Recommendations for the Submission of 
LOINC Codes in Regulatory Applications to 
the U.S. Food and Drug Administration 
 
 
 
 
 
 
LOINC Working Group:   
U.S. Food and Drug Administration (FDA), U.S. National 
Institutes of Health (NIH), Clinical Data Interchange Standards 
Consortium (CDISC), and Regenstrief Institute 
 
 
 
 
 
November 2017 
 
  1  LOINC Working Group (WG) Members and Affiliations ........................................................ 1 
Table of Contents 
2  Background ......................................................................................................................... 1 
2.1  Purpose of this Recommendation Document ............................................................... 1 
2.2  Introduction .................................................................................................................. 2 
2.3  CDISC Member Survey Regarding LOINC Readiness ................................................. 3 
2.4  Pre-Requirement Submissions of LOINC Codes to FDA .............................................. 3 
3  Working Group Considerations ........................................................................................... 3 
4  Working Group Recommendations ..................................................................................... 6 
5  Potential Future Phases ...................................................................................................... 8 
6  References ......................................................................................................................... 8 
7  Appendices ......................................................................................................................... 9 
7.1  Abbreviations ............................................................................................................... 9 
7.2  Helpful Links ................................................................................................................ 9 
7.3  Educational Resources and Events ............................................................................10 
7.3.1  CDISC .................................................................................................................10 
7.3.2  LOINC..................................................................................................................10 
 
 
 
i  1  LOINC Working Group (WG) Members and Affiliations 
 
Member Name  Professional Affiliation 
Swapna Abhyankar, M.D.  Regenstrief Institute/LOINC 
Lauren Becnel, Ph.D.  CDISC 
Boris Brodsky  FDA 
Ron Fitzmartin, Ph.D.  FDA 
Margaret Haber  NCI 
Virginia Hussong  FDA 
Clement McDonald, Ph.D.  NLM 
Erin Muhlbradt, Ph.D.  NCI 
Eileen Navarro, M.D.  FDA 
Vaishali Popat, M.D.  FDA 
Colleen Ratliffe  FDA 
Lilliam Rosario, Ph.D.  FDA 
Jessica Voqui, Pharm.D.  FDA 
Daniel Vreeman, D.P.T.  Regenstrief Institute/LOINC 
Alan Williams, Ph.D.  FDA 
Lawrence Wright, Ph.D.  NCI 
 
2  Background 
2.1  Purpose of this Recommendation Document 
Regulated  clinical  research  is  carried  out  and  supported  across  multiple  sectors  including 
academic medical centers, biopharmaceutical companies, biotechnology companies, clinical 
research organizations, federal agencies, information technology vendors and others. The FDA 
will soon begin requiring the inclusion of a medical laboratory and observation terminology coding 
system, Logical Observation Identifiers Names and Codes (LOINC). While this requirement will 
help align semantics between healthcare and regulated clinical research, readiness for this 
requirement and understanding of LOINC can vary dramatically across these sectors. 
In January 2017, the FDA convened a Committee, including FDA, NIH, CDISC, and Regenstrief 
Institute, to evaluate the use of terminology standards, with a particular focus on LOINC.  The 
Committee formed a LOINC Working Group to: (1) review the relationship between the CDISC 
laboratory codes and the Regenstrief LOINC laboratory codes, (2) address the concerns raised 
by  the  CDISC  community  in  the  2017  survey,  and  (3)  develop  recommendations  for  the 
submission of LOINC within the CDISC data exchange format in applications to the FDA. 
1  This document, prepared by CDISC with inputs from the Working Group members, serves to 
provide the community with information about LOINC and to make recommendations to the FDA 
on the initial required scope. 
 
