manufacturing Archives - European Industrial Pharmacists Group (EIPG)

Patient involvement in the development, regulation and safe use of medicines


by Giuliana Miglierini The Council for International Organizations of Medical Sciences (CIOMS) has published the CIOMS report on “Patient involvement in the development, regulation and safe use of medicines”. The report marks an important step forward towards a harmonised approach to Read more

Webinar: Implementation of Contamination Control Strategy Using the ECA template


The next EIPG webinar will be held in conjunction with PIER and University College Cork on Friday 21st of October 2022 (16.00 CEST), on the implementation of Contamination Control Strategy (CCS) using the ECA* template. This is the second Read more

Real-world evidence for regulatory decision-making


by Giuliana Miglierini Digitalisation is rapidly advancing also in the regulatory field, as a tool to improve the efficiency and accuracy of processes used for the generation and use of data to inform the regulatory decision-making. To this instance, real-world Read more


First steps of the HERA Authority and comments from industrial and medical associations

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by Giuliana Miglierini

The new European Health Emergency preparedness and Response Authority (HERA) has started its operative phase. Initially launched in February 2021, HERA has been modelled by the European Commission on the example of the US’s DARPA agency, and it will be in charge of anticipating threats and potential health crises.

The first three calls for tender to support HERA’s setup have been published on the Commission’s website and will remain open until 29 October 2021. They are targeted towards addressing different aspects of the management of Covid-19 therapeutics and antimicrobial resistance.

A total sum of €7 million from the EU4Health programme will fund these activities. An info session on the three calls was delivered on 14 October 2021 by European Health and Digital Executive Agency (HaDEA) in collaboration with DG Santé (see more at this link). A summary of HERA’s activities in the field of crisis preparedness and emergency response is also available here. A budget of €6 billion from the current Multiannual Financial Framework 2022-2027 is available to fund HERA’s setup and activities, plus additional support from other EU programmes, for a total of almost €30 billion. HERA will be part of the internal Commission structure, and it is expected to become fully operational in early 2022.

HERA’s role is to improve the EU’s development, manufacturing, procurement and distribution of key medical countermeasures said the Commissioner for Health, Stella Kyriakides, following the recent Informal Meeting of Health Ministers in Ljubljana, Slovenia -. HERA will also be crucial in ensuring accessibility and availability of medicines. As I said to Ministers today, HERA is a joint undertaking, with Member States, EU Agencies, the European Parliament and other concerned stakeholders, including industry and civil society. HERA’s strength and success will come from our joint preparedness and joint response, and our capacity to bringing joint solutions. HERA is now operational and should be fully up and running early next year.

HERA’s first activities

The call for tender on antimicrobial resistancerefers to a service contract to run a study comprehensive of a technological review of the latest AMR medical-countermeasures (e.g.; medicines, medical devices, vaccines) and a gap analysis and assessment of needs amongst the EU Member States and key stakeholders. The study shall also include options for possible actions, funding and provision of support mechanisms, and exploration of available tools suitable to ensure the availability of safe and effective products in the European market. These products are expected to be immediately available to the EU and member states in the event of a public health emergency. The estimated total value of the tender is €1 million.

Stockpiling of medical countermeasures in the area of AMR is the subject of the second feasibility study (estimated total value €1 million). The study shall analyse physical stockpiling solutions compared to other options, providing identification and assessment of all available opportunities. The needs and availability of AMR countermeasures shall be also assessing, both at member states and EU level, as well as the mapping of relevant stockpiling systems currently operated at EU and/or global level (e.g. WHO). Possible funding mechanisms (including procurement options), identification and assessment of operational deployment mechanisms and considerations on liability and regulatory aspects and/or constraints are also to be included in the study.

The third feasibility study has the higher estimated total value (€5 million) and will focus on the design and prototype development for a mapping platform on Covid-19 therapeutics in the EU. The platform is expected to map the production capacity and supply of products intended to treat Covid-19, both already on the market and in R&D phases. Possible examples include ICU medicines, heparin, dexamethasone and antibiotics, in vitro diagnostics devices and/or companion diagnostics.

Comments from stakeholders

Many stakeholders released their comments to welcome the creation of the new Authority.

The creation of HERA is a first step to putting Europe on the front foot in addressing global health threats.”, said EFPIA Director General, Nathalie Moll. “The speed at which Europe became the epicentre of the Covid-19 crisis meant, as a region, we were simply reacting to issues as they arose, working together to find solutions as quickly as possible”.

