Evaluating the Immunogenicity Risk of Host Cell Proteins in Follow-On Recombinant Peptide Products; Establishment of a Public Docket; Request for Information and Comments, 60436-60438 [2024-16356]
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60436
Federal Register / Vol. 89, No. 143 / Thursday, July 25, 2024 / Notices
May 22, .2024
Anita 1:'argqsz:
Senior Director, Quality
Tltemto FisherSoientific
5823 Newton Drive
Carlsbad, CA. 9200~
Re: Revocation ofEUA200028
Dear Anita Targosz:
This letter is in responsdo the request from Mesa BiotechJnc. (a legal entity of Thermo Fisher
Scientific), made by Thenno FisherSoierttific, Inc. Otlbebalfof MesaBiotech Inc. in a letter
dated MayJ5, 2024, thatthe
Food and Drug Administration (FDA) revoke the EUA for the
AoculaS,'\R~CqV,2Testissued on Mm;h 23, 2020, amended on ApriJ3(), 2020:attdAugust3Q,
2020; reissued on January 7,. 2021, amended on February 3,2021 and September 23; 2021, and
reissued on Mar 16,. 2022, August 17,.2022 and March 15, 2023. Thermo Fisher Scientific Inc.
indicated thatthethave discontinued commercializaticm and support ofthe authoriZed product
lUld reqµestedthat the EUA be rev.9ked: FDA understands that as of the date of this letter there
are no viableAccul& SARS-CoV-2 Test reage11tsremilining in distribution.in the UnitedStates,
ns.
The authorization lifa devit:efotemergency use under section SIM◊fthe Federal Fodd, btug,
and C9smetic Act (the.Act) (21 U:s. C, 360bl:>b03) may~ pun;uant fo section S64(g)(2) of the Act,
be revokedwhencircum,sfmlces )llaj(e such revocation 1tpproptiatetoptote~the public, health, or
safety (section564(gX2)(C)oftheAct), BecauseMesa:Siotech fno., through Thernto Fisher
Scientific,Jnc.,..has requested that FDA.revoke the EUA for theAccula SARS•CoV-2 Test, FDA
has de:tel'!llined.that: it is ¥fitopriate tq protect the public health.or safety to revoke this
authorization. Acc-ordingly, FD.1\herebyr¢vokes EUA200Q28 furtlie A9cul• SARS°CoV~'4'l'est,
pursuanito·section564(gX2).(C) oftheAct. As of the date ofthis letter, the Acoula SARS~CoV~2
Test is no longlalrauthorizedforernergencyuse by FDA.
Nqtice ofthisrevocati9n willbe published intheJtMeral.Regt:ster,. pursuant to section 564(h)(l)
ofthe.Acl
sliicerefy,
!Isl/
Dated: July 18, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
Notice; establishment of a
public docket; request for information
and comments.
ACTION:
[FR Doc. 2024–16345 Filed 7–24–24; 8:45 am]
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
ddrumheller on DSK120RN23PROD with NOTICES1
[Docket No. FDA–2024–N–2980]
Evaluating the Immunogenicity Risk of
Host Cell Proteins in Follow-On
Recombinant Peptide Products;
Establishment of a Public Docket;
Request for Information and
Comments
AGENCY:
Food and Drug Administration,
HHS.
VerDate Sep<11>2014
19:41 Jul 24, 2024
Jkt 262001
The Food and Drug
Administration (FDA or Agency) is
establishing a public docket to collect
information and comments on
evaluating and mitigating the
immunogenicity risk of host cell
proteins (HCPs). For the purpose of this
request, FDA is specifically interested in
comments on suitable methods to
detect, identify, and quantify HCPs, on
achievable residual amounts of HCPs for
recombinant peptide products, and on
the use of in vitro, in silico
immunogenicity assessment (IVISIA) of
HCPs in a recombinant peptide
(rPeptide) product. For the purpose of
this request, a ‘‘follow-on’’ peptide
product refers to the applications
SUMMARY:
BILLING CODE 4161–01–P
PO 00000
Frm 00088
Fmt 4703
Sfmt 4703
currently evaluated through the
505(b)(2) pathway. Although follow-on
recombinant peptide products can rely
on FDA’s findings of safety and
effectiveness for a listed drug that is a
peptide product, differences in
recombinant expression systems used
during the peptide production could
result in quality attribute differences,
including in the HCP profile, which in
turn, could contribute to differences in
immunogenicity risks between a followon recombinant peptide product and the
listed drug. The public comments
collected will help FDA develop
recommendations on how HCP control
and characterization can support
comparative immunogenicity risk
assessment between a recombinant
follow-on peptide and the listed
product.
