MedDRA®
POINTS TO CONSIDERCOMPANION DOCUMENT
ICH-Endorsed Guide for MedDRA Users
Release 2.0
October 2020
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Table of Contents
SECTION 1 –INTRODUCTION ............................................................................. 1

SECTION 2 –DATA QUALITY ............................................................................... 2

2.1 The Importance of Data Quality .................................................................. 2
2.2 Characteristics of Good Quality Data ......................................................... 3
2.3 The Role of MedDRA in a Data Quality Strategy ........................................ 3
2.4 Components of an Organisational Data Quality Strategy ........................... 3
2.4.1 Data collection .................................................................................. 3
2.4.2 MedDRA coding considerations........................................................ 5
2.4.3 Training ............................................................................................. 7
2.4.4 Quality assurance checks ................................................................. 8
2.4.5 MedDRA versioning strategy ............................................................ 9
SECTION 3 –MEDICATION ERRORS ................................................................... 9

3.1 Coding Medication Errors – Questions and Answers ............................... 10
3.1.1 Use of LLT Medication error ........................................................... 11
3.1.2 Selecting more than one term ......................................................... 11
3.1.3 Medication error vs. off label use .................................................... 12
3.1.4 Potential medication errors ............................................................. 12
3.1.5 Selecting the most specific term ..................................................... 12
3.1.6 MedDRA Concept Description for medication error ........................ 13
3.1.7 Stages of the medication use system ............................................. 14
3.1.8 Coding the root cause ..................................................................... 14
3.1.9 Do not infer a medication error ....................................................... 14
3.1.10 Device use errors, wrong technique, and device malfunction......... 15
3.2 Examples for Coding Medication Errors ................................................... 15
3.2.1 Accidental exposures to products ................................................... 16
3.2.2 Miscellaneous medication errors/issues ......................................... 17
3.2.3 Product administration errors/issues............................................... 21
3.2.4 Product confusion errors/issues...................................................... 26
3.2.5 Dispensing errors/issues................................................................. 27
3.2.6 Monitoring errors/issues.................................................................. 28
3.2.7 Preparation errors/issues ................................................................ 29
3.2.8 Prescribing errors/issues ................................................................ 30
3.2.9 Product selection errors/issues ....................................................... 33
3.2.10 Product storage errors/issues ......................................................... 34
3.2.11 Product transcribing errors/communication issues ......................... 35
SECTION 4 –PRODUCT QUALITY ISSUES ........................................................ 36

4.1 Background .............................................................................................. 36
4.2 Examples for Coding Product Quality Issues ........................................... 37
4.2.1 Product physical issues .................................................................. 37
4.2.2 Product contamination/sterility issues ............................................. 38
4.2.3 Product distribution issues .............................................................. 39
4.2.4 Product label issues ........................................................................ 39i

4.2.54.2.6
4.2.7

Counterfeit ...................................................................................... 40
Product supply and availability........................................................ 41
Packaging issues ............................................................................ 41

4.3 Data search and retrieval of product quality issues .................................. 41ii

1. INTRODUCTION
The MedDRA Term Selection: Points to Consider and MedDRA Data Retrieval
and Presentation: Points to Consider documents provide valuable guidance to
MedDRA users worldwide on general term selection and data retrieval principles
as well as providing specific examples of approaches to coding and analysis.
However, there are certain topics where users could benefit from having moredetailed information pertaining to the use of MedDRA than can be covered in theexisting documents.
The purpose of this Companion Document is to supplement the Points toConsider (PtC) documents by providing additional details, examples, andguidance on specific MedDRA-related topics of global regulatory importance. It
was developed and is maintained by the same working group that was charged
by the ICH Management Committee to develop the PtC documents. The working
group consists of representatives of ICH regulatory and industry members, theWorld Health Organization, the MedDRA Maintenance and Support Services
Organization (MSSO), and the Japanese Maintenance Organization (JMO).
The Companion Document is intended to be a “living” document and is updated
based on users’ needs, rather than being tied to MedDRA releases. Like the PtC
documents, the Companion Document is available in English and Japanese;
however, if certain examples are not relevant or are difficult to translate, thesewill not be included in the Japanese version.
The contents of the document are agreed by all ICH parties; it does not specify
regulatory requirements, nor does it address database issues. Organisations areencouraged to document their own coding and data retrieval conventions inorganisation-specific guidelines which should be consistent with the PtC
documents and this Companion Document.
Users are invited to contact the MSSO Help Desk with any questions orcomments about the MedDRA Points to Consider Companion Document.

12. DATA QUALITY
This section will discuss important data quality and data entry principles related
to the use of MedDRA in the clinical trial and postmarketing environments. It will
not address specific regulatory requirements, database structure issues, fileformat conventions, data workflow applications, or other topics which are beyond
the scope of MedDRA.
In both the development and marketing of human medicinal products, datacollection is a critical and ongoing process. As noted in the MedDRA Term
Selection: Points to Consider (MTS:PTC) document, the quality of originalreported information directly impacts the quality of data output.
High Quality
Data Input

High Quality
Data Output

Data are applied to make inferences, test hypotheses, draw conclusions, makestatements, and report findings about the safety and efficacy ofbiopharmaceutical products. Since data are used for activities ranging fromcoding to information categorisation, retrieval, analysis, and presentation,
ensuring access to high quality data is paramount. Quality data support safetyfunctions including signal detection, data analysis, and product label
development. This section will describe some of the practices and processes
which should be part of an organisational data quality strategy.
2.1

THE IMPORTANCE OF DATA QUALITYAs the regulated biopharmaceutical industry strives for greater harmonisation ofsafety reporting regulations and standards, there is an increasing emphasis on
safety surveillance and data quality. In addition to supporting patient/subject
safety, increased data quality facilitates communication of complete and accurate
information to those involved in clinical research and post-marketing processes(including regulatory bodies, sponsoring companies, study site personnel andmarketing authorisation holders). Collection of high quality data can also result ingreater time and cost efficiency during product development and marketing (e.g.
less querying of incomplete data, decrease site monitoring costs and reduce therisk of delayed regulatory approval).
The quality of adverse event data is central to safety monitoring in clinical trials,
to the risk assessment of marketing applications and in the evaluation of safety
signals within postmarketing data. Adverse events are typically generated bycomplaints from study subjects, patients or their caregivers. These verbatim
terms may be either coded manually or coded automatically with autoencoder
tools by selecting MedDRA Lowest Level Terms (LLTs). Users need to be awarethat some LLTs are rather non-specifc and that further clarification of thereported information may be necessary. Small deviations in coding can result insignificant issues and produce misleading analyses. Coding selections may varyeven in apparently simple cases.Given this variability, it is important tothoughtfully evaluate adverse event data rather than relying on any specificrecommendation or guidance.

2

2.2

CHARACTERISTICS OF GOOD QUALITY DATA

Quality data have several common features. Foremost, these data should be
both complete and accurate. Whenever possible, the most concise form of data
should be collected, provided that this can be done without sacrificing either
completeness or accuracy. Within an organisation, data quality is fostered bycomprehensive, consistent, transparent and documented data handlingprocesses. Quality data is, by definition, supported by the available information.
For example, clinical diagnoses should be consistent with the available medical
history, physical findings, laboratory and investigational results. Furthermore,quality data should be capable, when appropriate, of supporting data-related
associations (e.g. when performing a causality assessment of an adverse event
which could be related to a product).
2.3

THE ROLE OF MEDDRA IN A DATA QUALITY STRATEGY

As a standardised and validated clinical terminology used in both clinicaldevelopment and postmarketing surveillance, MedDRA should play an importantrole in a sound data quality strategy. Since MedDRA is used to “code”
information during data entry, it is important to consider the principles in the
MTS:PTC document to ensure the selection of coding terms with the highest
specificity and analytical quality. The large number of available LLTs provides ahigh degree of granularity. However, even the granularity of MedDRA cannot
overcome “low quality” primary information.
2.4

COMPONENTS OF AN ORGANISATIONAL DATA QUALITY STRATEGY

The development and implementation of an organisational data quality strategy is
a complex task which involves the input, support and collaboration of many
stakeholders. Many of the principles of high quality data collection are the same
in both the clinical trial and postmarketing environments. This section will discussa framework for acquiring data of high quality.
2.4.1 Data collection
Whether in a clinical trial, a postmarketing safety call center, or a healthcare
professional’s office, there is often only one opportunity to capture complete andaccurate information. Since data output quality is determined by data input
quality in a database, there are important consequences from these initial steps.
For those collecting information (e.g. a study site physician/nurse, apostmarketing call center employee, a dispensing pharmacist, an emergency
room physician), certain practices will help to maximise the quality of thecollected data:• During data collection, completeness and accuracy need to be weighedagainst the risk of collecting “unimportant” information. This is particularly
true if time limitations are present. It is advisable to minimise the amountof unimportant information placed in dedicated data fields for key concepts
such as adverse events. Otherwise, the data coding and management canbe further complicated.

