IVD Technology Magazine | IVDT Article Index
Originally published March, 1997
Coming of electronic age at DCLD
Janice A. Kates, Katie M. Smith, Joseph L. Hackett, and Terry McDonald
After a successful first effort, FDA's Division of Clinical Laboratory Devices is looking for more electronic submissions from IVD makers.
The winds of change are blowing throughout FDA, but nowhere so favorably as in the agency's Center for Devices and Radiological Health (CDRH). After several years of suffering caused by an extensive backlog of product submissions, the device center is making strong efforts to get out from under its ever-increasing mountain of paperwork, including product applications, correspondence, and medical device reports.
A key factor in the center's progress toward this goal has been its encouragement of and support for the use of advanced computer technologies, especially for product submissions. In the past two years, several divisions of the center's Office of Device Evaluation (ODE) have undertaken pilot programs to test the viability of electronic submissions from industry. These cooperative efforts between FDA and industry have been extremely productive, helping to pave the way to a paperless future in which regulatory information will move in and out of the agency electronically.
This article describes a pilot project undertaken by Hybritech, Inc. (San Diego), to prepare an electronic product submission to FDA--the first such submission to involve the device center's Division of Clinical Laboratory Devices (DCLD).
Technicians demostrate FDA's new videoconferencing system, which enables sponsors and reviewers to jointly review and modify product submission documents.
Background
In June 1994, FDA's Office of Information Systems (OIS) and ODE began the first pilot project to test the feasibility of accepting medical device applications electronically. The two participating device makers submitted premarket approval (PMA) supplements on both paper and diskette to ODE's Division of Cardiovascular, Respiratory, and Neurological Devices (DCRND). The electronic versions were downloaded to an agency file server and thereby made available to the reviewers.
In the course of this pilot project, agency reviewers encountered several difficulties, including an inability to display graphics on-screen, printing problems, inconsistent pagination, and unwieldy document navigation. Most seriously, reviewers discovered instances of inconsistency between the paper and on-screen copies available to them that resulted from differences among the operating systems and software versions used by the agency and the sponsors. Because of these difficulties, the DCRND reviewers eventually abandoned the electronic versions in favor of the paper copies.
Agency reviewers acknowledged that electronic review resulted in no saving of time during the first pilot project. Undaunted, however, they rapidly decided to undertake a second project with the express purpose of solving the problems they had encountered.
To eliminate the difficulties caused by incompatible operating systems and software, the agency selected a software suite known as Adobe Acrobat for use in the second project. This product consists of several programs, each with distinct functions. The Acrobat Reader permits a document to be viewed on-screen exactly as it appears on paper, regardless of the software applications used to create it or the computer systems used to view it. This is accomplished by using Acrobat Distiller or Exchange, programs that translate the document into a format known as a portable document format (.pdf) file.
Acrobat Exchange also enables the sponsor to add to the document such intelligent navigation features as bookmarks and hypertext links. In essence, bookmarks automate the table of contents, enabling readers to move directly to a particular topic by clicking on the bookmark text. Hypertext links are navigation tools that make it easier to read a document on-line. A link is a selected area of text that the reader clicks on in order to move to another area of the document. Using other features of the Acrobat suite, reviewers can add electronic notes, or they can cut-and-paste to annotate the document and create an electronic review log.
The second pilot project was clearly far more successful than the first, resulting in a feasible methodology for electronic submission and review of medical device applications. This success made it possible for other ODE divisions and device manufacturers to make use of this emerging technology.
Project Plan
In November 1994, one of the device manufacturers involved in the CDRH pilot project made a presentation about it at a Drug Information Association meeting in San Francisco. The presentation made it apparent that electronic submissions could provide numerous benefits to both the agency and the sponsor, including higher-quality submissions, accelerated and more consistent reviews, less downtime while awaiting responses to questions, and more direct communication between agency and sponsor. Hearing of this presentation and learning of the strong potential of electronic submissions, Hybritech management soon decided to embark on an exciting journey into the realm of bits and bytes.
In early 1995, Hybritech representatives devoted themselves to gathering information and constructing a project proposal. Next, they contacted OIS and DCLD in order to see if they were interested in receiving an electronic submission. Both offices indicated that they were receptive to the idea, so in June 1995 a group of Hybritech representativestraveled to Rockville, MD, to plan with DCLD for the company's first electronic submission.
The Hybritech plan had three elements. The first was the projected delivery of a product submission on diskette. The company anticipated that many software applications would be used in preparing the document, and that scanned images would also be incorporated. For this reason, the company planned to use the Acrobat Distiller so that reviewers would be able to access an electronic version that duplicated the paper submission. Furthermore, Acrobat Exchange would be used to create bookmarks and hypertext links that would assist the reviewer in document navigation.
The second element involved the use of Internet E-mail for reviewer-sponsor communications. It was agreed that no materials of a sensitive or proprietary nature would be sent over the Internet without encryption. E-mail had the potential of helping to avoid voice-mail phone-tag. Being self-documenting, it had the further advantage of saving reviewer time by obviating the need for handwritten communication logs.
