REGULATION OF

COMBINATION
PRODUCTS IN THE
EUROPEAN UNION
INTRODUCTION: LEGAL BASIS
In Europe there are two regulatory routes for drug-device combination products:
1. Medical Devices Directive 93/42/EEC (MDD)/Active Implantable Medical
Devices 90/385/EEC (AIMDD)
2. Medicinal Products Directive 2001/83/EC (MPD)

As a general rule, a combination product is regulated either by the MDD/AIMDD for

the assessment procedure relevant to medical devices or by MPD for the marketing
authorization procedure applicable to medicinal products.
LEGAL BASIS
The appropriate regulatory procedure depends upon the principle mode of action of
the combination product.
1. Drug-delivery products presented as an integral combination with a medicinal
product are regulated as medicinal products. Example: pre-filled syringes.
2. Drug-delivery products presented separately from the medicinal product are
regulated as medical devices. Example: drug delivery pump.
3. A medicine that is incorporated within a medical device where the main mode of
action is due to the device. Example: drug-eluting stent.
COMBINATION PRODUCTS:
PRINCIPAL MODE OF ACTION
The principal intended action of a combination product is based on
1. Mechanism of action of the device
2. Medicinal substance aspects

MEDDEV
MEDDEV stands for MEDical DEVices Documents.
The MEDDEV Guidance Documents are developed by various working groups on behalf
of the European Commission to assist stakeholders in implementing directives related to
medical devices.
MEDDEV 2.1/3
The EC guidance document MEDDEV 2.1/3 provides detailed information on the
classification criteria between medical devices and medicinal products.

In cases where it is not clear which regulatory regime applies, numerous examples
and explanatory notes are provided to aid in the decision making process.
COMBINATION PRODUCTS
REGULATED AS MEDICINAL
PRODUCTS
This refers to devices and the medicinal product forming a single integral product,
which is intended exclusively for use in the given combination and which is not
reusable.

Examples:
1. Pre-filled syringes
2. Aerosols containing a medicinal product
3. Patches for transdermal drug delivery
COMBINATION PRODUCTS
REGULATED AS MEDICAL DEVICES
This refers to devices that are intended to administer a medicinal product, but are not
combined with a specific medicinal product.
They may be re-useable and may be used with different medicinal products.

Examples:
1. Drug delivery pump
2. Nebulizer
3. Syringe, jet injector
 COMBINATION PRODUCTS REGULATED
AS DEVICES INCORPORATING –
ANCILLARY MEDICINAL SUBSTANCE
The principal mode of action is attribute to the device element and medicinal substance has a lesser, secondary
effect.
The substance incorporated in the device must meet the following conditions:
1. The substance, if used separately, may be considered a medicinal product.
2. The substance is liable to act upon the human body.
3. The action of this substance is ancillary to that of the device.

Examples:
4. Drug eluting stents
5. Catheters coated with heparin
6. Bone cements containing antibiotic
THE CONSULTATION PROCESS
The European Medicines Agency (EMA) must be consulted for all medical devices
incorporating ancillary human blood derivatives, e.g. human albumin etc.
In accordance with MEDDEV 2.1/3, the notified body should ensure that data
supplied by the manufacturer in relation to the device and its intended use includes a
segment regarding the medicinal substance being incorporated with ancillary
purpose.

Detailed submission guidance is available on the websites of EMA, MHRA and

other competent authorities.
 INFORMATION TO BE
PROVIDED ON THE
ANCILLARY MEDICINAL
SUBSTANCE
GENERAL :
- Information addressing the safety, quality and usefulness of the medicinal substance. This has to
prepared by the manufacturer, submitted to the notified body, and then forwarded to the competent
authority.
- A report should be prepared by the notified body and included with the application form.

QUALITY :
- Evidence should be provided
Relevant information should be provided on both that the drug substance is
- the drug substance itself manufactured to a high quality.
- the drug substance incorporated into the medical device.
INFORMATION TO BE
PROVIDED ON THE
ANCILLARY MEDICINAL
SUBSTANCE
SAFETY AND USEFULNESS :
- There should be a clear safety consideration for the ancillary medicinal substance at
the proposed dose.
- for well known medicinal substances – original data on all aspects of safety may
not be required.
- for new active substances, comprehensive data is required to address the
requirements. The evaluation of these active substances would be performed
according to the principles of evaluation of new active substances.
INFORMATION TO BE
PROVIDED ON THE
ANCILLARY MEDICINAL
SUBSTANCE
GUIDANCE:
The EMA and national competent authorities publish guidance on procedures and
documentation requirements for the consultation.
There are also a number of useful European guidelines relating to the quality, safety
and efficacy of medicinal substances as used in medicinal products. This can be
found on EMA website.
The guidelines need not be strictly adhered however, as for medicinal product
evaluation, justification for the use of different approaches should be provided.
THANK YOU!