3•In clinical trials, reporters should be encouraged to use consistent medical
terminology to describe similar medical concepts. The best strategy is tocarefully train study site personnel (especially investigators) about theimportance of consistency in data collection.

•

In clinical trials, data collection instruments (whether they are electronic or
paper case report forms) should be carefully designed to be easy to use,
enduring and sufficiently comprehensive to gather all the necessary
information. Since individual trials or clinical projects can span years, it isnever possible to spend “too much” time developing quality data collection
tools. Appropriate “subject matter experts” in data management,
information technology, statistics, quality assurance, and regulatorycompliance should be involved throughout the planning process. After
years into development, it is difficult, if not impossible, to compensate forneeded data which has not been adequately collected.

•

With the passage of time, the ability to seek clarification of incomplete
information becomes limited and very often, a reporter’s recollection ofimportant facts can change dramatically. Therefore, it is crucial to start the“query” process as soon as possible to obtain clarification from the data
source.

•When a report contains multiple diagnoses (such as a report of “broken
finger and hand abrasion” or “urinary bladder obstruction and cystitis”), it isusually appropriate to record these as separate concepts on the datacollection form•

Attempt to minimise spelling errors and the use of abbreviations andacronyms. The table below illustrates the difficulty of interpreting suchpoor or ambiguous data:•

Reported

Data Quality Challenge

Had MI

Does MI stand for myocardial
infarction, mitral insufficiency, mental
illness or mesenteric ischaemia?

Interperial

Was this word intended to represent“intraperitoneal” or “intraperineal”?

Nitro drip

Did this drip contain nitroglycerin or
nitroprusside?

Furthermore, without proper context, it is impossible to interpret other“vague” terms as shown in the table below:

4Reported

Data Quality Challenge

Congestion

Nasal, hepatic, venous, etc.?

Obstruction

Bronchial, intestinal, ureteral, etc.?

Infarction

Myocardial, cerebral, retinal, etc.?

Clarification of such terms should be requested at the time of data collection.
2.4.2 MedDRA coding considerations
MedDRA can be used to accurately code many types of reported information.
This includes not only diagnoses, signs and symptoms representing adverse
reactions/adverse events but also concepts such as medical and social history,
indications for product use, device-related events, surgical and medical
procedures, investigations, exposures, misuse and abuse, off label use,
medication errors, and product quality issues. For meaningful data review, it isimportant to ensure that all required information is coded consistently. Importantdata quality issues to consider include:• Steps should be taken to ensure that individuals responsible for MedDRA
coding have familiarity with the terminology as well as the requisitetraining to utilise it effectively. Particular attention should be paid to therelevant coding principles outlined in the MTS:PTC document. In
environments where MedDRA coding is performed by a number ofindividuals, it is important to have a consistent organisational approach.
•Appropriately trained individuals should review MedDRA coding•

It is an important concept that all adverse events and adverse reactions
from a report should be coded, regardless of causal association. Similarly,
do not add information by selecting a term for a diagnosis if only signs or
symptoms are reported (MTS:PTC Section 2.10)•

It is important that reported information is coded accurately; it is not
appropriate to select terms for concepts which are less specific or lesssevere than the reported term (e.g., coding a convulsive seizure with LLTShakiness or coding peritonitis with LLT Belly ache)•

It is advisable to follow the “preferred” coding options specified in the
MTS:PTC document, especially for issues like the coding of provisionaland definitive diagnoses with associated signs and symptoms. If one
chooses to use an “alternate” coding option from the MTS:PTC, it is agood practice to document why this was done and to be consistent in theuse of this alternate choice.

•

It is important to distinguish medical conditions (typically found in the SOCof the primary manifestation site) from laboratory and test terms (which
are found in SOC Investigations)5•

Verbatim terms may contain more than one medical concept (such as areport of “fall and contusion”). It is important to consider each of thereported events and code as appropriate.

•

Consider the use of “split coding” (selecting more than one term) where
there is no single LLT within MedDRA which captures all of the concepts(MTS:PTC Section 2.8 and Section 3.5.4)•

Organisations may wish to create “synonym” lists of verbatim terms which
can then be coded to pre-determined LLTs. An example of a synonym listis shown below:
Reported Verbatim
LLT
Throbbing above temple
Aching all over head
Pulsing pain in head

In a synonym list, each of these verbatim
reports would be coded using LLTHeadacheSynonym lists may be particularly helpful in some circumstances, e.g. whenthose involved in report coding have limited medical expertise, when coding is inseveral geographical sites or when an autoencoder is being extensively used. It
is also important to ensure that terms selected for a synonym are true synonyms
for the coded medical concept.
• Medical and surgical procedures are generally not adverse events.
However, if only a procedure is reported, then an appropriate term is used
to code the procedure (MTS:PTC Section 3.13.1). On the other hand, if aprocedure is reported with a diagnosis, then the preferred option is toselect an appropriate term to code both the procedure and diagnosis. The
alternate option is to code only the reported diagnosis (MTS:PTC Section
3.13.2). Some organisations have data collection forms with separate data
fields for adverse events and for procedures; this aids entry of data in theappropriate category.
•In the context of safety reporting, death, disability and hospitalisation areoutcomes, not adverse events. Therefore, they are generally not codedwith MedDRA. Instead, they are recorded in the appropriate datacollection field for outcomes. One exception to this recommendation iswhen death, disability, or hospitalisation is the only reported verbatim.
These concepts are coded with MedDRA while clarification of theunderlying cause is sought (see MTS:PTC Section 3.2 for further
information). In addition, death terms that add important clinicalinformation (e.g. LLT Sudden unexplained death in epilepsy, LLT Foetal
death) should be selected along with any reported ARs/AEs.

6

•When vague, ambiguous, or conflicting information is reported, MedDRA
has codes which can be utilised while attempts are made to clarify the
information. For example:

Vague information (see also MTS:PTC Section 3.4.3):
Reported
LLT Selected
Appeared red

Unevaluable event

Comment“Appeared red” reported
alone is vague; this
could refer to a patient’s
appearance or eventhat of a product (i.e., apill, a solution, etc.)

Ambiguous Information (see also MTS:PTC Section 3.4.2):
Reported
LLT Selected
Comment
Patient had medical
history of AR

Ill-defined disorder

It is not known what
medical condition thepatient had (aortic
regurgitation, arterial
restenosis, allergic
rhinitis?), so LLT Illdefined disorder can beselected

Conflicting Information (See also MTS:PTC Section 3.4.1):
Reported
LLT Selected
Comment
Severe anaemia with ahaemoglobin of 19.1
g/dL

Haemoglobin abnormal

LLT Haemoglobin
abnormal covers both of
the reported concepts(note: haemoglobinvalue of 19.1 g/dL is ahigh result, not a low
result as would be
expected in severe
anaemia

2.4.3 Training
Appropriate ongoing training is a key part of a good data quality strategy.
Training should be given to all persons involved in the collection, transcription,categorisation, entry, coding, and review of information. Organisational training
practices and procedures should be documented in writing and continuallyreviewed for updates. Training should be performed by appropriately qualified
individuals who are knowledgeable about the organisation’s standardised
procedures and focused on compliance. Cross-training of key functions is7

advisable to ensure a consistent approach and to preserve data quality
standards during periods of unexpected personnel changes.
Given that organisations may commonly use unfamiliar or remote study sites forclinical trial conduct, it is also important to ensure that study site personnel (e.g.,
investigators, study nurses, clinical study coordinators, clinical research
associates, site pharmacists) are well trained in all relevant aspects of clinical
trial conduct including:• Correct use of the assigned data collection instruments•

Training in appropriate techniques for interviewing of study
subjects/patients [e.g. the use of non-directed questioning, reporting ofadverse events as diagnoses (when possible) rather than lists of signs
and symptoms, precautions to avoid unblinding]•Knowledge of relevant regulatory considerations related to quality datacollection•

Adequate knowledge of the use of MedDRA for coding purposes, asapplicable. This is particularly important for concepts such as coding of
definitive versus provisional diagnoses (with or without symptoms) and notinferring diagnoses•

A thorough understanding of and compliance with an organisation’s
agreed-upon “data query” process to clarify information
The “Data Quality, Coding and MedDRA” presentation in the ‘General/Basics’
section of the “Training Materials” page of the MedDRA website(https://www.meddra.org/training-materials) is another useful resource. This
customisable slide set is intended for use at investigator meetings and fortraining personnel involved with data collection (such as clinical research
associates and clinical coordinators). It provides an overview of the importanceand benefits of good quality data as it relates to MedDRA.
2.4.4 Quality assurance checks
A thoughtful and thorough quality assurance (QA) process supports the goal of
maximising data quality. QA checks during the data management process ensurecompliance with established organisational procedures and metrics. Examples of
inaccurate MedDRA coding which QA checks could identify include:
ReportedAllergic to CAT scan