The lessons learnt during the pandemic revealed a number of weaknesses in Europe’s ability to respond to a public health crisis. HERA’s ability to balance coordination and unity with agility and responsiveness as threats emerge shall be central to its success, according to EFPIA. The Federation, together with Vaccines Europe, supports an end-to-end approach to govern HERA’s activities, and a collaborative, partnership-based model to maximise the strength of each stakeholder in a highly coordinated approach.

The association representing the generic and biosimilar industry, Medicines for Europe, wrote in a note that HERA should “be an efficient agency with strong links to healthcare industries”. A joint industrial cooperation forum to coordinate interactions of manufacturing associations and EU authorities, a regulatory framework able to prioritise the supply of essential medicines and the elimination of the proposal for redundant manufacturing capacity are just some suggestions made by the Association, which is more favourable towards manufacturing investment in a wide range of medicine production types, as outlined in the Structured Dialogue.

Reserve policies should be also revised in order to avoid waste, costly destruction, and distorting supplies of medicines to certain (smaller) EU countries. The functioning of joint procurement system should be also addressed and improved by the Commission, to avoid distortions in the internal market and provide accurate demand estimates.

The Federation of the European Academies of Medicine (FEAM) published in May 2021 a report jointly prepared with the Wellcome Trust, highlighting the opportunity in the short term not to overstep HERA’s role in relation to others European authorities (e.g. the European Centre for Disease Prevention and Control) as a pre-requirement to ensure its success.

The new-born Authority should also try to harmonise the European research and development landscape for pandemic preparedness and response, in order to remain “relevant and active between emergencies”.


Consultation on the reform of the European pharmaceutical legislation

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by Giuliana Miglierini

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 an 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.


Medical Cannabis in Europe

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by Giuliana Miglierini

Business based on medicinal products containing cannabis-derived substances has greatly developed in Europe in recent years, due to the many beneficial pharmacological properties offered by the plant Cannabis sativa. The global medical cannabis market is rapidly expanding (36% compound annual growth rate/CAGR 2017-2024), with Germany as the leading country (49,5% CAGR).

The medical use of cannabis in Europe refers to the EU Parliament’s resolution 2018/2775 of 13 February 2019, aimed to clearly and unambiguously distinguish between “medical cannabis” and “cannabis-based medicines”. The second ones have undergone clinical trials as all medicinal products and have been assessed by competent regulatory authorities to achieve approval. Only cannabis-based medicinal products should be considered for a safe and controlled medical use, suggests the Parliament resolution.

According to an article by Lipnik-Štangelj and Razinger (Arh Hig Rada Toksikol 2020;71:12-18), just one medicine characterised by a 10% concentration of cannabidiol (CBD, one of the main active components of cannabis) was centrally approved in 2019 by EMA for the therapy of intractable childhood epilepsy. Other medicinal products containing other types of cannabinoids have received approval through mutual recognition procedure or at the national level.

EU’s member states have not yet adopted a uniform approach on how to regulate the cultivation, manufacturing and use of medical cannabis; there is also a lack of uniform indications as for the modalities and contents of the labelling of cannabis-derived medicinal products. An extensive discussion of different legislative and regulatory frameworks relevant to the medical use of cannabis and cannabinoids have been addressed by a report published in 2018 by the European Monitoring Centre for Drugs and Drug Addiction.

The German approach

One of the first European countries to invest in medical cannabis has been Germany, where cultivation is allowed exclusively for medical purposes. A targeted Cannabis Agency (Cannabisagentur) was created in 2017 as a part of the local regulatory agency German Federal Institute for Drugs and Medical Devices (BfArM), in parallel with the coming into force of the Cannabis as Medicine Act.

The Agency has selected by a tender procedure three companies allowed to cultivate cannabis in Germany (Aphria RX GmbH, Aurora Produktions GmbH and Demecan GmbH), for a total production of approx. 2600 kg per year. BfArM started in July 2021 the state sale of medical cannabis from German cultivation, maintaining also open the possibility to import the plant for medical use.

The characteristics of the standardised cannabis extracts are described in a dedicated monograph of the German Pharmacopeia; the cultivation of the plant and the manufacturing of medical cannabis, which is a prescription drug, is also subject to the German narcotics law regulations (BtMG), to Good Agricultural and Collection Practices (GACP) and to Good Manufacturing Practices (GMP). German pharmacies can buy medical cannabis directly from the dedicated portal of the Cannabis Agency; a GMP/GDP-certified company is in charg of distribution. The price established by BfArM for pharmacies is 4,30 €/g.