2.2  Introduction 
Standards for biomedical research data exchange and terminology support data retrieval, system 
interoperability and research reproducibility by providing common structures and shared meaning 
for the collection, aggregation, analysis and exchange of clinical and non-clinical research data 
between or among electronic systems. Per the FDA websites Study Data Resource page, 
Having standard, uniform study data enables FDA scientists to explore many new research 
questions by combining data from multiple studies. Data standards also help FDA receive, 
process, review, and archive submissions more efficiently and effectively. 
The FDA Data Standards Catalog explicitly states which standards the FDAs Center for Biologics 
Evaluation and Research (CBER), and, Center for Drug Evaluation and Research (CDER), accept 
and/or require for regulatory submissions, alongside effective dates for each data exchange or 
terminology standard. Standards referenced in the FDA catalog include the CDISC Study Data 
Tabulation Model (SDTM) data exchange/tabulation standard and LOINC, a terminology standard 
maintained by the Regenstrief Institute. LOINC is a freely available international standard for 
identifying health measurements, observations, and documents that is ubiquitous in health data 
systems worldwide and is an essential ingredient of system interoperability. Presently, LOINC is 
utilized in more than 172 countries and has been adopted as a national standard in nearly 30 
countries, including the United States. 
The FDA Data Standards Catalog currently specifies CDISC data exchange standards for the 
submission of clinical study datasets to CBER and CDER. It also includes the requirement for 
LOINC codes to populate the LBLOINC variable in the laboratory (LB) domain specification 
when  study  data  are  submitted  to  the  FDA  using  CDISC  data  exchange  standards.  This 
requirement applies to new drug applications (NDAs), abbreviated new drug application for 
generics  (ANDAs),  biologics  license  applications  (BLAs),  and  e-submissions  of  some 
investigational new drugs (INDs) in accordance with section II.A of the FDA guidance document 
Providing Regulatory Submissions in Electronic Format  Standardized Study Data1. The latest 
version of the FDA Data Standards Catalog at the time of writing this recommendations document 
is v4.5.2 (04-13-2017). The requirement for LOINC codes begins for studies that start after March 
15, 2020 for NDAs, ANDAs and certain BLAs, and on March 15, 2021 for certain INDs. 
   