Feels pressure in eye

Inaccurately
Selected LLTAllergic to cats

QA Review Outcome
This inaccurate LLT was selectedby an autoencoder which matched
the words “Allergic to CAT scan”
from the reported termThis inaccurate LLT refers to thename of the test for intraocular8

Intraocularpressurepressure; the appropriate term toreflect the symptom being
described in the report would be
LLT Sensation of pressure in eye

These checks can identify coding errors with MedDRA before the database islocked and erroneous data become part of a data analysis.
The MSSO-maintained Unqualified Test Name Term List is a comprehensive
collection of all unqualified test name terms at the Preferred Term (PT) andLowest Level Term (LLT) levels in SOC Investigations. The Unqualified Test
Name Term List can be found on the “Support Documentation” page on the
MedDRA website. It may be applied by regulatory authorities and industry as a
QA check of data quality in clinical trial and pharmacovigilance databases. Test
name terms without qualifiers (e.g., LLT Blood glucose, LLT CAT scan) do not
represent ARs/AEs but are intended to point to an actual value in a specificdatabase field. For example, in the section for Results of Tests and Proceduresin the ICH E2B ICSR electronic transmission standard, unqualified terms may be
used in the data element capturing the test name. Unqualified Test Name terms
are not intended for use in other data fields capturing information such as
ARs/AEs. The Unqualified Test Name Term List is intended as arecommendation only, providing a standard tool for checking coding quality.
2.4.5 MedDRA versioning strategy
Given the twice-yearly releases of new MedDRA versions, organisations shouldhave a documented versioning strategy to address these updates. The MSSO
has created a Best Practice document which contains sections entitled“Recommendations for MedDRA Implementation and Versioning for Clinical
Trials” and “Recommendations for Single Case Reporting Using Semi-annual
Version Control”. This document is found on the “Support Documentation” pageon the MedDRA website.
In addition, the MSSO has provided a MedDRA Version Analysis Tool (MVAT)
which facilitates the identification and understanding of the impact of changes
between any two MedDRA versions, including non-consecutive ones (see the“Tools” Page on the MedDRA website).
3. MEDICATION ERRORSThe purpose of this section is to expand on the section on medication errors in
the MedDRA Term Selection: Points to Consider (MTS:PTC) document and toprovide guidance on scenarios that are medication errors as well as scenarios
informative for medication errors or scenarios that are confused with medication
errors. Additionally, guidance and examples of coding of some scenarios areprovided. This section has two main sub-sections; the first sub-section provides
answers to commonly asked questions about coding medication errors. The
second sub-section provides examples for coding medication errors. Examples
are based on MedDRA Version 23.0.
The document is a living document and the content of this section will be updated
based on user feedback. Users are invited to contact the MSSO Help Desk withany questions or comments about the MedDRA Points to Consider Companion
9Document.

Acknowledgments
The PtC Working Group would like to acknowledge the significant contributionsof the following individuals to this section of the Companion Document:
Georgia Paraskevakos, Patient Safety Specialist, Health Canada.
Jo Wyeth, Postmarket Safety Program Lead, FDA CDER, OSE, Division of
Medication Error Prevention and Analysis (DMEPA).
BackgroundFor coding purposes, terms that reflect medication errors are grouped in the HighLevel Group Term (HLGT) Medication errors and other product use errors andissues (from MedDRA Version 20.0 onwards). However, terms located elsewherein the MedDRA hierarchy can also be used to code cases describing medication
errors. To aid data retrieval of the widely dispersed coding terms, theStandardised MedDRA Query (SMQ) Medication errors was developed, with anarrow and a broad scope, as a tool for standardised retrieval of suspected
medication error cases.
The HLGT Medication errors and other product use errors and issues contains
numerous terms:• Types of errors (e.g., LLT Wrong drug),• Terms combining the type of error with a stage of the medication use
system (e.g., LLT Wrong drug prescribed)• Describing the potential for error• Intercepted errors that did not reach the patient• This HLGT also contains terms for situations when it is uncertain whether
the reported incident is an error
Each PT is grouped into one of the High Level Terms (HLTs), either for
accidental exposures, stages of the medication use system*, product confusion,or the HLT grouping for various other PTs not elsewhere classified.
*For the purposes of this document, the medication use system encompasses acontinuum of activities after release of the product into the healthcare system
during which a medication error can occur, including procurement, storage,prescribing, transcribing, selecting, preparing, dispensing, administering, andmonitoring. The medication use system excludes activities related to the entire
manufacturing process including manufacturer distribution and storage.
3.1

CODING MEDICATION ERRORS – QUESTIONS AND ANSWERS

This sub-section provides answers to commonly asked questions about coding
medication errors.

10

3.1.1 Use of LLT Medication error
When is it acceptable to use the Lowest Level Term (LLT) Medication error?
Can the term be selected if there is no appropriate MedDRA term for theerror?
• The use of LLT Medication error should be avoided unless there is
NO other information reported about the medication error•

Check all the LLTs in HLGT Medication errors and other productuse errors and issues for the most specific term possible•

If a specific error is reported but no suitable LLT is available, theprocedure for a change request should be followed (see theChange Requests page on the MedDRA website). In the interim,
select the closest available term to code the reported error. Theremay be rare instances when LLT Medication error is the closest
term and can be selected.

3.1.2 Selecting more than one term
Should terms for all reported errors related to the same incident be
selected?
Sometimes the ‘originating error’ (also referred to as the initial error) results inconsequent errors. For example, it was reported that “a prescribing error for thewrong drug consequently resulted in the wrong drug being dispensed andadministered.”•The ‘originating’ error should be coded as the priority. Additional or‘consequent’ errors can be coded if they are stated in the report. In
the above example, the priority is to code LLT Wrong drugprescribed; LLT Wrong drug dispensed and LLT Wrong drug
administered are terms for consequent errors and can also be
added.

•

Avoid ‘double coding’ the same error. In other words, do not use
multiple LLTs to capture a singular error that is reported with both ageneral and a specific verbatim; code only the specific error. For
example, if it is reported that there was an administration error inthat the wrong drug was administered, select only LLT Wrong drug
administered for the specific error. Do not use an additional LLT
Drug administration error for the general description because thiswould not add any meaningful information (even though the two
LLTs are linked to different PTs).

•

Bear in mind that some organisations will have their databaseconfigured in a way that counts at LLT level and therefore if two
LLTs which map to the same PT are used this may impact on
signal detection.

11

3.1.3 Medication error vs. off label use
It is reported that “a prescriber ordered a much higher dose than per label”,
but it is not stated if this was a mistake or off label use; should terms forboth possibilities be selected, as in differential diagnoses?
• Do not double code a singular event by selecting a term for an error
and a term for off label use when neither is stated but both arepossible; this approach is not helpful.
•

When a scenario is unclear, try to obtain clarification; if still
unknown, select the most applicable term for what is reported
without inferring what is not reported. For example, if it is only
reported that Drug X was prescribed at a much higher dose thanper label (no information that it was in error or off label use), selectLLT Prescribed overdose (HLT Overdoses NEC).

•

Off-label use terms should only be selected when off label use isspecifically mentioned in the reported verbatim information.

3.1.4 Potential medication errors
How should terms be selected for reports that describe the potential for
error?
For example, a report stated that ‘two drug labels look alike and could result insomeone getting the wrong drug’.
• Potential errors should be designated as such by selecting the LLTCircumstance or information capable of leading to medication error or
LLT Circumstance or information capable of leading to device use
error.
•

Also, select terms that represent information about the error that could
potentially occur. For the above example, select three terms:
o For the potential error (LLT Circumstance or information
capable of leading to medication error)o For the contributing scenario (LLT Drug label look-alike)o For the type of error that could occur (LLT Wrong drug)

3.1.5 Selecting the most specific term
How should terms that have overlapping concepts with other terms be
used?
For example, a report described a patient who did not allow a product adequate
time to reconstitute before self-administering.
• The most specific available LLT should be selected for the reported
information. For the above example, select LLT Inappropriate
reconstitution technique (PT Product preparation error) because it
is more specific than LLT Wrong technique in product usage
process (PT Wrong technique in product usage process). Coding a12

singular error by selecting two error terms is useful only when thisprovides meaningful additional information, i.e. when the single LLTcannot describe the entire reported scenario.
3.1.6 MedDRA Concept Description for medication error
Does the MedDRA Concept Description for medication error include abuse,misuse, or off label uses?
The MedDRA Concept Description for medication error is taken from the National
Coordinating Council for Medication Error Reporting and Prevention (US)* and is
as follows:
Medication errors are defined as any preventable event that may cause or lead toinappropriate medication use or patient harm while the medication is in thecontrol of the health care professional, patient or consumer. Such events may berelated to professional practice, health care products, procedures and systems,
including prescribing, order communication, product labeling, packaging andnomenclature, compounding, dispensing, distribution, administration, education,
monitoring and use.
* National Coordinating Council for Medication Error Reporting and Prevention (US); 2001. About
medication errors. https://www.nccmerp.org/about-medication-errors. Accessed 1 March, 2020.

