Guidance for Industry 

Indexing 

Structured Product Labeling 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

June 2008 

Electronic Submissions 

Revision 1 
Guidance for Industry 

Indexing 

Structured Product Labeling 

Additional copies are available from: 

Office of Training and Communications 

Division of Drug Information, HFD-240 

Center for Drug Evaluation and Research 

Food and Drug Administration 

5600 Fishers Lane 

Rockville, MD 20857 

(Tel) 301-827-4573 

http://www.fda.gov/cder/guidance/index.htm

or 

Office of Communications, Training and 

Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research 

Food and Drug Administration 

1401 Rockville Pike, Rockville, MD 20852-1448 

 (Tel) 800-835-4709 or 301-827-1800 

http://www.fda.gov/cber/guidelines.htm 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

June 2008 

Electronic Submissions 

Revision 1 
TABLE OF CONTENTS 

I. INTRODUCTION............................................................................................................. 1

II. BACKGROUND ............................................................................................................... 1

A. When Did the Use of SPL Become a Requirement? ...................................................................1

B. Why Is Indexing SPL So Important?...........................................................................................2

III. FDA'S STRATEGY FOR INDEXING SPL................................................................... 4

A. Why Is FDA Indexing SPL?..........................................................................................................4

B. How Will FDA Index SPL?...........................................................................................................4

C. Participation in SPL Indexing ......................................................................................................5
Contains Nonbinding Recommendations 

Guidance for Industry1

Indexing Structured Product Labeling 

This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It 

does not create or confer any rights for or on any person and does not operate to bind FDA or the public. 

You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 

and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 

implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate 

number listed on the title page of this guidance. 

I. INTRODUCTION

This guidance explains that FDA's Center for Drug Evaluation and Research (CDER) and Center 

for Biologics Evaluation and Research (CBER) will index the content of labeling for human drug 

and biological products using SPL (Structured Product Labeling). Indexing refers to the 

insertion of machine-readable tags, which do not appear in actual printed labeling, that enable 

users with clinical decision support tools and electronic prescribing systems to rapidly search and 

sort product information. This guidance also describes how applicants can participate in the SPL 

indexing process. Having consistently and accurately indexed content of labeling is an important 

step toward the creation of a fully automated health information exchange system. 

This guidance has been revised to correct a formatting error on page 4. 

FDA’s guidance documents, including this guidance, do not establish legally-enforceable 

responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should 

be viewed only as recommendations, unless specific regulatory or statutory requirements are 

cited. The use of the word should in Agency guidances means that something is suggested or 

recommended, but not required. 

II. BACKGROUND 

A. When Did the Use of SPL Become a Requirement? 

On October 31, 2005, FDA stated that SPL in extensible markup language (XML) format is the 

only electronic format for content of labeling2

 that CDER can process, review, and archive.3 

 

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 This guidance has been prepared by the Center for Drug Evaluation and Research in cooperation with the Center 

for Biologics Evaluation and Research at the Food and Drug Administration. 

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Contains Nonbinding Recommendations 

This also applied to annual report submissions.4 Currently, the content of labeling must be 

submitted to CBER in electronic format (21 CFR § 601.14; see also guidance for industry: 

Providing Regulatory Submissions in Electronic Format-Content of Labeling). CBER soon will 

begin recommending that content of labeling be submitted in SPL. SPL is also a key component 

of Facts@FDA,5 which makes regulated product information in SPL format publicly available 

on the National Library of Medicine’s DailyMed Web site and on the FDA Data Standards 

Council Web site ("Data Standards Web site").6

A Health Level Seven (HL7)7

 standard, SPL is used to make possible the electronic exchange of 

the content of labeling and other regulated product information using the extensible markup 

language (XML). Specifically, the SPL standard enables the inclusion of indexing elements, 

which are machine-readable tags that can be added to product labeling to enable users to rapidly 

search and sort product information. 

B. Why Is Indexing SPL So Important? 

Indexing the content of labeling with SPL will greatly enhance users' ability to automatically 

search and sort product information. The American healthcare community (e.g., federal 

healthcare agencies, healthcare providers, healthcare professionals, and industry) is working 

toward the creation of a fully-automated health information system. Eventually, patients, 

healthcare professionals, and providers will have electronic health records, electronic prescribing 

systems, and an array of clinical decision support systems and tools at their disposal. Being able 

to electronically access labeling information and to search and sort that information is an 

important step toward the creation of a fully automated health information exchange system. 

