Notice2022-19713
Alternative or Streamlined Mechanisms for Complying With the Current Good Manufacturing Practice Requirements for Combination Products; List Under the 21st Century Cures Act
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Published
September 13, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
As required by the 21st Century Cures Act (Cures Act), the Food and Drug Administration (FDA, Agency, or we) is finalizing a list of alternative or streamlined mechanisms for complying with the current good manufacturing practice (CGMP) requirements for combination products. A combination product is a product composed of any combination of a drug, a device, and/or a biological product.
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[Federal Register Volume 87, Number 176 (Tuesday, September 13, 2022)]
[Notices]
[Pages 56066-56070]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-19713]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-N-2065]
Alternative or Streamlined Mechanisms for Complying With the
Current Good Manufacturing Practice Requirements for Combination
Products; List Under the 21st Century Cures Act
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: As required by the 21st Century Cures Act (Cures Act), the
Food and Drug Administration (FDA, Agency, or we) is finalizing a list
of alternative or streamlined mechanisms for complying with the current
good manufacturing practice (CGMP) requirements for combination
products. A combination product is a product composed of any
combination of a drug, a device, and/or a biological product.
DATES: This notice is published in the Federal Register on September
13, 2022.
ADDRESSES: For access to the docket, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
and insert the docket number, found in brackets in the heading of this
document, into the ``Search'' box and follow the prompts and/or go to
the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville,
MD 20852, between 9 a.m. and 4 p.m., Monday through Friday, 240-402-
7500. Publicly available submissions may be seen in the docket.
FOR FURTHER INFORMATION CONTACT: John Barlow Weiner, Office of
Combination Products, Food and Drug Administration, 10903 New Hampshire
Ave., Bldg. 32, Rm. 5130, Silver Spring, MD 20993, 301-796-8930,
<a href="/cdn-cgi/l/email-protection#2d47424543035a484443485f6d4b494c0345455e034a425b"><span class="__cf_email__" data-cfemail="caa0a5a2a4e4bdafa3a4afb88aacaeabe4a2a2b9e4ada5bc">[email protected]</span></a> or <a href="/cdn-cgi/l/email-protection#fd9e92909f94939c89949293bd9b999cd395958ed39a928b"><span class="__cf_email__" data-cfemail="2b4844464942454a5f4244456b4d4f4a05434358054c445d">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
On January 22, 2013, FDA issued a final rule on CGMP requirements
for combination products (see 78 FR 4307 and part 4, subpart A (21 CFR
part 4, subpart A)) (CGMP Rule). The drugs, devices, and biological
products included in combination products are referred to as
``constituent parts'' of the combination product. Combination products
include ``single-entity'' combination products, the constituent parts
of which are physically, chemically, or otherwise combined or mixed and
produced as a single entity (see Sec. 3.2(e)(1) (21 CFR 3.2(e)(1)))
(e.g., prefilled syringes and drug-eluting stents), and ``co-packaged''
combination products where the constituent parts are packaged together
in a single package or as a unit (see Sec. 3.2(e)(2)) (e.g., a
surgical or first-aid kit).\1\ Section 4.4 (21 CFR 4.4) outlines how
manufacturers of single-entity and co-packaged combination products
(hereafter ``CP manufacturers'') can demonstrate compliance with
applicable CGMP requirements, including through implementation of a
streamlined approach to meet the requirements of both the drug CGMP and
the device quality system (QS) regulations.
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\1\ There are also ``cross-labeled'' combination products (Sec.
3.2(e)(3) and (4)). See Ref. 1 for additional information regarding
CGMP requirements for them, as well as use of the ``streamlined
approach'' if a device and drug or biological product constituent
part of a cross-labeled combination product are manufactured at the
same facility.
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In December 2016, the Cures Act (Pub. L. 114-255) was signed into
law. Section 3038(c) of the Cures Act mandated that FDA publish in the
Federal Register a list identifying types of combination products and
manufacturing processes for which ``good manufacturing processes'' may
be adopted that vary from the requirements set forth in Sec. 4.4, or
that FDA proposes can satisfy the requirements in Sec. 4.4 through
``alternative or streamlined mechanisms,'' and to review this list
periodically. In accordance with this statutory mandate, FDA published
a proposed list on June 13, 2018 (83 FR 27609).