As a general principle, intentional uses such as abuse, intentional misuse, offlabel use, and intentional overdose are not medication errors. However, whether
a scenario is an error or not may depend on the reason or cause.
For example:•••

If confusion with some aspect of the product causes or results inincorrect product use or misuse (e.g. the device was confusing so
the person administered an extra dose to make sure he got a fulldose), it would usually be considered an error, and not intentional
misuseOccurrence of an adverse drug reaction (ADR) may cause thepatient to stop therapy; this is not intentional misuse or an error.
Therapy cessation due to an ADR is usually captured elsewhere in
the database, and only the ADR is coded in the case.
Patient may decide to take their medication less frequently thanprescribed; this is usually classified as intentional misuse, not a
medication error

Drug abuse and details describing how the drug is abused (route ofadministration, preparation) do not constitute medication errors
Note that situations such as product quality or product supply issues outside
one’s control are also not usually classified as medication errors, but can result
in medication errors. For example, device malfunction or packaging defect(product quality issues) can result in an incorrect dose administered.

13

3.1.7 Stages of the medication use system
When is it appropriate to use a medication error term without the stage ofthe medication use system?
Some MedDRA terms have both the type of error and stage of the medication
use system (e.g., LLT Wrong drug prescribed); some terms have only the type oferror (e.g., LLT Wrong drug); and some terms have only the stage (e.g., LLT
Drug prescribing error).
• Using a single LLT
For example, a report stated that ‘the pharmacy dispensed the wrong drug’. It is
important to highlight both the stage and the type of error where it is known. In
this example, this is possible using a single LLT Wrong drug dispensed (insteadof two LLTs: LLT Wrong drug and LLT Wrong drug dispensed).
• Using more than one LLT
For example, a report of ‘mistakenly prescribed the wrong strength’ should be
coded with LLT Wrong strength and LLT Drug prescribing error because noavailable single term captures the reported information in full.
If the stage is not known, there are terms for the type of error only, such as LLTWrong drug, LLT Wrong schedule, LLT Wrong strength, etc.
3.1.8 Coding the root cause
Is it recommended to code the root cause if stated in the case report?
When the root cause is provided, select a term for the root cause if possible
because root causes are critical to understanding why an error occurred andidentifying interventions that can be undertaken to prevent the error.
•

For example, a product quality issue may lead to a medication error; insuch a case, the product quality issue is the root cause of the error.
Select terms for both the quality issue and the error.

•

For example, a communication issue may lead to a medication error; insuch a case, the communication issue is the root cause of the error.
Select terms for both the communication issue (e.g., LLT Patient
misunderstanding health care provider instructions for product use)
and the error.

•

For the broader patient safety concepts, the root cause may not be
represented in MedDRA and should be documented in free text (e.g.
narrative field) if known. These include issues such as human factors(stress, fatigue) or system issues (training deficiencies, unclear
instructions).

3.1.9 Do not infer a medication error
Is it acceptable to use specific medication error codes for information not
explicitly stated in the case report?
The selected LLTs should reflect only the information stated in the case report; it
14

should not be assumed that a medication error occurred if this is not clearlyreported as such.
For example, the report that only stated ‘The nurse administered 50 mg of Drug
X’ is not an informative report and should not be submitted as such; further
information should be sought or a dose qualification referencing the prescribing
information should be provided in the narrative.
Ideally, at the point of data capture, the reason for reporting as a medication error
should be included in the narrative, e.g. ‘the patient was accidentally given 50 mg
which is more than the prescribed dose’. Alternatively, if it is not possible toclarify with the reporter but the prescribing information recommends a smallerdose, then the report should reference the prescribing information in the
narrative, e.g. “the nurse administered 50 mg of Drug X, whereas therecommended dose in the prescribing information is 5 mg.”

3.1.10 Device use errors, wrong technique, and device malfunction.
What is the difference between a device use error, wrong technique, anddevice malfunction?
When evaluating medication errors involving devices, it is important to capture
the specific device related event that led to the error. Such events can beproblems with the device itself (including device malfunctions), or they can beproblem with the way the device is used by the person (device use error or wrong
technique). In MedDRA, device use errors refer to broad errors in using thedevice appropriately, e.g., LLT Unintentional device use beyond labelled
duration. In contrast, the wrong technique in device usage process concepts
refer specifically to the technical aspect of not properly using the device (e.g.,
LLT Incorrect needle gauge used, LLT Wrong injection technique). Device
malfunction refers to failure of the device to perform as intended when used inaccordance with the labelling. A malfunction of a device is not considered adevice use error or a wrong technique error.
Sometimes the reports do not have enough information to determine if theincident is related to a device issue/malfunction, device use error, or wrong
technique. Clarification should be sought since these are very importantdistinctions. Attempt to code the verbatim information and avoid inferences.
3.2

EXAMPLES FOR CODING MEDICATION ERRORSThis sub-section provides examples for coding medication errors in various
categories.
The tables are organised in the following way:
• The first column describes a scenario15•The second column indicates whether this scenario is considered a
medication error in the context of the MTS:PTC or not, or if this is
unknown from the provided information•

The third column provides the selected LLT(s) and, if helpful, the relevantPT(s) or HLT(s)•The fourth column provides additional comments and explanations
regarding the term selection

The LLTs may fall into more than one category and the concepts presented may
overlap across tables.
3.2.1 Accidental exposures to products
Scenario
Person tried to commit
suicide by overdosing onprescription opioids andheroinMedication
error?
No

Person took street heroin
to get high but died of aheroin overdose

No

Parent accidentally
injected himself in the
thumb while using an
auto-injector to administer
the drug to the child

Yes

LLT

Comment

Multiple drug
overdose
intentional

This is not a
medication error as
the person intended
to overdose

Attempted suicide
Overdose

It is not known thatthe overdose wasintentional; do not
Opioid abusecode as accidental
overdose because
the scenario is in thecontext of drug
abuse, not a
medication error.
Death would be
captured as an
outcome.
Accidental
The parent was not
exposure while
the intended patient
administering drug and was accidentally
exposed to the drug.
The selected LLT
captures the reported
information withspecificity, e.g., thatthe accidental
exposure occurred
while administering
the drug.

16

Scenario
Patient with visual
impairment experienced
choking after accidentallyswallowing a desiccant
tube that was the same
colour and similar size as
the tablets in the bottle

Medication
LLT
Comment
error?
Yes
Accidental ingestion Accidental exposureof productis captured as well as
desiccantthe contributing factorof look-alike productconfusion.
Product
LLT Visualappearance
impairment
would beconfusion
captured in medical
history.
Choking2-year-old child took some
antibiotics that wereaccidentally left on the
kitchen counter
Adolescent died ofoverdose after taking 200
doses of a nasal inhalantin under 15 minutes, in an
attempt to get highYes

Accidental drug
intake by child

No

Drug abuse

Adult ingested 2 tablets of
100 mg strength

Unknown

Adult intentionallyingested 2 tablets of 100
mg strength for his backpain instead of therecommended 1 tablet

No

Overdose in thecontext of abuse is
not a medication error
Overdose
norIntentional misuse(which implies
therapeutic use
according to the tablein MTS:PTC, Section
3.16). Death would be
captured as an
outcome.
This is not an
informative report andfurther information
should be sought.
There is nothing tocode in the provided
text.
Intentional misuse This is an example ofby dose change
intentional misuse
and is not a
medication error

3.2.2 Miscellaneous medication errors/issues
Scenario
Pharmacist reported thatthe product label was

Medication
error?
Yes

LLT

Comment

Circumstance or This is an example of ainformation
potential medication error
17

Scenario

Medication
error?

confusing and that it could
result in a patient
receiving the wrong
dosage form

LLT

Comment

capable ofleading to
medication error

Patient drew her insulin
out of the pen with asyringe because she was
confused by the numbers
marked on the pen, anddid not want to mistakenly
take too much insulin
using the pen

Yes

Patient experienced
hypoglycaemia after heused his insulin pen
cartridge as a vial. He
reported that he did so
because he had leftover
insulin syringes and did
not want to waste them.
The pharmacist selected awrong adapter device thatwas incompatible with thedrug; the device started
dissolving when it wasused to transfer the drug
from the vial to the bag foradministration
Patient did not wait therecommended 10
seconds when using the

No

Yes

since the report does notstate that the wrong
product was actuallydispensed oradministered. The LLT
Product label
Circumstance or
confusion
information capable ofleading to medication
Wrong dosage
error captures that theformerror is a potential one.
The most specific codefor the reported type of
potential medication error
should be selected andthe contributing factor,
label confusion.
Wrong device
The patient uses a wrong
useddevice to prevent anerror, due to her initialconfusion with the pen
Product design
markings.
The confusion
confusionand the consequent useof the wrong device areboth within a scenario of a
medication error, so there
is no need to add
Intentional device misuse.
Intentional
This is an example ofdevice misuse
Intentional misuse: there
is a therapeutic purposebutthere is no mention of
Hypoglycaemia
a medication error

Wrong device
usedDrug-device
incompatibility

Yes

Capture both that thewrong device was used
and that it is incompatible
with the drugWrong technique Do not select LLT Device
in device usage use error, since this is aprocess
broader term than the18

Scenario

Medication
error?

autoinjector pen because
he misunderstood how to
use the pen

The patient forgot to have
her hormonal IUD
replaced after therecommended 5 years. In
the 7th year after device
was originally inserted,
she became pregnant.

