manufacturing Archives - European Industrial Pharmacists Group (EIPG)

A new member within EIPG


The European Industrial Pharmacists Group (EIPG) is pleased to announce the Romanian Association (AFFI) as its newest member following the annual General Assembly of EIPG in Rome (20th-21st April 2024). Commenting on the continued growth of EIPG’s membership, EIPG President Read more

The EU Parliament voted its position on the Unitary SPC


by Giuliana Miglierini The intersecting pathways of revision of the pharmaceutical and intellectual property legislations recently marked the adoption of the EU Parliament’s position on the new unitary Supplementary Protection Certificate (SPC) system, parallel to the recast of the current Read more

Reform of pharma legislation: the debate on regulatory data protection


by Giuliana Miglierini As the definition of the final contents of many new pieces of the overall revision of the pharmaceutical legislation is approaching, many voices commented the possible impact the new scheme for regulatory data protection (RDP) may have Read more

The EU Parliament voted its position on the Unitary SPC

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by Giuliana Miglierini

The intersecting pathways of revision of the pharmaceutical and intellectual property legislations recently marked the adoption of the EU Parliament’s position on the new unitary Supplementary Protection Certificate (SPC) system, parallel to the recast of the current SPC Regulation (EC) 469/2009. The unitary SPC system will apply also to plant protection products (under different regulations), and it will allow for the obtainment of up to 5 years IP protection beyond the life of the patent.

The new system will complement the unitary patent system, as part of the overall “EU patent package” announced in 2023, and which also includes the proposed regulation on compulsory licensing (we wrote about this last week) and the one on standard essential patents. According to the EU Parliament, the procedure on unitary SPCs will now stop after the European elections.

A report on the potential impact of the unitary supplementary protection certificates on access to health technologies, prepared by the Policy Department for Citizens’ Rights and Constitutional Affairs for the Parliament’s Committee for Legal Affairs, is also available.

The main amendments to the Commission’s proposal

The text adopted by the Parliament on 28 February 2024 (together with the legislative resolution on the recast of the SPC regulation) refers to the proposed new regulation amending Regulation (EU) 2017/1001 (EU trademark), Regulation (EC) 1901/2006 (medicinal products for paediatric use) and Regulation (EU) 608/2013 (custom enforcement of intellectual property rights).

The report of the rapporteur, Tiemo Wölken, specifies the entities or people that provided him with input in the preparation of the document, among which are also EFPIA and Medicines for Europe.

The amended text highlights the importance of pharmaceutical research in ensuring the EU’s competitiveness, but also the difficulty of establishing a direct link between this and the rules aimed to support research in innovative medicinal products. The point is that “authorised medicines from third countries are equally eligible to receive all Union incentives, just as Union-based innovative companies can equally benefit from incentives in third countries”. This may lead to companies moving their activities in other countries offering greater protection.

The adopted text better specifies cases for which manufacturing is possible in the EU in presence of a still valid unitary SPC, i.e. export to a third country, where protection does not exist or has expired, or storing the product in order to be ready to enter the EU market upon expiry of the corresponding SPC (the so-called EU “day-one” entry).

To obtain granting of the unitary SPC, the product should fall within the scope of one or more claims of the basic patent. To this instance, the Parliament made specific reference to the description and drawings of the patent, and to the skilled-on-the-art “person’s general knowledge in the relevant field and of the prior art at the filing date or priority date of the basic patent”. The same applies also to active ingredients in combination products, each of which needs to be specifically identifiable. The approved text removes any reference to the concept of “therapeutic equivalence”.

The Parliament specified that the information on granted unitary SPCs provided in the register should not be used for patent linkage or other administrative decisions related to generics or biosimilars. The text also clarifies how to consider “economically linked” parties, that are not entitled to obtain multiple SPCs for the same product.

A single procedure and a digital-by-default process

The main objective of the unitary SPC system is to allow the submission of a single application to obtain extension of the IP protection in all European countries which are part of the EU’s unitary patent system. The digital-by-default principle should guide the entire procedure leading to the grant of a unitary SPC, starting from the submission of the application to the European Intellectual Property Office (EUIPO) using a format to be made available by the EUIPO itself. Combined applications for supplementary protection certificates should also be made possible.