Currently, health information suppliers take the information from the content of product labeling 

to populate databases that are used in clinics and hospitals to help prevent prescribing errors. In 

the past, much of this information was input by hand. Since October 31, 2005, FDA has been 

making labeling information for prescription drugs available free of charge on the Internet 

through the use of SPL. Full-text search of the content of labeling has obvious limitations, 

 2

 Content of labeling refers to all text, tables, and figures associated with prescribing information. It does not 

include carton and immediate container labels. 

3

 See 21 CFR §§ 314.50(l)(1)(i) and (l)(5) and 314.71(b); see also Memorandum 32 ("Content Labeling") to FDA 

Docket No. 92S-0251. 

4 See Guidance for Industry: SPL Standard for Content of Labeling Technical Qs & As, Question #41. See 21 CFR 

314.81(b)(2)(iii) (note, however, that applicants should not submit SPL with an annual report if there are no changes 

to the previously submitted SPL). 

 

5 See http://www.fda.gov/oc/datacouncil/drug_labels.htm. 

6 See http://dailymed.nlm.nih.gov/dailymed/about.cfm and http://www.fda.gov/oc/datacouncil/drug_labels.htm.

7 See http://www.hl7.org. HL7 is a one of several American National Standards Institute-accredited Standards 

Developing Organizations (SDOs) operating in the healthcare arena. Most SDOs produce standards (sometimes 

called specifications or protocols) for a particular healthcare domain such as pharmacy, medical devices, imaging or 

insurance (claims processing) transactions. Health Level Seven’s domain is clinical and administrative data. 

 

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Contains Nonbinding Recommendations 

however. For example, users searching for hepatotoxicity will miss labelings that use the term 

liver toxicity. The addition of indexing elements, chosen from standards adopted for use in the 

healthcare setting, will address this problem. 

Once FDA has indexed the content of labeling using SPL, health information suppliers will be 

able to package indexed information about a product and make it available to healthcare 

professionals and others through health information systems, such as clinical decision support 

tools and electronic prescribing systems. In addition, the prescription drug information that FDA 

already has made available on the Internet will be much more useful, because the indexing 

elements will enhance user ability to quickly access, search, and analyze the labeling information 

needed to make critical healthcare decisions. SPL indexing elements are not intended to be used 

by clinicians in lieu of the full prescribing information, nor do they serve as the basis for product 

promotional activities. 

Having consistently and accurately indexed content of labeling also will greatly enhance the safe 

use of medical products. In July 2006, the Institute of Medicine of the National Academy of 

Sciences estimated that more than 1.5 million people annually are injured due to medication 

errors. The cost of treating hospital-based medication errors alone is conservatively estimated at 

more than $3.5 billion annually, and this cost does not include estimates for lost wages and lost 

productivity.8 One source of many errors is prescribing errors, which can result in avoidable 

adverse drug reactions. For instance, if a patient with asthma is taken to the hospital in an 

emergency situation for an unrelated physical injury, the SPL indexing elements would enable 

the hospital to use its computer system to quickly identify all drugs contraindicated in patients 

with asthma and treat the patient accordingly. Among other benefits, the SPL indexing elements 

also could enable the hospital’s computer system to ensure that medications prescribed by the 

hospital to treat the patient’s injury do not adversely interact with other medications that the 

patient is taking to treat his or her asthma. In short, the SPL indexing elements, when coupled 

with other computer technologies, will provide patients and healthcare providers with better and 

more timely access to important healthcare information. 

Finally, indexing the content of labeling directly supports FDA’s mission, because this effort will 

help Americans “get the accurate, science-based information they need to use medicines ... to 

improve their health.”9 Indexing also addresses a recommendation in the Institute of Medicine’s 

2006 report on drug safety, which identified the need for improved communication between 

FDA and the public about drug safety and efficacy information.10 SPL indexing will greatly 

facilitate this communication by helping create a more robust nationwide system for promoting 

the safe and effective use of drugs. 

 

8 See http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=11623. 

 

9 See FDA Mission Statement at http://www.fda.gov/opacom/morechoices/mission.html. 

10 See “The Future of Drug Safety: Promoting and Protecting the Health of the Public,” cited at 

http://www.iom.edu/CMS/3793/26341/37329.aspx. 

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Contains Nonbinding Recommendations 

III. FDA'S STRATEGY FOR INDEXING SPL 

A. Why Is FDA Indexing SPL? 

FDA has been piloting the addition of SPL indexing elements to labeling that has been submitted 

by sponsors pursuant to the new content and format regulation for prescription drug labeling.11 

Although a number of different approaches were tried during the pilot program, based on our 

experience and on feedback from industry and other SPL users, we have determined that the 

most efficient strategy is for FDA, rather than individual applicants, to index the information 

received in SPL. Moreover, it is important that indexing be done consistently to enable 

comprehensive searches to find all relevant information, including appropriate synonyms. FDA's 

exclusive indexing of the SPL information furthers this goal. 

