new chemical entities 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

EFPIA’s Annual Report on the Pharmaceutical industry 2022

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by Giuliana Miglierini

In the 21 years from 2000 to 2021 – in which time we’ve come through the Global Financial Crisis and a pandemic – EFPIA companies have more than doubled production, increased exports by a factor of six, and recorded a trade balance that puts it far ahead of other high-tech sectors in Europe”, writes EFPIA’s Director General Nathalie Moll commenting the Annual Report2022.

Despite this marked growth, many challenges are still to be faced to allow the European pharmaceutical industry to maintain and even strengthen its role as primary hub of innovation, thus contributing to the overall success of the EU’s economy. It can be expected, for example, that the energy crisis will be highly impacting pharmaceutical productions, also in the form of increased difficulties to guarantee a constant supply of raw materials. This would represent just the last drop adding to existing regulatory barriers slowing down R&D and to the impact of fiscal austerity policies that may discourage investors.

At the same time, we have seen the growth of Brazilian, Chinese and Indian markets outstrip growth in the top 5 European markets. Our global competitors have prioritised life sciences and we must respond with similar ambition”, adds Nathalie Moll.

The 2021 of the pharmaceutical industry

According to EFPIA’s Annual Report 2022, the value of production for the research-based European pharmaceutical industry has grown from 127.5 billion euro in year 2000 to 300 billion in2021. Even more relevant is the growth of export, increased from €90.9 bln to €565 bln over the same period. In 2021 imports counted for €390 bln, with a positive trade balance of €175 bln.

The research-based pharma industry employed last year 840,000 units (125,000 of which in R&D) and invested €41.5 bln in research and development activities.

The total European pharmaceutical market value at ex-factory prices increased from €89.4 bln in 2000 to €255 bln in 2021. The pharmaceutical expenditure supported by statutory health insurance systems (and referred to ambulatory care only) grown from €76.9 bln to €157.5 bln over the same time.

Despite these positive figures, EFPIA warns about the danger of migration of many R&D activities from Europe towards fast-growing markets such as Brazil, India and China, thanks to the more favourable conditions. The pharmaceutical market in these countries grown, respectively,11.7%, 6.7% and 11.8% in the period 2016-2021, compared to 5.8% of top EU countries (France, Germany, Italy, Spain and United Kingdom) and 5.6% of the US.

North America still represents the wider market area for pharmaceuticals (49.1%, vs 23.4% for Europe), and accounts for the higher proportion of new launches (64.4%, vs 16.8% of top five EU countries). In 2020 China marked the higher pharmaceutical R&D expenditure (78,5 billion Yuan, from 1.9 bln Yuan in 2000), overcoming for the first time the US ($72.4 bln), while Europe is positioned far behind (€39,7 bln). Not less interesting is the 3.2% market share assigned to emerging, high-growth pharmaceutical markets including many African, South American and Asiatic countries (Algeria, Argentina, Bangladesh, Brazil, Colombia, Chile, China, Egypt, India, Indonesia, Kazakhstan, Mexico, Nigeria, Pakistan, Philippines, Poland, Russia, Saudi Arabia, South Africa, Turkey and Vietnam).

Parallel trade is a characteristic of the European pharmaceutical market, due to the persistent fragmentation of many policies in different countries. Denmark saw in 2020 the higher share of parallel imports in pharmacy market sales (26.9%), well above other countries (e.g. 10.9% Sweden,9.1% UK, 8.3% Germany).

 Issues slowing down R&D

According to EFPIA, the length of time needed to bring a new medicine to the market (up to 12-13 years) is still a major issue impacting the attractiveness of European R&D. An average of one-two new synthetic substances out of every 10 thousand exiting the labs passes all the scrutiny steps needed to reach approval. The total costs of R&D was estimated in 2014 to reach €1.97 billion, indicates the report.

Germany, Switzerland and the UK are the European countries more active in research and development (€7.8 bln, €7.4 bln and € 5.6 bln expenditure in 2020, respectively). Clinical research accounts for the higher percentage of investment (44.1%, mainly in phase III studies), far above pre-human and pre-clinical research (14.9%) and phase IV studies aimed to post-marketing surveillance (11.5%). Approval studies account for 4.3% of the total R&D expenditure.

The US generated 159 new chemical entities (both chemical and biological) in years 2017-2021, almost doubling Europe (72) and a group of other countries (71), excluding Japan (41). Even more worrying, in 2021 China lagged just behind Europe as originator of new active substances launched for the first time on the world market (18 vs 19, respectively), while the US confirmed its leading position (35). According to EFPIA, this trend is associated with a marked lower annual growth rate of pharmaceutical R&D expenditure in Europe (4.0% for years 2017-2021), compared to that in the US (8.5%) and China (12.9%). Despite this, health industries still position at the first place of the ranking of industrial sectors by overall R&D intensity (12.4%, vs 8.7% of ITC services and 7.4% of ITC products).