2  2.3  CDISC Member Survey Regarding LOINC Readiness 
When the FDA requirement for the use of LOINC was published, some CDISC members 
expressed concern about inclusion of LOINC in electronic submissions. CDISC launched a 
member survey in the first quarter of 2017 to better understand these concerns, their prevalence 
and member readiness. This survey is informational only, as it does not necessarily represent the 
full breadth of global clinical researchers knowledge and use of LOINC. 
Data were collected from 180 respondents (Figure 1), 
which  showed  that  16%  were  currently  collecting 
LOINC codes in at least some studies, whereas 84% 
were not. Nearly 10% of respondents reported never 
having heard of LOINC. For those that were collecting 
LOINC codes, they reported doing so for 15-50% of 
their total volume of trials and noted that LOINC codes 
were  useful,  when  they  were  received,  as  they 
provided a more precise description of the collected 
assay. They also mentioned that local and academic 
laboratories were unable to provide LOINC codes 
Figure 1. Organizations engaged in  in many cases. 
regulated research that are currently 
Among the 85% of respondents who did not collect 
collecting LOINC codes. N = 180. 
LOINC codes, some indicated that they had been 
requesting LOINC codes from central laboratories, 
but the codes had not been provided. Other concerns included realm specificity for sponsors 
engaged in global trials, availability of LOINC codes for complex new tests and from smaller 
laboratories, and inconsistency among different laboratories with regard to the application of 
LOINC codes. In general, the respondents were concerned about the lack of clear guidance with 
regard  to  FDA  requirements  for  use  of  LOINC  and  the  potential  for  each  organization 
implementing bespoke solutions that may not truly meet regulatory need. 
The  FDA/Clinical  Data  Interchange  Standards  Consortium  (CDISC)/United  States  National 
Institutes of Health (NIH)/Regenstrief Institute LOINC Working Group (Working Group) was 
created to address some of the respondents concerns and provide specific recommendations for 
the use of LOINC in clinical trial data submissions to the FDA. 
2.4  Pre-Requirement Submissions of LOINC Codes to FDA  
Currently, FDA supports, and in the near future will require, the use of LOINC codes in clinical 
trials.  Until  required,  the  Working  Group  encourages  sponsors  to  voluntarily  follow  these 
recommendations and any others that the FDA may issue when submitting laboratory data to 
FDA. 
3  Working Group Considerations 
It is important to recognize that LOINC includes two major divisions, Laboratory and Clinical, and 
that the FDAs current support of LOINC for submitting clinical trial data to CBER and CDER, as 
identified in the FDA Data Standards Catalog, is limited to the laboratory division. The LOINC 
3  Laboratory division generally aligns with the CDISC SDTM LB (laboratory) domain. 
One of the primary differences between LOINC and the CDISC LB domain is that LOINC terms 
are pre-coordinated and CDISC LB concepts are post-coordinated.  According to Stevens and 
Sattler, A pre-coordinated [set of information or terminologies] has all the terms and relationships 
between them needed by an application; it is static; what you see is what you get. A post- 
coordinated [set of information or terminologies] has the building blocks for the terms needed in 
an application such that they can be built as required, and so that their relationship can be 
determined as required; it is dynamic; the ontology is much more than what you see, since you 
can compose new expressions from the given building blocks.3 This means that in LOINC, a 
single concept represents the combination of several different aspects of a laboratory test, such 
as the analyte being measured, the timing (e.g., point in time versus 24-hour collection), and the 
specimen type, while the CDISC LB domain contains three separate concepts for the analyte, 
timing, and specimen type. 
Pre-coordination and post-coordination both offer benefits.  Pre-coordinated data support more 
rapid data entry and reuse. For example, it is far easier in busy clinical environments to enter a 
single  piece 
of  data  that 
contains 
multiple  data 
elements, 
rather  than 
spend 
additional 
time  entering 
each  data 
element 
individually. 
LOINC  fully 
specified 
names  are 
pre-
coordinated 
using  a  six 
part  model 
that 
distinguishes 
Figure 2. Comparing pre-coordinated LOINC and post-coordinated CDISC 
among  tests 
LB Variables for a laboratory test measuring Albumin in serum or plasma. Two 
with clinically 
pre- coordinated LOINC codes (blue boxes, left) are shown. Each LOINC code is a 
different  single  entity comprised of six primary Parts. For Post-Coordinated CDISC LB 
meanings.  variables (green, right) and associated controlled terminologies (grey, right) for the 
albumin test are shown with C-code identifiers from the National Cancer 
The six parts, 
Institutes Enterprise  Vocabulary Services. 
also  called 
Dimensions, are  the Component, Property, Timing, System, Scale, and Method. All axes other 
4  than the Method have a value for every LOINC term.  The Method may or may not have a value. 
LOINCs pre-coordinated names match the level of specificity of common laboratory test ordering 
and reporting paradigms where there are separate fields for indicating the test name, the test 
result value, units of measure, reference range, etc. As of version 2.61 (June 2017), the LOINC 
release now contains an artifact linking the pre-coordinated LOINC terms to the set of LOINC 
parts of which it is composed3.  Having these codes and relationships facilitates secondary 
aggregation and analysis of primary data coded with LOINC.  
On the other hand, CDISC is post-coordinated for ease of granular data analysis. Each aspect of 
the test (e.g., analyte, specimen, etc.) has a different identifier, which makes it easier to aggregate 
and analyze data based on the specific combination of concepts that are relevant to the research 
question. See Figure 2 for a comparison of pre-coordination and post-coordination, where multiple 
CDISC SDTM LB domain variables map to a single LOINC code. Related LOINC codes may 
require representation by different variables and CDISC controlled terms. Figure 2 includes two 
LOINC codes: one with data in all six major parts, 2862-7, and a less specified, method-less 
LOINC code, 1751-7. The related code, 2862-7, specifies albumin measurements were made by 
electrophoresis, which maps to CDISCs LB.METHOD variable. For the method-less LOINC, 
LB.METHOD cannot be mapped. Similarly, some LOINCs do not specify a specific System, which 
maps to LB.SPEC, and instead indicate that the System is XXX to denote that it can be one of 
several locations or specimen types. End users should utilize the most specific LOINC possible, 
where known information matches the LOINC part values for that code, without over specifying 
by selecting a LOINC code that has one or more part values that are more granular than what is 
known for the result data (Figure 3). End users should not over specify LOINCs. If the method is 
not known, for example for a laboratory test as shown in Figure 3, mapping to LOINC 2862-7 
would be over specifying because it includes a defined method, and LOINC 1751-7 would be a 
more appropriate match because it is method-less. 
Figure 3. Selecting the most 
specific LOINC available 
without over specifying. For an 
albumin test from either serum or 
plasma where the  analyte was 
measured by the electrophoresis 
method and is reported in g/dL, 
LOINC 2862-7 is appropriate as 
indicated by a green arrow. 
 
 
A mapping between the six major LOINC parts and CDISC LB variables is provided in Table 1. 
Harmonizing the CDISC lab domain variable values with the LOINC Part values represents a 
substantial volume of work. In the absence of clear use cases for such harmonization, the Working 
5  Group declared it to be out of scope for this initial set of recommendations, but it may be 
considered in future work. 
 
