Combination Products – Medicinal Products That Include a Medical Device

Changes in the Law

The 26^th of May 2021 will mark the first day that the Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (later ‘Regulation 2017/745’) will fully apply after the 4 years transitional period. This regulation concerns medical devices – that are also regulated in Poland in the Medical Devices Act of 20 May 2010 (later MDA).

Medicinal Products, on the other hand, are regulated in Poland in the Pharmaceutical Law Act of 6 September 2001 (later PLA). Medicinal products are also regulated by the Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (later ‘Directive 2001/83/EC’) and the Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Union procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (later ‘Regulation 726/2004’).

Article 117 of the Regulation (EU) 2017/745 introduces significant changes for some combination products.

What are Medical Devices?

In the light of article 2 section 38 of MDA, Medical Device is:

a tool, instrument, appliance, software, material or other article, whether used alone or in combination, including combination with a software intended by its manufacturer for use specifically for diagnostic or therapeutic purposes and necessary for its proper application, intended by the manufacturer for human use in:

a) diagnosing, preventing, monitoring, treating or alleviating the course of the disease,

b) diagnosing, monitoring, treating, alleviating or compensating for the effects of an injury or handicap,

c) examining, replacing or modifying the anatomical structure or the physiological process,

d) birth control

– which does not achieve the essential intended effect in the body or on the human body by pharmacological, immunological or metabolic means, but the action of which can be aided by such means.

It’s introduction to the market requires a much shorter and less complicated procedure than when a medicinal product is concerned.

What are Medicinal products?

Article 2 section 32 PLA defines a medicinal product as:

a substance or mixture of substances presented as having properties for the prevention or treatment of human or animal diseases or administered to make a diagnosis or to restore, correct or modify the physiological functions of the body through a pharmacological, immunological or metabolic action.

Previous Regulations

Regulation 2017/745 on medical devices to a small extent concerns also Directive 2001/83/WE and medicinal products. In case of a medical device which, when placed on the market or put into service, incorporates, as an integral part, a substance which, if used separately, would be considered to be a medicinal product as defined in point 2 of Article 1 of Directive 2001/83/EC, including a medicinal product derived from human blood or human plasma as defined in point 10 of Article 1 of that Directive  or which is intended to administer a medicinal product as defined in point 2 of Article 1 of Directive 2001/83/EC, those devices are regulated by the regulation 2017/745.

However, in certain cases, the combination products are regulated by the Directive 2001/83/WE, which influences how they are put on the market. Those cases are underlined in article 1, section 8 and 9 od the Regulation 2017/745:

1. a) if the action of that substance [as understood above] is principal and not ancillary to that of the device, the integral product shall be governed by Directive 2001/83/EC or Regulation (EC) No 726/2004 of the European Parliament and of the Council, as applicable;
2. b) if the device intended to administer a medicinal product and the medicinal product are placed on the market in such a way that they form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product shall be governed by Directive 2001/83/EC or Regulation (EC) No 726/2004, as applicable.

Those regulations concern the medicines with an integral device and not co-packaged products and devices. They are the ones affected by the newest changes. As examples of the medicines with an integral device the European Medicines Agency lists, for example, pre-filled syringes and pens, patches for transdermal drug delivery and pre-filled inhalers.

New Regulations

Article 117 of the Regulation 2017/745 made changes to the Annex I to Directive 2001/83/EC. The changes affect chemical, pharmaceutical and biological information for medicinal products containing chemical and/or biological active substances. In particular, the changes apply to the content of requirements and basic principles.

Before the implementation, point 12 of Section 3.2 read:

Where applicable and if needed, a CE marking which is required by Community legislation on medical devices shall be provided.

It also listed elements special attention should be paid to.

Whereas, the new point 12 introduces a new requirement for the medicines with integral devices:

Where, in accordance with the second subparagraph of Article 1(8) or the second subparagraph of Article 1(9) of Regulation (EU) 2017/745 of the European Parliament and of the Council, a product is governed by this Directive, the marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements set out in Annex I to that Regulation contained in the manufacturer’s EU declaration of conformity or the relevant certificate issued by a notified body allowing the manufacturer to affix a CE marking to the medical device.

If the dossier does not include the results of the conformity assessment referred to in the first subparagraph and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation (EU) 2017/745, the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements set out in Annex I to that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question.

As mentioned before, the new regulation will fully apply starting 26 May 2021. Considering the fact that the Regulations of European Union become binding throughout the European Union on the day they enter into force, they do not require implementation (unlike the directives) and the rules apply directly.

Sources:

1. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance) (OJ L 117 5.5.2017, p. 1);
2. Act of 20 May 2010 on medical devices (i.e. Journal of Laws of 2020, item 186, as amended);
3. Act of September 6, 2001, Pharmaceutical Law (i.e. Journal of Laws of 2020, item 944, as amended);
4. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (OJ L 311 28.11.2001, p. 67);
5. Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Union procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ L 136 30.4.2004, p. 1);
6. https://www.ema.europa.eu/en/human-regulatory/overview/medical-devices.