Regulatory Beat: FDA Proposes New Systems and Procedures for E-filing Labeling and Other Data

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BioPharm International, BioPharm International-08-01-2004, Volume 17, Issue 8

One main component of an e-prescribing system is access to accurate, up-to-date information on prescription drugs and biologics based on FDA-approved labeling.

Everyone in Washington is jumping on the national electronic health information bandwagon. The Medicare Modernization Act (MMA) requires the government to establish technical standards for an electronic prescribing system, and federal officials are taking action to comply. As a result, FDA is stepping up efforts to set standards and policies for a broad range of electronic filing and reporting activities.

Jill Wechsler

In April, President Bush set a 10-year goal for developing an e-medical records system. Health and Human Services Secretary Tommy Thompson appointed a national health information technology coordinator and announced HHS support for the work of Health Level 7 (HL7), a voluntary health standards development organization. In addition, the National Committee on Vital and Health Statistics (NCVHS) is working on technical standards for e-health billing and e-prescribing. The Medicare bill calls for HHS to establish initial e-prescribing standards by September 1, 2005 in order to conduct a pilot project during 2006.


One main component of an e-prescribing system is access to accurate, up-to-date information on prescription drugs and biologics based on FDA-approved labeling. The agency is establishing a new system to provide this information in a form that will be accessible to all computer systems. This builds on FDA's efforts over the past decade to develop policies and systems for electronic submission of data and documents to the agency. FDA has supported efforts at the International Conference on Harmonisation (ICH) to establish common standards and formats for e-filing of market applications for new drugs and biologics and for collecting data on adverse events.

The federal e-health program is accelerating a number of FDA initiatives and giving IT activities a higher profile in the agency. In April, FDA Acting Commissioner Lester Crawford named Randy Levin director for health and regulatory data standards in the Office of the Commissioner. Levin's responsibilities include representing FDA in government-wide e-health activities and overseeing agency initiatives as chair of the FDA Data Council. Levin comes to the commissioner's office from CDER, where he headed the organization's Office of Information Management (OIM). He will continue to serve as CDER's associate director for medical informatics and will function as scientific advisor and consultant to CDER management on medical informatics and information management.



A current priority for FDA is establishing an electronic labeling system for drugs and biologics. The aim is to speed up FDA review of initial labeling and post-approval changes and to be able to communicate such changes quickly to pharmacists, physicians, and patients. To move forward in this area, FDA issued a new rule in December requiring manufacturers to submit product labeling data electronically when filing a new drug application, supplement, or annual report.

Initially, this change appeared fairly straightforward because FDA and manufacturers have been sending and receiving labeling content electronically in PDF since 1999. But in February, FDA published a draft guidance calling for a switch from PDF to the XML-based Structured Product Labeling (SPL) system by the end of 2004 (see "Guidance for Industry: Providing Regulatory Submissions in Electronic Format — Content of Labeling,"

Manufacturers generally supported the new system but requested more time to carry out such a major change. According to BIO, small biotech companies in particular anticipated difficulty adopting SPL quickly. Astra Zeneca estimated that, in a best-case scenario, it would take a manufacturer six to nine months to set up, configure, validate, and test an SPL system once it became available.

At a meeting with manufacturers in June, Levin addressed these concerns and offered a more flexible implementation timetable. Seven software vendors attended this meeting to demonstrate their interest and capability for providing SPL software to industry. Even though the December e-labeling rule became effective in June, Levin emphasized that until FDA establishes a system for receiving and storing manufacturer data in SPL, the agency will accept e-labeling data in either PDF or SPL formats. FDA hopes that the first phase of this project, which involves completing regulations, standards, and systems needed to switch labeling content from PDF to SPL, will be completed for prescription drugs by next July and for all drugs by 2006.


According to FDA and industry experts, the switch to SPL may be complex, but it offers important benefits. The system will not only distribute labeling information quickly and more broadly, but the restructuring of labeling information involved will yield better organized and more consistent information based on a set format. Multiple computer systems will be able to access the labeling information, while it also will remain in a human- readable format. SPL will also facilitate labeling review, editing, storage, dissemination, analysis, and other functions. FDA will be able to evaluate labeling changes by section, making it unnecessary for a manufacturer to submit the entire document if changing only one piece of information is necessary.

At the recent Drug Information Association (DIA) annual meeting in Washington, CDER Medical Officer Steve Gitterman said that development of the SPL system was "a landmark event in patient healthcare" because it provides a mechanism to make labeling changes immediately available to the medical community. The new system will allow for faster FDA turnaround on labeling review and public access to more accurate labeling information.

A small group within the HL7 technical committee on Regulated Clinical Research Information Management (RCRIM-TC) initially developed the SPL standard. SPL uses Clinical Document Architecture (CDA), which allows information to be exchanged in XML. The plan calls for manufacturers to submit labeling information to FDA, which will transmit it to the National Library of Medicine; NLM in turn will make the information available electronically to all users through its DailyMed system.

The RCRIM-TC also is establishing standards related to clinical product development, including standards for transmitting clinical laboratory data from labs to sponsors and for submitting electro-cardiogram data to FDA. In the works is a standard for manufacturers to file stability data electronically with FDA.

Despite general support for the SPL e-labeling system, the implementation process will have to address a number of issues. One concern is how FDA will deal with labeling already under review and amendments to labeling previously filed in PDF. Another is whether the SPL standard fits electronic filing requirements established for the Common Technical Document (CTD). Levin said there is no problem because the CTD primarily organizes the submission but can accommodate data in SPL, PDF, or other formats. What may be more difficult is using SPL to submit adverse drug event reports with different regulatory authorities around the world, according to Levin.


Once FDA establishes the SPL e-labeling system, that data will provide the agency with the information it requires to track each FDA-registered drug and where it is manufactured. This data is part of the FDA Unified Registration and Listing System (FURLS). This is FDA's master list of food and drug facilities, which contains key information on every drug or biologic made at each plant. The listings identify products by national drug codes and provide information on ingredients, strengths, shape, and color.

Using up-to-date electronic data will provide more accurate listing information, Levin explained, which FDA can use to schedule and track plant inspections, user fee billing, and other agency activities. The current paper-based system often carries incorrect NDC numbers and out-of-date information, particularly from drug repackagers and relabelers.

In what some observers describe as a "perfect storm" in drug information communication, the FDA e-labeling initiative will allow manufacturers to update product labels daily, and an industry "paperless labeling" initiative will distribute that information electronically to prescribers, pharmacists, and patients. These users will be able to use the information to reduce prescribing errors and adverse drug events as well as improve patient care.