Yes

Pharmacy software had abuilt-in dose calculator
that was misprogrammedby the pharmacy. The
error resulted in a childgetting the wrong dose.

Yes

LLT

Comment

selected LLT Wrongtechnique in device usage
process. The selected
LLT represents atechnical error with using
the device.
Unintentional
LLT Unintentional device
device use
use beyond labelled
beyond labelled duration (PT Device use
duration
error) represents a broad
error in using the device
appropriately
according to
Pregnancy withrecommendations
for its
IUD
intended use.
Deviceprogramming
error
Dose calculation
error associatedwith device

While hospitalized, patient
experienced anunspecified medication
error but no adverse event

Yes

Nurse administered thewrong dose after using a

Yes,
consequent

Wrong dose
administered
Medication error

This is not an informative
report but is an example
where the verbatim iscaptured with LLT
Medication error.
According to the
MTS:PTC, if a medication
error report specificallystates that there were noclinical consequences,the preferred option is toselect only a term for the
medication error.
Alternatively, a term forthe medication error andthe additional LLT No
adverse effect can beselected (see MTS:PTC,
Section 3.21).
Mobile medical The issue with the mobile
application issue application is the cause of19

Scenario
faulty mobile medical
device (app) thatmiscalculated the patient’s
insulin needs

Medication
error?
to a device
issue

LLT

Comment

the dose calculation error
and the subsequent
Dose calculation
administrationof theerror associated
wrong
dose
with device
Wrong dose
administered

Patient split their tablet(labelling doesn’t advise
against splitting the tablet)

No

Provider prescribed half atablet once daily, unawarethat the labelling states toswallow the tablets whole.
Patient split the tablets.

Yes

Prescriber advised patientto split tablet. The
labelling states thattablets should beswallowed whole.

Unknown

Patient should be on Drug
A but instead got Drug B;
it is unclear where theerror occurredYes

A generic was incorrectly
substituted for the brandname product although
the physician specificallyprescribed the brandYes

The report does not
mention an error, instead
it confirms that this is nota medication error
because the label does
not advise not to split.
There is nothing to codein the provided text.
Product
This is a prescribing error
prescribing error that resulted in the patient
splitting the tablet. This is
not a case of off label
Tablet split byuse,
as the prescriber
mistake
was unaware that thetablet should not be split.
Product
Select LLT Productprescribing issue prescribing issue since it
is not known whether thisis unintentional (amedication error) or
intentional (off label use).
The report does notindicate whether theprescriber was aware thatthe tablets should beswallowed whole.
Wrong drug
This is a “Wrong drug”
medication error; thestage where the error
occurred is not stated(e.g., at prescribing,dispensing, selection, or
administration)
Product
substitution error(HLT Medication
errors, product20

Scenario

Medication
error?

name product with nosubstitution
Patient had thrown
medicated opioid patches
in the open waste bin
instead of disposing as
recommended in thelabel. Their childexperienced an overdose
after playing with thepatches.

LLT

Comment

use errors andissues NEC)
Yes

Incorrect
disposal of
medication
Accidental
exposure to
product by child

The route of exposure isnot specified in theverbatim information andtherefore cannot be
coded

Accidental
overdose

3.2.3 Product administration errors/issues
3.2.3.1 Dose omission
As per the MedDRA Concept Description, dose omission is ‘the failure toadminister an ordered dose to a patient before the next scheduled dose, if any.
This excludes patients who refuse to take a medication, a clinical decision (e.g.,contraindication), or other reasons not to administer (e.g., patient sent for test).”For the purposes of retrieval and analysis, in general, a dose omission should beconsidered to be a suspected medication error. However, there are scenarios
where doses are missed which are not considered medication errors. The cause
or contributing factors for the dose omission are necessary to determine if theomission is a medication error or not, and consequently to select the appropriate
MedDRA terms. Scenarios where dose omission occurs can be generallygrouped as follows:o Dose omission unintentional (error) (e.g., patient misunderstood
instructions; pen device jammed and patient could not deliver thedose; patient forgot to take dose)o Dose omission intentional (e.g., patient skips a dose of anantidiabetic because of low blood sugar, medicine held one dayprior to surgery)o Dose omission that is unspecified (cause / contributing factors
unknown)o Therapy interruption (neither an error nor intentional. Due to nonclinical or external factors such as supply, insurance, financial
issues, etc.)21Scenario
Health provider reported
a problem that resulted
in leakage where the twosyringes wereconnected. This led tothe dose not being given.

Medication
error?
Yes

LLT

Comment

Syringe connection
issueThis is an example
of a device issue
leading to a
medication error.

Device leakage

Patient was not given thedose of the drug, as thenurse accidentallyadministered the diluent
to the patient instead ofusing the diluent toreconstitute the vial
containing the active
ingredient

Yes

Missed dose

Unknown

Patient couldn’t takemedication for a week
because the pharmacy
was out of the
medication

No

Patient missed her dose
because she did not
notice that one of thedosage units in the
package was empty

Yes

Patient did not takemedication this week
because he could notafford it

No

Drug dose omission by
deviceMissed dose in error

In this scenario,
dose omission is anerror caused by
Active ingredient not
failureto reconstituteadded to diluent
the vial with the(PT Productdiluent.
The specificpreparation error)
term LLT Missed
dose in error should
Single component of a be selected if thetwo-component
report indicates that
product administered the dose omission isan error.
Missed dose (PTProduct doseomission)

Temporary interruption This event is neitherof therapy
intentional nor a
medication error.
Use
LLT Temporary
Product availability
interruption of
issue
therapy and capturethat external factors
caused theinterruption oftherapy.
Missed dose in error
This event of
missing a dose isdue to a productPackage empty units
packagingquantity(PT Product packaging
issue
quantity issue)
Inability to afford
This is neither a
medicationdose omission inerror nor an
intentional dose
Temporary interruption
omission.
Use LLTof therapy
Temporary22

Scenario

Medication
error?

LLT

Comment
interruption oftherapy and capturethat external factors
caused theinterruption oftherapy.
This is an example
of an intentionallyomitted dose

The afternoon dose washeld because the patient
was scheduled for a
medical procedure

No

Intentional doseomission

Patient’s blood sugar
was low so he decided toskip the prescribedevening dose of insulin

No

Intentional doseomission

This is an example
of an intentionallyomitted dose by thepatient

Patient took the drug asprescribed but broke out
in a red itchy rash anddid not take theremaining doses

No

Itchy rash

Stopping therapy
because of an
adverse event does
not represent anerror or intentional
misuse.
Discontinuation oftherapy is typically
captured as an
outcome.

Patient habituallyskipped prescribed
antipsychotic
The on-body infuser fell
off the patient’s arm andshe missed the doseNo

Treatment
noncompliance

Yes

Missed dose in error

Patient forgot to take his
medication on one day
during the week

Drug delivery device
fell off skin

Yes

Capture theunintentional missed
dose and that it
occurred because
the delivery device
fell off. In this case it
is not stated whether
this is an adhesion
issue.

