Susan Haigney

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In her end-of-the-year message, Emer Cooke, executive director of the European Medicines Agency (EMA) promoted the agency’s successes in 2024, including the recommendation of 114 drugs for approval, collaborations with EU Member States and regulators from other regions, and efforts to combat drug shortages.

The marketing authorization recommendations made in 2024 by EMA included 48 new active substances, 16 of which were for rare diseases. “It is the first time since 2009 that we have been able to deliver more than 100 positive opinions,” Cooke stated in the press release (1). “This is good news for patients, but also a very encouraging indication of the competitiveness of the European pharmaceutical sector.”

Noteworthy marketing authorization recommendations went to the first Alzheimer’s disease medication in the European Union to slow progression of the disease and the first Chikungunya vaccine for adults. A new antibiotic was also approved to fight infections caused by multidrug-resistant bacteria, which is a positive development as antimicrobial resistance continues to be a threat to public health.

EMA collaborated with a variety of partners in 2024 to deal with multiple industry challenges. The agency worked with EU Member States to transition ongoing clinical trials to the Clinical Trials Information System. “Ten thousand applications have been submitted in the system since January 2022. This marks the end of a three-year transition period that began when the Clinical Trials Regulation became applicable,” Cooke stated in the release. The agency also worked with the African Medicines Agency to share experience and knowledge and to support a pilot program for joint evaluation of drugs in Africa.

To combat the ever-present problem of drug shortages, EMA worked with EU Member States in 2024 to ensure medicines were available to patients. Efforts included recommendations to keep the supply of critical vulnerable drugs strong. Communication was increased regarding key drugs, such as glucagon-like peptide-1 receptor agonists. In addition, the European Shortages Monitoring Program was established so that information regarding drug shortages can be exchanged quickly and efficiently between regulators and pharma companies. The Task Force on Availability of Authorised Medicines for Human and Veterinary Use, established in 2016, also concluded its work in 2024. “Fast forward to today, and one pandemic later, the activities started by the group have been enshrined in law and added to our public health mandate. The Task Force can be incredibly proud of what it has achieved, including the just published second version of the Union list of critical medicines,” Cooke stated.

“In 2025, EMA will continue its mission to protect public and animal health—with determination, with enthusiasm and passion. We are tirelessly working on reinventing and improving ourselves,” Cooke said in the release. “Next year, the Agency will maintain its focus on accelerating and optimizing the assessment of key medicines, improving both accessibility and availability of medicines, as well as working on approaches to future-proofing medicines regulation in the EU [European Union] in preparation for the new pharmaceutical legislation. I am expecting 2025 to be another exciting year for medicines regulation.”

1. EMA. Emer Cooke, EMA’s Executive Director: 2024 Achievements in Medicine Regulation. Press Release. Dec. 17, 2024.

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Emer Cooke, executive director of EMA, is encouraged by the competitiveness of the European pharmaceutical market.

Innovation, Collaboration, and Performance Were Highlights for EMA in 2024

In a press release posted on FDA’s website on Dec. 20, 2024, Endo USA, Inc. announced it was voluntarily recalling all lots of Adrenalin Chloride Solution (EPINEPHrine nasal solution, USP) 30 mg/30 mL (1 mg/mL) 30 mL vials. The recall was issued because the product, which is a vasoconstrictor for topical application that predates the 1938 Federal Food, Drug & Cosmetic Act, was never approved by FDA. The product was also found to be misbranded by FDA with a misleading label that is similar to one for an FDA-approved drug, Adrenalin (epinephrine injection, USP) (1 mg/mL) 30 mL vial, which is also produced by Endo. The approved Adrenalin (epinephrine injection, USP) (1 mg/mL) 30 mL vial has not been recalled.

According to FDA, the labeling similarity makes telling the difference between the non-sterile topical product and the sterile injectable product difficult. This could lead to administration errors.

“Intravenous administration of the unapproved non-sterile topical Adrenalin Chloride Solution (EPINEPHrine nasal solution, USP), instead of the approved sterile Adrenalin (epinephrine injection, USP) (1 mg/mL) 30 mL vial for injection, would result in non-fatal serious and/or severe, health outcomes related to delayed or inadequate treatment of the underlying condition (anaphylaxis, hemodynamic instability, hypotension) or infection due to intravenous administration of a non-sterile product,” the press release stated (1). “In addition, there is a high probability that intravenous administration of the nasal product will result in patients receiving the wrong dose of epinephrine in emergency situations for serious, life-threatening conditions such as the treatment of anaphylaxis, blood pressure support, and cardiac arrest. If these events are not treated with the correct dose of epinephrine, patients may be at risk for death.”

