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FDA is expanding electronic data submission programmes to improve regulatory operations, and ensure appropriate and safe drug use.
Federal health officials are taking steps to establish national electronic medical records and health information systems. The aim is to improve patient care by making it easier for health care professionals to access information regarding medical products and patient health issues. Prescribing drugs electronically is a key element, critical in reducing medication errors and improving compliance.
The US Food and Drug Administration (FDA) has launched an ambitious programme to support these efforts, beginning with a new rule requiring drug manufacturers to file product labelling information electronically. The agency is developing systems for the e-submission of applications for testing and marketing new drugs, and for capturing new drug use information. These initiatives will help build databases on product safety, efficacy and quality to provide the public with timely information concerning medication use through the National Library of Medicine.
These programmes build on a series of FDA policies issued during recent years to clarify how industry may submit required regulatory documents in electronic format. In January 1999, FDA published a guidance regarding formatting e-submissions, which was updated in a new draft guidance published last October (2003). A November 1999 guidance addresses submitting abbreviated new drug applications (ANDAs) electronically. Last August (2003), the agency issued recommendations for electronic filing of the common technical document (CTD); this establishes a novel format for registering new drugs around the world based on recommendations from the International Conference on Harmonization (ICH). ICH agreements are also changing FDA policies for the e-submission of postmarketing expedited safety reports and for periodic adverse drug event (ADE) reports. In addition, the agency expects that a recent clarification of its electronic records and signatures policy under Part 11 will help manufacturers develop electronic record keeping and filing systems. Separately, the Bush administration seeks to improve public health by encouraging lower drug prices, an issue that has entered international trade talks (see sidebar "Trade negotiations").
Until now, FDA e-submission programmes have been voluntary for pharma companies. The agency has been working to formulate uniform standards and terminologies for submitting electronic data to help manufacturers develop information systems that can interrelate. The aim is to be able to capture complex information regarding medical products, practices and health conditions, and transfer the data over secure networks.
FDA officials are moving forward with mandated electronic data submissions, starting with drug labelling information. The agency issued a final regulation in December (2003) requiring manufacturers to submit the content of the package insert or professional labelling in electronic format, including all text, tables and figures (www.fda.gov/OHRMS/DOCKETS/98fr/03-30641.htm). The rule establishes a standard format for filing market applications and supplements for new drugs and biologics, including generic drugs.
The aim is to improve the review process and speed up dissemination of labelling changes and important product information to doctors and patients. The data will become part of an electronic library of labelling information for all FDA regulated products, which will make it easier for people to search for information on drug side-effects, comparisons with other drugs and product benefits. FDA is collaborating with the National Library of Medicine's DailyMed project, which will provide medication information to the public.
In announcing the e-labelling requirement at the December (2003) meeting of the National Council on Patient Information and Education (NCPIE), FDA commissioner Mark McClellan observed that "using modern information technology (IT) to improve public health is no longer optional at FDA." He expects the new programme will allow manufacturers to quickly provide FDA with updated information on drug risks and benefits. That information will then help physicians and consumers make "head-to-head comparisons between drugs so that they can make the best choices," he noted. The new initiative is "the first step in developing an e-library of all FDA labels that can be readily searched and used by professionals and consumers alike," and reduce the need for doctors to search through thousands of pages in reference books.
As far as new mandates go, this one is not highly controversial. Most large pharma companies have been voluntarily submitting labelling information electronically for some time, and the technical process for doing so uses portable document format (PDF), which is inexpensive and widely available. 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 to provide ample warning before making any changes.
The agency published a proposed e-labelling rule last May, received only a few comments and finalized the proposal with little change. The e-labelling requirement becomes effective in June and only applies to the content of the package insert, including references in annual reports, and not to all the various types of labels on packages and containers or those submitted with advertising material.
New team at HHS
FDA officials anticipate that this policy will greatly facilitate its review of thousands of labelling changes submitted each year. When a manufacturer files even a minor change in professional labelling, the agency has to conduct a manual word-for-word comparison using two paper copies.
Still to come are further regulations for restructuring the content of professional drug labelling to make it more readable and useful to prescribers. A related initiative aims to replace paper package inserts with electronic information. Pharmaceutical manufacturers back this campaign and have been working to reduce opposition from pharmacists. Tests of a paperless labelling system are under way.
