Streamlining Electronic Regulatory Submissions With Submission-ready Pdf Files

As the business world turns its attention fromformat, the leading players in Life Sciences and
back office automation to front office efficiencyPharmaceuticals were quick to make the
the need to streamline document and informationtransition; recognizing the opportunity to
management is starting to play an increasinglystreamline their own processes and take
important role. This has never been more relevantadvantage of the inherent cost savings. Even
than in the pharmaceutical industry. Enterprisecompanies not required to make eCTD compliant
Content Management applications, eCTD softwaresubmissions are seeing the advantages of an
and other information management tools allelectronic workflow in accelerating time to market.
provide benefits that are designed to betterThey are finding ways to leverage the technology
manage information and streamline documentand transform eCTD into suitable printed CTD.
workflows. As much as these applications aid inThese companies have also seen the way the
general contributions to document management,wind is blowing with the news that the European
there are still further requirements in regulatoryUnion has mandated that all 27 member countries
submissions that the generalities of thesebe ready to accept eCTD submissions by 2009.
applications don’t address. The cost ofCan the chapter of paper submissions be nearing
government and regulatory compliance leaves aits end? Can the rest of the world be far behind?
lot of room for improvement, a key area beingThere is no shortage of document workflow,
the document conversion and publishing process.rendering and output solutions available but the
The real and opportunity costs of non-compliancerequirements for eCTD compliant submissions are
leave most companies spending an inordinateunique and require an integrated solution that puts
amount of time and money ensuring documentthe focus where it belongs, squarely on delivering
quality and compliance. What if there was a toolfinal submissions that can handle the complex,
that would not only automate documentever-evolving landscape of this leading edge
conversion and publishing but reduce the need toindustry. The documents for an Investigational
perform quality checks and balances? StreamliningNew Drug Application (IND) or New Drug
the sub mission process not only saves moneyApplication (NDA) submission are always “in
but it can generate millions of dollars on the backplay”, constantly under review, endlessly
end of the life cycle of the product. This articleannotated and eternally being “improved”.
talks about real-world process improvements,These improvements must not corrupt the
cost reductions and the opportunities forperfection of the submission, which is often the
streamlining document submission processes,result of post-production re-rendering where
highlighted by applications with proven trackcritical errors are made or repeated.
records.Software applications, like those offered by Adlib
Time to market has always been a criticalSoftware, avoid these pitfalls by focusing on
success factor for manufacturers and marketersdocument rendering quality while employing a
of consumer products. But when every day’sdesign philosophy of stable, open protocols and
delay can mean millions against your bottom linestandards such as XML and Web services.
and when your product might mean theAdlib’s document transformation technologies
difference between life and death for millions ofstreamline the rendering process for documents
people worldwide, the stakes are that muchbeing used in the submissions process. By
higher. These are the stakes that leaders of Lifeintegrating seamlessly into the document
Sciences and Pharmaceutical companies mustworkflow, any source document can be easily
contend with every time a new drug orrendered automatically into a submission-ready
technology is faced with regulatory approval. ForPDF.
a blockbuster drug like LIPITOR® orRobust rendering is the core
NEXIUM®, that are now prescribed in excess ofRobust PDF rendering forms the backbone of any
$10 million every day, reaching the marketplacedocument management workflow and is the
quickly can make or break the financial quarter orlifeblood that flows through the entire eCTD
even a full fiscal year. High stakes indeed.submission lifecycle. By creating higher quality
The regulatory minefieldrenditions, quality assurance churn can be reduced
For Life Sciences and Pharmaceutical companies,to only minutes per document. This is a significant
time to market is always held hostage, to someprocess acceleration over traditional QA cycles,
degree, by the global regulatory landscape. Fewsearching for missing, broken and invalid
industries face regulation on the same scale andhyperlinks, that usually takes hours to complete.
level of complexity. Such intense oversight andThe cost savings, projected over submissions
scrutiny is reasonable for an industry of suchrunning into the hundreds of thousands or even
intricacy and potential impact on the health andmillions of pages, have proven to be enormous.
