Numerous laws, regulations, guidelines and other requirements specific to children place demands on medical device manufacturers.
However, these regulations don’t define what a child is or, in some cases, contradict one another.
This problem affects a lot of terms that regulations use in connection with particular age groups:
For clinical investigations, the MDR requires that:
where research is undertaken on breastfeeding women, particular care is taken to avoid any adverse impact on the health of the child.
The investigation plan must contain information on the subjects, including
if applicable, information on vulnerable subjects involved such as children, pregnant women, immuno-compromised or, elderly subjects.
MDR Annex XV, Chapter 2, Section 3.6.3
The consent for the participation of minors in clinical investigations must be given by their legally designated representative (MDR Article 68(2) a) . Where necessary, the minor must also assent to participation (MDR Article 63(7)). Even then, the requirements for clinical investigations with minors are high (Article 65).
If manufacturers use substances that are carcinogenic, mutagenic or toxic to reproduction (‘CMRs’), the manufacturers must justify their use. This justification must address whether
the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials.
MDR Annex I, paragraph 10.4.2
In general, manufacturers of medical devices must use critical substances intended for the treatment of children (and other vulnerable patient groups)
information on residual risks for those patient groups and, if applicable, on appropriate precautionary measures shall be given in the instructions for use.
MDR Annex I, paragraph 10.4.5
The MDR does not explicitly mention specific age groups, such as children or adolescents, in the context of the clinical evaluation. But it insists that manufacturers compare the age of the patient population when discussing clinical equivalence.
But this leads to a problem because manufacturers often don’t specify an age range for the patient population, preferring to use terms such as “children” or “adolescents”.
Manufacturers must identify the “patient population [...] and other considerations such as patient selection criteria” in the intended purpose and, therefore, in the technical documentation (Annex II, Section 1; Annex IX, Chapter II, Section 5.1.d).
Notified bodies are allowed to restrict the intended purpose of a device to certain patient groups (Article 56 on certificates of conformity).
Several MDCG documents also use terms such as child or infant without defining them.
The MDCG 2019-9 guideline identifies the requirements for summaries of safety and clinical performance as established in Article 32 of the MDR.
Part of the report must include the intended purpose, which in turn should include the indications for the use of the device.
“The indications shall be described. […] The target population(s) shall be specified, for example if the device is intended for adults and/or children and/or infants/neonates.”
But there is no definition of the terms child or infant.
The MDCG 2020-16 guideline should help classify medical devices. The IVDR specifies the classification rules in Annex VIII. Several rules consider risks to the offspring of the individual being tested without defining what constitutes an offspring.
The MDCG document defines the term offspring as follows:
“is the result of conception, at all stages of development, embryo and foetus, premature and full term neonates, child and adult.“
MDCG 2020-16 Section 2
This definition uses other terms such as embryo, fetus, premature, child and adult. The guideline defines some of the terms, e.g., embryo (see below). However, the guideline does not define the term child.
A whole range of regulations define different age levels. Unfortunately, these definitions are not consistent.
Section 1 of the German Jugendschutzgesetz (german) defines children as “persons who are not yet 14 years old,” and adolescents as persons who have reached the age of 14 years but are not yet 18 years old.
But Section 2 of the German Jugendarbeitsschutzgesetz (german) gives a different definition. According to this definition, a child is a person who is “not yet 15 years old” and an adolescent a person who has reached the age of 15 years but is not yet 18 years old.
The guidelines for clinical trials in pediatric populations uses the following definitions:
“In contrast to ICH E11 guideline which refers to children as individuals aged from 2 to 11 years, when the term “children” is used within these recommendation, it is used consistently with the recitals of the Clinical Trials Directive to mean minors.”
The next section then defines the term minors.
“Article 4 of the Clinical Trials Directive refers to children as minors. When quoting or referencing the Clinical Trials Directive in relation to legal competence, the term “minor” will be used, and it applies to all individuals from birth until the legal age of adulthood (usually 18 years and above, rarely 16 years).”
The aforementioned ICH 11 document from the EMA works with the following age classes and definitions:
0 to 27 days
Infants and toddlers
28 days to 23 months
2 to 11 years
12 to 16-18 years (dependent on region)
The FDA provides a similar definition in its “Annual Report Premarket Approval of Pediatric Uses of Devices FY 2017”.
Birth until 1 month of age
Greater than 1 month until 2 years of age
Greater than 2 years until 12 years of age
Greater than 12 years through 21 years of age [i.e., up to but not including the 22nd birthday]
These definitions are based, among other things, on other definitions, e.g., those of the Food, Drug and Cosmetic Act.
The previously mentioned MDCG 2020-16 guideline does not define the term child but it does define the terms embryo and fetus even if does not differentiate them completely and, in some places, equates them:
“an unborn refers to stages in human development after zygote formation. A zygote is considered an embryo in particular from the period of conception to approximately the eighth week, and considered a foetus following this period until birth. Samples from the embryo or foetus include samples from the embryonic/foetal membranes, fluids and excretions, the umbilical cord, and maternal samples (e.g. blood) containing embryonic/foetal material to be examined.“
The title of standard ISO/IEC Guide 50 is Safety aspects — Guidelines for child safety in standards and other specifications.
Babies or infants
Those not yet walking
Children who can walk, but whose ambulatory skills are not fully developed and exhibit strong exploratory behavior
Persons aged under 14 years
Those past the toddler stage, but still developing basic skills, such as those aged 3 to 8 years […]
Those who are not yet adolescents: the upper age limit can vary, so the term can refer to those from approximately age 9 to age 12, 13 or 14. It is an age group that is increasingly independent, is capable of performing most adult tasks […]
You can read the standard free of charge here.
The Kassenärztliche Bundesvereinigung (KBV) uses other definitions:
Up to the end of the 28th day of life
From the start of the 29th day of life up to the end of the 12th month of life
From the start of the 2nd year of life up to the end of the 3rd year of life
From the start of the 4th year of life up to the end of the 12th year of life
From the start of the 13th year of life up to the end of the 18th year of life
From the start of the 19th year of life
ISO 7176-19:2008(en) on wheelchairs takes a different approach. It defines age classes by their weight:
22 kg <= weight < 43 kg
Weight >= 43 kg
Other categories are possible depending on the type of device:
When manufacturers define indications or contraindications, they should take specific situations such as the following into account when choosing the classification characteristics:
There is no consensus on what constitutes a child, adolescent, or adult. The definitions use different terms, use different measures (age, weight) and contradict one another.
The fact that regulations seem to ignore one other and cause problems for manufacturers as a result is unfortunate. For example, how should a manufacturer evaluate the equivalence of devices if it is not clear what the manufacturer of the equivalent device means by the term child?
On the other hand, it is understandable that different age groups have to be defined differently in different contexts:
When it is an issue of making sure a child cannot trap their finger, the size of the child is the decisive parameter. In some other contexts, cognitive abilities are a more appropriate measure to use for classification, and in others, motor skills are the most appropriate.
Therefore, as a manufacturer, you should not specify your intended patient population using undefined terms such as child. Instead, you should define the classification characteristics context-specifically.
When doing this, first check whether you can use existing definitions.
This will save you unnecessary discussions during audits and authorization procedures.
Get in touch if the Johner Institut can help you formulate precise intended purposes and, as a result, create the basis for an “audit-proof” qualification, classification, clinical evaluation and authorization of your devices.
Thanks to Bernward Reszel for his help compiling the lists!