The recalled lots are packaged as 30 mL vials in individually packed cartons under national drug code number (NDC) #42023-103-01 that say, “Nasal Solution USP” and “For Topical Application” on the package. The following lots of Adrenalin Chloride Solution (EPINEPHrine Nasal Solution, USP) for topical application 30 mg/30 mL (1 mg/mL), which were distributed nationwide from Oct. 10, 2023 through Dec. 11, 2024, are recalled:

NDC 42023-103-01. Lot 82809. Expiry date: 03/2026

NDC 42023-103-01. Lot 79637. Expiry date: 11/2025

NDC 42023-103-01. Lot 77776. Expiry date: 07/2025

NDC 42023-103-01. Lot 74716. Expiry date: 05/2025

NDC 42023-103-01. Lot 71835. Expiry date: 01/2025

NDC 42023-103-01. Lot 72916. Expiry date: 01/2025.

Notification is being provided by the company to direct consumer accounts. Wholesalers are advised to discontinue the recalled lots immediately. Endo states in the press release that the company has not reported adverse events associated with the product in the past five years. Adverse reactions may be reported to FDA through its MedWatch Adverse Event Reporting program.

This is not the first recall for Endo in 2024. In July, the company recalled one lot of Clonazepam Orally Disintegrating Tablets, USP (C-IV) 0.25 mg tablets (also seen as Clonazepam Orally Disintegrating Tablets, USP (C-IV) 0.125 mg tablets 60-count) because an incorrect strength appeared on the cartons of some packs (2). The product strength was listed as 0.125 mg and not 0.25 mg. The inside blister strips, however, had the correct strength of 0.25 mg noted. The error was made by a third-party packager.

1. FDA.Endo USA, Inc. Issues Voluntary, Nationwide Recall of Adrenalin Chloride Solution (EPINEPHrine Nasal Solution, USP) Due to the Potential for Administration Errors. Press Release. Dec. 20, 2024. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/endo-usa-inc-issues-voluntary-nationwide-recall-adrenalinr-chloride-solution-epinephrine-nasal


2. FDA. Endo USA, Inc. Issues Voluntary, Nationwide Recall of One Lot of Clonazepam Orally Disintegrating Tablets, USP (C-IV) Lot Number 550147301 Due to Mislabeling: Incorrect Strength on Product Carton. Press Release, July 17, 2024. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/endo-usa-inc-issues-voluntary-nationwide-recall-one-lot-clonazepam-orally-disintegrating-tablets-usp

The company is voluntarily recalling all lots of Adrenalin Chloride Solution (EPINEPHrine nasal solution, USP) 30 mg/30 mL (1 mg/mL) 30 mL vials due to misleading labeling and its status as an unapproved drug. 

Endo Recalls Adrenalin Chloride Solution 

The European Medicines Agency (EMA) announced on Dec. 16, 2024 that a report (1) has been published that details the results of a pilot program for the creation and testing of electronic product information (ePIs) in regulatory procedures. According to the report, the European Union’s regulatory system is prepared for the introduction of ePIs, and implementation of ePIs can be phased into regulatory procedures. More development in functionality, however, still needs to be done, according to EMA. This development will begin in 2025. EMA and the Heads of Medicines Agency developed the ePI project, which was also supported by the EU4Health funding program.

The pilot’s report recommends that a phased implementation approach happen after all functionalities are in place. This approach will begin with voluntary adoption for centrally authorized products. Implementation will expand to nationally authorized products depending on the readiness and resources of each European Union (EU) Member State.

Drug product information is provided with each authorized drug in the EU and includes a summary of product characteristics, labeling, and packaging leaflet. These documents, which can be found in the drug’s packaging and as a PDF on regulators’ websites, explain how the drug should be prescribed and used.

“The introduction of product information in an electronic format (ePI) compatible with digital platforms opens new possibilities for patients and healthcare professionals to access and interact with vital, up-to-date information about their medicines,” EMA states in the press release (2).

Key indicators that were evaluated during the pilot included time needed to create an ePI, the percentage of ePIs that are successfully created and published, and usefulness of IT tools and guidance materials. These indicators were factored into the recommendations regarding future work that might be needed to implement ePI into current regulatory processes. The report states that enhanced guidance to support users and an update to business processes should be performed to ensure minimal disruption during implementation.

