total Capital and O&M Cost (rounded) [f]

                                                                            $0
Grand TOTAL (rounded) [f]

                                                                      $200,000

[a]  We have assumed that there are approximately 55 respondents operating boilers and that 10% of the existing facilities will have new construction/reconstruction.
[b]  This ICR uses the following labor rates: $157.61 per hour for Executive, Administrative, and Managerial labor; $123.94 per hour for Technical labor, and $62.51 per hour for Clerical labor.  These rates are from the United States Department of Labor, Bureau of Labor Statistics, June 2021, "Table 2. Civilian Workers, by Occupational and Industry group."  The rates are from column 1, "Total Compensation."  The rates have been increased by 110% to account for the benefit packages available to those employed by private industry.
[c]  New boilers test for NOx. We have assumed that 5 percent of respondents would repeat initial performance test due to failure.
[d]  The rule requires existing boilers to conduct an initial compliance test within 90 days from the installation of the pollution control equipment used to comply with the NOx emission limits. We have assumed that 5 percent of respondents would repeat annual performance test due to failure.
[e]  Calibration drift checks on the air flow sensor on the NOx CEMS are performed daily.
[f]  Totals have been rounded to 3 significant figures.  Figures may not add exactly due to rounding.

Table 10: Annual Respondent Burden and Cost  -  Basic Chemical Manufacturing, Petroleum and Coal Products Manufacturing, Pulp, Paper, and Paperboard Manufacturing, Year 2

                                  Burden Item
                           (A)
Hours per Occurrence
                       (B)
Occurrences/ Respondent/ Year
                     (C)
Hours/ Respondent/ Year
(A x B)
                           (D)
Respondents/
Year[a]
                       (E)
Technical Hours/Year
(C x D)
                     (F) Managerial Hours/Year
(E x 0.05)
                     (G)
Clerical Hours/Year
(E x 0.10)
                               (H)
Cost/ Year[b]
1. APPLICATIONS
                                      NA

2. SURVEY AND STUDIES
                                      NA

3.ACQUISITION, INSTALLATION, AND UTILIZATION OF TECHNOLOGY AND SYSTEMS
                                      16
                                       1
                                      16
                                       0
                                       0
                                       0
                                       0
                                                                            $0
4. REPORT REQUIREMENTS

A. Familiarize with regulatory requirement
                                       1
                                       1
                                       1
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
B. Required Activities

New, Reconstructed, Modified Sources - Testing [c]

Initial NOx Performance Test (boiler)
                                      24
                                       2
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Repeat NOx Performance Test
                                      24
                                       2
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Existing Sources - Initial Testing [d]

Initial NOx Performance Test (boiler)
                                      24
                                       2
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Repeat NOx Performance Test
                                      24
                                       2
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
New and Existing Sources - Monitoring [e]

Daily Calibration Drift Tests - NOx CEMS
                                      0.3
                                      330
                                      99
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
C. Create Information (Included in 4B)

D. Gather Existing Information (Included in 4E)

E. Write Report

New, Reconstructed, Modified Sources

Notification of Demonstration of CEMS
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Notification of Initial Performance Test
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Report of Performance Tests
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Submit Quarterly Electronic Reports to Administrator of NOx Emission Rates data, Excess Emissions, Missing and Excluded Data, "F" factor, and other CEMS data.
                                      24
                                       4
                                      48
                                       0
                                       0
                                       0
                                       0
                                                                            $0
Existing Sources

Notification of Demonstration of CEMS
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Notification of Initial Performance Test
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Report of Initial Performance Test Results
                                       2
                                       1
                                       2
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Submit Quarterly Electronic Reports to Administrator of NOx Emission Rates data, Excess Emissions, Missing and Excluded Data, "F" factor, and other CEMS data.
                                       2
                                       4
                                       8
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
Subtotal for Reporting Requirements

                                       0

                                                                            $0
5. RECORDKEEPING REQUIREMENTS

A. Familiarize with regulatory requirement

B. Plan Activities

C. Implement Activities

D. Record Data
                                      NA

E. Time to Transmit or Disclose Information

Existing Sources

Data Collection
                                      0.4
                                      12
                                      4.8
                                      55
                                      264
                                     13.2
                                     26.4
                                                                    $36,450.88
Records of Monthly Fuel Use
                                      0.4
                                      12
                                      4.8
                                      55
                                      264
                                     13.2
                                     26.4
                                                                    $36,450.88
New Sources

