The term "sampling kit" is not defined by the IVDR or any other regulation. Nevertheless, there are (indirect) regulatory requirements that IVD manufacturers and medical laboratories must be aware of and consider. The requirements depend on the particular constellation.
This article presents five constellations. It provides clarity and helps to avoid regulatory hassles and minimize regulatory efforts.
In the absence of an official definition, we determine for this article:
A sampling kit is a set of devices which, according to the assembler of the kit, are used together by a user to collect human samples (e.g., blood, saliva, tissue, urine) and to store and/or transport them properly for further in vitro diagnostic testing.
Definition: Johner Institute
For example, sampling kits for a tissue sample may include the following products:
Sampling kits can be used both for sampling at home and in a health institution, e.g., in a doctor's office.
Depending on the intended use, the sample can be taken by the patient (as in a product for self-testing) or by a healthcare professional (as in a product for near-patient testing, also referred to as Point-of-Care-Testing, POCT).
The timing of the diagnostic itself distinguishes sampling kits from self-tests and POCT. It is done after the sample has been shipped to a medical laboratory and is performed by laboratory personnel, not at the point of sample collection.
Example: Testing for SARS-CoV-2 infection
Sampling kit: set provided by a medical laboratory to a practicing physician or health care professional with a return box to ship the professionally collected specimen to the laboratory for PCR testing for SARS-CoV-2 RNA.
Direct-to-consumer test (DTC): Sampling kit purchased at a brick-and-mortar retailer or online with a return shipping box to ship a sample collected by a layperson to a laboratory for PCR testing for SARS-CoV-2 RNA.
Near-patient test (POCT): rapid antigen test performed at a so-called corona testing center.
Self-test: Antigen test for self-testing with own sample collection, purchased e.g., in supermarkets, pharmacies, or online.
Sampling kits are often not marketed by classical IVD manufacturers but by health institutions such as medical laboratories that offer in vitro diagnostic testing and are thus IVD operators themselves.
These laboratories usually ship the sampling kits to physicians' offices. The physicians then collect the sample using the products provided in the kit and return it to the laboratory in the sample container also provided in the kit.
This practice is also occasionally used by CE-IVD manufacturers with affiliated medical laboratories.
A special feature that is mostly found in genetic tests is the direct-to-consumer test (DTC test). In this variant, the sampling kit is not sent to a doctor's office or other health institutions but directly to the patient: The patient orders the kit online or purchases it at a retail store.
In this case, the layperson carries out sampling, packaging, and return shipment. If the layperson must perform further activities after sampling, the threshold for self-testing is exceeded, with far-reaching regulatory consequences.
DTC Testing can be offered by medical laboratories (pure operators or operators with in-house IVD) as well as by manufacturers of CE-IVD with an attached medical laboratory.
The FDA defines DTC tests as follows:
In vitro diagnostics (IVDs) that are marketed directly to consumers without the involvement of a health care provider are called direct-to-consumer tests (also referred to as DTC). These tests generally request the consumer collect a specimen, such as saliva or urine, and send it to the company for testing and analysis.
Sampling kits do not perform diagnostics - unlike self-tests and near-patient tests. Therefore, they are handled differently from the other two product types in regulatory terms.
The requirements for a sampling kit depend on its regulatory classification, which in turn depends on the contents of the kits.
The regulatory classification is not trivial because neither the IVDR nor other regulations define the term "sampling kit."
Facilities that ship sampling kits to healthcare professionals (e.g., physicians' offices), directly to patients or deliver them to retailers must assess what type of device they are placing on the market. Is it one of these five constellations?
The following sections describe these constellations.
A procedure pack exists if the sampling kit is a combination of one or more CE-marked medical devices and IVDs or non-medical devices.
In this combination, a sampling kit, in the vast majority of cases, constitutes a procedure pack within the meaning of the MDR.