FDA received six comments on this proposed list, has considered
them, and is now publishing a list after such consideration (see
section II of this document). In response to the comments, FDA added
and refined examples and provided additional clarity regarding FDA's
expectations for CP manufacturers when applying mechanisms presented in
this list. FDA also added reference to a guidance on how to request FDA
feedback on combination products, which provides additional detail on
interacting with
[[Page 56067]]
FDA, including with respect to CGMP issues addressed in this list.
While FDA has provided examples in this notice of the types of
mechanisms that may be appropriate, CP manufacturers should consider
the suitability of an approach in the context of their product and
manufacturing process. For these examples, we have recommended engaging
the Agency before adoption of some, whereas others may be evaluated on
inspection as appropriate. Additional approaches may be permissible as
well for evaluation on a case-by-case basis for a particular product
and CP manufacturer. FDA continues to apply a risk-based approach to
evaluating alternative or streamlined mechanisms for ensuring the
quality of combination products, and as FDA and CP manufacturers
develop additional data and rationales, this list may be expanded,
including to provide additional examples or to identify types of
combination products for which alternative or streamlined mechanisms
may be applicable.
II. List of Mechanisms for Complying With Sec. 4.4 CGMP Requirements
for Combination Products
A. Introduction
Sections II.B and II.C present mechanisms for demonstrating
compliance with relevant combination product CGMP requirements. Where
applicable, reference is made to sections of the ``Guidance for
Industry and FDA Staff: Current Good Manufacturing Practice
Requirements for Combination Products'' for additional information
(Ref. 1). FDA will continue to evaluate this list in light of Agency
experience and stakeholder input. CP manufacturers are welcome to
propose other approaches not described, including approaches to other
requirements set forth in Sec. 4.4 for which FDA is not currently
describing mechanisms for demonstrating compliance in the sections
below.
For each mechanism described below, CP manufacturers should
consider what documentation would be sufficient to support that the
mechanism, including the specific approach for implementing it, assures
appropriate control of the manufacture of the combination product to
ensure safety and effectiveness of the product. Appropriate evidence
and an explanation of the rationale to support the approach should be
accessible at the manufacturing facility for review during facility
inspections regardless of whether the approach has been discussed with
FDA.
In some cases, CP manufacturers may need to interact with FDA to
gain approval or otherwise notify FDA of a manufacturing change (see
section III.A). For example, if a CP manufacturer utilizes a
bracketing/matrixing design for stability studies, this approach should
be submitted to FDA either as a proposal at the time of premarket
review or as a postmarket change.
For additional discussion on how to interact with FDA regarding the
mechanisms described below, see section III.
B. Mechanisms for Complying With Drug CGMP Requirements (Part 211)
Specified in Sec. 4.4 <SUP>2</SUP>
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\2\ Several drug CGMP mechanisms included in this list depend
upon use of a more broadly defined batch. FDA notes that approaches
that depend upon broadly defined batches may increase the number of
distributed products implicated when corrective actions are
necessary to address postmarket issues.
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FDA interprets the mechanisms identified in the sections below as
means to demonstrate compliance with the following part 211 (21 CFR
part 211) requirements specified in Sec. 4.4:
1. Section 211.165 Testing and Release for Distribution
Use of samples that are not finished combination products, but that
are representative of the finished combination product with respect to
the characteristics and attributes being tested, when performing
testing required by Sec. 211.165 (21 CFR 211.165) to determine whether
the drug constituent part, and thus the combination product, meets
relevant final specifications. To meet the requirements of Sec.
211.165, the CP manufacturer using this mechanism would need to
establish, including where appropriate through bridging studies and
other quantitative means, that any differences in the manufacturing
process for the representative samples as compared to the finished
combination product do not affect the drug constituent part (i.e., to
establish that there is no difference in the quality attributes related
to the drug constituent part in the representative sample as compared
to the attributes related to the drug constituent part in the finished
combination product). For example, as part of product release testing,
drug-eluting lead CP manufacturers could perform release testing for
identity, potency, or other quality attributes on a representative lead
tip assembly that contains the drug constituent part, rather than on
the finished combination product containing the full electronic and
mechanical assembly, so long as they can establish that the
representative lead tip assemblies meet the relevant acceptance
criteria and there are no statistically significant differences in the
test results for the representative lead tip assemblies compared to the
finished combination product.