Data Collection
                                      1.5
                                      330
                                      495
                                       0
                                       0
                                       0
                                       0
                                                                            $0
Records of Monthly Fuel Use
                                      0.1
                                      330
                                      33
                                       0
                                       0
                                       0
                                       0
                                                                            $0
F. Time to Train Personnel
                                      80
                                       1
                                      80
                                       0
                                       0
                                       0
                                       0
                                                                            $0
G. Time for Audits
                                      NA

Subtotal for Recordkeeping Requirements

                                      607

                                                                       $72,902
Total Labor Burden and Cost (rounded) [f]

                                      600
                                                                       $70,000
Total Capital and O&M Cost (rounded) [f]

                                                                            $0
Grand TOTAL (rounded) [f]

                                                                      $100,000

[a]  We have assumed that there are approximately 55 respondents operating boilers and that 10% of the existing facilities will have new construction/reconstruction.
[b]  This ICR uses the following labor rates: $157.61 per hour for Executive, Administrative, and Managerial labor; $123.94 per hour for Technical labor, and $62.51 per hour for Clerical labor.  These rates are from the United States Department of Labor, Bureau of Labor Statistics, June 2021, "Table 2. Civilian Workers, by Occupational and Industry group."  The rates are from column 1, "Total Compensation."  The rates have been increased by 110% to account for the benefit packages available to those employed by private industry.
[c]  New boilers test for NOx. We have assumed that 5 percent of respondents would repeat initial performance test due to failure.
[d]  The rule requires existing boilers to conduct an initial compliance test within 90 days from the installation of the pollution control equipment used to comply with the NOx emission limits. We have assumed that 5 percent of respondents would repeat annual performance test due to failure.
[e]  Calibration drift checks on the air flow sensor on the NOx CEMS are performed daily.
[f]  Totals have been rounded to 3 significant figures.  Figures may not add exactly due to rounding.

Table 11: Annual Respondent Burden and Cost  -  Basic Chemical Manufacturing, Petroleum and Coal Products Manufacturing, Pulp, Paper, and Paperboard Manufacturing, Year 3

                                  Burden Item
                           (A)
Hours per Occurrence
                       (B)
Occurrences/ Respondent/ Year
                     (C)
Hours/ Respondent/ Year
(A x B)
                           (D)
Respondents/
Year[a]
                       (E)
Technical Hours/Year
(C x D)
                     (F) Managerial Hours/Year
(E x 0.05)
                     (G)
Clerical Hours/Year
(E x 0.10)
                               (H)
Cost/ Year[b]
1. APPLICATIONS
                                      NA

2. SURVEY AND STUDIES
                                      NA

3.ACQUISITION, INSTALLATION, AND UTILIZATION OF TECHNOLOGY AND SYSTEMS
                                      16
                                       1
                                      16
                                       0
                                       0
                                       0
                                       0
                                                                            $0
4. REPORT REQUIREMENTS

A. Familiarize with regulatory requirement
                                      20
                                       1
                                      20
                                       0
                                       0
                                       0
                                       0
                                                                         $0.00
B. Required Activities

New, Reconstructed, Modified Sources - Testing [c]

Initial NOx Performance Test (boiler)
                                      24
                                       2
                                      48
                                      5.5
                                      264
                                     13.2
                                     26.4
                                                                    $36,450.88
Repeat NOx Performance Test
                                      24
                                       2
                                      48
                                     0.275
                                      13
                                     0.66
                                     1.32
                                                                     $1,822.54
Existing Sources - Initial Testing [d]

Initial NOx Performance Test (boiler)
                                      24
                                       2
                                      48
                                      55
                                     2,640
                                      132
                                      264
                                                                   $364,508.76
Repeat NOx Performance Test
                                      24
                                       2
                                      48
                                     2.75
                                      132
                                      6.6
                                     13.2
                                                                    $18,225.44
New and Existing Sources - Monitoring [e]

Daily Calibration Drift Tests - NOx CEMS
                                      0.3
                                      330
                                      99
                                      55
                                     5,445
                                    272.25
                                     544.5
                                                                   $751,799.32
C. Create Information (Included in 4B)

D. Gather Existing Information (Included in 4E)

E. Write Report

New, Reconstructed, Modified Sources

Notification of Demonstration of CEMS
                                       2
                                       1
                                       2
                                      5.5
                                      11
                                     0.55
                                      1.1
                                                                     $1,518.79
Notification of Initial Performance Test
                                       2
                                       1
                                       2
                                      5.5
                                      11
                                     0.55
                                      1.1
                                                                     $1,518.79
Report of Performance Tests submitted via CEDRI or analogous electronic reporting
                                       2
                                       1
                                       2
                                     4.95
                                      9.9
                                     0.495
                                     0.99
                                                                     $1,366.91
Submit Written Request to Administrator documenting Initial Performance Test and an Alternative Monitoring Plan (Alternative to CEMS).[f]
                                      10
                                       1
                                      10
                                     0.55
                                      5.5
                                     0.275
                                     0.55
                                                                       $759.39
Submit Quarterly Electronic Reports to of NOx Emission Rates data, Excess Emissions, Missing and Excluded Data, "F" factor, and other CEMS data.
                                      24
                                       4
                                      48
                                       4
                                      192
                                      9.6
                                     19.2
                                                                       $26,510
Existing Sources

