Using Oracle’s Argus Safety to Comply with ICH E2B(R3)

September 12, 2019 posted by


Thank you everyone for joining BioPharm’s
webinar. Today we will be discussing about Oracle Argus Safety and how one can plan the
new individual case safety reporting standards, known as E2B (R3) and upcoming ICSR Reporting
changes. My name is Andrew Mitchell and I am the European
Safety Management Practice Lead at BioPharm Systems.
I have spent the last nine years in implementations of Argus Safety and EDC systems at a varied
selection of companies, including working foresees European Parts Manager on the global
social source team. All in all I’ve managed fifteen implementation projects. This agenda
for today as follows first acknowledgements and slides, then we will dive on IDMP, the
new standard of Identification of Medical Products that is to be implemented alongside
the ICSR 3 reporting standards, they exist together. Then we will be discussing some
highlights in the current status of each ICSR 3, before looking at the differences between
the existing XLM and HL7. European Medicines Agency also has additional requirements and
these will be documented in the European Implementation Guides, so we will be discussing those along
with one of these additional requirements can be implemented in Argus Safety. The second
half of the presentation will talk about our predictions for the Oracle Roadmap for this
case safety management systems. These protections are not official from Oracle and should not
be taken as such. Then we will be looking at how companies can plan ahead and continue
with a question and answer session which we are very fortunate to have on this call Kapil
Kedia, Principal Product Manager of Argus Safety. And then we will end with a wrap up
and a mechanism for feedback. If anybody has any questions during this webinar
you are all on mute, so please put them in the chat window and then we can deal with
them during the question and answer session. Thank you very much. So first I would like
to give acknowledgement in this webinar includes information shared during the European Medicines
Agency meeting, that was held in London on 5th April, 2011. These meetings are organized
by DIA. If anybody is very interested in this topic I would recommend attending some of
these meetings. These slides will be available on our website within 24 hours and if you
have any questions, I will give you details of how you can get in contact with us. I want
to discuss about IDMP, which is ICH M5 Guideline. There is required accurately Identification
of Medicinal Products (IDMP) involved in adverse events. In order to do this, we need unique
and unambiguous identification of the active substance of a product, the units of measurements,
the ingredients, the dosage forms, units of presentation and route of administration.
This will be required for the full marketed products and optional for investigational
products. So instead of your products just being a company product if you have any system
now or non-company products just being who drugged end products where they will be structured
capturing of private information. Identification of Medicinal Products (IDMP)
has 5 standards. The first standard is Medicinal Product Information, MPID, this is what in
Argus Safety you would call your license, the trade name of your product. Then the second
standard is a Pharmaceutical Product Information, PHPID. This is your global product, next one
is identification substances, Pharmaceutical Dose Forms, Units of Presentation, Routes
of Administration and Packaging and units of Measurement.
The timeline for IDMP, the concept paper was approved in 2003 and that was the ICMH M5
Data elements and standards for drug dictionaries. And then in 2005 the guideline was released
for initial consultation and in 2006 the strategy was changed and it was decided to develop
it in collaboration with the Standards Development Organizations, or SDOs. The current Status
is the Final Draft International Standard, FDIS ballot results due Q3 in 2011 with publication
expected to follow, so that is when IDMP will become an international standard.
So this is happening at the same time as E2B (R3) which is what most people are aware of
E2B (R3) is a new ICSR Standard, its aim to improve Pharmacovigilance reportings across
ICH regions. This is brought on by advances in pharmacovigilance science, changing requirements
and a need to improve consistency, accuracy and detail of information in adverse event
reporting. Formal consultation began 2005, like IDMP, but in 2008 the decision was taken
to join T Develop SDR3 with SDO’s There are several constraints as well, the FDA is required
to meet HL7 standard. Europe and Canada required standard to be ISO or CEN, in order to be
incorporated into their legislation. ICH are developing an Implementation Guide to define
the use of the standard and EU Implementation Guide has its additional requirements and
so are releasing an additional implementation guide for EU.
Some of the highlights of E2B (R3) are a single report for multiple recipients, so you can
generate one file that can be sent to more than one recipient. Additionally the focus
of E2B (R3) is to structure the file reports that are accepted by everybody. So while you
may send slightly different information to a regulation agency, as what you are sending
to a license partner or maybe to the Japanese authorities, the structure of the file is
the same. The European additional requirements and USA
vaccine expectations will be added onto your E2B(R3) report, that is going to the FDA or
other regional authority, to national authority. Those agencies are expected to ignore the
information that is not relevant to them, whether that is going to happen the way or
whether you will choose to send different reports to different individual recipients
is going to be for companies to decide. One of the challenges that are sending single
reports, to multiple recipients will generate multiple response messages, so your signal
report may be accepted without warnings by the French authority but the German authorities
admit because their expectation causality is different.
