Sampling Kits from a Regulatory Perspective

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.

1. Sampling kit: definition & examples

a) Definition

In the absence of an official definition, we determine for this article:

b) Example

For example, sampling kits for a tissue sample may include the following products:

• Biopsy punch
• Disinfection pad
• Specimen container with fixation solution
• Transport packaging
• Label with patient ID and recipient address
• Instructions for use

c) Differentiation between sampling kits, near-patient tests, and self-tests

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.

d) Context in which sampling kits are used

Placing on the market by health institutions (laboratories)

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.

Direct-to-Consumer Testing (DTC tests)

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.

2. Regulatory classification of sampling kits

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."

a) Overview of possible regulatory classifications

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?

• Procedure pack
• Medical device or in vitro diagnostic medical device
• Accessories
• DTC test
• Isolated device

The following sections describe these constellations.

b) Sampling kit as procedure pack

Definition

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.

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:

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).

Requirements

The requirements for a sampling kit to count as a procedure pack and not as a medical device or IVD are:

• At least one of the products in the set is a medical device or an accessory to it.
• All devices in the set are used within their intended purpose.
• All devices are compliant with the regulatory requirements applicable to them and bear, for example, a CE marking.

Regulatory requirements for procedure packs

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.

c) Sampling kit as IVD

The IVDR determines that specimen receptacles are considered IVDs:

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.

d) Sampling kit as accessory

There is also a qualification of sampling kits as accessories.

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

• specimen receptacles are IVDs,
• the set rarely has an intended use specifically to support the intended use of specific IVDs,
• this qualification can be avoided with the procedure pack approach under Article 22 of the MDR.

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.

e) Sampling kits for DTC tests

In a direct-to-consumer test, the sampling kits are sent directly to the patient for them (as laypersons) to collect the samples.

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).

f) Waiver of a sampling kit

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).

3. Regulatory requirements

Depending on the regulatory classification of a sampling kit, assemblers must comply with various regulatory requirements. This chapter summarizes some of them.

a) MDR and IVDR requirements

Tab. 1: Regulatory requirements for sampling kits

b) Guidelines and standards

• MDCG 2021-26 Q&A on repackaging & relabelling activities under Article 16 of Regulation (EU) 2017/745 and Regulation (EU) 2017/746
• MDCG 2021-27 Questions and Answers on Articles 13 & 14 of Regulation (EU) 2017/745 and Regulation (EU) 2017/746
• MDCG 2018-6 Clarifications of UDI related responsibilities in relation to article 16
• MDCG 2018-3 Rev.1 Guidance on UDI for systems and procedure packs
• MDCG 2018-4 Definitions/descriptions and formats of the UDI core elements for systems or procedure packs
• ISO/TS 20658:2023: Requirements for the collection and transport of samples for medical laboratory examinations
• ASTM D4169-22: Standard Practice for Performance Testing of Shipping Containers and Systems

c) Further specifications with reference to packaging and transport

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:

• Agreement concerning the International Carriage of Dangerous Goods by Road: UNECE ADR, Wikipedia article
• Specifications of the German Ministry of Transport
• Guidelines for packing instruction P650 (German)
• Proper shipping of patient samples by the German Employer's Liability Insurance Association for Health Services and Welfare Care (BGW, German)

d) Further information

The following articles may be helpful for further reading and for specific questions:

• article on distributor obligations
• article on in-house IVD (IH-IVD, also LDT)
• article on performance evaluation of IVDs

4. Summary and conclusion

a) The regulatory case-by-case assessment is necessary

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.

b) Regulatory requirements vary widely

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).

c) The classification can be influenced

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.

d) Consider special case DTC

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.