The case in Greece

Greece also approved in 2018 a specific legislation on cannabis for medical use (Law 4523/2018, amending Law 4139/2013), providing the full reference framework for the cultivation, manufacturing, regulatory approval and distribution of cannabis-based medicinal products.

According to data by the Greek Ministries of Development and Investments and Rural Development and Food published in April 2020 by the Medical Cannabis Network, estimates of investments in the sector are reaching €1,68 billion and more than 8.000 employees.

The government aims to improve the attractiveness of Greece for cannabis cultivation and instalment of manufacturing plants – thanks to the favourable climatological and working conditions – as a way to support the expansion of the national economy. To this regard, possible competitors are Portugal, Malta or Cyprus, all countries characterised by similar favourable conditions.

Greece currently allows for the cultivation of cannabis with a THC content not exceeding 0,2%. A new law has passed in the Greek Parliament to regulate the production, export and distribution of final medical cannabis products with a THC content of more than 0,2%.

The new law is expected to create a special framework for cannabis businesses based in Greece and devoted to export only; their activities may be also subject to laws, regulations and GMP/GDP guidelines of the importing country.

Companies interested in establishing this sort of productions currently need to fulfil a wide set of conditions in order to receive permits for cultivation and authorisation by the Greek National Organisation for Medicines (EOF) to produce and market their products, which are classified as medicines. Criteria for authorisation are listed in the joint Ministerial Decision released in connection to the 2018 Law. The issuing of the permit by Greek authorities usually needs about three months time.

The common licence level allows for the initial establishment of a new manufacturing facility; the majority of companies which applied so far have received this type of licence (57/100). The second level of the licence refers to the authorisation to operation.

According to the experts interviewed by Medical Cannabis Network, current issues still to be solved include “establishing a clear definition of the type of greenhouses needed for a particular crop and the specific type of finished medicinal products that will eventually be allowed to circulate commercially”.

Malta, the QP for cannabis medicine production needs to be a pharmacist

Malta has issued in 2018 the Production of Cannabis for Medicinal and Research Purposes Act, the law governing the sector of medical cannabis for prescription.

The document provides detailed information on Quality & Stability of cannabis-based medical products (Appendix I), Security & Transportation (Appendix II) and Cultivation, Harvesting & Packaging (Appendix III).

Malta’s Medicines Authority is responsible for the evaluation of the technical and scientific documentation submitted by the applying companies, and for the issuing of the authorisations for import and wholesale distribution of cannabis-based products for medicinal use. Only finished products are allowed, they must also comply to the relevant legislation of the destination country.

The Maltese framework for the production of medical cannabis is characterised by the fact the Qualified Person (QP) responsible for the manufacturing plant has to be engaged by the license holder and must be a pharmacist registered with the Maltese Pharmacy Council and resident in Malta. This provision differs from the requirements outlined in Directive 2001/83/EC governing the manufacture and import of medicinal products for human use, transposed into the local Medicines Act and subsidiary legislation, where many other types of degrees (Pharmacy, Medicine, Veterinary, Chemistry, Pharmaceutical Chemistry and Technology, or Biology) are also considered.

Medical cannabis products licensed under the Medicines Act (Chapter 458 of the Laws of Malta) or manufactured under GMP can be sourced by licensed importers or wholesale distributors, provided the possession of the necessary approvals and permits. A Letter of Intent (LOI) from a Malta Enterprise is also needed to run operations related to medicinal cannabis production, analysis and research. The local regulatory agency can run inspections of the manufacturing facilities to verify their compliance to GxP; EU-GMP certification is needed prior to the starting of the manufacturing activities.

Research activities on medical cannabis is also supported through the Advanced Scientific Initiatives Directorate, in particular in the case of established organisations for scientific collaboration.

A pool of beneficial active ingredients

The plant Cannabis sativa contains a very rich pool of more than 480 compounds, among which are more than 100 cannabinoids. D9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the main cannabinoid substances present in cannabis, the first one representing the main psychoactive and addictive constituent of the plant. On the other hand, CBD has no intoxicating or addictive properties. Many other cannabinoids possess an interesting pharmacological and therapeutic profile, and have been studied for possible use as neuroprotective agents (e.g. in case of anxiety disorders, depression, post-traumatic stress disorder), and for their effects as anti-emetics or on chronic pain (e.g. in cancer disease), inflammation, bacterial infections, etc.