Another highlight and significant changes of E2B (R3) is the inclusion of case attachments
and you can add PDF of your literature results and lab articles and again you can send a
report to multiple recipients, because you may send different source documents to different
authorities or license partners. For CROs they are likely to want to send everything
to sponsor while to regulatory authorities companies often only want to send the minimal
information. IDMP: Structured Drug Information is included in E2B (R3) as mentioned earlier.
Another significant change has been Concept of Amendment to E2B (R3), so instead of just
sending a follow up report you can see what is called an amendment report towards change
its internal assessment or whether it is simply a correction like a typo and you want to send
your reporting recipients an updated report. Now it is worth noting that if your internal
reports are causing the additional reports to be upgraded to many of those that could
trigger an inspection, but on the other hand if you are not sending any upgrades or any
amendments then it would look like you are not reviewing your data so there is a balance
to be struck. Additionally E2B (R3) reports will be based
on reaction and event level seriousness not case level seriousness and there are lots
of additional data elements such as: drug taken by father, a drug taken beyond expiration
data, batch lot tested and found within/not within specifications, counterfeit product,
overdose, so there is significantly more information will be required or requested to send and
able to send what exists in the current reporting standard.
The current status of E2B (R3) is that we’re in the middle of all final draft international
standard pallets and those results are due out in June, 2011, publication expected around
then as well following the actual standard, the last ballot rounds, the US vaccine reporting
requirements were added. ICH implementation guides and the EU implementation
guides are running in parallel and the finalization is due June 2011, then there will be a six
month consultation and approval due the second quarter of 2012, the same as for the European
Implementation Guide. Additionally it is important to bear in mind the 2010 European Pharmacological
Legislation, because this is in parallel with these changes. 90 day reporting of all non-serious
adverse events may be required by some national authorities in 2012 and single reporting to
the European Medicines Agencies is expected by 2015 once the Eudravigilance system has
been ordered in 2014. Once that happens then instead of reports being submitted to the
National Authorities via the Eudravigilance gateway reports would just be sent directly
to EMA. But that is some time away. Until then certainly the 90 day reporting of non-serious
adverse events, it is just a significant change for many organizations especially smaller
pharmaceutical companies or CROs who maybe are processing one to 500 cases a month but
only 10 of them are required for the reporting. And for companies using the EB Web Trader
you may wish to consider whether the load is going to mean you should be looking to
implement electronic gateway. But we will get into that in more detail later.
So this is a look at how the current E2B (R2): XML structure compared with the E2B (R3) HL7
Messaging structure which is metadata driven. As touched upon earlier the EU Implementation
Guide has additional requirements to the ICH. Those requirements include reporting on advanced
therapies, reporting on medicinal product defects. They want additional information
on counterfeit medicines so they want to know the counterfeited medicine was suspected or
confirmed. For drug overdose they want additional information as well, they will want to know
whether it was intentional or accidental drug overdose. They will want additional information
on drug misuse or off-label usage. There are some additional elements that they are adding
to the message so the study information; some of the study information fields will be repeatable.
You can have Study Registration Number and Study Registration Country, repeatable so
that you can include the EudracT and the National Numbers in your reports. Additionally the
Drug Characteristic value instead of just having Suspect, Concomitant and Interacting,
they’ll be adding an additional value for drug not administered and this will be for
use with clinical trials and medication errors. The additional information that is included
in E2B (R3) file will not lead to reductions in other regions and it be loaded by European
Medicines Agency and the Eudrvigilence System and similar additions for FDA Vaccine reporting.
And we may also see the same additions for Japan.
One of the changes that I want to look at in slightly more detail is historical drug
information. These are elements of B. 1. 8 and B.1.10.8, relevant past drug history and
relevant past drug parent history. The EMA would like this information to be treated
identically to suspect, concomitant and treatment products. They would like to include substance/specified
substance, drug dosage information, pharmaceutical dose form and route of administration. Now
how we would see that being added in August, just as an example this is instead of the
right of infections trading captured on the screen, that is captured today. You can see
historical drugs being captured in a similar matter to how suspect concomitant in treatment
drugs, so you will be able to capture transmission that would require changes to that.
How will that impact you and what are the predicted changes to the Oracle Roadmap? We
know that E2B(R3) functionality is scheduled for 2013 release. It cannot come out before
that because the standards will be available in 2013, products under Application Unlimited,
programs will be Oracle AERS and Empirica Trace, what that currently means is that there
is the new additional development of these products, so we can expect these products
not to support functionality for E2B (R3). Products under Sustained Support so like Oracle
in 2013 is likely to be Oracle Argus Safety v6.x, that is also likely to have service
packs released, that will support this new functionality. Products under Premium Support
will be released in 2015, we expect to be version six and onwards and scheduled new
releases. The current version of Oracle Argus Safety is v9.0, it will have the new functionality.
