Changes Proposed to Require Electronic Distribution of Package Inserts

January 22, 2015

By Anne K. Walsh

This post relates to the all-important package insert, which provides health care professionals with the latest information about the approved uses of a prescription drug or biological product, as well as information necessary for the safe and effective use of the product.  Last month, FDA proposed getting rid of the well-known, but little-used, paper form of the package insert, and instead requiring manufacturers to distribute this information electronically via FDA’s electronic database,  No change was proposed to the substantive content of the package insert.  The Drug and Device Law Blog aptly evaluated the product liability implications of this change; this post considers the regulatory impact of this proposal. 

To be clear, patients receiving a prescription drug will continue to receive a paper copy of the warning, risk information, or special instructions related to the drug.  FDA’s proposal only relates to the prescribing information intended for health professionals. 

FDA has been considering electronic distribution for a long time.  In 2007, FDA held a public hearing to solicit views on the feasibility of an electronic-based system, and the benefits associated with it.  In the intervening eight years, the health industry has only increased its reliance on electronic-based systems, including the labeling information supplied on DailyMed, a public database maintained by the National Library of Medicine, a sister agency of FDA.  In fact, FDA has been coordinating with the National Library of Medicine to ensure DailyMed provides the current package insert information for drugs.  The website states: 

DailyMed provides trustworthy information about marketed drugs. DailyMed is the official provider of FDA label information (package inserts). This Web site provides a standard, comprehensive, up-to-date, look-up and download resource of medication content and labeling found in medication package inserts.

The National Library of Medicine (NLM) provides this as a public service and does not accept advertisements. The drug labeling information on this Web site is the most recent submitted to the Food and Drug Administration (FDA) and currently in use; it may include, for example, strengthened warnings undergoing FDA review or minor editorial changes. These labels have been reformatted to make them easier to read.

In contrast, the language on FDA’s labeling website states:

The drug labels and other drug-specific information on this Web site represent the most recent drug listing information companies have submitted to the Food and Drug Administration (FDA). (See 21 CFR part 207.)  The drug labeling and other information has been reformatted to make it easier to read but its content has neither been altered nor verified by FDA.  The drug labeling on this Web site may not be the labeling on currently distributed products or identical to the labeling that is approved. 

Obviously this disclaimer language will need to be removed if the proposed rule is accepted.  It is unclear why FDA proposes to populate its currently unreliable database, rather than rely on the already existing and well-regarded DailyMed database. 

As a side note, FDA’s labeling website also includes information on OTC drugs, homeopathic drugs, unapproved drugs, and medical devices, with similar disclaimers that this information may not be current or even accurate.  It is unclear whether FDA will impose similar electronic and verification requirements on those product manufacturers in the future. 

According to FDA, and the study it commissioned, prescribing physicians and nurses typically do not receive the paper version of the package insert because they do not dispense drugs.  They already use a variety of electronic databases (like DailyMed) to access prescribing information.  Pharmacists, who do dispense drugs and do receive the package insert from manufacturers, complain the package insert is difficult to read due to the small font size, thin paper, and multiple folds.  FDA also found a long delay (up to 39 months) after a change is made to a drug’s prescribing information before the change actually appears in the printed prescribing information attached to a drug product.  FDA claims these delays raise concerns about use of outdated information in clinical decision-making. 

Under the proposal, manufacturers would be required to submit to FDA’s website ( the updated labeling every time there is a change in the labeling.  This must be done within 2 days after approval of a Prior Approval Supplement, and simultaneously with a Changes Being Effected submission.  The rule also would require manufacturers to verify that the information on the website is accurate, complete and up-to-date, and to notify FDA if this is not true, even if it is FDA’s fault for not promptly posting the information. 

The proposal also would require manufacturers to revise the product’s immediate container label and outside package to identify the FDA labeling website and a toll-free telephone number to process requests for prescribing information if the Internet is unavailable.  The manufacturer would be responsible for establishing the toll-free number, and staffing it 24 hours a day, 7 days a week, so that the prescribing information can be sent to a requestor by e-mail, fax, or paper.  Therefore manufacturers still would need to print and have on hand paper copies of the latest package insert, even though the proposal is intended to eliminate confusion from paper versions.

FDA references the July 2013 Government Accountability Office Report titled “Electronic Drug Labeling: No Consensus on the Advantages and Disadvantages of its Exclusive Use.”  Recognizing some of the challenges for electronic access, FDA proposes to exempt companies in circumstances when compliance with the rule could adversely affect the safety, effectiveness, purity, or potency of the drug; is not technologically feasible; or is otherwise inappropriate.  Examples of such circumstances include a product which requires multiple steps for reconstitution, a product that is intended for use in an emergency room, a product that may be stockpiled for use during an emergency, and cell therapy products that require proper handling and multiple steps. 

FDA proposes an effective date of 6 months from publication of the final rule, and a compliance date 2 years subsequent, to give manufacturers time to make preparations to comply with the rule.  FDA also proposes a staggered compliance date to allow blood and blood components more time for compliance.  Comments on the proposal are due by March 18, 2015.