“procedure pack” means a combination of products packaged together and placed on the market with the purpose of being used for a specific medical purpose
The IVDR does not recognize the concept of a procedure pack. IVDs do count as medical devices:
However, the MDR does not feel responsible for IVDs:
“This Regulation does not apply to in vitro diagnostic medical devices covered by Regulation (EU) 2017/746”
MDR, Article 1(6)
Nevertheless, the concept of "procedure pack" can also be applied to IVDs, provided that the pack contains at least one medical device CE-marked in accordance with the MDR (or MDD), especially since the definition fits sampling kits very well and the MDR also explicitly provides for IVDs as components of procedure packs (see Article 22 MDR, Section 1).
If the sampling kit also contains a medical device as defined by the MDR, the procedure pack concept is applicable under the conditions stated below.
An example is a set for blood sampling consisting of a medical device, the butterfly (winged infusion set), and a specimen receptacle as IVD (blood tube).
If the sampling kit does not contain a CE-marked medical device, but, e.g., exclusively IVDs, placing it on the market according to MDR Art. 22 is not possible.
The requirements for a sampling kit to count as a procedure pack and not as a medical device or IVD are:
For genetic tests, manufacturers ship sterile swabs ("cotton swabs") that qualify as medical devices and a transport tube filled with a buffer that counts as a specimen receptacle and, thus, as an IVD. This combination is a procedure pack as defined by the MDR.
Assemblers of procedure packs do not have to undergo a conformity assessment or affix a CE marking to the procedure pack. But they must fulfill the obligations imposed on them by Article 22 of the MDR plus UDI and registration.
The IVDR determines that specimen receptacles are considered IVDs:
“specimen receptacles shall also be deemed to be in vitro diagnostic medical devices”
IVDR, Article 2(2)
The regulation also defines the term specimen receptacle:
A sampling kit can also combine two IVDs, e.g., a sample tube and a buffer. If a laboratory now ships this sampling kit to its customers (healthcare professionals), then there is a placing on the market of an IVD - at least class A. In such cases, the laboratory must fully apply the IVDR.
However, a sampling kit typically contains not only one or more specimen receptacles (and thus one or more IVDs) but other devices. Then, there is a possibility that this sampling set itself is not to be considered an IVD. We recommend that you check this with your sampling kits to ensure proper implementation of regulatory requirements.
There is also a qualification of sampling kits as accessories.
accessory for an in vitro diagnostic medical device’ means an article which, whilst not being itself an in vitro diagnostic medical device, is intended by its manufacturer to be used together with one or several particular in vitro diagnostic medical device(s) to specifically enable the in vitro diagnostic medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical functionality of the in vitro diagnostic medical device(s) in terms of its/their intended purpose(s)
IVDR, Article 2(4)
This qualification would only be applicable if the set is intended to support certain IVDs specifically and does not itself contain any IVDs. In most cases, such qualification as an accessory is not possible or appropriate because
In addition, accessories without critical characteristics are classified as class A IVDs under rule 5a), which means that the IVDR must be complied with accordingly on a circumferential basis.
In a direct-to-consumer test, the sampling kits are sent directly to the patient for them (as laypersons) to collect the samples.
Placing on the market such sets as procedure packs according to Article 22 MDR is only possible if the devices contained therein (with the exception of the sample receptacle) are also intended for use by laypersons in their respective intended use.
Therefore, the assembler should take special care when compiling the sampling kits and the instructions for use and should also consider usability studies.
If the use of the kit components by laypersons was not intended (except for the sample container, see Manual on Borderline and Classification in the Community Regulatory Framework for Medical Devices Version 1.22 05-2019, Chapter 2.1 last paragraph), the sampling kit must be placed on the market as a CE-marked device for self-testing. Thus, the set would fall into at least Class C according to IVDR, Annex VIII, Rule 4.
Suppose all other components of the kit meet the requirements for layperson self-testing. In that case, the kit can still only be marketed as a procedure pack under MDR Article 22 or as an IVD of a class lower than Class C if the layperson is not required to perform any activities after sampling that exceed the threshold for self-testing.