The application for a unitary SPC would be based on an already existing centralised marketing authorisation issued by EMA. Information on any direct public financial support received for research related to the development of the product for which the SPC is requested should be also provided.

In charge of the examination would be a new SPC division created within the EUIPO. The examination would be run by an examiner from the Office and two examiners from national competent authorities, with sufficient expertise (at least one examiner with a minimum of five years’ experience in the examination of patents and supplementary protection certificates).

The examination opinion should be issued within six months of the publication of the application. A new amendment has been introduced to allow for an expedited examination (4 months) in case, for example, of imminent expiry of the basic patent. Should multiple oppositions be filed against an examination opinion, they should be jointly dealt with by the EUIPO, with issuing of a single decision. The Parliament has maintained the pre-grant opposition procedure, which attracted many criticisms as it might result in increased uncertainty for patentees.

From a market perspective, access to products covered by unitary SPCs should be favoured in countries where the right-holder does not have the intention to launch them, by mean of voluntary agreements to licence the corresponding rights in those markets. A new Recital underlines the importance of a timely entry of generics and biosimilars in the UE market in order to increase competition, reduce prices and ensure sustainability of national healthcare systems and access to affordable medicines.

Comments from Medicines for Europe

The European association of the generic and biosimilar industry, Medicines for Europe, published a note highlighting the possible impact the new unitary SPC may have, due to the significant geographical extension of the IP protection also in countries where the concerned medicines are not normally launched or launched very late.

It would be very important to prevent a possible misuse of the system, is the request of the industrial association. To this instance, the safeguards identified by the Parliament for the examination of applications before the granting of a unitary SPC are considered adequate, as for transparency and quality of the procedures. Furthermore, according to Medicines for Europe, the pre-grant opposition mechanism included in the Parliament’s position should prove useful to prevent invalid (non-innovative) SPCs from being enforced and ultimately invalidated in Court.

The explicit ban of the patent linkage is also considered very important, and it should be coupled to transparency of SPC expiry dates in the register so to ensure these data would not be misused to implement unlawful and anti-competitive patent linkage strategies.

The position of the Parliament goes in the right direction and rightfully bans patent linkage. The pre-grant opposition will ensure a timely grant of SPCs for innovative drugs (a maximum 14 months or 12 with an expedited procedure) and prevent monopoly extensions for those drugs that do not have a legal right to an SPC because they are not innovative. The ban of patent linkage will serve access to medicines by preventing pricing and reimbursement or tender procedure delays for generic and biosimilar medicines at SPC expiry. Medicines for Europe will engage constructively with the EU institutions to ensure the most efficient, quality, and fair SPC system possible for the future.”, said Adrian van den Hoven, Director General of Medicines for Europe, commenting on the report.

You can find here more comments on the approved and deleted amendments.


How AI is Changing the Pharma Industry and the Industrial Pharmacist’s Role

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Svala Anni, Favard Théo, O´Grady David

The pharmaceutical sector is experiencing a major transformation, propelled by groundbreaking drug discoveries and advanced technology. As development costs in the pharmaceutical industry exceed $100 billion in the U.S. in 2022, there is a pressing need for innovative solutions to accelerate drug development. The urgency stems from a renewed focus on novel approaches, driven by the complexities of advanced therapeutic modalities like mRNA, CGT, and synthorins. This blog delves into the influence of Artificial Intelligence (AI) on overcoming the unique hurdles within the manufacturing domain of the pharmaceutical industry. It specifically emphasizes the crucial partnership between AI and human expertise, shedding light on the vital role of industrial pharmacists in optimizing manufacturing processes.

The demands for precision, quality, and compliance in pharmaceutical manufacturing present challenges, notably in managing rising costs and intricate logistical processes. The adoption of various AI technologies, including generative AI (GenAI), represents a strategic shift, aiming to augment human capabilities while automating routine tasks and facilitating knowledge transfer in the ever-evolving landscape of pharmaceutical production

The fourth industrial revolution is upon us with the development of cyber physical systems and the fifth industrial revolution is on the horizon with the advancement of artificial intelligence (AI) in partnership with humans to enhance workplace processes. The factory of the future is here with digitalization, AI, Big data, robotics and advanced manufacturing becoming the norm rather than the exception in the pharmaceutical industry.