(See also section IV.B.5 of Ref. 1 for additional information on
testing and release for combination products.)
2. Section 211.166 Stability Testing
Use of bracketing and matrixing approaches to stability studies for
combination products. Principles for bracketing and matrixing
approaches to meet the requirements of Sec. 211.166 (21 CFR 211.166)
have already been addressed by the Agency, including in The
International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use (ICH) guidelines with regard to drug
products (Refs. 2 and 3), and such principles can also be applied to
combination products. CP manufacturers could utilize a bracketing/
matrixing design, if appropriate, for stability studies. For example,
when assessing stability for a prefilled syringe that is marketed in
various fill volumes, one of the approaches that a CP manufacturer
could utilize, if appropriate, is bracketing based on the smallest and
the largest fill volume of product configurations. In determining the
extremes for a bracketing approach and/or when justifying the use of a
matrix design for single-entity combination products, it is important
that the drug-device interactions and variations in the manufacturing
processes are considered. For co-packaged combination products, such
approaches can only be applied to the drug constituent part of the
product.
Leveraging stability data for an already marketed combination
product. Mechanisms that use prior stability knowledge, data, or
information for an existing product to support stability assessment for
a modification to that product may be appropriate when a new
combination product is a modification of an already marketed product
and the modification does not have the potential to impact the
stability of the drug constituent part. For example, when developing
new lengths of a drug-coated catheter product for which the catheter
materials, drug coating, manufacturing process, and packaging
configurations are largely unchanged from existing marketed sizes, the
CP manufacturer would generally be able to leverage existing stability
data to establish initial product shelf life or to support reduced
stability data requirements, so long as characteristics of the product
that could impact stability (e.g., materials, packaging configuration)
remain the same. However, if the device constituent
[[Page 56068]]
part of a drug-coated catheter includes a new material that is in
contact with the drug coating or is a new design with a different drug-
coated area or geometry, for example, new stability studies would
generally be needed under Sec. 211.166.
(See also section IV.B.6 of Ref. 1 for additional information on
stability requirements for combination products.)
3. Section 211.167 Special Testing Requirements
Defining ``batch'' based on the drug constituent part rather than
the finished combination product for purposes of special testing
requirements for pyrogens and endotoxins. For example, a CP
manufacturer of a combination product consisting of a device that is
coated with a drug, where a larger batch of coating is used to
manufacture several ``batches'' or ``lots'' of the overall combination
product, may be able to define a batch for purposes of pyrogen and
endotoxin testing as a set of combination products that were all
manufactured using the same coating batch for purposes of meeting the
requirements of Sec. 211.167 (21 CFR 211.167). As with the other
mechanisms described in this list, this mechanism would only
potentially be available if there would be no impact on the endotoxin
or pyrogen levels for the finished combination product from subsequent
manufacturing processes, including when the constituent parts are
combined to produce the final combination product (e.g., there are no
statistically significant differences in pyrogen or endotoxin test
results for the combination product immediately following the coating
process step as compared to the finished combination product). When
defining the batch, CP manufacturers should consider whether such risks
may be introduced later in the production process.
(See also section IV.B.7 of Ref. 1 for additional information on
special testing requirements for combination products.)
4. Section 211.170 Reserve Samples
Keeping reserve samples that are representative of the finished
combination product. CP manufacturers may use validated surrogates as
representative samples to meet the requirements of Sec. 211.170 (21
CFR 211.170), provided the surrogate is appropriate, both in terms of
the manufacturing process and the characteristics of the container
closure. For example, it may be permissible to maintain as a reserve
sample only the drug-containing subassembly of a single-entity
combination product, such as only the distal tip subassembly (with
drug-containing collar) of a pacemaker lead without the associated
internal electronic components, or the drug constituent part of a co-
packaged combination product, such as the prefilled cartridge of a
combination product that is distributed as a prefilled cartridge with
an injector system. Such approaches would generally be permissible
under the regulation when: (1) all subsequent manufacturing process
steps to produce the final combination product are shown not to affect
the drug constituent part, (2) the immediate container closure has
essentially the same characteristics as that for the drug constituent
part as packaged in the combination product for distribution, and (3)
the representative samples are suitable for all required testing of the
drug constituent part for which the reserve samples are being kept.
