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 
 
1
 
Guidance for Industry
Indexing Structured Product Labeling 

 
 
 
 
This guidance represents the Food and Drug Administrations (FDAs) 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. 
 
FDAs guidance documents, including this guidance, do not establish legally-enforceable 
responsibilities. Instead, guidances describe the Agencys 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   
                                                 
1 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 Medicines 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 Sevens 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 hospitals computer system to ensure that medications prescribed by the 
hospital to treat the patients 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 FDAs 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 Medicines 
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 applicants 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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