“In order to promote ePI adoption by companies, it is recommended to consider putting a process in place for a limited time period to allow first-time ePI submission and publication outside of a regulatory procedure. Importantly, regulators participating in the pilot found that it will be necessary to link ePI submission to the electronic application form and, for centrally authorized products, to the IRIS procedure management system, which will require a significant development effort,” the report states (1).

The pilot involved EMA, the national authorities of Denmark, the Netherlands, Spain, and Sweden, and industry. Twenty-three ePIs from real regulatory procedures were published as part of the pilot, of both centrally and nationally authorized medicines. The ePIs were created following the EU ePI Common Standard, “which provides a harmonized structure throughout all Member States ensuring the information works across different e-health platforms for citizens in the EU.” These ePIs can be found on the 

1. EMA; HMA. ePI Pilot Report. Experience Gained from Creation of ePI during Regulatory Procedures for EU Human Medicines. Dec. 16, 2024. 

https://www.ema.europa.eu/en/documents/report/electronic-product-information-epi-report-experience-gained-creation-epi-during-regulatory-procedures-eu-human-medicines_en.pdf


2. EMA. Successful Pilot Paves the Way for Implementation of ePI. Press Release. Dec. 16, 2024.

A pilot program to explore creation and testing of ePIs in regulatory procedures shows positive results.

Electronic Product Information Moves Forward in Europe

The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended 17 drugs for market authorization at its December meeting, EMA announced on Dec. 13, 2024. The approvals include five orphan drug recommendations and six biosimilar recommendations.

Among the approval recommendations is a monoclonal antibody, Kavigale (sipavibart), for COVID-19 prevention in immunocompromised people aged 12 and older. “Following the recommendation for approval of Kavigale, EMA’s Emergency Task Force (ETF) has issued an updated statement on the loss of activity of anti-spike protein monoclonal antibodies due to emerging SARS-CoV-2 variants and recommends healthcare professionals to check the current epidemiological situation in their region,” the agency stated in a press release (1). Kostaive (zapomeran), a self-amplifying messenger RNA vaccine, was also recommended for the prevention of COVID-19.

Orphan drugs recommended by CHMP include the following:

Andembry(garadacimab), which prevents recurrent attacks of hereditary angioedema

Beyonttra (acoramidis), which treats a wild-type or variant transthyretin amyloidosis in adult patients with cardiomyopathy

Rytelo(imetelstat), which treats adults with transfusion-dependent anemia due to very low, low, or intermediate risk myelodysplastic syndromes

Seladelpar Gilead(seladelpar lysine dihydrate), which treats primary biliary cholangitis

Emcitate(tiratricol), which treats peripheral thyrotoxicosis in patients with Allan-Herndon-Dudley syndrome.

The following six biosimilars were recommended for authorization:

Avtozma (tocilizumab) was given positive recommendation for treating rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, chimeric antigen T cell (CAR-T cell)-induced severe or life-threatening cytokine release syndrome and COVID-19.

Eydenzelt (aflibercept) treats eye diseases such as neovascular age-related macular degeneration, macular oedema secondary to retinal vein occlusion, diabetic macular oedema, and myopic choroidal neovascularization.

Osenvelt (denosumab) prevents bone complications in adults with advanced bone cancer and treats adults and skeletally mature adolescents with giant cell bone tumors.

Stoboclo (denosumab) treats osteoporosis in menopausal women, bone loss linked to hormone ablation in men at increased risk of fractures, and bone loss associated with long-term treatment with systemic glucocorticoid.

Yesintek (ustekinumab) treats adults and children with plaque psoriasis and adults with psoriatic arthritis or Crohn’s disease.

Zefylti (filgrastim) treats neutropenia and the mobilization of peripheral blood progenitor cells.

Other positive opinions given by CHMP include:

Nemluvio (nemolizumab), which treats atopic dermatitis and prurigo nodularis

Welireg(belzutifan), to treat tumors associated with von Hippel-Lindau disease and advanced clear cell renal cell carcinoma

Paxneury (guanfacine), which treats children with attention-deficit hyperactivity disorder

Tuzulby (methylphenidate hydrochloride) to treat children with attention-deficit hyperactivity disorder.

The December recommendations bring the total of drugs recommended for approval by CHMP for 2024 to 114.

CHMP also extended recommendations for several drugs, including Ofev for the treatment of progressive fibrosing interstitial lung diseases (ILDs) in children and adolescents, Blincyto, Bridion, Flucelvax Tetra, Jemperli, Omvoh, Rekambys, and Vocabria.