Table 1.  A comparison of LOINC Parts to CDISC Laboratory (LB) Domain Variables 
LOINC Part  CDISC Standard Equivalent 
(entire column represents a single LOINC  (each row represents a single CDISC 
code)  code) 
Component  LBTEST/CD + other variables 
Property  - 
Time  MULTIPLE: Various Timing Variables 
System  SPEC+LOC 
Scale  - 
Method  METHOD + other variables 
 
4  Working Group Recommendations 
In general, the Working Group recommends that where a valid LOINC code exists for a given lab 
value, the community should provide the code in LBLOINC. Many laboratories have mapped their 
internal codes to LOINC codes and will make such mappings available in electronic messages or 
as standalone mapping files. Increasingly, in vitro Diagnostic (IVD) vendors are making mappings4 
of their internal test codes to LOINC codes available for their products, which will increase the 
efficiency and consistency of identifying appropriate LOINC codes. If such LOINC codes are not 
available from the laboratory, the Working Group recommends that sponsors not attempt to derive 
a mapping to LOINC as they create the SDTM files. Lab test names are notoriously ambiguous, 
and making assumptions in the mapping process without confirming with the test performer can 
lead to serious data quality issues. 
Based on CDISC 2017 LOINC survey data, the Working Group also feels it is important that the 
requirement for LOINC code submissions start with a subset of common diagnostic lab tests that 
are  also  used  within  clinical  research  in  order  to  ease  researchers  adoption  of  the  FDA 
requirement. To create this list, the CDISC Lab Working Group assessed the most commonly 
utilized lab tests in clinical trials as defined by three major central laboratories, the LOINC 2,000+ 
and data summarizing LOINC codes that have been received by the FDA. These LOINC codes 
are predicted to represent ~80-90% of the routine care labs also utilized within clinical trials. A 
mapping of this subset of common LOINC codes to specific combinations of CDISC LB domain 
variables and controlled terminologies has been created by the CDISC Lab Working Group. At 
the time of writing this recommendation document, this mapping document was undergoing 
6  review  by  the  CDISC  Lab  Working  Group  and  key  members  from  the  CDISC  Controlled 
Terminologies  Team  and  this  LOINC  Working  Group.  The  mapping  document  and  an 
implementation guide will be made available from the CDISC Lab Working Group on the CDISC 
and Regenstrief websites. 
The Working Group specifically recommends that: 
  Regardless of whether a LOINC code is available or not for a given lab test record, 
submitters must still submit lab data in CDISC format, including the use of CDISC 
controlled terminology for lab variables. 
  Sponsors should include LOINC codes for any test where a valid LOINC code exists for 
new trials electronic submissions per the FDA Data Standards Catalog requirement dates. 
  LOINC codes that contain specified methods should be utilized over similar LOINC 
o
codes that do not have a method specified in the Method part as appropriate. See 
Figures 2 and 3 for detail. 
  When the specimen type for a lab test is known and/or where the reference range 
o
differs by specimen types, a LOINC code with a specific System (such as Ser/Plas, 
Urine, CSF, etc.) should be used instead of a similar LOINC code that has XXX 
as the System.  
  Sponsors may submit LOINC codes for lab tests outside of the common subset 
o
described above when it becomes available. The Working Group recommends that 
sponsors be encouraged to do so in order to allow the community and regulatory 
officials to adapt to the new requirement. When provided, LOINC codes for other 
lab tests should be accepted by FDA. 
  The most specific LOINC code should always be used without over-specifying 
o
details that are not known by the sponsor, such as method or scale. 
  LOINC codes with a status of deprecated or discouraged should not be submitted. 
o
  Appropriate status for a LOINC code is defined in the LOINC Manual 
Section 11.2 Classification of LOINC Term Status. 
  For any lab test where a LOINC code is not submitted, the reason for its omission should 
be noted in the clinical Study Data Reviewers Guide. 
  The Working Group proposes that a starter set of reasons be predetermined 
o
(perhaps as CDISC terms) for consistency of reporting, including: 
  Performing laboratory unable to determine if appropriate LOINC code 
exists 
  Performing laboratory indicates that no appropriate LOINC code currently 
exists 
  LOINC code specified in LB.LOINC applies to LB.ORRES (original result) rather than to 
LB.STRES(C/N)  (standardized  result).  Such  an  approach  is  consistent  with  the 
recommendation that LB.LOINC should be taken from original laboratory result (i.e., the 
data transfer itself), and not be derived/converted into another form. 
  LOINC codes should be submitted for human clinical studies only. 
 