Forgot to take product23

3.2.3.2 Other administration errors/issues
Scenario
Patient accidentally took
1 tablet twice daily
instead of the prescribed
1 tablet once daily

Medication
error?
Yes

Tablet was crumbled,
but was stilladministered to thepatient

Yes,
consequent
to a productquality issue

Patient had difficulty
removing the tablet fromthe thick blister pack;she managed to force itout but the tablet
crumbled into manypieces that fell to thefloor. She found andtook only one piece ofthe dose.
Syringe plunger couldn’t
be completely pushed
down so the patient

Yes

Yes,
consequent
to a delivery
device issue

LLT

Comment

Once daily dosetaken more
frequently

When available, it isimportant to select a
specific LLT for thereported scenario,
rather than just the LLTthat matches the PT
Inappropriate scheduleof productadministration, allowing
further sub-analyses
on the LLT level.
Although the LLT does
not capture that it was
accidental, it falls
under HLT Productadministration errors
and issues.
Tablet physical issue “Tablet was crumbled”
in this scenario is a
product
quality issue
Poor quality drug
(LLT Tablet physicaladministeredissue); do not select a
medication error termsuch as LLT Tablet
crushed incorrectly.
The error is that a
product with a known
quality issue(“crumbled”) was stilladministered to thepatient.
Product blister“Tablet crumbled” inpackaging issue
this scenario is not a
product quality issueand does not need toIncorrect dosebe coded. Code theadministeredreported blister
packaging issue andthe consequent partial
dose administration.
Device delivery
system malfunction

Capture both thedevice issue and theconsequent medication
error. LLT Device
24Scenario

Medication
error?

received only half of hisscheduled doseA patient reported that
he followed the
directions for use, but
the device jammed andmost of the injection
sprayed all over his
hands

Yes,
consequent
to a delivery
device issue

LLT

Comment

Incorrect dose
administered bydevicedelivery system
malfunction is more
specific than LLTSyringe issue.

Device delivery
system malfunction

Do not infer a missed
dose, since it is notreported in the
narrative

Accidental exposure
while administering
drug

Exposure via skincontact
Contraindicated drug The report states thatadministered
the patient is taking acontraindicated drug;
circumstances are notprovided
Drug administered atinappropriate site

Patient taking
contraindicated drug

Unknown

The drug wasadministered in theabdomen rather than thearm muscle asrecommended
Patient inquired about
possible overdose
symptoms because she
accidentally took an
extra dose

Unknown

Yes

Extra dose
administered

Patient reported taking
an expired drug for his
headache
Patient experienced
respiratory arrest after
the nurse
misprogrammed theinfusion pump to deliver
the drug over 5 minutes

Unknown

Expired drug used

Yes

Drug administration
rate too fast

The patient is only
inquiring about
overdose symptoms(not reporting an
overdose).
Although the LLT does
not capture that it was
accidental, it falls
under HLT Productadministration errors
and issues.

Pump programming
error
25

Scenario

Medication
error?

instead of the intended
50 minutes
The patient used acracked insulin cartridge
which resulted in apartial dose
administered

LLT

Comment

Respiratory arrest

Yes

Partial dose delivery
by device
Cartridge cracked

3.2.4 Product confusion errors/issues
Scenario
Patient was dispensed
Drug Y instead of Drug
X. The two drugs had
similar looking
packaging.

Medication
error?
Yes

LLT

Comment

Look alikepackagingWrong drug
dispensed
Product label
confusion

Patient purchased overthe counter (OTC) Drug
X 10 g instead ofintended Drug X 5 g
because of label
confusion
Patient accidentally took
the wrong drug for aweek because thetablets looked identicalto his daily vitamin
tablets
Mix-up of 5 mg/ml with50 mg/ml product

Yes

Yes

Wrong strength

Patient was dispensed‘Drillo’ instead of ‘Millo’,
as the pharmacist
misheard the name ofthe drug as ‘Drillo” when

Yes

Drug name soundalike

Wrong drug strength
selected
Yes

Look alike pill
appearance
Wrong drug
administered
It is unclear whether
the patient wasadministered the drug.
‘Strength’ pertains to
the product itself; ‘dose’is the amount of drug
the patient receives /should receive.

Wrong drug
dispensed
26

Scenario

Medication
error?

LLT

Yes

Look alikepackaging

Comment

the physician ordered itover the telephone
Patient experienced skinulceration after applying
the wrong topical cream.
Error attributed to thecreams packaged in thesame size tube withsimilar red font and black
background.

Wrong drug
administered
Skin ulceration

3.2.5 Dispensing errors/issues
Scenario
Patient complained thatthe generic didn’t work
as well as the innovator
drug

A generic wassubstituted for the brandname product

Medication
error?
No

Unknown

LLT

Comment

Product substitution
issue brand to
generic

This is a productquality complaint

Drug effectdecreased
Product substitution
Code only what is(HLT Therapeutic stated. The report does
procedures NEC)not specify an error.

Patient received expired
patches from thepharmacy
Patient took the drug
daily instead of on theintended weekly
schedule because theclinic wrote the wrong
directions on the vial

Yes

Expired drug
dispensed

Yes

Wrong directions
typed on label (PTProduct dispensing
error)

Drug was not dispensed
in the original container,
although the labelling
advises that the drug
must be kept in theoriginal container

Yes

Once weekly dosetaken more
frequently
Drug not dispensed
in original container

27

Scenario
The prescription wasillegible and resulted in
the pharmacy
dispensing the wrong
strength
Pharmacy dispensed
drug with the pharmacy
label obscuring therecommended storage
information. Productstored at wrong
temperature.

Medication
error?
Yes

Yes

LLT

Comment

Wrong drug strength
dispensed

Written prescription
illegible
Drug dispensing
error
Pharmacy label
placed incorrectly(PT Productdispensing error)

Product storageerror

3.2.6 Monitoring errors/issues
Scenario
Patient was hospitalizedwith thromboembolism
because his INR wasn’t
monitored asrecommended in thelabelling
Literature report
hypothesised a possible
drug interaction caused
the patient to experiencehypotension

Medication
error?
Yes

LLT

Comment

Drug monitoringprocedure not
performed
Thromboembolism

No

Drug interaction
Hypotension

28

Scenario

Medication
error?
Patient experienced typeYes
I hypersensitivity after
receiving amoxicillin
during surgery. The
patient’s e-health record
had a documented
history of amoxicillin
allergy. The error was
attributed to the lack ofinteroperability between
the anaesthesia softwareand the hospital’s ehealth record.
Patient on anticoagulant
Yes
undergoing surgery but
due to an oversight, it
was not stopped prior tosurgery as
recommended in thelabelling and patient
experienced
postoperative bleeding
Provider prescribed twoYes
drugs with known druginteraction because he
was unaware of theinteraction potential

LLT

Comment

Hypersensitivity type I
Documented
hypersensitivity toadministered drug
Device computer
software issue

Medication monitoring
error
Failure to suspend
medication
Postoperative
bleeding
Labelled drug-druginteraction medication
error
Drug prescribing error

3.2.7 Preparation errors/issues
Scenario
Caregiver wasn’t aware
to remove the innercover from an insulin
pen needle when
preparing the pen
Product wasreconstituted with thewrong diluent

Medication
error?
Yes

Yes

LLT

Comment

Product assembly
error during
preparation for use

Wrong solution usedin drug reconstitution

29

Scenario
Pharmacy compounded
the wrong strength
product

Medication
error?
Yes

LLT

Comment

Product
compounding error
Wrong strength
Product preparation
error

Patient received only
one component of a
two-component productbecause the nurse
wasn’t aware that thetwo components
needed to be mixed
together before
administration
Pharmacy prepared
incorrect concentration
because of confusion
related to the way thestrengths for the two
active ingredients werestated on the label
The technician didn’t
follow the instructions to
mix the contents of thevial for 5 minutes afterreconstitution

Yes

Yes

Product preparation
error

Respiratory therapist
put the canister in an
inhaler the wrong way

Yes

Product assembly
error during
preparation for use

Single component of
a two-component
product administered

Yes

Wrong concentration
prepared
Product label
confusion
LLT Product preparation
error (HLT Productpreparation errors andissues) is more specificthan LLT Wrongtechnique in productusage process (HLT
Medication errors,
product use errors andissues NEC)

3.2.8 Prescribing errors/issues
Scenario
Drug prescribed in error
for unauthorised use

Medication
error?
Yes

LLT

Comment

Drug prescribing
errorThis is a prescribing
error. Off label use
should not be coded inaddition. Off label use is30

Scenario

Medication
error?

LLT

Comment
an intentional act not anerror.

Unintentionallyprescribed Drug X
instead of Drug Y
because the names
sounded alike

Yes

Prescribed 4 mg/kg
instead of 0.4 mg/kg.
Prescriber realised
immediately and called
nurse but nurse hadalready administered the
drug.
Patient was switched todifferent insulin productbut dose adjustment was
not written on theprescription. Patient
administered the wrong
dose and experienced
hypoglycaemia.

