Regulatory Beat: Electronic Information Systems Promote Drug Development, Patient Safety

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BioPharm International, BioPharm International-02-01-2004, Volume 17, Issue 2

FDA expands electronic data submission programs to improve regulatory operations and ensure appropriate and safe drug use.

Federal health officials seek to improve patient care by establishing national electronic medical records and health information systems that can make it easier for health care professionals to access information on medical products and patient health. In December, FDA launched an ambitious program to support these efforts, beginning with a new rule requiring manufacturers of drugs and biologics to file product labeling electronically. The agency is developing systems for electronic submission of market applications, clinical trial data, and information on drug use in the real world. These initiatives establish databases on product safety, efficacy, and quality, providing the public with timely information on appropriate medication use through the National Library of Medicine.

These programs build on a series of FDA policies that clarify how industry may submit required regulatory documents in electronic format. FDA published guidance on formatting electronic submissions in January 1999 and updated it in a draft guidance published last October. In August, the agency issued recommendations (based on those from ICH) for electronic filing of the Common Technical Document (CTD), a common format for submitting clinical and manufacturing information to register new drugs and biologics around the world. Based on ICH standards, FDA also is establishing procedures for electronic submission of postmarketing expedited safety reports and periodic adverse drug experience reports. FDA anticipates that a recent clarification of its electronic records and signature policy under 21 CFR Part 11 will help manufacturers develop electronic recordkeeping and filing systems for all these programs.

Mandatory E-labeling

Up until now, FDA e-submission programs were voluntary while the agency worked to establish standards and terminologies for submitting electronic data. Several years of experience in receiving and evaluating electronic filings will allow agency officials to move forward with mandated electronic data submissions, starting with drug labeling. FDA issued a final regulation in December requiring manufacturers to electronically file the package insert or professional labeling for drugs and biologics, including all text, tables, and figures.


FDA officials anticipate that electronic submission will greatly facilitate its review of the thousands of labeling changes made each year. Currently, when a manufacturer files even a minor change in labeling, the agency must conduct a manual word-for-word comparison of two paper copies. The new policy also seeks to speed up dissemination of labeling changes and important product information to doctors and patients. The labeling data will become part of DailyMed, an electronic library of labeling information for FDA-regulated products. Patients and prescribers will be able to search this library — a joint project of FDA, the National Library of Medicine, and the Veterans Health Administration — for information on drug side effects and product benefits.

In announcing the e-labeling requirement at the December 9 meeting of the National Council on Patient Information & Education (NCPIE), FDA Commissioner Mark McClellan observed that "using modern information technology to improve public health is no longer optional at FDA." He expects manufacturers to quickly provide FDA with updated information on drug risks and benefits, which will help physicians and consumers make "head-to-head comparisons between drugs so that they can make the best choices."

As far as new mandates go, this one is not highly controversial. Most pharmaceutical companies have been submitting labeling information electronically for some time on a voluntary basis using the inexpensive and widely available portable document format (PDF). FDA reserves the right to recommend new file formats and software in the future in response to technological advances but promises to consult with industry and provide ample warning before making any changes. FDA published a proposed e-labeling rule in May 2002. The agency received only a few comments and finalized the proposal with little change. The e-labeling requirement becomes effective this June and applies only to the package insert's content (including references in annual reports) — not to all the various types of labels on packages and containers or submitted with advertising material.

Expanding Information Systems

The e-labeling rule is just one part of a broader FDA strategy to spur development of a national electronic health information system. In a speech before the Urban Institute in Washington, DC in November, McClellan described his vision for using modern information technologies to collect and analyze data that can help deliver "safer, higher value, and less costly medical care." The initiatives include:

  • Electronic data systems for clinical trials. FDA is collaborating with the National Cancer Institute (NCI) to establish the Cancer Biomedical Informatics Grid, which includes an electronic system for the submission and evaluation of information from cancer trials. A first step announced in November is to build a national system that will allow cancer researchers to submit INDs electronically to FDA. This will accelerate FDA review and speed new treatments to patients at a lower cost. FDA aims to use this experience with NCI "as a model for how we manage information across all of the different therapeutic areas and in every clinical trial," McClellan also said at the Urban Institute. Cancer research provides a good place to start because many investigators and NCI cooperative groups currently use advanced information systems that allow investigators to enter clinical information electronically. Such systems will help researchers quickly gain answers to questions about test treatments and also provide useful information on benefits and risks of treatments to patient subgroups, including minorities, women, children, and seniors.
  • Analysis of pharmacogenomic (PG) information. FDA issued a proposal in November encouraging drug researchers to share with FDA information on how genetic differences in patients affect their response to therapies. The draft guidance on Pharmacogenomic Data Submissions clarifies when such data should be filed as part of an NDA or BLA and also defines an alternative pathway to provide research information separate from official submissions. The initiative will use electronic information systems to compile PG information on which treatments are likely to be more effective or more safe for certain patients while camouflaging sponsors' identities.
  • Tracking drug products. FDA is finalizing a proposal issued last year to require bar coding of national product codes on all prescription drugs, biologics, and blood products to reduce dispensing and treatment errors. Implementation requires establishing large data banks to collect and issue product identification information. Barcoding and other information technologies also may help curb distribution of unapproved and illegal drug products. FDA's Counterfeit Drug Task Force is encouraging use of electronic "track and trace" systems to establish electronic pedigrees and follow a product from manufacturer to end user. Manufacturers are testing radio frequency tracking systems and exploring approaches for establishing integrated databases that can be used throughout the drug distribution system.
  • Expanded adverse event (AE) reporting. To ensure the safe use of medical products after approval, FDA is expanding its current spontaneous AE reporting system and adopting innovative statistical methods to identify "signals" of drug problems more quickly. Because this voluntary reporting system is fairly limited, FDA also wants to establish broader active surveillance systems. Some initiatives involve linking directly into health plan electronic medical record systems to scan for possible problems with a new product.
  • Electronic prescribing. The emergence of low-cost Web technologies and the increased physician use of hand-held devices promise to boost e-prescribing, which can reduce errors and improve treatment decisions. McClellan believes FDA's e-labeling policy will encourage e-prescribing. He notes that e-prescribing is used on less than 10% of drug prescriptions in doctors' offices today but expanded use could eliminate more than two million adverse drug events each year.

In addition, an important but less noticed provision in the recently approved Medicare reform bill supports development of e-prescribing programs. First, it instructs the Department of Health and Human Services to establish e-prescribing standards in two years, followed by a one-year pilot in 2006 to test the system, leading to final standards in 2008.

The bill also provides grants for prescribers to install e-prescribing programs and, more importantly, allows Medicare managed care plans and pharmacy plan operators to pay bonuses to doctors and hospitals that participate in e-prescribing programs. E-prescribing is expected to encourage physicians to comply with drug formularies in order to improve patient safety, quality of care, and achieve cost savings. One year after adoption of final standards, all Medicare providers will have to follow the new standards if they want to use electronic prescribing systems.