E:\FR\FM\25JYN1.SGM
25JYN1
EN25JY24.001</GPH>
1effi-eyE. Shuren, M.D., J.D.
Director
center for Devices andRadiofogical Health
Food and Drug Administration
Federal Register / Vol. 89, No. 143 / Thursday, July 25, 2024 / Notices
Although you can submit
comments and information at any time,
to ensure that the Agency considers
your comment in our development of
recommendations, submit either
electronic or written information and
comments by September 23, 2024.
ADDRESSES:
DATES:
ddrumheller on DSK120RN23PROD with NOTICES1
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are
solely responsible for ensuring that your
comment does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
as a manufacturing process. Please note
that if you include your name, contact
information, or other information that
identifies you in the body of your
comments, that information will be
posted on https://www.regulations.gov.
• If you want to submit a comment
with confidential information that you
do not wish to be made available to the
public, submit the comment as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
Written/Paper Submissions
Submit written/paper submissions as
follows:
• Mail/Hand Delivery/Courier (for
written/paper submissions): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, FDA will post your comment, as
well as any attachments, except for
information submitted, marked and
identified, as confidential, if submitted
as detailed in ‘‘Instructions.’’
Instructions: All submissions received
must include the Docket No. FDA–
2024–N–2980 for ‘‘Evaluating the
Immunogenicity Risk of Host Cell
Proteins in Follow-On Recombinant
Peptide Products; Establishment of a
Public Docket; Request for Information
and Comments.’’ Received comments,
those filed in a timely manner (see
ADDRESSES), will be placed in the docket
and, except for those submitted as
‘‘Confidential Submissions,’’ publicly
viewable at https://www.regulations.gov
VerDate Sep<11>2014
19:41 Jul 24, 2024
Jkt 262001
or at the Dockets Management Staff
between 9 a.m. and 4 p.m., Monday
through Friday, 240–402–7500.
• Confidential Submissions—To
submit a comment with confidential
information that you do not wish to be
made publicly available, submit your
comments only as a written/paper
submission. You should submit two
copies total. One copy will include the
information you claim to be confidential
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS
CONFIDENTIAL INFORMATION.’’ The
Agency will review this copy, including
the claimed confidential information, in
its consideration of comments. The
second copy, which will have the
claimed confidential information
redacted/blacked out, will be available
for public viewing and posted on
https://www.regulations.gov. Submit
both copies to the Dockets Management
Staff. If you do not wish your name and
contact information to be made publicly
available, you can provide this
information on the cover sheet and not
in the body of your comments and you
must identify this information as
‘‘confidential.’’ Any information marked
as ‘‘confidential’’ will not be disclosed
except in accordance with 21 CFR 10.20
and other applicable disclosure law. For
more information about FDA’s posting
of comments to public dockets, see 80
FR 56469, September 18, 2015, or access
the information at: https://
www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
www.regulations.gov 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, 240–402–7500.
FOR FURTHER INFORMATION CONTACT:
Mohsen Rajabiabhari, Office of Clinical
Pharmacology, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Silver Spring, MD
20993–0002, 240–402–2794.
SUPPLEMENTARY INFORMATION:
I. Background
FDA for purposes of this notice uses
the term ‘‘peptide’’ to refer to alpha
amino acid polymers composed of 40 or
fewer amino acids.1 Peptides can be
isolated from natural sources or
1 See, e.g., FDA Final Rule ‘‘Definition of the
Term ‘Biological Product’ ’’ (85 FR 10057, March 23,
2020).
PO 00000
Frm 00089
Fmt 4703
Sfmt 4703
60437
produced synthetically or through
recombinant expression in a host cell.
Peptides that are isolated from
recombinant (i.e., genetically-modified)
prokaryotic or eukaryotic host cells
using cell culture/fermentation
techniques are called recombinant
peptides (rPeptides).