The final element of the plan involved the use of personal videoconferencing. Although personal videoconferencing can be useful in the mutual review of any document, it was believed that it would be especially beneficial in resolving product labeling issues. The videoconferencing unit consisted of a 486 personal computer with an on-board camera and speaker, Intel ProShare communication software, and an integrated services digital network (ISDN) line. This desktop system would enable a reviewer and sponsor to work on a copy of the document simultaneously, while seeing and speaking to one another.
To prepare FDA personnel for the submission, OIS agreed to hold two half-day training sessions for four reviewers, two each from DCLD's Clinical Chemistry/Toxicology and Immunology branches. (Later, reviewers from the Microbiology Branch also attended a training session.) As training material, Hybritech agreed to provide a previously approved product application in electronic format, with a Hybritech employee attending the first training class to answer any questions about the document. Both FDA and Hybritech were satisfied that the project was feasible, so the Hybritech representatives headed back to San Diego and immediately began preparations for their first electronic submission.
A page from Hybritech's electronic 510(k) submission, showing bookmarks (at left), hypertext links (boxed items), and a reviewer's electronic post-it note.
What you'll need
Companies that want to join the electronic revolution at FDA's Division of Clinical Laboratory Devices may have to do a little homework to determine what sorts of hardware and software are best for their purposes. Because each company's needs are different, it is virtually impossible to predict what the total costs might be for any particular company. One place to start is with the following sample list of hardware and software items that Hybritech, Inc. (San Diego), developed for the three elements of the project described in the accompanying article.
Electronic product submission
Adobe Acrobat suite (Reader, Exchange, Distiller)Document scanner
CD writer
CDs
Diskettes
Internet connection (service provider)Encryption software (e.g., ViaCrypt PGP)
Personal videoconferencing
Personal computer486 minimum (Pentium preferred)
8 MByte RAM minimum (16 MByte preferred)
17 MByte minimum free disk space
DOS 5.0 or higher
Windows 95, Windows 3.1, or Windows for Workgroups 3.11
Intel ProShare
ISDN line
Costs for training company personnel to use this equipment may also vary greatly, depending in part on how sophisticated the company's employees already are with computers. But companies that go electronic now will have a big advantage: with the success of its earlier pilot program, DCLD now has a number of personnel that have been trained to handle electronic submissions.
Submission and Aftermath
Finally, in fall 1995, Hybritech delivered a PMA supplement to FDA's document mail center. The document was submitted in the form of three paper copies and a diskette. The paper version totaled 229 pages; the electronic version totaled 2 MByte and contained text, data tables, graphs, and scanned images all distilled into a single .pdf file. The file also contained numerous bookmarks and hypertext links. Acrobat Exchange was used to create these document navigation aids. Following a quick-paced review, Hybritech received FDA approval to market the product.
When the time arrived to review the Hybritech project--to reflect on what went well and what could be improved--videoconferencing seemed the perfect vehicle. In order to set up a date and time for the conference and to plan its agenda, E-mail messages were sent back and forth between Hybritech and DCLD. Finally, in April 1996, six Hybritech representatives met with seven FDA representatives to review their first experience with electronic submission. Since the meeting took place entirely by means of a personal videoconferencing system, however, no air travel or hotel stays were involved.
FDA feedback concerning the electronic submission was extraordinarily positive. Reviewers were delighted with the ease of document navigation, and were especially happy with the cut-and-paste and full-text search capabilities. One reviewer expressed the wish that all product applications could be submitted and reviewed electronically. Both DCLD and Hybritech expressed a desire to increase the use of E-mail and videoconferencing to facilitate a more interactive review process. Overall, the project was deemed an enormous success.
Conclusion
Since the postmortem videoconference, Hybritech has submitted several electronic product applications to DCLD. One improvement that has been made is to download the submission onto a CD-ROM, which has much greater storage capacity and is more secure than a diskette. Furthermore, a CD-ROM is easier to manage from a technical standpoint, because large files can be written to the medium without the need for compression. Hybritech intends to submit all its future product applications on CD-ROM.
With the Hybritech project successfully behind it, DCLD is now encouraging other IVD manufacturers to take advantage of the benefits of electronic submission. There are times when interaction between FDA and regulated industry can be somewhat cumbersome. But the Hybritech/DCLD electronic submission project has demonstrated that both agency and industry can benefit by working productively together.
Acknowledgment
The authors wish to acknowledge the support and enthusiasm of Paulette Loeh, principal data management specialist, Denise Garcia, regulatory affairs assistant, and Pat Woods, regulatory affairs specialist, all of Hybritech, Inc. (San Diego); Neil Goldstein, deputy director of FDA's Office of Systems and Management; Stuart Carlow, director of FDA's Division of Information Dissemination; Doreen Melling, scientific reviewer in FDA's Immunology Branch; and Ann Hawthorne, chemist in FDA's Clinical Chemistry Branch.