Notification of Demonstration of CEMS
                                       2
                                       1
                                       2
                                      55
                                      110
                                      5.5
                                      11
                                                                    $15,187.87
Notification of Initial Performance Test
                                       2
                                       1
                                       2
                                      55
                                      110
                                      5.5
                                      11
                                                                    $15,187.87
Report of Initial Performance Test Results submitted via CEDRI or analogous electronic reporting
                                       2
                                       1
                                       2
                                     49.5
                                      99
                                     4.95
                                      9.9
                                                                    $13,669.08
Submit Written Request to Administrator documenting Initial Performance Test and an Alternative Monitoring Plan (Alternative to CEMS).[f]
                                      10
                                       1
                                      10
                                      5.5
                                      55
                                     2.75
                                      5.5
                                                                     $7,593.93
Submit Quarterly Electronic Reports via CEDRI or analogous electronic reporting to EPA of NOx Emission Rates data, Excess Emissions, Missing and Excluded Data, "F" factor, and other CEMS data.
                                       2
                                       4
                                       8
                                      55
                                      440
                                      22
                                      44
                                                                    $60,751.46
Subtotal for Reporting Requirements

                                    10,968

                                                                    $1,316,871
5. RECORDKEEPING REQUIREMENTS

A. Familiarize with regulatory requirement

B. Plan Activities

C. Implement Activities

D. Record Data
                                      NA

E. Time to Transmit or Disclose Information

Existing Sources

Data Collection
                                      0.1
                                      330
                                      33
                                      55
                                     1,815
                                     90.75
                                     181.5
                                                                   $250,599.77
Records of Monthly Fuel Use, Average Hourly NOx emission rates, 30-day average NOx emission rates, Excess Emissions data, missed monitoring day data, "F" factor, and CEMS monitoring data.
                                      0.1
                                      330
                                      33
                                      55
                                     1,815
                                     90.75
                                     181.5
                                                                   $250,599.77
New Sources

Data Collection
                                      1.5
                                      330
                                      495
                                       0
                                       0
                                       0
                                       0
                                                                            $0
Records of Monthly Fuel Use, Average Hourly NOx emission rates, 30-day average NOx emission rates, Excess Emissions data, missed monitoring day data, "F" factor, and CEMS monitoring data.
                                      0.1
                                      330
                                      33
                                       0
                                       0
                                       0
                                       0
                                                                            $0
F. Time to Train Personnel
                                      80
                                       1
                                      80
                                       0
                                       0
                                       0
                                       0
                                                                            $0
G. Time for Audits
                                      NA

Subtotal for Recordkeeping Requirements

                                     4,175

                                                                      $501,200
Total Labor Burden and Cost (rounded) [f]

                                    15,100
                                                                    $1,820,000
Total Capital and O&M Cost (rounded) [f]

                                                                    $8,910,000
Grand TOTAL (rounded) [f]

                                                                   $10,700,000

[a]  We have assumed that there are approximately 55 respondents operating boilers and that 10% of the existing facilities will have new construction/reconstruction.
[b]  This ICR uses the following labor rates: $157.61 per hour for Executive, Administrative, and Managerial labor; $123.94 per hour for Technical labor, and $62.51 per hour for Clerical labor.  These rates are from the United States Department of Labor, Bureau of Labor Statistics, June 2021, "Table 2. Civilian Workers, by Occupational and Industry group."  The rates are from column 1, "Total Compensation."  The rates have been increased by 110% to account for the benefit packages available to those employed by private industry.
[c]  New boilers test for NOx. We have assumed that 5 percent of respondents would repeat initial performance test due to failure.
[d]  The rule requires existing boilers to conduct an initial compliance test within 90 days from the installation of the pollution control equipment used to comply with the NOx emission limits. We have assumed that 5 percent of respondents would repeat annual performance test due to failure.
[e]  Calibration drift checks on the air flow sensor on the NOx CEMS are performed daily.
[f]  10 percent of respondents are assumed to submit a written request to Administrator for an alternative monitoring procedure (instead of use of CEMS).
[g]  Totals have been rounded to 3 significant figures.  Figures may not add exactly due to rounding.