So this is something to be taken into consideration for companies that are either not on Argus
and are considering when they should be switching systems or if they should switch systems and
companies that are using Argus systems and are planning what their systems will be for
the future. So planning ahead, smaller companies should
consider investing in automated 3rd party gateway software such as Axway Interchange,
which formally was Ciclone or bTrade , which is a cheaper option, though it doesn’t integrate
quite as nicely into Oracle Argus Safety, rather than relying on the EV Web Trader if
they are going to be submitting a lot more reports. And for having E2B(R3) Compliant
Safety System, you are looking to have that in place in 2014 and they are really expected
to be two products on the market that will support this functionality in Oracle Argus
Safety or ARISg, so companies will need to either upgrade to a compliant version or switch
systems and we are looking to switch systems, and a migration is required, it is recommended
to do this early to reduce the size of the project, risk and spread the financial impact
of these compliance changes. It is far easier if you are existing clients and wish to move
especially if you are not a small organization to do this to an earlier version of Argus
Safety like 7.0 was released a few weeks ago and then looking at upgrading and having more
upgrading to large-scale projects, just before compliance to E2BR3 is required. So I know
we are only talking about 2014 and for many companies these projects can take eighteen
months plus and so some of you are looking at your budgets for next year. If there are
any questions, this is the time and I will also un-mute Kapil for him to be available
for comment. We had one question on ESP URs reporting for
non SAEs and not being applied for preregistration for clinical trials and that is our understanding
as well. Also, this presentation does not cover the EPS URs so please limit questions
to what is relevant for this particular topic: individual case safety reporting. So there
will be changes to EPS UR requirements from European authorities once the non-serious
events will report this. For companies that are currently using Aris
Global’s ARISg, you can continue to use that but it is on the limited platform so we do
not expect this functionality to be available for that. You will still be able to use it
but Oracle isn’t expected to be bringing out any additions other than bug fixes.
There is a question about multiple acknowledgements for single reports. How that works is that
when you send an HBR3 report you can choose multiple recipients you can generate, well
we do not know how that will behave but the expectation is that you will be able to go
to multiple authorities and that single file will lead to your gateway and be received
by multiple agencies and you will get an acknowledgement back from each agency that receives your file.
You would likely have a single reporting profile for how you map those files but you could
decide to send different sources, for example documents to different recipients.
Then there was a question on IDMP. And yes, IDMP is a requirement for ESBR3 and it needs
to be implemented. E2B (R3) requires product information to be structured.
FDA timelines, FDA does not have an announcement yet on their timelines on informational day
meeting, may be on the 12th or 13th of May, so we may have more information on that. The
European Medicines Agency will have more information on their implementation 10-24 months after
the implementation guide comes out. We are pushing 18, but We do not have any information
on how long HDM2 is supported although there will be very…one of the complications is
how to covert HDM2 and HDM3 back and forth without losing anything and there are guidelines
for that already. So companies that have in-house system or are using E2B(R3) integrations,
that functionality will still be around. Oracle had a presentation earlier today and there
was an expectation that E2B(R2) will still define ideas of E2B(R3) and we can expect
the European Medicines Agency mandatory E2B submission.
Andrew Mitchell: Kapil, can you hear me? Kapil: yes, I am here, can you hear me?
AM: Do you want to comment about the plans or Argus and especially if there are any plans
for customers on AERS? K: Yes, I am here mostly to comment on Airs
cause I am not being with the team but I can get the information for clients who are interested
in AERS but from an Argus perspective we are waiting for the final regulations because
they are on their final draft implementation cycle but if something changes we want to
make sure there are no surprises. But June 2012 is when they will come into place. Then
we will have 18-24 months before companies need to be compliant, we worry on the technical
implementation of how to change Argus for the interchange module because that is the
interchange module in the Argus safety suite. We will keep an ear posted for when the regulations
are finalized
and those will be posted and sent to each customer via support team.
AM: When you are upgrading Argus, it was a step by step upgrade, so a 4.1.2 through the
different patches and service packs but now when you upgrade for example Argus Safety
version 7 will there be a far simpler process to upgrade to a version which comes out and
be compliant or will they need to jump through all of the hoops?
K: They will have to upgrade for sure. I cannot comment on what version or what the point
release would be because there may be internal hard fixes but we will give them an upgrade
through the Argus Safety database upgrade which we support and they can quickly jump
from x version to y version and you have on previous versions we also all those with previous
versions to come forward, which is required for a 7 perspective and then they can automatically
upgrade. AM: Thank you. Are there any questions for
Kapil? No questions, thank you everyone for attending this has been a bit shorter than
I expected, probably spoke too fast. This will be available for download in 24 hours
and if anyone wishes to contact us they can reach me directly or we can be contacted by
our telephone numbers.

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