HCPs are process-related impurities
derived from the host cell that may
copurify with the recombinant peptide
of interest and be present in the final
drug product. HCPs are characterized
and routinely well controlled during
manufacturing of the peptide product.
The types and amounts of HCPs in a
product differ depending on many
parameters, including differences in the
expression cell substrate, culture
conditions, the purification process, and
amongst different facilities. Therefore,
for a proposed follow-on rPeptide
product, differences in HCP profiles
between the follow-on product and the
listed drug would be expected, and such
differences have the potential to impact
the safety and/or efficacy of the followon product by increasing that product’s
immunogenicity risk. Advances in
technology may support the use of
IVISIA methods to assess comparative
immunogenicity risk.
II. Request for Information and
Comments
Interested persons are invited to
provide detailed information (including
any supportive data) and comments on
suitable methods to detect, identify, and
quantify HCPs and the minimal residual
amounts of HCPs achievable in
commercial lots of rPeptide products.
Specifically, to assess the potential
impact of HCP differences, FDA is
interested in responses to the following
questions:
1. What is the lowest and routinely
achievable level of total HCPs across
your well-controlled rPeptide
manufacturing process(es), and how are
they calculated/established?
2. What are the challenges in reducing
HCP levels?
3. What analytical methods are
currently being used to detect, identify,
and quantify HCPs in a rPeptide
product? Do you conduct comparative
assessments of HCPs, such as ELISA
(enzyme-linked immunosorbent assay)
vs LC/MS/MS (liquid chromatography
tandem mass spectrometry), during
manufacturing development? What is
the sensitivity of these methods for
detecting HCPs and their limits of
quantification? Are you using a
combination of orthogonal analytical
methods (such as ELISA + LC/MS/MS)
for HCP control during process
development and manufacturing?
E:\FR\FM\25JYN1.SGM
25JYN1
60438
Federal Register / Vol. 89, No. 143 / Thursday, July 25, 2024 / Notices
4. What is the generally achievable
percent coverage 2 of the HCP spectrum
for your HCP quantification assay? What
considerations, (e.g., percent coverage of
HCPs, other coverage characteristics,
etc.), are important in choosing methods
to evaluate HCPs?
5. Are there any qualitative or
quantitative characteristics of HCPs
associated with a higher likelihood of
adverse clinical sequelae?
6. What tools (in silico, in vitro or in
vivo studies) do you currently use or
plan to use to compare the potential
immunogenicity risk of two products
with different HCP profiles? What is
your approach to risk assessment of
HCPs based upon such data?
The public comments collected will
help FDA develop recommendations on
how HCP control and characterization
can support comparative
immunogenicity risk assessment
between a recombinant follow-on
peptide and the listed product.
III. Electronic Access
Persons with access to the internet
may obtain relevant guidance at https://
www.fda.gov/regulatory-information/
search-fda-guidance-documents/
clinical-pharmacology-considerationspeptide-drug-products.
Electronic Submissions
Dated: July 18, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024–16356 Filed 7–24–24; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2024–N–3228]
Biosimilar Product Development
Guidance; Establishment of a Public
Docket; Request for Information and
Comments
AGENCY:
Food and Drug Administration,
HHS.
Notice; establishment of a
public docket; request for information
and comments.
ACTION:
The Food and Drug
Administration (FDA or Agency) is
announcing the establishment of a
docket to obtain information and
comments that will assist the Agency in
assessing how best to advance the
ddrumheller on DSK120RN23PROD with NOTICES1
SUMMARY:
2 HCP coverage is an estimate of the percentage
of HCPs specific to a cell substrate detected or
covered by the capture antibodies of the ELISA.
This coverage analysis is often done using 2D
techniques.
VerDate Sep<11>2014
19:41 Jul 24, 2024
Jkt 262001
development of new biosimilar
biological products (biosimilars or
biosimilar products), as part of the
Biosimilar User Fee Amendments of
2022 (BsUFA III). As FDA continues to
advance the development of biosimilars,
we are seeking input from industry on
whether biosimilar product
development would be best served by
focusing on product class-specific
guidance documents that address
common development issues that apply
to a broad class of products, or by
developing product-specific guidance
documents, similar to the approach
taken in the Generic Drug User Fee
Amendments (GDUFA) program.
