quality Archives - European Industrial Pharmacists Group (EIPG)

Consultation on the reform of the European pharmaceutical legislation


A new step in the review of the overall framework governing the pharmaceutical sector has been announced by the European Commission on September 28th: the launch of a first phase of public consultation will enable to collect opinions from Read more

Consultation open on the ICH Q13 guideline on continuous manufacturing


by Giuliana Miglierini The new ICH Q13 guideline on the continuous manufacturing of drug substances and drug products aims to harmonise at the international level this rapidly growing sector of pharmaceutical production, providing manufacturers with a flexible approach for the Read more

The new guideline on combination products between medicines and medical devices


by Giuliana Miglierini The new “Guideline on quality documentation for medicinal products when used with a medical device” (EMA/CHMP/QWP/BWP/259165/2019), adopted by the European Medicines Agency in July 2021, will come into force starting 1st January 2022. The first draft of the Read more

Consultation on the reform of the European pharmaceutical legislation

, , , , , , , , , , , , , , , , , , , , , , , ,

A new step in the review of the overall framework governing the pharmaceutical sector has been announced by the European Commission on September 28th: the launch of a first phase of public consultation will enable to collect opinions from all the stakeholders of the pharmaceutical sector as a pre-requisite for the revision of the existing general pharmaceutical legislation on medicines for human use.

The initiative builds on the previous public consultation which represented the basis for the drafting of the Pharmaceutical Strategy for Europe released by the Commission in November 2020. The final target is the creation of a future-proof and crisis-resilient regulatory framework for the pharmaceutical sector. The pharmaceutical industry represents one of the main contributors to the European economy, with 800.000 direct jobs and €109.4 billion trade surplus in 2019, and €37 billion contribution to research investment.

Today we take an important step for the reform of EU’s pharmaceutical legislation by the end of next year. A regulatory framework for pharmaceuticals, which is modernised and fit for purpose, is a key element of a strong European Health Union and crucial to addressing the many challenges this sector is facing. I call on all interested citizens and stakeholders to help us shape EU rules for the future, responding to patients’ needs and keeping our industry innovative and globally.”, said the Commissioner for Health and Food Safety, Stella Kyriakides.

Details of the consultation

The consultation is open until 21 December 2021 and is published in the form of a online questionnaire to be filled in by stakeholders and members of the general public, including patients and patient’s organisations, pharmacists and doctors, associations active in public health, healthcare professionals and providers, academia, researchers, regulators, EU’s institutions and the pharmaceutical industry. A combined evaluation roadmap/Inception Impact Assessment published in April 2021 is also available at the consultation’s webpage, together with a document on the consultation strategy (link).

The main issues touched by the consultation include all the 4 pillars of the Pharmaceutical Strategy, for each of which both legislative and non-legislative actions are envisaged.

A main area of interest looks to address unmet medical needs and ensure access to affordable medicines for patients, namely in the areas of antimicrobial resistance and rare diseases. The commitment to respond to environmental challenges is another key point of attention. New incentives for innovation and future-proofing the regulatory framework for novel products shall support the availability of next-generation therapeutics for European citizens and the competitiveness of the European markets. Quality and manufacturing of medicines, and the repurposing of older products are other topics looking for innovative approaches to be defined within the revision of the pharmaceutical legislation.

The Covid pandemia showed the importance to developed measures to enhance crisis preparedness and response mechanisms in all European countries, and to ensure diversified and secure supply chains are in place to reduce dependency of supply from extra-EU countries. A stronger EU voice on the theme of medicines shortages shall be also pursued by promoting a high level of quality, efficacy and safety standards.

The consultation aims to better understanding of all implications of the possible policy options, and to provide evidence to the Commission on the functioning and delivery of the current legislation with respect to its initial objectives. The impact of new potential options on the different stakeholders shall be also assessed. The exercise aims to identify areas of broad agreement among stakeholders as well as differences of views on other topics, and the causes of contention.

A brief overview of the legislative process

The revision of the pharmaceutical legislation is just one of the many legislative actions undertaken by the von der Leyen Commission in order to completely innovate the reference framework for medicines’ development, production, authorisation, commercialisation and postmarketing monitoring. The last revision of the pharmaceutical legislation occurred almost 20 years ago.

The Pharmaceutical Strategy defines the general targets, to be then synergistically implemented by mean of actions specific to the different fields. The revision of the general pharmaceutical legislation is one of the main flagship initiatives towards this target, and it is also being supported by an ongoing study run by an external contractor and expected to close in Q1 2022.

Among other actions which shall contribute to the goals of the Strategy are the proposal of the new regulation on Health Technology Assessment, the EU Health Data Space, the revision of the current legislation on rare diseases and paediatric medicines and actions to address shortage of medicines in the EU’s market.