Using samples from representative lots of a larger batch for
retention of reserve samples. To meet the requirements of Sec.
211.170, CP manufacturers may be able to use bracketing and matrixing
approaches to retain reserve samples from certain lots to adequately
represent the broadly defined batch of the combination product. For
example, where relevant lot-release tests, analytical procedures, and
acceptance criteria are the same for the product matrix and the
relevant aspects of the manufacturing process are the same, CP
manufacturers might be able to retain reserve samples of appropriately
varied sizes of a drug-coated combination product from across that
matrix.
(See also section IV.B.8 of Ref. 1 for additional information on
reserve sample requirements for combination products.)
C. Mechanisms for Complying With Device Quality System Requirements
(Part 820) Specified in Sec. 4.4
FDA interprets the mechanisms identified in the sections below as
means to demonstrate compliance with the following part 820 (21 CFR
part 820) requirements specified in Sec. 4.4:
1. Section 820.30 Design Controls
Using existing pharmaceutical development practices and
documentation that align with the design control principles and
requirements of Sec. 820.30 (21 CFR 820.30). Robust pharmaceutical
development practices would address many design control requirements to
assure compliance with Sec. 820.30 where applicable (Ref. 4). CP
manufacturers need to demonstrate how development processes,
procedures, and terminology align with design control principles and
requirements in Sec. 820.30, when applicable, including developing
additional design control elements, if necessary. When evaluating the
adequacy of existing pharmaceutical development processes and related
documentation, particular attention should be given to postmarket
management of design changes to the combination product and the
alignment of change control practices with the principles and
requirements of Sec. 820.30, as applicable.
(See also section IV.A.2 of Ref. 1 for additional information on
the requirements of Sec. 820.30 as they apply to combination
products.)
2. Exemption of Combination Products From Device QS Regulation
Exemption of the combination product from provisions of the device
QS regulation (part 820) if the device constituent part of the
combination product is itself exempt from the device QS requirements
specified in Sec. 4.4(b)(1) (i.e., the intended use of the device as a
constituent part falls within the scope of the relevant exemption).
Some devices are exempt from certain provisions of the device QS
regulation (see, for example, liquid medication dispensers such as cups
and droppers that fall within the scope of Sec. 880.6430 (21 CFR
880.6430); see also, for example, limitations to device exemptions
under 21 CFR 880.9). Accordingly, a combination product is exempt from
the associated provisions of the device QS regulation specified in
Sec. 4.4(b)(1) if the device constituent part falls within the scope
of the relevant exemption; i.e., if the intended use of the device in
the combination product is not a new intended use and does not
otherwise raise different safety and effectiveness questions for the
device. This circumstance will most frequently apply to co-packaged
combination products. For example, an oral dosing syringe (a liquid
medication dispenser under Sec. 880.6430) that is co-packaged with a
drug may be exempt from all provisions of the device QS regulation
except for 21 CFR 820.180 (general requirements concerning records) and
21 CFR 820.198 (requirements concerning complaint files) when marketed
as a stand-alone device (and hence the combination product may also be
exempt from such provisions). Accordingly, if the CP manufacturer for
the co-packaged combination product is using a streamlined approach
based on drug CGMP requirements (see Sec. 4.4(b)(1)), the CP
manufacturer does not need to demonstrate compliance
[[Page 56069]]
with the device QS requirements because the product is exempt from all
device QS requirements specified in Sec. 4.4(b)(1) and, therefore,
must only be compliant with the drug CGMP requirements. However,
incorporating such a dispenser into a primary container closure system
or co-packaging of such a dispenser with a drug with a narrow
therapeutic index, for example, each may constitute a new intended use
for the dispenser or raise different safety and effectiveness questions
related to performance of the dispenser, such that the relevant
exemption would not apply.
(See also section III.C.3 of Ref. 1 for additional information on
the exemption from provisions of the device QS regulation for
combination products.)
III. Interacting With FDA on Mechanisms for Complying With CGMP for
Combination Products
A. Process for Interacting With FDA
In some cases, CP manufacturers may need to interact with FDA to
gain approval or otherwise notify FDA of a manufacturing change. In
other cases, although a submission or notification is not required, CP
manufacturers may want to discuss potential use of CGMP mechanisms with
FDA. CP manufacturers are encouraged to interact early with FDA on any
such contemplated use of alternative or streamlined CGMP mechanisms for
combination products (see also Ref. 5 regarding interactions with FDA
on combination products).
