e-dossier submission: regulatory and procedural guidance: pepgra
DESCRIPTION
It is an immense improvement over spending hours in a file room digging through files, taking out volume after volume just being able to pull up a 2-year-old investigational new drug (IND) application and look at it in a current view as well as a historical view in a few clicks. The secret to this significant change is the Popular Electronic Common Technical Document (eCTD), which represents a major advance in the global march towards electronic regulatory submissions. learn More: http://bit.ly/2UrwyGV Need Help: Uk: +44- 7424810299 Email: [email protected] Whatsapp: +91 9884350006TRANSCRIPT
Copyright © 2020 pepgra. All rights reserved 1
E-DOSSIER SUBMISSION: REGULATORY AND PROCEDURAL
GUIDANCE
Dr. Nancy Agens, Head,
Technical Operations, Pepgra
In Brief
This particular write-up presents a
background about e-dossiers that are
submitted to regional authorities by
pharmaceutical companies for drug
registrations. The write-up highlights the
pre-requisites and procedures while
submitting an e-dossier.
Keywords: e-dossiers, eCTD, electronic
submissions, ICH, MHRA,
I. INTRODUCTION
Right from 1990, the International
Conference for Harmonization of Technical
Requirements for Pharmaceuticals for
Human Use (ICH) has been consistently
striving to develop a framework which is
standardized with regards to drug
registrations. The objective of such a
standardized framework is to bring about a
harmony to the maximum extent possible,
the content and structure of the technical
information furnished to lend support to
marketing authorizations. Representatives
from Japan, the European Union and the
United States and from other regions that
function as observers are instrumental in
driving the ICH. The steering committee of
the ICH during November 2000 had ratified
guidelines which were established by the
ICH M4 working group, elucidating the
Common Technical Document (CTD) in
order to register pharmaceuticals that were
intended for use by humans (Bonn, 2007).
This implied that the paper version of the
CTD had realized Step 4 status, indicating
that the ICH members had reached a
consensus wherein each member was
committed to integrate the ICH guidelines
within the regulatory framework of each
region. Culmination of this last step is
termed as Step 5. Within the United States
(US), the FDA has officially embraced the
guidelines as laid down by the ICH as FDA
guidance. Within Europe, Volume 2B of
Notice of Applicants underwent
modifications during 2001 to incorporate the
CTD within the legislative system in
Europe. From July 2003 onwards, it has
been made mandatory for every applicant to
submit paper dossiers in the EU, Japan and
the US.
However, a growing need was felt
for facilitating electronic submissions. The
ICH M2 ESTRI (Electronic Standards for
the Transfer of Regulatory Information)
working group created the standard for
electronic message exchange for CTD which
was termed as the electronic common
technical document (eCTD). The eCTD
comes across as an electronic form of a CTD
that was paper based. The eCTD
specification outlines the criteria to take into
account electronic submissions as
technically acceptable. In addition, the
standards as laid down by the eCTD outline
the mediums to develop and convey an
electronic submission that matches the CTD
definitions (Bonn, 2007). The focus here is
to offer the capability to convey the CTD
from industry to a regulatory authority.
Also, the eCTD considers the necessity to
extend assistance over the entire lifecycle of
an electronic submission or dossier. The
eCTD standard founded on the initial
version 3.0 specification realized Step 4
Copyright © 2020 pepgra. All rights reserved 2
during October 2002, and is being executed
across regions, escalating it to Step 5.
Therefore, the objective of this article is to
outline the regulatory and procedural
guidance for e-dossier submission.
II. FUNDAMENTALS OF ELECTRONIC
SUBMISSION
The specification for eCTD
elucidates the format for the message and
the procedure for moving submission
documents and processing instructions to an
agency system. Standards as laid down by
the eCTD offers a medium to capture every
interaction that occurs between agencies and
industry, in such a way that it sheds light on
modifications between multiple
submissions. This lifecycle view of the
submission can be realized with the help of
the XML format. By using the XML format,
it is possible to describe every document
that is included within the submission. In
addition, it also offers instructions to the
system that receives the submission, thus
enabling data management, which elucidates
the submission. Such data is popularly
known as meta data and examples of meta
data at the level of submission comprises
information pertaining to the submission
type, the agency that will receive the
submission and the applicants who submit
(FAMHP, 2016). Examples pertaining to
meta data at the level of document would
comprise of information regarding the
version, descriptive information as in name
of documents and time stamps and language.
On the whole, the ability of the XML to
segregate content from structure holds the
key in terms of its versatility and increasing
popularity. It has several uses, enabling
users to restyle and reformat to match
diverse media types, recognize elements,
reuse portions, exchange data and sustain
and output several versions for the same
document.
As an outcome, extra specifications
have been setup by several regions on the
basis of XML format for content in the
eCTD standard. These are frequently replace
document files that are unstructured (eg; -
doc, -pdf, -rtf) with XML documents that
are highly structured and exemplified by the
FDA’s Study Tagging File (STF) or
Europe’s electronic Application Form
(eAF), in tandem with initiatives at labeling
like the FDA’s structured product labeling
(SPL) and EMEA’s product information
management (PIM). This trend can also be
viewed as a consistent extension of the
eCTD standard making the submitted
information largely granular and more in a
position to be managed with ease by systems
which are automated. This, more often
augments the efficiency and quality of the
process of regulatory review.
II. ACCEPTANCE OF E-DOSSIERS
The NCA Medicines and Healthcare
products Regulatory agency (MHRA) in the
UK has been since 2005 accepting electronic
submissions while the paper format has been
completely stopped since 2007. As a matter
of fact, MHRA has made eCTD a mandatory
requirement. While Belgium has embraced
eCTDs largely, they still accept other
formats. The same holds true for the
Netherlands, Norway, Germany, Sweden,
France, Denmark, Ireland and Austria. For
nations like Romania, Cyprus, Spain, Czech
Republic, Finland, Iceland, Lithuania,
Latvia, Poland, Bulgaria, Estonia, Greece,
Italy, Slovak Republic, Hungary,
Liechtenstein, Luxembourg, Malta and
Slovenia, no information is available with
regards to eCTD standards.
III. CONCLUSION
Application of the eCTD standard
within the XML format tends to allow an
Copyright © 2020 pepgra. All rights reserved 3
applicant’s submission documents to be
reused within diverse regional markets. The
submission is made up with five key
modules wherein the first module comprises
of all documentation specific to the region.
Exchange of this very initial module with a
module pertaining to another agency enables
a highly effective re-submission process
across diverse markets, without feeling the
need to modify the documentation or the
meta data from the rest of the four modules.
Yet another benefit is that by creatively
utilizing XML meta data, it is possible to
outline the table of contents in different
manners, enabling an application to have
views that are specific to discipline (for
instance; clinical vs. chemistry), lifecycle
views that are cumulative which reveals
every document and its existing state, views
that are specific to submission revealing
only the delta amongst submissions, module
specific views etc., every additional
particulars encouraging assembly efficiency
and reviews.
REFERENCES
[1] Bonn (2007). Electronic Submission and the
MRP/DCP: How to Compile a Dossier That Will be
Accepted at the European Agencies. [Online]. der
Rheinischen Friedrich-Wilhelms. Available from:
https://dgra.de/media/pdf/studium/masterthesis/mast
er_benning_l.pdf.
[2] FAMHP (2016). eSubmission Guidelines. [Online].
Available from:
https://www.famhp.be/sites/default/files/downloads/
eSubmission Guideline revision 2
13final30102015.pdf.