 
7  5  Potential Future Phases 
The Working Group may reconvene in the future to make further recommendations. The Working 
Group considered topics such as the inclusion of additional LOINC codes for tests that are not 
routinely performed, LOINC codes for labs performed on non-human subjects, and codes for more 
clinically-focused variables. Though it is highly desirable for regulators to easily and routinely 
analyze standard of care lab tests that have assigned LOINC codes, challenges exist to this 
approach for research lab tests, most of which will not have an assigned LOINC code. 
Regarding  the  pre-coordinated  LOINC  model  and  post-coordinated  CDISC  model,  a 
harmonization of CDISC LB domains with LOINC represents a substantial volume of work. In the 
absence of clear use cases for such harmonization, the Working Group determined that it was 
out of scope for this initial set of recommendations, but it may be considered in future work. 
6  References 
1.  Providing Regulatory Submissions In Electronic Format  Standardized Study Data. 
United States Food and Drug Administration 
https://www.fda.gov/downloads/Drugs/Guidances/UCM292334.pdf.  Accessed  May  15, 
2017. 
2.  Robert Stevens and Uli Sattler (2013) Post-coordination: Making things up as you go 
along.  Ontogenesis.  http://ontogenesis.knowledgeblog.org/1305.  Accessed  June  23, 
2017. 
3.  Dan  Vreeman.  (2017)  LOINC  Version  2.61  and  RELMA  Version  6.20  Available.  
https://loinc.org/news/loinc-version-2-61-and-relma-version-6-20-available/.  Accessed 
June 23, 2017. 
4.  IICC News. (2017) IVD Industry Connectivety announces LIVC specification for digital 
publication  of  LOINC  to  vendor  IVD  test  results  in  clinical  laboratories.  
http://ivdconnectivity.org/iicc_announces_livd_specification/. Accessed June 26, 2017. 
   
8  7  Appendices 
7.1  Abbreviations 
Abbreviation  Description 
ANDA  Abbreviated New Drug Application 
BLA  Biologics License Applications 
CBER  Center for Biologics Evaluation and Research 
CDER  Center for Drug Evaluation and Research 
CDISC  Clinical Data Interchange Standards Consortium 
CRO  Contract Research Organization 
FDA  United States Food and Drug Administration 
IND  Investigational New Drug 
LB  Laboratory 
LOINC  Logical Observation Identifiers Names and Codes 
MB  Microbiology 
NCI  United States National Cancer Institute 
NDA  New Drug Application 
NIH  United States National Institutes of Health 
NLM  United States National Library of Medicine 
SDRG  Study Data Reviewers Guide 
SEND  Standard for Exchange of Non- Clinical Data 
SDTM  Study Data Tabulation Model 
 
7.2  Helpful Links 
CDISC Homepage: http://www.cdisc.org 
CDISC SDTM webpage: https://www.cdisc.org/standards/foundational/sdtm 
CDISC SDTM Implementation Guide webpage: 
https://www.cdisc.org/standards/foundational/sdtmig 
LOINC Homepage: https://loinc.org/ 
FDA Study Data Standards Resources, including the Data Standards Catalog:  
https://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/default.htm 
 
 
 
9  7.3  Educational Resources and Events 
7.3.1  CDISC 
CDISC  SDTM002A  SDTM Basics, CDISC  SDTM003A  Basics of the SDTM 
Implementation Guide, and CDISC  SDTM010A  Findings Domains:  
https://secure.trainingcampus.net/uas/modules/trees/store/wcatalog.aspx?cat=1029&ci=  
10&vtype=2&pi=0 
CDISC Public Courses: https://www.cdisc.org/education/public-courses  
SDTM Standard in PDF: https://www.cdisc.org/standards/foundational/sdtm  
SDTM IG in PDF: https://www.cdisc.org/standards/foundational/sdtmig 
SDTM in Other Machine-Readable Formats (CDISC Members Only and Individual 
Academic Researchers Upon Request): https://www.cdisc.org/members-only/share-  
exports 
 
7.3.2  LOINC 
LOINC Getting Started Guide: https://loinc.org/get-started/ LOINC overview video: 
https://youtu.be/OJYQ2xHNIUU LOINC and RELMA Workshops: 
https://loinc.org/meetings 
LOINC Essentials eBook, which covers the basics of LOINC and specific mapping 
strategies: https://danielvreeman.com/loinc-essentials/ 
10