Yes

Patient was prescribed 2times the appropriate
dose due tocomputerised prescriber
order entry (CPOE) error
Patient with intractableseizures and taking
multiple drugs wasprescribed acontraindicated drug
Patient was prescribed
0.5 mg to be taken by
splitting the 1 mg tablet

Yes

Patient prescribed 1
tablet daily for insomnia
for many years. The
product directions state

Drug prescribing
error
Drug name soundalike
Drug doseprescribing error

It is important to be able
to identify the confusion
as a root cause

Even though the error
was detected it was notintercepted in time

Wrong dose
administered
Yes

Drug doseprescribing error
Wrong dose
administered
Hypoglycaemia
Drug doseprescribing error
CPOE error

Unknown

Contraindicateddrug prescribedUnknown

Unknown

Medicallyprescribed
prolongation oflabelled treatment

LLT Seizures should be
captured as medical
history

No event to code basedon the stated information.
It is not known if this is aprescribing error, off label
use, or neither. If this is
the ONLY information,
this is not a case andshould not be recorded.
The selected LLT
captures both the"prescribing" concept andthe "duration" concept
31

Scenario
that the product should
not be taken for morethan 2 weeks.
An elderly man felt dizzyand fell after he wasinappropriately
prescribed Drug A

Patient hospitalised forwithdrawal symptoms
after his unspecified
opioids were
inappropiately
downtitrated
Patient prescribed 0.25
mg (off-label startingdose)
Physician ordered thewrong rate ofadministration for the IVdrug, and the patient
experienced hypotension

Drug indicated for IV
administration was used
off label via the oral
route

Medication
error?

Unknown

Unknown

LLT

Comment

duration (PTProduct prescribing
issue)
Inappropriate
Select LLT Inappropriateprescribingprescribing only when
specifically stated in the
narrative; otherwise,
Dizzyselect LLT Productprescribing issue or aFallsimilar term when it isunknown if the productwas prescribed off label
or in error
Opiate withdrawal
symptoms
Inappropriate drug
titration

No

Off label dosing

Yes

Incorrect drug
administration rate
Hypotension

No

Drug prescribing
error
Off label use
Intravenous
formulation
administered byother route

LLT Intravenous
formulation administeredby other route (PTIncorrect route of productadministration, HLT
Product administration
errors and issues)
provides additional
information about the
specific type of off label
use. The term is not an
off label use term itself; itis a general product use
issue term that can beused in combination withother terms to capture
32

Scenario

Medication
error?

LLT

Comment
detail about off label use,
misuse, medication
errors, etc.

Patient accidentallyreceived duplicate
therapy because theprescriber didn’t realisethe 2 drugs had thesame active ingredient

Yes

Duplicate drugprescription error
Duplicate therapy
with same active
substance

3.2.9 Product selection errors/issues
Scenario
The elderly patient
confirmed that due to thecataract, the patient did
not see well and ended
up buying the infant
formulation
Pharmacist selected thewrong drug because ofname confusion, but theerror was caught andcorrected before thedrug was dispensed
The hospital selected thewrong bag and thepatient received atransfusion of the wrong
blood type prior to andduring surgery
Clerk ordered the wrong
drug from the wholesaler
because the drugs werelisted next to each otherin the catalogue and thenames looked very
similar

Medication
error?
Yes

Yes

LLT

Comment

Product selection
errorThis is not a productname confusion.
Cataract would be
captured as medical
history.

Intercepted wrong
drug selected

It is important to capture
the cause of the error

Drug nameconfusion
Yes

Wrong productselectedTransfusion withincompatible blood

Yes

Wrong drug
selected
Drug name lookalike33

3.2.10 Product storage errors/issues
Scenario
Healthcare facility
reported storing
reconstituted drug insyringes past therecommended 30 days,
and administering it topatients. One of thesesyringes was used by apatient who reported
that the drug didn’t work.
Vaccine product wasstored in the pharmacy
at excessive
temperatures

Medication
LLT
error?
Yes
Improper storage ofunused productExpired drug
administered

Comment
LLT Poor quality drug
administered should not
be selected because theselected LLT Expired drug
administered is more
specific

Lack of drug effect

Yes

Product storage
error temperature
too high

The pharmacy staff
member could not finddrug as it had
inadvertently beenplaced on the wrong
shelf
Boxes of the drug sentfrom the manufacturer
were left outside atexcessive temperatures
over the weekend when
the wholesaler was
closedYes

Drug stored inwrong location

Pharmacy delivered thedrug to the patient’s
home while the patient
was hospitalised. The
package was outside attemperatures below
freezing for two days
(drug should not befrozen).
Manufacturer issued arecall of certain lots ofDrug X that were foundto be exposed toinappropriate storage
conditions by thewholesaler

Yes

No

No

This is a medication error,
as the error occurred in
the product use system

Manufacturing
This storage problem is
product storage
not a medication error
issue (HLT Product because it occurred under
distribution andmanufacturing distribution
storage issues,and storage activities,
SOC Productprior to the productissues).
reaching the medication
use system
Product storage
This is a medication error,
error temperatureas the error occurred in
too low
the product use system

Manufacturing
product storage
issue
Recalled productThis storage problem is
not a medication error
because it occurred under
manufacturing distribution
and storage activities,
prior to the product34

Scenario

Medication
error?

LLT

Comment
reaching the medication
use system

Pharmacy mistakenly
stocked the wrong drugin the automateddispensing system.
Reporter attributed theerror to both drugs being
packaged in similar
sized vials with lookalike container labels.

Yes

Drug label lookalike
Wrong drug
stockedProduct packaging
confusion

3.2.11 Product transcribing errors/communication issues
Scenario

Healthcare provider called
in a prescription for Drug A,
but pharmacy wrote down
the prescription as Drug B
Pharmacy dispensed 800
mg strength instead of 600
mg due to data entry error

Physician ordered insulin
pens, but a transcription
error transpired with thepharmacy and the patient
was dispensed insulin in avial with syringes instead
Patient had an issuecommunicating and wasgiven the possible
diagnosis of autism

Medicationerror?
Yes

Yes

Yes

LLT

Comment

Transcription
medication error

Product data entry
error
Wrong drug
strengthdispensed
Transcription
medication error
Wrong device
dispensed

No

Communication
disorderAutismDespite the terms “issue”
and “communicating” inthe example, this is not a
medication error andshould not be captured
under LLT Productcommunication issue, butrather should be captured
under LLT
Communication disorder35

4. PRODUCT QUALITY ISSUES
The purpose of this section is to expand on the section on product quality issues
in the MedDRA Term Selection: Points to Consider (MTS:PTC) document. Thisparticular section is intended to facilitate term selection for product quality issues
for distributed products reported in the clinical setting. This section does notprovide suggestions for the use of the MedDRA terminology which covers
specific manufacturing deviations or non-conformances. Additionally, guidanceand examples for coding of some scenarios are provided. This section has threemain sub-sections:•••

Background: concept of product quality issues in medical products
Examples for coding product quality issues (based on MedDRA Version
23.0)
Data search and retrieval strategies: guidance and considerations

Acknowledgments
The PtC Working Group would like to acknowledge the significant contributionsof the following individuals to this section of the Companion Document:
Georgia Paraskevakos, Patient Safety Specialist, Health Canada.
Kirubel Assegid, Chemist, US, FDA
Elise Murphy, Supervisory Consumer Safety Officer, US, FDA
Maria R. Thomas, Consumer Safety Officer, US, FDA

4.1 BACKGROUND
It is important to recognise product quality issues as they may have implications
for patient safety. Product quality issues are defined as abnormalities, also
known as non-conformances (failures to conform with established productspecifications), that may be introduced in any phase of the supply chain. These
include the manufacturing, labelling, packaging, shipping, handling or storage ofthe products. Product quality terms may be used to report product defects toregulatory authorities and may also be used in organisations' internal databases
to track and trend quality issues or deviations. Product quality issues may occur
with or without clinical consequences. Not all product quality issues are readily
detectable to the user.
Product quality issues may be reported in the context of adverse events or as
part of a product quality monitoring system. Likewise, patient safety data may
facilitate surveillance for evidence of product quality issues. MedDRA coding
conventions for product quality issues promote consistency in data entry,
facilitating data retrieval that is required to support health risk assessment whena non-conforming product is detected in the marketplace.
Other important concepts that may be reported into a product quality monitoring
system include consumer preference complaints in which the reporter makes noallegation against the product quality, but communicates dissatisfaction with the
product or packaging design. Examples include request for a liquid form of asolid dosage form, a suggestion to change the package configuration from bottle36to blister or to increase the quantity of tablets per bottle, and a request for a dyefree version of a children’s suspension. While these may not represent productquality non-conformance and/or there is no discrete clinical consequence, these
may be valuable to inform enhancements to the product and packaging designand labelling, and may influence the product benefit-risk profile.
Familiarity with HLGT Product quality, supply, distribution, manufacturing andquality system issues (in SOC Product issues) is essential for term selection.
Under this HLGT are categories of specific product quality issues such as
HLT Product packaging issues, HLT Product physical issues, HLT Counterfeit,
falsified and substandard products, and HLT Product contamination and sterility
issues. MedDRA Lowest Level Terms (LLT) that most accurately reflects thereported verbatim information should be selected. This may be achieved by useof the search function or by use of the SOC window of a browser to navigate the
MedDRA hierarchy down to the appropriate LLT.
SOC Product issues is focused on issues related to products rather than clinicalor patient related concepts and therefore, the majority of terms are single-axial
and have no need for multi-axial links to other patient related “disorder” SOCs.
However, product terms that also denote a patient related issue may be multiaxial to preserve the link to patient safety. For example, PT Transmission of an
infectious agent via product is linked to primary SOC Infections and infestations
and has a secondary link to SOC Product issues. The fact that most productquality terms are single-axial and are located in SOC Product issues should betaken into account when designing queries and other retrieval strategies.
Explanations of the interpretations and uses of certain product quality issue
terms (e.g., “Product coating incomplete”) are found in the MedDRA Introductory
Guide (Appendix B, MedDRA Concept Descriptions).
4.2

EXAMPLES FOR CODING PRODUCT QUALITY ISSUES
4.2.1 Product physical issues
Scenario

LLT

Comment

Pharmacist opened bottleof tablets and detected anirregular odour that wasdue to mould

Product odour abnormal

A term has been added for thereporter’s statement that theabnormal odour is the result ofcontamination with mould. This isalso a form of biocontamination(see Section 4.2.2).