wellbeing of much of the world’s population.Submission-ready PDFs are infinitely flexible and
At the same time, the agencies that imposecontain an almost limitless set of features. These
these regulations, like the Food and DrugPDF outputs can be readily equipped with essential
Administration (FDA) in the United States, faceelements like version control, downgrading, font
intense pressures of their own.embedding, automated Table of Contents
Recent media and congressional examination ofcreation, audit history and submission taxonomy.
several high-profile cases in the drug industryThese PDF documents are also flexible and
have put the FDA and its internationalscalable at every stage of the submission
counterparts firmly on the defensive. This is notlifecycle, particularly important given the
good news for the industry. Scandals surroundingFDA’s increasingly aggressive use of
first the cardiovascular effects associated withpost-marketing “risk minimization action
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs),plans” (RiskMAPs), including the requirement to
and more recently the “sleep driving” andsubmit additional safety information (such as
“sleep eating” side effects of popular newlarger safety studies to screen earlier for
insomnia treatments are causing a significantrelatively rare potential adverse reactions), after
retrenchment within the regulatory community.the original submission is made.
The FDA in particular is facing growing pressureThe right instruments: powerful, flexible and nimble
for congressional action to address these issuesWhen it comes to partnering with leading edge
but the proposals currently under consideration, inplayers in Life Sciences and Pharmaceuticals, Adlib
the opinion of many industry players, would harm,Software is uniquely positioned to supercharge
not improve, patient safety by making it morethe submissions process with its powerful
difficult to get promising new drugs approved anddocument transformation framework anchored
into the hands of doctors and patients.by Adlib Express Server and Express Web
The FDA has also been perceived in the past asServices. For more than 10 years, Adlib has
“cozying up” to the industry and ofenabled several key industry players to gain a
rushing promising new drugs and technologies tocompetitive advantage by maximizing the
market without an adequate paper trail. The resultefficiency of document workflows. The difference
of this perception, justified or not, is heightenedwith Adlib Software’s solutions compared to
scrutiny, leading the agency to becomesome of the other PDF rendering engines is that
progressively more conservative and defensive inAdlib Software cut its teeth working with global
its decision-making and in its approach toLife Sciences partners to ensure that the quality
reviewing and approving submissions for newand fidelity of its PDF renditions not only meet but
medicines and technologies. At the same time,exceed the demands of regulatory submissions.
promising new areas of study such as the HumanSeveral of Adlib’s customers have reported
Genome Project (HGP) are turbo-chargingsavings amounting to millions of dollars with the
innovation and discoveries in the researchmajority of the direct cost savings coming from
community. In fact, the Wall Street Journalsubstantial QA cycle time reductions due to
recently cataloged over $1 billion worth ofunprecedented confidence in PDF rendering quality.
currently pending IPO filings and there is a growingQA has been reduced to a couple of minutes
collection of existing bio-engineering companiescompared to what used to take hours. Given the
applying HGP concepts in the marketplace.sheer volume of document rendering that takes
The combination of more rigorous oversight,place for just one submission and multiply that by
increasing threats of litigation and the explosion ofthe number of submissions performed each year,
complex, technology-driven areas of researchthe numbers add up quickly. The indirect impact,
have created a perfect storm for companiesalthough harder to measure may even have a
looking to succeed in this complicated landscape. Itgreater impact on the bottom line. By streamlining
has also led to an atomic explosion in the size andthe submission process and providing higher quality
complexity of submissions related to new drugssubmissions, product hits the market sooner. As
and technologies. Though this cutting edgementioned earlier, each day gained could be worth
research is conducted using the latest technology,millions of dollars in extra sales. Not a bad ROI is it.