<bullet> Pre-Submissions and Meeting Requests. CP manufacturers who
want to obtain FDA feedback prior to making a premarket submission or
submitting a postmarket supplement or who otherwise want to obtain
feedback on their CGMP approach, may interact with FDA via the
processes available for such questions at the lead Center \3\ for the
combination product (see Ref. 5). For combination products reviewed
under a new drug application (NDA) or a biologics license application
(BLA), such interactions will generally be through Type C meetings
(Ref. 6). For combination products reviewed under an abbreviated new
drug application (ANDA), such interactions will generally be through
the pre-ANDA program or controlled correspondence for a premarket
application (Refs. 7 and 8). For combination products reviewed under a
device premarket submission (e.g., a premarket approval application
(PMA), de novo classification, or premarket notification (510(k)),
these interactions will generally be via the pre-submission process
(Ref. 9). Regardless of the type of submission or meeting, such
interactions should be focused on a general discussion of the CGMP
approach the CP manufacturer wishes to pursue and associated
justification to support the approach.\4\ Only representative data is
typically appropriate in these interactions; complete data should be
included in the subsequent premarket submission or postmarket
supplement and/or be maintained at the manufacturing facility, as
appropriate.
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\3\ A combination product is assigned to an Agency center
(Center for Biologics Evaluation and Research, Center for Drug
Evaluation and Research, or Center for Devices and Radiological
Health) that will have primary jurisdiction (i.e., be the ``lead
Center'') for that combination product's review and regulation.
Assignment of a combination product to a lead Center is based on a
determination of which constituent part provides the primary mode of
action of the combination product (21 U.S.C. 353(g)). Manufacturers
who are unsure of the lead Center for their combination product or
of whether their product is a combination product, should contact
the Office of Combination Products.
\4\ Note that to discuss a mechanism for complying with CGMP
requirements for which the CP manufacturer is referencing
information in a master file, the CP manufacturer must have the
appropriate authorization from the master file holder (see, e.g., 21
CFR 314.420 and 814.20(c)). The authorization should clearly
identify the specific information within the master file that is
being made available to reference. For more information on
biologics, device, and drug master files, see CBER's master files
for CBER-Regulated Products web page (available at <a href="https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/master-files-cber-regulated-products">https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/master-files-cber-regulated-products</a>), CDRH's master files web
page (available at <a href="https://www.fda.gov/medical-devices/premarket-approval-pma/master-files">https://www.fda.gov/medical-devices/premarket-approval-pma/master-files</a>), and CDER's drug master files web page
(available at <a href="https://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs">https://www.fda.gov/drugs/forms-submission-requirements/drug-master-files-dmfs</a>), respectively.
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<bullet> Premarket Review. CP manufacturers should include in their
original submission for NDAs, BLAs, ANDAs, and PMAs information on any
alternative or streamlined mechanisms for complying with combination
product CGMP requirements. For PMAs, this information should be
included in the manufacturing section of the PMA. For information
regarding where to place information in NDAs, BLAs, or ANDAs, refer to
``eCTD Technical Conformance Guide'' (Ref. 10).
<bullet> Postmarket Supplements or Notifications to FDA. Postmarket
changes to implement a combination product CGMP mechanism for NDAs,
ANDAs, BLAs, and PMAs may require submission of a supplement or
notification to FDA.\5\ CP manufacturers should consult related
guidances relevant to the type of constituent part(s) included in the
combination product (e.g., Refs. 11 to 13, as appropriate). If a CP
manufacturer has questions on the appropriate submission type or the
need for a submission, they can contact the lead Center for assistance.
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\5\ Requirements for postmarket supplements are contained, for
example, in 21 CFR 314.70 and 314.97 (NDAs and ANDAs), 21 CFR 601.12
(BLAs), and 21 CFR 814.39 (PMAs). Any questions on whether FDA
review is required for a postmarket CGMP mechanism should generally
be directed to the lead Center.