If the activities exceed collection and packaging, the kit is classified as a device for self-testing (Borderline Manual Version 1.22 05-2019, Chapter 2.1).
In the case of genetic tests, please note further regulatory requirements such as the German Genetic Diagnostics Act (GenDG), which permits certain diagnostic tests only after prior medical consultation.
Organizations such as laboratories can avoid more stringent regulatory requirements, as they have to be fulfilled, for example, when placing a new IVD on the market, not only by taking a "procedure pack" approach. For example, they can consider not packaging sampling kits at all and still provide devices to their customers.
Laboratories should word their offers (website, product catalogs) and invoices very carefully. This is the only way to make it clear whether they are placing entire sets on the market or only providing individual, already CE-marked devices on the market, which may be shipped together.
If the laboratories resell devices (or even pass them on free of charge), they must fulfill their obligations as distributors (among other things, the so-called distributor QMS is required); these are described in the IVDR Articles 14, 16, 22 and 24 (1) c).
Depending on the regulatory classification of a sampling kit, assemblers must comply with various regulatory requirements. This chapter summarizes some of them.
Placing on the market of procedure packs
MDR, Article 22: Systems and procedure packs
MDR, Article 29(2): Registration of devices
Placing on the market of an IVD
IVDR, Article 10: General obligations of manufacturers
Making a CE-marked device available on the market
IVDR/MDR, Article 14: General obligations of distributors
IVDR/MDR, Article 16: Cases in which obligations of manufacturers apply to importers, distributors or other persons
IVDR, Article 22/MDR, Article 25: Identification within the supply chain
Tab. 1: Regulatory requirements for sampling kits
If material is also provided in the sampling kit for sample return shipment to the laboratory, a wide range of international specifications for the shipment of biological material must be observed. These depend on which material (potentially human-pathogenic, infectious, etc.) is being shipped from where to where (Germany, Europe, USA, etc.) and how (airplane, over water/land). The following specifications, among others, may be relevant:
Should laboratories combine the sampling kit with an in-house IVD procedure, the performance evaluation of the in-house IVD (IH-IVD) must take sampling and transport into account. This is required by the IVDR in Annex I, Section 9.1.
The following articles may be helpful for further reading and for specific questions:
The concept of a "sampling kit" is not known in legislation such as the IVDR. Therefore, legal manufacturers must clarify how these sets are to be classified from a regulatory point of view in the specific context. Only in this way they can specifically identify and implement the applicable regulatory requirements.
Depending on the classification, requirements are easy to meet (e.g., if only distributor obligations apply) or very high (e.g., if a new conformity assessment procedure must be undergone).
If you want to avoid having to comply with the entire IVDR as an IVD legal manufacturer, you can assemble your sampling kit in such a way that the requirements for procedure packs, according to MDR, Article 22, are met. This saves a lot of effort.
However, this procedure requires that the user instructions for the sampling kit do not change the intended use of the individual contents of the kit under any circumstances.
Anyone who finds even these requirements too high should check whether placing a set on the market is necessary at all. If not, the legal manufacturers can limit themselves to a role as distributors and only send individual products to professional users instead of newly assembled sets.
This is not possible with direct-to-consumer tests. Here, too, it is rather unlikely that a kit contains products exclusively for self-testing. Then there is a risk of placing a class C or even D IVD on the market.
If this is the case, extensive regulatory requirements must be met: From a complete technical documentation according to Annex II and III of the IVDR including a detailed documentation on the usability to the involvement of a Notified Body for the evaluation of the technical documentation and the QM system during the conformity assessment procedure.
Avoiding effort with the right strategy
Johner Institute's IVD experts help develop a regulatory strategy that allows laboratories and other organizations to market their devices legally while avoiding unnecessary risks and expenses (e.g., for a conformity assessment).
Contact us for a free consultation. After that, you'll know what options are available to you.