DATES: Submit either electronic or
written comments, data, or information
by October 23, 2024.
ADDRESSES: You may submit data,
information, and comments as follows.
Please note that late, untimely filed
comments will not be considered. The
https://www.regulations.gov electronic
filing system will accept comments
until 11:59 p.m. Eastern Time at the end
of October 23, 2024. Comments received
by mail/hand delivery/courier (for
written/paper submissions) will be
considered timely if they are received
on or before that date.
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are
solely responsible for ensuring that your
comment does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
as a manufacturing process. Please note
that if you include your name, contact
information, or other information that
identifies you in the body of your
comments, that information will be
posted on https://www.regulations.gov.
• If you want to submit a comment
with confidential information that you
do not wish to be made available to the
public, submit the comment as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
Written/Paper Submissions
Submit written/paper submissions as
follows:
PO 00000
Frm 00090
Fmt 4703
Sfmt 4703
• Mail/Hand Delivery/Courier (for
written/paper submissions): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, FDA will post your comment, as
well as any attachments, except for
information submitted, marked and
identified, as confidential, if submitted
as detailed in ‘‘Instructions.’’
Instructions: All submissions received
must include the Docket No. FDA–
2024–N–3228 ‘‘Biosimilar Product
Development Guidance; Establishment
of a Public Docket; Request for
Information and Comments.’’ Received
comments, those filed in a timely
manner (see ADDRESSES), will be placed
in the docket and, except for those
submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
https://www.regulations.gov or at the
Dockets Management Staff between 9
a.m. and 4 p.m., Monday through
Friday, 240–402–7500.
• Confidential Submissions—To
submit a comment with confidential
information that you do not wish to be
made publicly available, submit your
comments only as a written/paper
submission. You should submit two
copies total. One copy will include the
information you claim to be confidential
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS
CONFIDENTIAL INFORMATION.’’ The
Agency will review this copy, including
the claimed confidential information, in
its consideration of comments. The
second copy, which will have the
claimed confidential information
redacted/blacked out, will be available
for public viewing and posted on
https://www.regulations.gov. Submit
both copies to the Dockets Management
Staff. If you do not wish your name and
contact information to be made publicly
available, you can provide this
information on the cover sheet and not
in the body of your comments and you
must identify this information as
‘‘confidential.’’ Any information marked
as ‘‘confidential’’ will not be disclosed
except in accordance with 21 CFR 10.20
and other applicable disclosure law. For
more information about FDA’s posting
of comments to public dockets, see 80
FR 56469, September 18, 2015, or access
the information at: https://
www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
www.regulations.gov and insert the
docket number, found in brackets in the
E:\FR\FM\25JYN1.SGM
25JYN1
]]>Agencies
[Federal Register Volume 89, Number 143 (Thursday, July 25, 2024)]
[Notices]
[Pages 60436-60438]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-16356]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2024-N-2980]
Evaluating the Immunogenicity Risk of Host Cell Proteins in
Follow-On Recombinant Peptide Products; Establishment of a Public
Docket; Request for Information and Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; establishment of a public docket; request for
information and comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is
establishing a public docket to collect information and comments on
evaluating and mitigating the immunogenicity risk of host cell proteins
(HCPs). For the purpose of this request, FDA is specifically interested
in comments on suitable methods to detect, identify, and quantify HCPs,
on achievable residual amounts of HCPs for recombinant peptide
products, and on the use of in vitro, in silico immunogenicity
assessment (IVISIA) of HCPs in a recombinant peptide (rPeptide)
product. For the purpose of this request, a ``follow-on'' peptide
product refers to the applications currently evaluated through the
505(b)(2) pathway. Although follow-on recombinant peptide products can
rely on FDA's findings of safety and effectiveness for a listed drug
that is a peptide product, differences in recombinant expression
systems used during the peptide production could result in quality
attribute differences, including in the HCP profile, which in turn,
could contribute to differences in immunogenicity risks between a
follow-on recombinant peptide product and the listed drug. The public
comments collected will help FDA develop recommendations on how HCP
control and characterization can support comparative immunogenicity
risk assessment between a recombinant follow-on peptide and the listed
product.
[[Page 60437]]
DATES: Although you can submit comments and information at any time, to
ensure that the Agency considers your comment in our development of
recommendations, submit either electronic or written information and
comments by September 23, 2024.
