Section I: Marketing Authorization Transfers, Renewals, and Administrative Changes
Chapter 1: United States
6
MA Withdrawal—FDA-Initiated
FDA-initiated withdrawals without the appli-
cant’s cooperation are relatively rare.
21 CFR 314.150(a), (b), and 21 CFR
314.151 describe the circumstances that can
prompt FDA to propose withdrawal of an NDA
or ANDA. Typically, FDA proposes this action
in the face of significant, serious situations, such
as a finding of imminent hazard to public health,
a new serious safety problem that cannot be
mitigated with labeling or other risk management
tools, new information that indicates a lack of
substantial evidence of effectiveness from adequate
and well-controlled studies, or a finding that the
NDA or ANDA contains an untrue statement
of material fact. An applicant will be offered the
opportunity for a public hearing to discuss the
issues prompting the proposal for withdrawal
before the withdrawal becomes effective.
The regulations at 21 CFR 601.5 are analo-
gous to those at 21 CFR 314.150(a) and (b) and
describe the circumstances under which FDA
will initiate revocation of a BLA.
The regulations at 21 CFR 314.530 and
601.43 describes specific, expedited withdrawal
procedures and criteria for new drugs and bio-
logics, respectively, approved based on surrogate
endpoints and/or with restrictions to ensure
safe use (i.e., drugs or biologics approved under
“accelerated approval”). Withdrawal under 21
CFR 314.530 or 601.43 is most likely to occur
when confirmatory studies fail to demonstrate
clinical benefit.
In accordance with 21 CFR 314.152
and 601.8, NDA, ANDA, and BLA with-
drawals and revocations are published in
the US Federal Register. See, for exam-
ple, https://www.federalregister.gov/
documents/2020/05/14/2020-10367/
janssen-pharmaceuticals-inc-et-al-withdraw-
al-of-approval-of-16-new-drug-applications.
Conclusion
This chapter reviewed the applicable US regula-
tions and guidances that address MA transfers
and other administrative (i.e., non-scientific,
clinical, or technical) postapproval changes. To
ensure continued compliance with all applicable
regulations after approval, US MA applicants
must make timely notification to FDA of these
administrative changes, as appropriate, consistent
with these regulations and guidances. While the
letter of these requirements varies from country
to country, as will be seen throughout this book,
certain principles apply regardless of the coun-
try or regulator, namely applicants’ obligations
to keep regulators aware of dossier content as it
evolves after initial approval, regardless of how
minor the change is perceived to be.
References
1. Drug vs new drug. FDA website. https://www.access-
data.fda.gov/scripts/cder/training/otc/topic3/topic3/
da_01_03_0030.htm#:~:text=In%20general%2C%20
a%20drug%20is,for%20use%20under%20the%20con-
dition.
2. Biologics License Applications (BLA) Process
(CBER). Current as of 27 January 2021. FDA
website. https://www.fda.gov/vaccines-blood-bi-
ologics/development-approval-process-cber/
biologics-license-applications-bla-process-cber#:~:tex-
t=The%20Biologics%20License%20Application%20
(BLA,under%2021%20CFR%20600%20
%E2%80%93%20680.
3. Abbreviated New Drug Application (ANDA).
Current as of 14 January 2022. FDA website. https://
www.fda.gov/drugs/types-applications/abbreviat-
ed-new-drug-application-anda.
4. 21 CFR Part 314.72, Change in ownership of an appli-
cation. Revised as of 1 April 2014.
5. SOPP 8403: Issuance, Reissuance, and Voluntary
Revocation of Biological Products Licenses. Effective
date 25 October 2020. FDA website. https://www.fda.
gov/media/108918/download.
6. Drug Master Files: Guidelines. Current as of 16
November 2017. FDA website. https://www.fda.gov/
drugs/guidances-drugs/drug-master-files-guidelines.
7. Guidance for Industry: Changes to an Approved NDA
or ANDA. April 2004. FDA website. https://www.fda.
gov/media/71846/download.
8. 21 CFR Part 314.150(c), Withdrawal of approval of an
application or abbreviated application. Revised as of 1
April 2014.
9. 21 CFR Part 601.5, Revocation of license. Revised as of
1 April 2014.
All URLs were accessed on 9 May 2022.