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B. Submission Content
When submitting information on a CGMP mechanism, CP manufacturers
should refer to applicable guidance (see section V below) as the
primary reference regarding what information to provide. Along with
other information indicated in relevant guidance (see section V), the
following content should be included:
<bullet> Applicable CGMP Regulation. Identify the applicable CGMP
regulation to which the described mechanism relates. For example, if a
submission includes a mechanism related to stability testing, indicate
that Sec. 211.166 is the applicable CGMP requirement.
<bullet> Applicable Products. If the mechanism is to be applied to
multiple products and/or product configurations, list all related
sizes, strengths, etc., as well as all related application numbers.
<bullet> Prior, Related Interactions with FDA. If the CP
manufacturer has had previous interactions with FDA relevant to the
proposed mechanism, either for the product addressed in the submission
or for related products, the CP manufacturer should provide reference
to those interactions. Where applicable, the CP manufacturer may cross-
reference previously submitted information.
<bullet> Justification and Scientific Data. Include a justification
to support that the proposed mechanism assures adequate manufacturing
control to ensure product safety and effectiveness. When describing a
CGMP alternative or streamlined mechanism in a premarket or postmarket
submission, the description should be accompanied by such data as may
be necessary to support the approach. When proposing a change from a
CGMP approach that was reviewed previously by FDA, such justification
should include analysis of how the proposed approach compares to the
previously reviewed approach as an effective manufacturing control,
including representative data, as appropriate, to substantiate the
analysis.
<bullet> Exemption from Part 820. For interactions with FDA
regarding whether a combination product is exempt from the provisions
of part 820 specified in Sec. 4.4(b)(1), the submission should include
a description of the device constituent part and justification
[[Page 56070]]
that: (1) the intended use of the device in the combination product is
consistent with the intended use of a separately marketed device that
has been exempted from the requirements of part 820 specified in Sec.
4.4(b)(1), and (2) the use of the device constituent part in the
combination product does not raise any different device performance-
related safety and effectiveness questions as compared to a separately
marketed device.
C. FDA Engagement
CP manufacturers are encouraged to discuss combination product CGMP
mechanisms with FDA. In some cases, CP manufacturers may need to
interact with FDA to gain approval or otherwise notify FDA of a
manufacturing change (see III.A above). Any questions on how to engage
FDA in such discussions should generally be directed to the lead Center
for the product (see Ref. 5). The lead Center will engage appropriate
expertise from within the lead Center and from other FDA Centers and
the Office of Combination Products, as needed, to support review (see
Ref. 14), and FDA will provide appropriate feedback (see section III.D
below).
D. FDA Review
FDA may review information from a CP manufacturer related to
alternative or streamlined mechanisms in pre-submissions and meetings,
premarket applications, postmarket supplements or notifications, and
during facility inspections. FDA may determine whether the data and
rationale presented by a CP manufacturer for a particular mechanism are
sufficient to demonstrate that the mechanism, as proposed or
implemented, is acceptable. In such cases, FDA generally will notify
the CP manufacturer and/or applicant regarding acceptability of the
mechanism, consistent with existing policies and practices for the
submission type and, if the Agency finds the approach insufficient, FDA
intends to provide the scientific and/or regulatory basis for this
determination.
IV. Paperwork Reduction Act
This notice refers to previously approved collections of
information found in FDA regulations. These collections of information
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521). We
note that the information collected under the underlying CGMP
regulations for drugs, devices, and biological products, including
current good tissue practices for human cells, tissues, and cellular
and tissue-based products, found in parts 211, 820, 600 through 680,
and 1271 (21 CFR parts 211, 820, 600 through 680, and 1271), have
already been approved and are in effect. The provisions of part 211 are
approved under the OMB control number 0910-0139. The provisions of part
820 are approved under OMB control number 0910-0073. The provisions of
parts 606 and 640 are approved under OMB control number 0910-0116. The
provisions of part 610 are approved under OMB control number 0910-0116
and OMB control number 0910-0338 (also for part 680). The provisions of
part 1271, subparts C and D, are approved under OMB control number
0910-0543.