GenAI excels in promoting collaboration while surpassing traditional task automation. It is key in transmitting complex knowledge crucial for maintaining quality, compliance, and safety in pharmaceutical manufacturing. AI empowers experts to document processes using everyday devices, transforming this raw data into straightforward, visual instructional guides.

The pharmaceutical industry confronts distinct manufacturing challenges, including complex processes and rigorous regulatory standards. AI can offer several innovative and compliant solutions. In addition, AI platforms swiftly update training materials, creating dynamic learning environments that keep the workforce informed about the latest developments. These platforms are redefining roles by taking over mundane tasks, thereby freeing human workers to focus on more strategic and creative roles. Furthermore, AI guarantees uniform training across global operations, ensuring consistent processes and fostering global standardization.

Combining humans and AI creates a powerful team that may benefit everyone. AI helps make learning experiences unique for each person, fitting their own way of learning. It also makes it easy for people to get the information they need anytime, thanks to the latest tech advancements. AI is great at helping people from different cultures and who speak different languages work together better. It can give feedback right away, so mistakes don’t spread. Plus, AI holds onto valuable knowledge, reducing the chance of losing important information when people leave or retire. Together, all these benefits show how AI can make a big, notable change also in the pharmaceutical field.

AI – Shaping the Future of Pharmaceutical Industry

AI is transforming the pharmaceutical landscape, particularly in areas vital to industrial pharmacists, such as manufacturing, quality control, and distribution. These professionals play a pivotal role in skillfully integrating AI, serving as the human-in-the-loop to enhance efficiency and ensure safety in pharmaceutical operations.

AI elevates the manufacturing process, forecasts maintenance needs, and sharpens quality control. Industrial pharmacists are pivotal in deploying these AI-driven techniques, ensuring that operations are not only effective but also meet high-quality standards and regulatory requirements.

The Role of Industrial Pharmacists

Industrial pharmacists are essential contributors to this technological revolution, actively collaborating with data engineers and scientists. They play a pivotal role in ensuring regulatory compliance, upholding product quality, and leveraging AI to enhance drug development processes, inventory management, and distribution. Industrial pharmacists:

  • are essential in incorporating AI into manufacturing workflows.
  • ensure AI tools align with regulatory requirements and uphold product quality.
  • utilize AI to accelerate and economize the drug development process.
  • leverage AI for more effective inventory and distribution management.
  • analyze data generated by AI systems for informed decision-making in production and quality control.
  • ensuring the quality of pharmaceutical products, they play a crucial role in safeguarding patient safety.
  • leverage AI to identify eco-friendly manufacturing practices, contributing to sustainable pharmaceutical production.

Risks and Challenges

Using AI in the pharmaceutical environment involves navigating risks such as ensuring data privacy and security, maintaining regulatory compliance, addressing biases and ethical concerns, and dealing with the quality and reliability of data. Additionally, there are challenges related to intellectual property issues, integration with existing systems, scalability and maintenance, and dependence on external vendors. To effectively leverage AI benefits while minimizing these risks, a comprehensive strategy encompassing robust data governance, ethical AI practices, ongoing regulatory engagement, and careful technological and organizational change management is essential.

Conclusion

The pharmaceutical industry stands on the brink of a transformative era, driven by the profound potential of AI to reshape its landscape. The key to unlocking this potential lies in the proactive involvement of industrial pharmacists, who are urged to assume a more strategic and leading role in steering innovation.

Traditionally perceived as followers, industrial pharmacists now face a pivotal moment to transition into drivers of change. This isn’t merely a shift in perception; it is a call to action. The integration of AI offers a unique opportunity for pharmacists to shape the future of pharmaceutical care actively and courageously.

In this evolving landscape, industrial pharmacists are not just guardians of compliance but architects of efficiency, adaptability, and innovation. Collaborating seamlessly with AI technologies, they hold the power to propel the industry forward. Despite certain challenges, this collaboration looks promising – it isn`t just compliant and efficient but also dynamic and inventive.

The call to action is clear – pharmacists, especially those in industrial roles, are not merely spectators in this technological revolution; they are the forerunners, charting a course towards a more responsive and innovative pharmaceutical future.