Patient stated chewable
tablets were excessively
hard and he suffered abroken tooth. He suspects
the product was defective.

Medication too hard tochew

Product contamination
mould

Tooth fracture
Tablet physical issue

Note, product quality issue, LLT
Tablet physical issue, is based onreporter verbatim. In the absenceof this information, a productquality issue should not be
inferred.

37

Scenario

LLT

Comment

Mother states she gave
her child a suspension
labelled as cherry
flavoured and it had adistinct taste of mint
insteadWhen the nurse opened
the vaccine carton, the vial
was observed to containyellow liquid. The productlabel states it should becolourless.
The pharmacist opened
the medication bottle anddiscovered some of thetablets were broken
Patient found intact tabletsin her stool andcomplained that the tablet
must be of poor quality

Product taste abnormal

These reports only refer to adiscrepancy between labelled
taste/colour and actual
taste/colour. Either the productcontent is incorrect or the label isincorrect. An event within the HLT
Product label issues should be
coded only if the reporter
indicates that the label isincorrect.

A female patient noticed
that her contraceptive
medication smelled badand tasted differently than
beforeProduct colour issue

Tablet chipped

Tablet in stool

This LLT is under PT Productresidue present and located in
Product quality complaint the SOC Investigations. Although
this is not typically a product nonconformance, it is the patient
perception that something iswrong, or that the tablet is of poor
quality.
Product smell abnormal
Product taste abnormal

4.2.2 Product contamination/sterility issues
Scenario
Upon opening the sterile
packaging for a venous
catheter, the surgeon
noticed an insect present in
the inner packaging. She
discarded the unit andretrieved an alternate
package that was clean andintact.
Upon inspection of aprefilled syringe, the nurse
detected particles floating in

LLT

Comment

Product contamination This information may require
insectcollection and reporting by the user
facility, with or without evidence of
patient involvement.

Particle present inliquid product

LLT Product availability issue is amore general term, as it does not
specify the reason for unavailability.
38Scenario

LLT

Comment

the liquid. This was the last
Temporary
LLT Product supply issue is notavailable prefilled syringe for interruption of therapy appropriate in this example,
this drug at the clinic. The
because there is no mention of apatient’s treatment was
Product availability supply issue.
delayed until the following
issue
week when the syringe wasavailable again.
A consumer reported that
Product contamination
while examining the drug
glass
provided in an ampoule, she
noticed that there was apiece of glass inside
The patient reported
Fusarium infection LLT/PT Suspected transmission ofcontracting fusarium keratitis
an infectious agent via product isof her left eye. She
multi-axial, linking to SOC Infections
Keratitis fungal
suspected contamination ofand infestations as primary andher contact lens solution was
SOC Product issues as secondary.
Suspected productthe source.
contamination
Suspected
transmission of an
infectious agent via
product
4.2.3 Product distribution issues
Scenario

LLT

A patient complained thatthe medication shipment toher home was delayed. As aresult, she ran out of
medication, missed several
doses and developed
hyperglycaemia.

Product shipment
delay

Comment

Therapy interrupted

Hyperglycaemia

4.2.4 Product label issues
Scenario

LLT

The patient was unable toread the expiration date on
the medication bottle
because it had faded incolourProduct expiration
date illegible

Comment

39

Scenario

LLT

Comment

A consumer opened a carton
Product package
containing infant suspension
insert incorrect
in a bottle. The
accompanying package
insert was for the adult tabletform.
A patient stated he read theProduct label text
dosing schedule on a tube ofillegible
ophthalmic ointment
incorrectly because the print Once daily dose taken
was illegible. As a result, hemore frequently
used product twice a day
instead of the recommended
Irritation of eyes
once a day. He developed
irritation in his eyes.

4.2.5 Counterfeit
Scenario

LLT

Comment

A patient was contacted by
the infusion facility to inform
her that she had beentreated with counterfeit
medication. She wasadvised to return fortreatment.

Counterfeit productadministered

This LLT links to SOC Injury,
poisoning and procedural
complications as the primary SOC
and to SOC Product issues as thesecondary SOC. LLT Counterfeit
product administered should only
be selected if counterfeit has been
confirmed. Otherwise, LLT
Suspected counterfeit productshould be selected.

When inspecting a carton of
vaccines from a new
supplier, the clinic manager
noted that the productbranding was different fromprevious cartons. He
suspected that the material
was not authentic.
A consumer had been using
a drug for several years. The
newly purchased unit wasineffective compared to pastexperience. She suspectedthat the product wascounterfeit.

Suspected counterfeit
product

Suspected counterfeit
product
Drug ineffective40

4.2.6 Product supply and availability
Scenario

LLT

Comment

A patient was told by her
Product supply issue
pharmacist that her
medication was not available Drug therapy changed
due to a shortage in supply
following closure of several
manufacturing facilities. Her
physician prescribed analternative therapy.
The pharmacist informed theProduct unavailable
patient that his medication
due to pandemic
was not available due to the
COVID-19 pandemic

4.2.7 Packaging issues

4.3

Scenario

LLT

When the patient removed
the medication bottle fromthe carton, the tamper
evident seal was absent
On inspection of a
medication bottle, acustomer noticed that thechild resistant cap did notwork
A nurse noticed that theblister package was notcompletely sealed
A woman reported that her
contraceptive medication
was missing the placebo
tablets

Product container seal
issue

Comment

Failure of childresistant productclosureProduct blister
packaging separated
Package dosage units
missing

DATA SEARCH AND RETRIEVAL OF PRODUCT QUALITY ISSUES

Product quality issues may result in patient safety concerns, but these are notalways detectable to the manufacturer or the patient. When detected, an
opportunity is created to remediate the non-conformance and restore productsafety.
Appropriate data entry practices facilitate detection and retrieval of productquality issues in safety data. It is also important to be aware that multiple
databases might be used to capture product quality complaints, e.g., a safety
41

database and a quality database. Consider potential database specifics including
differences in data coding of adverse events and quality complaints between the
databases (e.g., different dictionaries or data that is not coded).
Broadly, medical safety data review may detect product quality deviations on acontinuous, periodic and ad hoc basis. During continuous, real-time review
product quality issues can be detected based on single Individual Case Safety
Reports (ICSRs) or based on batches/lots when these have a disproportionate
number of adverse event reports.
The periodic review for product quality issues is generally product specific.
Dependent on the scope of the review this can be done by means of aggregate
adverse event review performed on a fixed schedule, or by a review of events
reported to the quality system. If data is coded in MedDRA, the retrieval and data
output may be enhanced by developing and applying a customised data filter
based on MedDRA product quality issue terms. When creating and maintaining adata review strategy, it is important to document the review strategy and terms,
and to also document review and update of the terms with each MedDRA
release. Periodic review is usually performed to find anomalies in the data. Thus,
an increase in certain quality complaints might lead to the generation of a new
hypothesis. Further validation could then become necessary by searching foradverse event terms suspected to occur with this type of quality issue.
Data review may be lot specific (i.e., all adverse events for the material in scope)and/or problem specific (i.e., all material, with or without a lot number, for adefined list of adverse event terms). Distribution dates and locations may also be
incorporated into this type of data review strategy. The adverse event term list
should reflect the medical conditions that may result from exposure to nonconforming product. For example, assessment of a product containing an
undocumented potential allergen should include MedDRA terms reflecting
hypersensitivity concepts. SMQ Hypersensitivity could be applied to achieve thiswith efficiency. Assessment of a product subject to biocontamination should
include MedDRA terms reflecting infection concepts, both broad and specific tothe contaminant, if known.
Whether data assessment for product quality is continuous, periodic, or forcause, description of quality issues using MedDRA facilitates detection andretrieval. This improves the integrity of the medical assessment.

42