The pharmaceutical production

Switzerland, Germany and Italy are the leading European hubs for pharmaceutical production (€53.2 bln, €32.3 bln and €34.3 bln of value, respectively). This corresponds in Germany to a significant higher number of people employed in the sector (115,519, vs 66,400 in Italy and 47,000 in Switzerland). EFPIA also mentions that the research-based pharmaceutical industry generates about three times more indirect employment along its value chain (both upstream and downstream) than it does directly, thus significantly contributing to the overall European job market. This is even more true for highly skilled jobs, thus preventing the phenomenon of brain-draining towards more attractive countries for scientific talents.

The US remains the favoured trading partner for the EU pharmaceutical industry, accounting for 32.2% EU exports and 30.2% imports. Switzerland is at the first place for EU imports (36.4%, and 11.8% EU exports); more distanced are the UK, China and Japan.

Fragmentation still impacts the European market

Fragmentation of policies on price and reimbursement and different VAT rates for medicinal product sis a very typical phenomenon still limiting the potentiality of the European pharmaceutical market.

According to EFPIA, in 2020 the retail price of a medicine corresponded on average to 66.8% rewarding for the manufacturer, 17.4% for the pharmacist, 10.6% for the State and 5.2% for the wholesaler. The top 5 countries for market value at ex-factory prices were Germany (€42.9 bln), Italy (€23.4 bln), France (€29, 5 bln), the UK (€24.6 bln) and Spain (€17.6 bln); Russia also represented a relevant market (€18,4 bln). Italy sees the higher market share for generics (67.6%), well above Poland (58%) and Austria (49%). EFPIA also monitored the VAT rates applied to prescription and OTC medicines in different European countries, compared to the standard VAT rates. Malta (0%), Sweden (0%), France (2.1%), Switzerland (2.5%), Luxembourg (3%), Spain (4%), Lithuania, Croatia, Cyprus, Hungary (5%) marked the lower VAT rates on prescription medicines. In some case, these same rates applies also to OTC products (Croatia, Cyprus, Hungary, Luxembourg, Malta, Spain, Switzerland), while in other countries the rates for this category of medicines is higher (France 10%, Lithuania 21%, Sweden 25%).


Trends in Drug delivery and Formulation

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by Giuliana Miglierini

According to the 2021 Global Drug Delivery & Formulation Report, signed by Kurt Sedo, Vice President Operations, PharmaCircle LLC and published in a three-part series on Drug Development & Delivery, the Covid-19 pandemic seems to have had little impact on the regulatory approvals of new dosage forms and formulations. A positive sign from the pharmaceutical ecosystem, considering the difficulty to maintain normal operative conditions, the issues with international supply chains and the many hurdles to regulatory activities posed by the emergency.

According to Kurt Sedo, products newly approved by the FDA and based on new chemical entities have been the less affected, as they reflect a larger benefit for patients. On the other hand, are generics, together with new dosage forms and new formulations. Simple dosage forms continue to represent the great part of new approvals, while biologics prevail in terms of NCEs for injection.

The FDA approved in 2021 a total of 31 new products under the Biologics Licence Application (BLA) procedure, slightly more than in the previous two years. The increase is mainly linked to the higher number of vaccines and cell and gene therapies, while approval of biologic medicines maintained stable.

Approval trends by category of product

A marked decrease characterised Abbreviated New Drug Approvals (ANDA) (627 in 2021, vs 903 in 2020 and 962 in 2019). New Drug Applications (NDA) also slightly decreased. Analysing this category by type of product, the decrement is marked for new molecular entities and new dosage forms, while an opposite trend can be observed for new active ingredients and new formulations/new manufacturers.

As for administration route, the report indicates a marked prevalence of injection in all geographic areas (US 55%, EU 36%, JP 59%); oral drugs also continue to be highly represented. The author warns about the difficulty to reliably interpret the figures for European and Japanese approvals, as “The European Medicines Agency (EMA) approvals relate only to specific classes of pharmaceutical products and don’t capture the full range of products. The Japanese Pharmaceutical Medical and Medical Devices Agency (PMDA) published approvals are hard to access and properly assess”.