References:

Artificial trends: intelligence in the pharmaceutical industry: analyzing, innovation, investment and hiring

Insights to the Industrial Pharmacist role for the future: A concept paper from EIPG Advisory Group on Competencies, vol 2, 2023

Pizoń J, Gola A. Human–Machine Relationship—Perspective and Future Roadmap for Industry 5.0 Solutions. Machines. 2023; 11(2):203.

Zheng, S. (2023, Nov. 2). “Empowering the pharma workforce.” Pharma Manufacturing.

Contact for further information:
Anni Svala, Vice-President for European Affairs, European Industrial Pharmacists Group, [email protected]


EIPG Training Course: Annex 1

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Dear colleagues,

I am very pleased to announce the GMP/Annex 1 Professional Training Course which will be held as 8 webinars of about 2 hours each from the 3rd of April to the 29th of May (one module per week except 1st of May).

EIPG took care of defining the training plan, which is divided into 8 modules covering the entire contents of GMP/Annex 1, and the identification of the trainers who are all highly qualified professionals with specific experience in sterile medicinal products manufacture and control.

EIPG agreed with all trainers that for each module, the text of a few chapters/paragraphs of Annex 1 be presented, explained and commented focusing on the critical requirements and describing the implementation solutions with examples.

A Q&A section will be open as a chat during the training module and all trainers will ensure the presence of time slots for replying to the questions.

EIPG has found MakingLife Srl, an Italian innovative communication company, as a qualified partner to entrust all organizational, technical and commercial features for making this EIPG training course possible.

Training Course: Annex 1

Though this training was mainly developed for industrial pharmacists who are members of the associations joining EIPG, it is open to all professionals working in the pharmaceutical area who are interested in manufacturing sterile medicinal products.

As EIPG members, you are entitled to a discount of 25% of the price.

When you apply to buy the full course or single modules, you will have to put in a coupon number.

To get your coupon number you can use the following link to the MakingLife platform where you are requested to specify your name, association and e-mail address, which will be also used for the connection to the webinars:

To register yourself to this training courses, follow the below link.

You are invited to disseminate this announcement within your association promoting participation in this training course to your colleagues and also within your contact network with other professionals and non-EIPG members.

Piero Iamartino

President, European Industrial Pharmacists Group (EIPG)


The risk of a biosimilar void in Europe

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by Giuliana Miglierini

The undergoing revision of the pharmaceutical legislation aims, among others, to redefine data protection to better support competitiveness of generics and biosimilars and to favour the timely access of patients to treatments.

While the innovator pharma industry is claiming the proposed reform would reduce the attractiveness of Europe for R&D activities, a recent report from Iqvia analysed the status of biosimilar competition. According to the document, not all biological medicines experiencing loss of exclusivity (LoE) in the next decade would automatically face competition by the corresponding biosimilars. This would result in the creation of a “biosimilar void” on the market, with many originators losing protection without seeing the parallel development of their biosimilar versions.

Competition is not guaranteed

Biosimilar competition is not necessarily guaranteed, and emerging dynamics pose a risk to conventional notions of medicines lifecycles, states the report since its very beginning. The analysis refers to biological medicines that will lose protection in the period 2023-2032.

Despite the approx. 8-fold expected increase in LoE opportunity by value between 2012 and 2032 (from €4.4 billion to €32.2 bln, as result of loss of exclusivity for 110 biological medicines), data show a declining trend for years 2021-2023 (€4.3 bln). According to Iqvia, more than a half (55%) of biologics with LoE in the period 2023-2027 might experience the lack of a biosimilar in development.

The report highlights five areas of common perception to be addressed to better define the issue. The increasing complexity of many biological medicines coupled to new barriers to entry is one of the factors making the development of biosimilars interesting only for products referred to originators with large market shares. According to Iqvia, 27% of the 26 high-sales products that will reach loss of exclusivity by the end of 2032 do not have yet a biosimilar candidate in development in Europe (vs 45% at the global level), corresponding to a potential loss of approx. €8 bln market opportunity. The number of biosimilar candidates in the pipeline for high-sales biologics is also expected to decrease from 2027 onwards.