The new guideline on combination products between medicines and medical devices

, , , , , , , , , , , , , , , , , , , , , , , , , , ,

by Giuliana Miglierini

The new “Guideline on quality documentation for medicinal products when used with a medical device” (EMA/CHMP/QWP/BWP/259165/2019), adopted by the European Medicines Agency in July 2021, will come into force starting 1st January 2022.

The first draft of the guideline was presented in May 2019; according to EMA, the document aims to solve the often observed issues of inconsistent and/or incomplete data submitted to competent authorities. It also considers the amendment to Annex I of Directive 2001/83/EC introduced by Article 117 of the new Medical Devices Regulation ((EU)2017/745, MDR).

A Questions and Answers document to support in the implementation of the MDR and In Vitro Diagnostic Medical Devices Regulations ((EU) 2017/746) was also published by EMA in June 2021.

Three different combinations with medical devices

The guideline applies to the product-specific quality aspects of a medical device/device part, that may have an impact on the quality, safety and/or efficacy of the associated medicinal product, as defined by a specific risk assessment. The submitted documentation is part of the Quality part of a marketing authorisation dossier. Makers has also to prove the conformity of the device/device part to MDR’s requirements by mean of a EU Declaration of Conformity or CE certification released by the Notified Body that assessed the device.

The products covered by the new guideline include integral products made up of an integral and not reusable combination of the medical device/device part and the medicinal product (where the action of the medicinal product is principal), medical devices placed on the market co-packaged with a medicinal product, and referenced medicinal products to be used in conjunction with a specific medical device described in the product information (SmPC and/or package leaflet) and obtained separately by the user. The classification in one of the above mentioned categories of medicine/device combination impacts the information that should be submitted to competent authorities.

The guideline applies also to medicinal products intended to be used with a Class I medical devices, with electromechanical devices (including active implantable devices), electronic add-ons and digital elements of devices (if expected to impact the benefit-risk assessment of the medicinal product from a quality perspective). Combined advanced therapy products defined under Article 2(1)(d) of the ATMP Regulation fall out of the scope of Article 117, as well as veterinary products, in-vitro diagnostic devices (including companion diagnostics), system and procedure packs regulated under Article 22 of the MDR.

Examples of integral products include medicinal products with an embedded sensor performing an ancillary action, single-use prefilled syringes, pens or injectors, drug-releasing intrauterine devices or pre-assembled, non-reusable applicators for vaginal tablets, dry powder inhalers and preassembled, ready-to-use pressurised metered dose inhalers, implants containing medicinal products whose primary purpose is to release the medicinal product. For this type of products, the safety and performance of the device/device part has to reflect the relevant General Safety and Performance Requirements (GSPRs) described in Annex I of the MDR.

Examples of co-packaged or specifically referenced medical devices include spoons and syringes used for oral administration, injectors needles, refillable or reusable pens/injectors, dry powder inhalers and metered dose inhalers, nebulisers and vaporisers and single use or reusable pumps for medicinal product delivery. These two categories of products should comply with the requirements of the applicable medical device legal framework.

The approach to the overall product quality

The discussion of the quality of the device/device part on the Quality Target Product Profile (QTPP), Critical Quality Attributes (CQA) and overall control strategy of the medicinal product has to be included in the regulatory dossier.

More specifically, for integral products the EU Declaration of Conformity or the relevant EU certificate issued by a Notified Body for the device/device part has to be produced. Should this not be possible, the applicant has to provide an opinion (NBO) on the conformity of the device/device part with the relevant GSPRs, issued by a Notified Body enlisted in the NANDO website.

The information provided with the authorisation dossier shall be assessed by the competent authority to determine the overall benefit/risk ratio of the medicinal product. All information relevant to the device/device part has to be submitted using the usual eCTD format. Data on preexisting combination of the device/device part with an already approved medicinal product can be provided on a case-by-case basis and needs to be adequately justified. Early scientific and/or regulatory advice can be activated in the case of particularly innovative and emerging technologies.

The guideline provides a detailed description of the information to be submitted to competent authorities in relation to each of the different types of device/medicinal products combinations.

Reference is made to Module 1 (Product Information), Module 3.2.P (Drug Product), Module 3.2.A.2 (Adventitious Agents Safety Evaluation) and Module 3.2.R (Regional Information, Medical Device). This last section includes the Notified Body Opinion for integral medicinal products in the form of a summary technical report. Usability studies should be also available in the case supporting information is not included in the dossier, and the device/device part has not been used in the intended user population before, or where other aspects of the intended use, including changes to the clinical setting or use environment, are new or different from the intended use as confirmed by the EU certificate issued by a Notified Body or NBO.

The guideline also highlights the need the device/device part should be as advanced as possible in the development process (e.g. meets relevant GSPRs) by the time pivotal clinical trials commence. Any change to the device occurred during the trials has to be described, evaluated and justified with respect to the potential impact on the quality, safety and/or efficacy of the medicinal product. The guideline also provides information on how to manage the life cycle of the integral, co-packaged or referenced medicinal products.