Looking more in detail at the injection route of administration, intravenous injectable products remain the leading category (US 39%, EU 38%, JP 38%), followed by subcutaneous injection. Simple solutions with or without a dedicated delivery device were the most commonly approved injectable simple dosage forms in 2021. Tablets and capsules remained the favoured oral dosage forms, while granules and pellets are especially represented in paediatric formulations.

Small molecules are the more represented category of active ingredients (US 64%, EU 74%, JP 52%), followed by antibodies and peptides; this last category of API offer the advantage of a possible formulation as non-injectable dosage form.

A deeper insight on the main approvals

Part 2 of the series debates the main products approved in 2021. The trend hints to a higher interest towards products and technologies targeted to wider patient populations and more diverse applications. According to Sedo, mRNA and gene therapy platforms have decrease their appealing due to need of validation for applications different than vaccines in the first case and safety and durability concerns in the latter.

Skytrofa (Ascendis Pharma) is a pegylated form of the growth hormone lonapegsomatropin-tcgd for injection or subcutaneous administration, using the dedicated rechargeable and reusable auto-injector. The weekly administration is the main advantage, overruling the need of daily injections.

Invega Hafyera (Janssen Pharmaceuticals), containing paliperidone palmitate as the active ingredient, has been approved in the US to treat adult schizophrenia by intramuscular injection every 6 months. Despite the parent molecule has already lost its exclusivity, Kurt Sedo highlights the remarkable lifecycle management of the Invega family of products, which allowed Janssen to maintain significant revenues for almost 20 years.

Tyrvaya (Oyster Point Pharma) is indicated to treat dry eye using the nasal delivery route. The formulation containing varenicline is administered using the Aptar’s CPS Spray Pump, representing the first approval for this type of technology platform. The possibility to overcome issues in treating ocular conditions connected to the difficulty many patients may experience with the administration of classical ocular drops is the main point of innovation.

Acuvue Theravision (Johnson & Johnson Vision Care) are contact lenses firstly approved in Japan and containing ketotifen to treat allergic conjunctivitis. In this case too, the approach may be replicated to administer other types of drugs in the eye. Issues may be represented by the difficulty of patients in using contact lenses and the need to stabilise the active ingredient to prevent leaching.

Cabenuva Kit (ViiV Healthcare) contains the combination cabotegravir – rilpivirine to treat HIV infection. Firstly, approved in Canada, it is administered monthly by intramuscular injection. Long-acting formulations can prove interesting to overcome compliance issues which may result in serious consequences for patients, as already proved in the case of hepatitis.

The monoclonal antibody Susvimo (anibizumab; Genentech) is formulated as a refillable ocular implant to treat wet acute macular degeneration. After implantation, the intravitreal injections using the Port Delivery System (PDS) occur every 6 months.

Other relevant technologies mentioned among new 2021 approvals include the Medicago Virus Like Particles (VLP) technology, which uses tobacco-related plants as bioreactors to produce noninfectious VLP that mimic the target virus, and LICA technology (Ionis), based on Ligand Conjugated Antisense (LICA) to favour the interaction of ligands and their respective receptors.

The Denali Transport Vehicle (TV) platform uses specific antibodies, enzymes, oligonucleotides, or proteins to link to the transferrin receptor of the blood vessel wall in the brain, thus providing a way to pass the blood-brain barrier by endocytosis.

MedRing (Ligalli) is a smart vaginal insert containing a miniaturised liquid formulation drug container with pump, battery, antenna, electronics, and sensors to monitor various biometric parameters (e.g. glucose or ovulation status).

Q-Sphera (Midatech Pharma) provides a bioencapsulation process using a microfluidic device to obtain discrete droplets without use of surfactants, toxic solvents, biphasic mixtures, shear, or heat forces.

Products in the pipelines

Part 3 of the series addresses the expectations for new approvals of products still in the pipelines The trend shows a higher percentage of early-stage products (research and pre-clinical phases), which is attributed to the higher interest of investors towards new companies able to fill the pipelines with early stage projects. The impact of Covid-19 has proved to be more relevant on projects at the clinical stage.

Small molecules still represent the main focus of development (59% in 2021/22), even if a drop has been observed from values recorded in 2015/16 (66%). Biological products may pose issues due to their highly speculative nature, suggests the report, while oligonucleotide and RNA products still represent only the 2% of the total in the pipelines; a more mature technology are antibodies (12%).

Cancer continues to be the leading therapeutic area of development, followed by infectious diseases and drugs to treat the central nervous system. The report indicates a very high attrition rate for anti-infectives under development, while many anti-cancer therapeutics in the pipelines may be me-too products pursuing validated therapeutic mechanisms. As seen above, injectable formulations maintain the leading position also for products under development (52%), followed by oral formulations.