Speeding the path to FDA approval in the era of electronic submissions

An Investigational New Drug (IND) Application submitted tothe U.S. Food & Drug Administration (FDA) can easily run 10 or morevolumes, largely consisting of reviews and copies of published studies of thedrug in question. Many of the documents required come from published literaturesources, mainly in the form of scientific articles. Obtaining, assembling,transmitting and managing this volume of materials is a major task for anypharmaceutical company, whether it submits traditional paper documents to theregulatory agency or opts for electronic submission—and let's face it, it canbe time-consuming, expensive and downright exhausting.

In 2008, the FDA mandated that all electronic submissionsadhere to the electronic Common Technical Document (eCTD) format. This eCTDstandard poses additional distinct challenges as the scientific literature isnot published in this format, but needs to be reformatted to fit the FDA's standard.Even though it has been two years since the electronic system was implemented,many pharmaceutical companies are still struggling to navigate the approvalprocess efficiently.

There is help. Acquiring the necessary published literaturefor the regulatory approval process can be effectively standardized andfacilitated by a dedicated professional document preparation service.

The eCTD format: Advantages and pitfalls

First, a bit about the eCTD format itself. Designed by theInternational Conference on Harmonization, it represents a common organizationstructure for the submission of regulatory information to worldwide healthauthorities such as the FDA. An eCTD document is comprised of five modules:Administrative Information and Prescribing Information; Common TechnicalDocument Summaries; Quality; Nonclinical Study Reports; and Clinical StudyReports. The reason this format was chosen is because it is optimized forcopying/pasting, viewing/printing, annotating, facilitating the export of informationto databases, searching within and across applications and navigating throughthe document.

Additionally, the eCTD format offers an importantopportunity to make your company globally relevant, as it is standard acrossall markets worldwide. A successful pharmaceutical company is a globalpharmaceutical company.

As with all electronic submissions, delays can arise whenlast-minute requests for FDA-quality documents are made. It is no longeracceptable to have documents with anything but clean text. Making sure thesedocuments are acceptable can be a complex process that involves a number ofparties. Currently, workflow at many companies is decentralized with multipleinsourcing and outsourcing providers. A pharmaceutical company's Information Centermight bear responsibility for the task of removing any stray marks, whileregulatory affairs professionals might ensure that the documents are formatted,modified and assembled in a manner consistent with a regulatory agency'sspecifications. It involves a great deal of management and juggling before,during and after any submissions are made.

Companies need a centralized workflow system with standardsin place. The eCTD format requires enhanced and specific digital documentformatting and the inclusion of key navigation aids, making last-minuterequests even more problematic and delaying the drug approval process evenfurther. When the authorities reading a submittal encounter non-compliant PDFfiles, they can stop the review until the pharmaceutical company supplies themwith corrected versions—a situation that can cost you and your company hugesums in lost revenue by impacting the time to market and the stock price. Asthe adage goes, time is money, and this is particularly applicable when it comesto getting a drug through the regulatory approval process and successfully tomarket.

How a dedicated professional document service can help

There are services out there dedicated specifically tohelping you avoid the pitfalls and hold-ups associated with the approvalprocess. If a company's expertise lies in drug development, the company shouldfind a professional document repurposing company to manage the approvalprocess.

A dedicated eCTD document service can provide valuable aidto global pharmaceutical companies facing the challenges of regulatorysubmissions. Such a service is capable of processing orders for documentseither singly or in batches and procuring them—in as little time as a couple ofhours. It can ensure that the retrieved documents are digitally formatted tointernal and local regulatory specifications, and will oversee quality controland assurance processing. The service can also be set up to report on thedetails of usage for every document requested by the pharmaceutical company.And while the latter's Information Center may be overburdened, an independentservice can provide a dedicated project manager to oversee the entire process.

It is perhaps easier to envision how this alternative systemworks by imagining what happens when Company X requires a set of, say, 12documents on drug Y. First, Company X contacts the document service andspecifies the documents on drug Y that it needs. The document service thenretrieves those documents and pays copyright royalties to the documents'publishers. It then formats the document PDFs according to the specificationsof both the client and regulatory agencies such as the FDA.

One of the most striking differences between thisarrangement and the traditional submission process involves the timing ofdocument preparation. Traditionally, when paper versions of documents wereused, the preparation was undertaken immediately prior to submission. Withelectronic submission, documents can be prepared continuously from the start ofclinical trials, potentially saving considerable time and money later on.

Anyone skeptical of taking what has traditionally been anactivity overseen by the pharmaceutical companies themselves and assigning itto an outside service need only consider the advantages the latter can provide.An independent document service will not only have specialized expertise inmanaging information and electronic resources but also will have a thoroughfamiliarity with both the eCTD format and current copyright laws. The opinionsof some of those familiar with the electronic submission process are worthquoting.

"Invariably, [a] submission is held up waiting for that lastjournal article or monograph," notes Antoinette Azevedo, president ofe-SubmissionsSolutions.com. "It is better to collect them starting at the INDphase rather than waiting [until a later stage of the application process]."

Robin Holmes, an information services and contentmanagement consultant who formerly worked for Johnson & Johnson and JazzPharmaceuticals, observes, "An eCTD solution should be an information centerexpertise and deliverable. With this, the center can enhance document deliveryby leveraging existing purchases and removing a cause of submission delays."

Given the perspectives reviewed above, the advantages comeclear to a pharmaceutical company sharing the eCTD challenge of regulatorysubmission with a scholarly document service. The best step you can take tospeed your company's way through the regulatory approval process is to have yourregulatory affairs personnel or contract research organization contact asupplier for a content workflow analysis to find a solution that will benefityou, your financing and ultimately, the people who will reap the benefits ofyour drug.

Peter V. Derycz is the founding partner and president ofDerycz Scientific, a marketing services conglomerate focused on contentrepurposing tools and services, in Los Angeles.

From 2003 to 2004, he was CEO of the Puerto Luperon Co.,a luxury resort real estate development company. From 1990 to 2003, he waspresident, chairman and CEO of Infotrieve Inc., a global provider of contentmanagement technology and information services. He has also served as anadvisor to various organizations in the United States, Europe and Australia. Heholds nine Internet technology patents.