ADDRESSES:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2024-N-2980 for ``Evaluating the Immunogenicity Risk of Host Cell
Proteins in Follow-On Recombinant Peptide Products; Establishment of a
Public Docket; Request for Information and Comments.'' Received
comments, those filed in a timely manner (see ADDRESSES), will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday, 240-402-7500.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov 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, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Mohsen Rajabiabhari, Office of
Clinical Pharmacology, Center for Drug Evaluation and Research, Food
and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD
20993-0002, 240-402-2794.
SUPPLEMENTARY INFORMATION:
I. Background
FDA for purposes of this notice uses the term ``peptide'' to refer
to alpha amino acid polymers composed of 40 or fewer amino acids.\1\
Peptides can be isolated from natural sources or produced synthetically
or through recombinant expression in a host cell. Peptides that are
isolated from recombinant (i.e., genetically-modified) prokaryotic or
eukaryotic host cells using cell culture/fermentation techniques are
called recombinant peptides (rPeptides).
---------------------------------------------------------------------------
\1\ See, e.g., FDA Final Rule ``Definition of the Term
`Biological Product' '' (85 FR 10057, March 23, 2020).
---------------------------------------------------------------------------
HCPs are process-related impurities derived from the host cell that
may copurify with the recombinant peptide of interest and be present in
the final drug product. HCPs are characterized and routinely well
controlled during manufacturing of the peptide product. The types and
amounts of HCPs in a product differ depending on many parameters,
including differences in the expression cell substrate, culture
conditions, the purification process, and amongst different facilities.
Therefore, for a proposed follow-on rPeptide product, differences in
HCP profiles between the follow-on product and the listed drug would be
expected, and such differences have the potential to impact the safety
and/or efficacy of the follow-on product by increasing that product's
immunogenicity risk. Advances in technology may support the use of
IVISIA methods to assess comparative immunogenicity risk.
II. Request for Information and Comments
Interested persons are invited to provide detailed information
(including any supportive data) and comments on suitable methods to
detect, identify, and quantify HCPs and the minimal residual amounts of
HCPs achievable in commercial lots of rPeptide products. Specifically,
to assess the potential impact of HCP differences, FDA is interested in
responses to the following questions:
1. What is the lowest and routinely achievable level of total HCPs
across your well-controlled rPeptide manufacturing process(es), and how
are they calculated/established?
2. What are the challenges in reducing HCP levels?
3. What analytical methods are currently being used to detect,
identify, and quantify HCPs in a rPeptide product? Do you conduct
comparative assessments of HCPs, such as ELISA (enzyme-linked
immunosorbent assay) vs LC/MS/MS (liquid chromatography tandem mass
spectrometry), during manufacturing development? What is the
sensitivity of these methods for detecting HCPs and their limits of
quantification? Are you using a combination of orthogonal analytical
methods (such as ELISA + LC/MS/MS) for HCP control during process
development and manufacturing?
[[Page 60438]]
4. What is the generally achievable percent coverage \2\ of the HCP
spectrum for your HCP quantification assay? What considerations, (e.g.,
percent coverage of HCPs, other coverage characteristics, etc.), are
important in choosing methods to evaluate HCPs?
---------------------------------------------------------------------------
\2\ HCP coverage is an estimate of the percentage of HCPs
specific to a cell substrate detected or covered by the capture
antibodies of the ELISA. This coverage analysis is often done using
2D techniques.
---------------------------------------------------------------------------
5. Are there any qualitative or quantitative characteristics of
HCPs associated with a higher likelihood of adverse clinical sequelae?
6. What tools (in silico, in vitro or in vivo studies) do you
currently use or plan to use to compare the potential immunogenicity
risk of two products with different HCP profiles? What is your approach
to risk assessment of HCPs based upon such data?
The public comments collected will help FDA develop recommendations
on how HCP control and characterization can support comparative
immunogenicity risk assessment between a recombinant follow-on peptide
and the listed product.
III. Electronic Access
Persons with access to the internet may obtain relevant guidance at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-pharmacology-considerations-peptide-drug-products.
Dated: July 18, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-16356 Filed 7-24-24; 8:45 am]
BILLING CODE 4164-01-P