We note that the information collected under the related submission
types have already been approved and are in effect. The collections of
information regarding formal meetings with sponsors and applicants are
approved under OMB control number 0910-0429. The collections of
information regarding NDA and ANDA are approved under OMB control
number 0910-0001. The collections of information regarding the pre-ANDA
program and controlled correspondence are approved under OMB control
number 0910-0797. The collections of information regarding pre-
submissions are approved under OMB control number 0910-0756. The
collections of information regarding PMAs are approved under OMB
control number 0910-0231. The collections of information for premarket
notification (510(k)) are approved under OMB control number 0910-0120.
The collections of information for the de novo classification process
are approved under OMB control number 0910-0844. The collections of
information regarding BLAs are approved under OMB control number 0910-
0338. The collections of information regarding combination product
agreement meetings are approved under OMB control number 0910-0523.
V. References
The following references are on display in the Dockets Management
Staff (see ADDRESSES) and are available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also
available electronically at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. FDA has
verified the website addresses, as of the date this document publishes
in the Federal Register, but websites are subject to change over time.
1. ``Guidance for Industry and FDA Staff: Current Good Manufacturing
Practice Requirements for Combination Products,'' January 2017.
<a href="https://www.fda.gov/media/90425/download">https://www.fda.gov/media/90425/download</a>.
2. ``Guidance for Industry Q1D Bracketing and Matrixing Designs for
Stability Testing of New Drug Substances and Products,'' January
2003. <a href="https://www.fda.gov/media/71720/download">https://www.fda.gov/media/71720/download</a>.
3. ``Guidance for Industry Quality of Biotechnological Products:
Stability Testing of Biotechnological/Biological Products'' Q5C,
July 1996. <a href="https://www.fda.gov/media/71441/download">https://www.fda.gov/media/71441/download</a>.
4. ``Guidance for Industry Q8(R2) Pharmaceutical Development,''
November 2009. <a href="https://www.fda.gov/media/71535/download">https://www.fda.gov/media/71535/download</a>.
5. ``Guidance for Industry and FDA Staff: Requesting FDA Feedback on
Combination Products,'' December 2020. <a href="https://www.fda.gov/media/133768/download">https://www.fda.gov/media/133768/download</a>.
6. ``Draft Guidance for Industry Formal Meetings Between the FDA and
Sponsors or Applicants of PDUFA Products,'' December 2017. <a href="https://www.fda.gov/media/109951/download">https://www.fda.gov/media/109951/download</a>.
7. ``Guidance for Industry Formal Meetings Between FDA and ANDA
Applicants of Complex Products Under GDUFA,'' November 2020. <a href="https://www.fda.gov/media/107626/download">https://www.fda.gov/media/107626/download</a>.
8. ``Guidance for Industry Controlled Correspondence Related to
Generic Drug Development,'' December 2020. <a href="https://www.fda.gov/media/109232/download">https://www.fda.gov/media/109232/download</a>.
9. ``Guidance for Industry and FDA Staff Requests for Feedback and
Meetings for Medical Device Submissions: The Q-Submission Program,''
January 2021. <a href="https://www.fda.gov/media/114034/download">https://www.fda.gov/media/114034/download</a>.
10. ``eCTD Technical Conformance Guide,'' March 2022. <a href="https://www.fda.gov/media/93818/download">https://www.fda.gov/media/93818/download</a>.
11. ``Guidance for Industry Changes to an Approved NDA or ANDA,''
April 2004. <a href="https://www.fda.gov/media/71846/download">https://www.fda.gov/media/71846/download</a>.
12. ``Guidance for Industry Chemistry, Manufacturing, and Controls
Changes to an Approved Application: Certain Biological Products,''
June 2021. <a href="https://www.fda.gov/media/109615/download">https://www.fda.gov/media/109615/download</a>.
13. ``Guidance for Industry and FDA Staff: 30-Day Notices, 135-Day
Premarket Approval (PMA) Supplements and 75-Day Humanitarian Device
Exemption (HDE) Supplements for Manufacturing Method or Process
Changes,'' December 2019. <a href="https://www.fda.gov/media/72663/download">https://www.fda.gov/media/72663/download</a>.
14. FDA Staff Manual Guide SMG 4101 ``Inter-Center Consult Request
Process,'' June 2018. <a href="https://www.fda.gov/media/81927/download">https://www.fda.gov/media/81927/download</a>.
Dated: September 7, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-19713 Filed 9-12-22; 8:45 am]
BILLING CODE 4164-01-P
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