B. How Will FDA Index SPL? 

FDA will index the content of labeling for all products. The process therefore is not limited to 

products subject to 21 CFR 201.57 during the implementation period for that regulation. 

FDA intends to index the content of labeling using a phased implementation. Phased 

implementation will help maximize the utility of the indexing elements given available Agency 

resources and will ensure that all labeling will contain key indexing elements during the initial 

phases of the SPL indexing process. For drug and biological products, indexing information 

includes, among other things, the indication, limitations of use, conditions of use, and 

pharmacologic class of the drug. In the first phase, FDA plans to index the pharmacologic class 

for all labeling in SPL. We are indexing pharmacologic class first because (1) it is important for 

the safe use of drugs, (2) it is necessary for making future indexing meaningful (e.g., drug 

interactions), and (3) this choice leverages existing FDA resources. After pharmacologic class, 

FDA will decide which indexing elements should be added in future phases, and those decisions 

will be posted on the Data Standards Web site. FDA will solicit public input from SPL users and 

industry through public meetings and announcements (e.g., in the Federal Register) prior to 

announcing new indexing elements. 

FDA generally will make indexing decisions based on the content of labeling and the selected 

terminologies.12 For example, the pharmacologic class indexing element for a monoamine 

oxidase inhibitor is associated with the preferred term “monoamine oxidase inhibitors” and the 

associated code (N0000000184) from the Veterans Administration National Drug File Reference 

Terminology (NDF-RT).13 FDA would index a monoamine oxidase inhibitor as follows: 

 

11 See Guidance for Industry: SPL Standard for Content of Labeling Technical Qs & As. 

 

12 If an appropriate term is not available in an existing terminology, FDA will work with the relevant terminology 

maintenance organizations to identify a new term. 

13 NDF-RT includes the controlled terminology for mechanism of action, physiologic effect, and structural class, 

which are part of the Federal Medication Terminology standard. 

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Contains Nonbinding Recommendations 

<generalizedPharmaceuticalClass> 

 <code code=“N0000000184” codeSystem=“2.16.840.1.113883.3.26.1.5” 

displayName=“monoamine oxidase inhibitors”/> 

</generalizedPharmaceuticalClass> 

Because indexing serves only to electronically flag or identify information of a particular type, 

indexed elements are not visible in the printed labeling. These tags nonetheless can be used to 

sort and categorize the information so that it will be more readily accessible in electronic 

systems. 

FDA will use a coordinated approach for indexing to ensure consistency across all labeling and 

will consult with subject matter experts in the respective Centers' review divisions as necessary. 

To make the process as transparent as possible, FDA intends to list on the Data Standards Web 

site the terminologies and elements it plans to use to index the SPL for all labeling.14 To that 

end, FDA first will post for comment a list of pharmacologic class terms that it has selected for 

FDA-regulated active ingredients prior to indexing SPL containing those ingredients. 

Instructions on providing comments to these listings will be included on the Data Standards Web 

site. FDA intends to periodically update the term list. FDA may employ a similar 

announcement strategy for future indexing elements. 

C. Participation in SPL Indexing 

Applicants may suggest indexing terms when they submit their SPL file in their regulatory 

submission. See the SPL Implementation Guide for details on including indexing terms.15 

Because FDA will be indexing the content of labeling, applicants should not change indexing 

elements associated with existing SPL. 

In general, the SPL indexing process is independent from the labeling review process associated 

with a submission review cycle. As such, SPL indexing will not affect review times or delay 

approvals. However, indexing considerations may be incorporated in the standard labeling 

review discussions. Because FDA will add indexing terms as a separate file that references the 

SPL, the applicant’s SPL file will remain unchanged by the indexing process. 

We recommend that applicants submit any questions regarding an existing indexing element, 

including any requests to add or revise an element, to spl@fda.hhs.gov. Inquiries and requests 

will be forwarded to the appropriate FDA personnel, who will consider them and make any 

appropriate change to the indexing element. 

 

14 The timing of subsequent phases will depend on available FDA resources. 

15 The Implementation Guide can be found on the HL7 Web site at http://www.hl7.org or the Data Standards Web 

site at http://www.fda.gov/oc/datacouncil/spl.html. 

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Contains Nonbinding Recommendations 

Disagreements that cannot be resolved at this level should be handled according to procedures 

outlined in the guidance for industry Formal Dispute Resolution: Appeals Above the Division 

Level. 

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