Regulatory hurdles, therapeutic classes, and disease indication are expected to play a greater role in guiding decisions on biosimilar development, indicates the report. The attractiveness of the European market should also be considered. Oncology will remain the more interesting area, with 44% of all candidates in early to late development for LoE events occurring between 2023 and 2027. Immunology and ophthalmology are other therapeutic areas that might experience growing competition.

The current barriers to biosimilar development

According to Iqvia, the main constraints limiting the decision on biosimilars development are represented by cost and time. In the oncology area, for example, high costs have to be considered to purchase the reference comparator biologic medicine, and large patients populations are required to demonstrate relevant clinical endpoints. New therapeutic classes, i.e., PD-L1/PD-1 inhibitors, may also pose challenges for the design of pharmacokinetic and equivalence studies. From the manufacturing perspective, the increasing use of antibody-drug conjugates (ADC) would result in new barriers to entry.

According to Iqvia, the least attractive products for biosimilars development are those with less than €500 million annual sales in Europe. The report shows 93% of these products might fail to see biosimilar competition, compared to 27% of high-sales medicines. This negative trend would result in a “biosimilar void” corresponding to approx. €15 bln in lost savings. Iqvia also identified some exceptions that might experience a niche development, on the basis of specific technological and manufacturing know-how, platforms and market access excellence.

Another factor to be considered is reimbursement rate, that the report identifies in 51% for low-sales biologics with no biosimilar pipeline (approx. 30% lower than for products with a biosimilar pipeline). The management of the intellectual property referred to the originator should be also taken into consideration.

Orphan and one-off medicines

Despite the growing number of new biologics reaching marketing authorisation as orphan medicines, according to Iqvia biosimilar development is undergoing by now for only one product (eculizumab). No other orphan biologics are expected to face biosimilar competition in future, as annual sales of the 39 orphan medicines currently on the market are too low (approx. €105 mln).

A major factor limiting the development of biosimilars for orphan medicines is linked to the fact many of these therapies fall in the antibody-drug conjugates (ADC) and cell- or gene-therapies (ATMPs) categories (wave 3 biologics). This implies many challenges from the development and manufacturing point of view, higher upfront investments and a more complex setup for analytical and clinical testing.

According to Iqvia, there are currently 16 non-orphan biosimilar candidates under development, corresponding to wave 3 biologics. A limiting factor for this pipeline is identified in the still present fragmentation of the European regulatory system, e.g., reimbursement policies, incentives, and clinical standards. ATMPs, also referred to as one-off therapies, represent a particular case, being relatively young on the market. This leads to no expectation of LoE events in the next five years. The trend would then change, with some 10 products losing protection by 2040, but it should be considered together with the parallel declining of the number of eligible patients, as many of them might have been already treated with the one-off originator medicine.

Shifting standards of care

Another factor analysed by Iqvia is the impact on biosimilars development of the possible changes in the current standards of care, for example resulting from the availability of new and more user-friendly formulations of the originator (i.e., subcutaneous vs intravenous injections). The availability of second- and third generation versions of the original biologic should be considered as another factor limiting the possible market share of a biosimilar of the first-generation product. The picture is indeed furthermore complicated, as another frequent possibility, especially in the oncology area, sees the development of combination therapies based on the use of two or more biologics. As already said, some of them might be very costly (i.e. monoclonal antibodies and PD-1 inhibitors), and require a larger study population to demonstrate equivalence of the add-off effect.

The proposed solutions to fill the biosimilar void

The Iqvia report proposes several possible solutions to overcome the expected biosimilar void, starting from horizon scanning activities aimed at early identification of upcoming LoE events in order to prevent contractions in biosimilar development. Horizon scanning may also support market entry and granting of incentives based on demand. The development of biosimilars of orphan medicines might benefit of a default waiver of comparative efficacy studies, a suggested measure that according to Iqvia would not compromise the demonstration of biosimilarity. Improvements at the regulatory level might also help to streamline development, together with global convergence of regulatory guidance. Iqvia also suggests the adoption of clear regulatory pathways to incentivise the development of the next-generation, one-off biosimilar gene- and cellular treatments. Access might be improved by optimisation of market conditions, with incentives for clinicians combined with the introduction of prescription targets. New tender models would also be needed to favour multi-winner procurement practices.





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.