PharmTech.com Regulating Innovation, Quality, and Risk eBook January 2024 Pharmaceutical Technology
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11
Regul
ations
users at FDA/CDER to manually re-draw each struc-
ture for review and cheminformatics purposes. This
t i me-consum i ng task ca n un i ntent iona l ly i nt ro-
duce errors and is an inef f icient use of resources.
In contrast, submission of structures in the SD File
format allows them to be easily viewed in chemical
drawing sof tware, used in DMF review, submitted
for internal consultations, impor ted into (Q)SAR
sof tware for analysis, or used to create a record in
GSRS. The option to submit structures to the agency
in the eCTD as a single SD File with standardized
data fields that meets the FDA's cheminformatics
and cross-f unctional review needs has been a suc-
cess. In 2022, the agency received 99 SD Files with
a total of 2850 chemicals from industry under this
new paradigm. SD Files are acceptable in Module 3
and the continued inclusion of them in DMF submis-
sions to the FDA is encouraged.
Disclaimer
T h is paper ref lects t he v iews of t he aut hors a nd
should not be construed to represent FDA's views or
policies. The mention of commercial products, their
sources, or their use in connection with material re-
ported herein is not to be construed as either an ac-
tual or implied endorsement of such products by the
Department of Health and Human Services.
References
1. IC H . I C H M 7 ( R 2 ) A s s e s s m e n t a n d C o n t r o l o f
D N A R e a c t i v e ( M u t a g e n i c ) I m p u r i t i e s i n
Pharmaceuticals to Limit Potential Carcinogenic Risk,
Step 4 version (2023).
2. FDA. November 2022 version of the eCTD Technical
Conformance Guide https://w w w.fda.gov/dr ugs/
elect ron ic-reg u lator y-subm ission-a nd-rev iew/
electronic-common-technical-document-ectd
3. FDA. Quick Guide to Creating a Structure-Data File
(SD File) for DMF Submissions. FDA .gov. https://
www.fda.gov/drugs/drug-master-files-dmfs/drug-
master-file-dmf-submission-resources .
4. F DA . E le c t r on ic Su bm i s s ion s Ga t e w ay. F DA .
gov. ht t ps://w w w.fda.gov/indust r y/elect ron ic-
submissions-gateway
5. Molecular Design Lim ited (MDL) was acquired
t h r o u g h v a r i o u s a c q u i s i t i o n s b y D a s s a u l t
S y s t è m e s . B i o v i a (a s u b s i d i a r y o f D a s s a u l t
Systèmes) is the organization that now maintains
the SDF format.
6. A. Da lby, et. a l. J. Chem. Inf. Comput. Sci, online,
https://doi.org/10.1021/ci00007a012
7. SD files (multiple structures and optional data).
C T F I L E F O R M AT S B I OV I A D a t a b a s e s 2 0 1 6 .
Dassault Systèmes© 2015. ■
Barbara Scott* is a Master Reviewer
at FDA Center for Drug Evaluation
and Research/Office of Pharmaceutical
Quality/Office of New Drug Products/ Division of
Lifecycle Active Pharmaceutical Ingredients, Barbara.
Scott@fda.hhs.gov. David Green is a Senior
Pharmaceutical Quality Assessor at FDA Center
for Drug Evaluation and Research/Office of
Pharmaceutical Quality/Office of New Drug Products/
Division of Lifecycle Active Pharmaceutical Ingredients.
Marlene Kim is a Chemist at FDA Office of the
Commissioner/Office of Digital Transformation/Office
of Data, Analytics, and Research/Health Informatics
Staff. Naomi Kruhlak is Scientific Lead, Computational
Toxicology Consultation Service at FDA Center
for Drug Evaluation and Research/Office of
Translational Sciences/Office of Clinical
Pharmacology/ Division of Appliewd Regulatory
Science. Tyler Peryea is a Chemist at FDA Office of the
Commissioner/Office of Digital Transformation/Office of
Data, Analytics, and Research/Health Informatics Staff.
David Skanchy was the Division Director (retired) at
FDA Center for Drug Evaluation and Research/Office of
Pharmaceutical Quality/Office of New Drug Products/
Division of Lifecycle Active Pharmaceutical Ingredients.
*To whom all correspondence should be addressed.
TABLE I. Frequently asked
questions (FAQs).
Question Answer
In what section of the
eCTD should the SD
File be placed?
Module 3
Drug Substance: eCTD Section
3.2.S.3.2
Is there free software
available to generate
SD Files?
Yes, freely available and/or
commercial software can be used
to create an SD File (3).
Is it expected to link
the SD File in the XML
Index File?
The SDF file should be mapped via
XML. Otherwise, an error message
will be generated. For electronic
submission questions, email the
CDER Electronic Submission (ESUB)
Support Team at esub@fda.hhs.gov.
How are SD Files
included in the eCTD?
The SD File should be included
in section 3.2.S.3.2 of the eCTD
and contain the .sdf file extension.
For help with the Electronic
Submissions Gateway, email
esub@fda.hhs.gov. For help with
the eCTD see the eCTD Technical
Conformance Guide, p. 13 (2).
Are there step by
step instructions
available for creating
an SD File?
Yes, refer to the Quick Guide to
Creating a Structure-Data File
(SD File) for DMF Submissions for
help in creating the SD File and for
preferred column definitions for the
associated data fields (3).
How are complex
structures included
in an SD File? (e.g.,
proteins, peptides, or
unnatural amino acids)
Complex substances may
require additional data element
descriptors. A UNII for the
substance can be obtained by
contacting FDA-SRS@fda.hhs.gov.