The e-labelling rule is just one part of a broader FDA strategy for spurring development of a national electronic health information system. At a speech before the Urban Institute in Washington DC, McClellan described his vision for using modern IT to collect and analyse ADE information and thus deliver "safer, higher value and less costly medical care." These initiatives include the following:
Electronic data systems for clinical trials. FDA is collaborating with the National Cancer Institute (NCI) to establish the Cancer Biomedical Informatics Grid featuring an electronic system for submitting and evaluating cancer trial information. A first step, announced in November (2003), is to implement a system for electronically submitting investigational new drugs (INDs) for cancer therapies to FDA. This will build a system that will link cancer researchers across the US to FDA, allowing e-submission of clinical data. FDA will be able to review these applications faster, speeding new treatments to patients at a lower cost.
The larger goal for FDA is to use this experience with NCI and cancer therapies "as a model for how we manage information across all the different therapeutic areas and in every clinical trial," McClellan said. Working in the cancer area will further this effort because many cancer researchers and NCI cancer co-operative groups currently use advanced information systems. Investigators in these groups are already entering clinical information electronically, providing evidence of how this process can speed up the clinical trial process and more readily provide information to drug developers and FDA reviewers.
In addition to enhancing FDA's review process, e-information from clinical trials will accelerate clinical research by allowing researchers to quickly obtain answers to questions regarding test treatments. Research information data banks can also provide useful information concerning the benefits and risks of drugs to patient subgroups, including racial and ethnic minorities, women, children, seniors and others.
Pharmacogenomic information analysis. FDA issued a proposal in November (2003) to encourage drug researchers to share with it information on how genetic differences cause patients to respond differently to therapies (www.fda.gov/cber/gdlns/pharmdtasub.pdf). Drug manufacturers are collecting more pharmacogenomic (PG) data, but are reluctant to submit it for fear that it might raise "red flags" for the regulators. The draft guidance clarifies when such data should be filed as part of a new drug application (NDA) or biologic licence application (BLA).
The agency also defines another pathway for providing research information, separate from official submissions, to help improve regulatory processes and inform the research community. This involves using electronic information systems to analyse large amounts of data that can then be made available to the medical community. FDA says it will combine PG information submitted electronically to camouflage the sponsor while generating useful information on which treatments are likely to be more effective or more safe for certain patients.
Tracking drug products. FDA is finalizing a proposal issued last year requiring national product codes on all prescription drugs, biologics and blood products to prevent errors in dispensing and administering them. Implementation requires establishing large data banks to collect and distribute product identification information. The regulation is expected to encourage hospitals and clinics to adopt barcode readers and electronic record systems able to scan and interpret drug barcode information.
Drug barcoding may also help curb the distribution of unapproved and illegal drug products. FDA's counterfeit drug task force is encouraging a number of technologies, including electronic "track and trace" systems that are able to follow a drug from manufacturer to end-user. Use of radio-frequency identification systems and barcodes to establish electronic pedigrees is being encouraged, replacing cumbersome paper-based systems. Manufacturers are testing new tracking technologies and exploring approaches for establishing integrated databases that can be used at all stages of the drug distribution system.
Increased information on ADEs. To ensure the safe use of medical products after approval for market, FDA is expanding its current spontaneous ADE reporting system and adopting innovative statistical methods that are able to identify "signals" of drug problems more quickly. However, because this voluntary reporting system is fairly limited, the agency also wants to establish broader active surveillance systems to improve its capacity for detecting drug safety issues. Some initiatives involve linking directly into the electronic medical record systems of health care plans to scan medical records for signals that could indicate problems with new products. Once hospitals and physicians establish electronic medical records systems, ADE reporting could become automatic.
Electronic prescribing systems. The emergence of low cost web technologies and increased use of palm-sized devices among physicians promises to boost e-prescribing, thereby reducing errors and improving treatment decisions. Although e-prescribing is currently used for less than 10% of drug prescriptions, McClellan estimates that its implementation across the US could eliminate more than 2 million ADEs annually.
FDA's e-labelling policy will encourage e-prescribing, McClellan believes. In addition, an important but less noticed provision in the recently approved Medicare reform bill supports development of e-prescribing programmes. Although the legislation stops short of mandating that health plans and providers adopt such systems, the measure provides strong incentives to do so. It instructs the Department of Health and Human Services (HHS) to establish e-prescribing standards, the first of which will be developed in 2 years with input from standards organizations, providers, pharmacists and pharmacy benefit managers (PBMs). HHS will conduct a one-year pilot in 2006 to test the system and issue final standards in 2008 (see sidebar "New faces at HHS").
The bill also provides grants to assist prescribers with installing e-prescribing programmes and, more importantly, allows Medicare managed care plans and pharmacy plan operators to pay bonuses to doctors and hospitals that participate in e-prescribing. One year after adoption of final standards, all Medicare providers will have to follow the new standards if they want to use e-prescribing systems. E-prescribing is expected to encourage physicians to comply with drug formularies to improve patient safety, quality of care and yield cost savings.