Chapter 1: United States
6
MA Withdrawal—FDA-Initiated
FDA-initiated withdrawals without the appli-
cant’s cooperation are relatively rare.
21 CFR 314.150(a), (b), and 21 CFR
314.151 describe the circumstances that can
prompt FDA to propose withdrawal of an NDA
or ANDA. Typically, FDA proposes this action
in the face of significant, serious situations, such
as a finding of imminent hazard to public health,
a new serious safety problem that cannot be
mitigated with labeling or other risk management
tools, new information that indicates a lack of
substantial evidence of effectiveness from adequate
and well-controlled studies, or a finding that the
NDA or ANDA contains an untrue statement
of material fact. An applicant will be offered the
opportunity for a public hearing to discuss the
issues prompting the proposal for withdrawal
before the withdrawal becomes effective.
The regulations at 21 CFR 601.5 are analo-
gous to those at 21 CFR 314.150(a) and (b) and
describe the circumstances under which FDA
will initiate revocation of a BLA.
The regulations at 21 CFR 314.530 and
601.43 describes specific, expedited withdrawal
procedures and criteria for new drugs and bio-
logics, respectively, approved based on surrogate
endpoints and/or with restrictions to ensure
safe use (i.e., drugs or biologics approved under
“accelerated approval”). Withdrawal under 21
CFR 314.530 or 601.43 is most likely to occur
when confirmatory studies fail to demonstrate
clinical benefit.
In accordance with 21 CFR 314.152
and 601.8, NDA, ANDA, and BLA with-
drawals and revocations are published in
the US Federal Register. See, for exam-
ple, https://www.federalregister.gov/
documents/2020/05/14/2020-10367/
janssen-pharmaceuticals-inc-et-al-withdraw-
al-of-approval-of-16-new-drug-applications.
Conclusion
This chapter reviewed the applicable US regula-
tions and guidances that address MA transfers
and other administrative (i.e., non-scientific,
clinical, or technical) postapproval changes. To
ensure continued compliance with all applicable
regulations after approval, US MA applicants
must make timely notification to FDA of these
administrative changes, as appropriate, consistent
with these regulations and guidances. While the
letter of these requirements varies from country
to country, as will be seen throughout this book,
certain principles apply regardless of the coun-
try or regulator, namely applicants’ obligations
to keep regulators aware of dossier content as it
evolves after initial approval, regardless of how
minor the change is perceived to be.
References
1. Drug vs new drug. FDA website. https://www.access-
data.fda.gov/scripts/cder/training/otc/topic3/topic3/
da_01_03_0030.htm#:~:text=In%20general%2C%20
a%20drug%20is,for%20use%20under%20the%20con-
dition.
2. Biologics License Applications (BLA) Process
(CBER). Current as of 27 January 2021. FDA
website. https://www.fda.gov/vaccines-blood-bi-
ologics/development-approval-process-cber/
biologics-license-applications-bla-process-cber#:~:tex-
t=The%20Biologics%20License%20Application%20
(BLA,under%2021%20CFR%20600%20
%E2%80%93%20680.
3. Abbreviated New Drug Application (ANDA).
Current as of 14 January 2022. FDA website. https://
www.fda.gov/drugs/types-applications/abbreviat-
ed-new-drug-application-anda.
4. 21 CFR Part 314.72, Change in ownership of an appli-
cation. Revised as of 1 April 2014.
5. SOPP 8403: Issuance, Reissuance, and Voluntary
Revocation of Biological Products Licenses. Effective
date 25 October 2020. FDA website. https://www.fda.
gov/media/108918/download.
6. Drug Master Files: Guidelines. Current as of 16
November 2017. FDA website. https://www.fda.gov/
drugs/guidances-drugs/drug-master-files-guidelines.
7. Guidance for Industry: Changes to an Approved NDA
or ANDA. April 2004. FDA website. https://www.fda.
gov/media/71846/download.
8. 21 CFR Part 314.150(c), Withdrawal of approval of an
application or abbreviated application. Revised as of 1
April 2014.
9. 21 CFR Part 601.5, Revocation of license. Revised as of
1 April 2014.
All URLs were accessed on 9 May 2022.