it is remarkable how often the key results areWith its advanced publishing features and support
compiled and maintained on nothing morefor multiple formats including MS Office-based
sophisticated than a series of unconnected MSsources, Adlib Express Server applications give
Word documents and even hand-written forms.companies all of the advanced features necessary
Documentation for a single research study mayto significantly accelerate submission compliant
consist of tens of thousands of pages with a fulldocument workflows. Some of these features
submission including multiple study resultsinclude automated, accurate optical character
documents. Extend this over multiple jurisdictions,recognition (OCR) to create searchable files from
different languages, add in the complexity of jointimages and PDFs, stamping to create headers,
ventures, patent laws, sub-contracting andfooters, volume numbers and cross-references
outsourcing research and it is hardly surprising thatfrom hyperlinks, as well as dynamic Tables of
some FDA and EMEA (European MedicinesContents generation capabilities. Importantly, Adlib
Agency) submissions were traditionally deliveredExpress also normalizes hyperlink styles to meet
not by the box load but by the truck load.FDA standards and includes advanced
Electronic submissions: technology to the rescue?bookmarking control with the ability to merge and
When every day is critical, ensuring that you haveor volumize PDFs based on page count, size or
effective electronic regulatory submissionother variables. Adlib solutions are XML-ready with
processes and technologies in place is “tableXML Job Ticket support and Web services. A
stakes”. Having leading-edge documenttruly complete solution.
management technologies coupled withAdlib Software then takes things to the next level
collaborative document transformation tools, onwith its Exhibit product. Exhibit enables
the other hand, is a significant competitiveorganizations to leverage existing XML backbones,
advantage. The effective implementation of theseas well as folder structures for Rest of World
technologies can significantly accelerate submission(ROW) submissions in either paper or volumized
lifecycles that contributes directly to the bottomPDF formats. Exhibit works with eCTDs as well as
line.other submission formats (e.g. 510k) and with
Preparing submission compliant documents,other applications to provide the ultimate in
typically in PDF, is a time-consuming and highlyflexibility and interoperability.
iterative process critical to successful submissions.Exhibit was developed in partnership with several
As discussed earlier, the highly collaborative andworld leading pharmaceutical companies to
fractured nature of the research andautomate the process of creating paper-based
development process means that many of thesubmissions from eCTDs. It’s a collaborative
original source documents that make up thebrowser-based solution that optimizes the
submission need to be manually reworked. Thecapabilities of Adlib Express Server to prepare
rework stems from deficiencies inherent in MSelectronic submissions for print or volumized PDF
Word, particularly the inability to retain keydestinations. It includes the ability to convert
navigation information during conversion to PDF.electronic hyperlinks into paper-based bookmarks
This kind of manual rework is time-consuming,and references as well as automated features
prone to error and, not surprisingly, verythat allow for intelligent document assembly;
expensive. These deficiencies can be overcomemodifying Tables of Contents, page scaling, the
during the PDF creation process by having theapplication of headers and footers, page numbers
right technology in place.and the insertion of tabs and slip sheets. All of
Not all solutions are created equalthese advanced operations are available with
The excessive size of these submissions is also aExpress Server but leveraged through applications
significant burden for the agencies themselves. Forlike Exhibit.
its part, the FDA plans to streamline and simplifyThe benefits of a solution like Adlib Express
the process by moving all submissions to anServer is that the scalable conversion, publishing
automated electronic platform by the end ofand OCR functionality can be leveraged for not
2007, with the caveat that this may be pushedonly regulatory submission processes but it can
out to a later date. The standard, known asalso be applied across the entire enterprise to
eCTD (electronic Common Technical Documents)create a complete rendering framework for all
is an interface between industry and agency forsorts of document workflows. The robust
transferring regulatory information while at theinfrastructure of Adlib Express Server is designed
same time taking into consideration the facilitationto be a foundation for growth that allows Life
of the creation, review, lifecycle management andSciences and Pharmaceutical organizations to take
archival of the electronic submission. Theadvantage of existing investments in skills and
specification has set criteria that make electronictechnology to achieve document management
submissions technically valid, and anyefficiencies that truly support the critical work
eCTD-compliant submission prepared in anythey do on behalf of humanity and their
compliant environment can be transferred toshareholders. These solutions are also flexible and
another environment built on technology fromscalable enough to act as the launching pad for
another vendor. In theory it sounds ideal,adopting innovative new methods of information
however in practice it should be remembered thatmanagement to achieve competitive advantages
not all technologies are created equal.over time.
With the FDA demanding the use of the eCTD