Also during the December meeting, CHMP chose to withdraw Alofisel (darvadstrocel) from the market after data showed its effectiveness was not what had been anticipated. Alofisel had been approved to treat complex anal fistulas in adults with Crohn’s disease.

Meeting highlights from the Committee for Medicinal Products for Human Use(CHMP) 9-12 December 2024

EMA recommended 17 drugs for marketing authorization in December, including treatments for rare heart conditions, anemia, and liver disease.

Several Orphan Drugs Among Medicines Recommended for Approval by EMA in December

FDA announced on Dec. 12, 2024 that the Center for Drug Evaluation and Research (CDER) has created a Center for Real-World Evidence Innovation (CCRI). The CCRI will coordinate, advance, and promote the use of real-world data (RWD) and real-world evidence (RWE) when making regulatory decisions at CDER (1).

Patient health data from sources such as electronic health records, medical claims, and product and disease registries are considered RWD. Real-world evidence can be generated from this RWD to provide insight into the effectiveness of drugs. According to FDA, patient data has increased in volume and complexity during the past few decades, this data has transformed the way drugs are developed, manufactured, and used. The CCRI will advocate, coordinate, and promote these data within CDER including initiatives related to emerging technologies.

"CDER’s new Center for Real-World Evidence Innovation represents a major step forward in our efforts to unlock the full potential of RWD to inform clinical and regulatory decisions," said CDER Director Patrizia Cavazzoni, MD (2). "We are creating a focal point within CDER to identify ways in which we can utilize RWE to streamline the development of effective and safe medicines for conditions with unmet need."

In 2023, FDA published its guidance on RWD,

Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products

on how to design a registry or use an existing registry to support regulatory decision-making about the safety and effectiveness of a drug (3). The guidance includes information about a registry’s fitness-for-use, linking a registry to other data sources for supplemental information, and supporting FDA review of submissions.

The guidance defines a registry “as an organized system that collects clinical and other data in a standardized format for a population defined by a particular disease, condition, or drug exposure.” Real-word data are defined in the guidance document as “data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources.” RWE is defined by FDA as “the clinical evidence about the usage and the potential benefits or risks of a medical product derived from analysis of RWD” (3).

FDA isn’t the only regulatory body utilizing RWD in decision making. In Europe, the European Medicines Agency (EMA) promotes using RWD as part of its Regulatory Science Strategy of 2025 (4). The agency plans on creating a framework to delivery and analyze RWD during a product’s lifecycle. It will then implement processes to use these data in regulatory assessments. EMA also published RWD catalogues in March 2024 to help regulators, pharma companies, and researchers to use RWD for determining the safety and effectiveness of drugs. And in April 2024, EMA released guidance on the types of studies that can be used to perform RWE generation (4).

1. FDA. CDER Center for Real-World Evidence Innovation (CCRI). 

https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/cder-center-real-world-evidence-innovation-ccri


2. FDA. CDER Establishes New Center for Real-World Evidence Innovation. 

https://www.fda.gov/drugs/drug-safety-and-availability/cder-establishes-new-center-real-world-evidence-innovation

Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products 

(CDER, CBER, December 2023).
4. Barton, C. Using RWD in Non-Interventional Studies. 

The Center for Drug Evaluation and Research’s new center will coordinate and promote use of real-word data in regulatory decisions.

FDA Creates CDER Center for Real-World Evidence Innovation 

TekniPlex Healthcare, a contract development and manufacturing organization, announced on Dec. 12, 2024 that it will be showcasing expanded capacity and capabilities of its injection blow molded bottles and five-layer blown film at the Pharmapack Europe event in Paris on Jan. 22–23, 2025. The company will also be featuring its sustainability-minded blister packaging and coated polyvinyl chloride (PVC) structures.

The company has added substantial injection blow molding capacity for multidose vial packaging at its Modena, Italy, facility. The capacity will allow the company to support pharmaceutical liquid applications including ophthalmic products. TekniPlex’s standard bottles range from 5–30 mL and are manufactured in ISO 8 cleanrooms.

TekniPlex Healthcare’s vertical bellow bottles, used for surgical powders and wound management, come in 3 mL or 9 mL volumes and have tamper-evident cannula caps that eliminate the need for secondary packaging. The bottles can be customized with silk screening and color variations.

The company is also expanding its production of multilayer brown film and cleanroom bags at its Puurs, Belgium, facility. Extruded blown films and bags with up to five layers, with a particular focus on polyethylene–ethylene-vinyl alcohol–polyethylene (PE-EVOH-PE) constructions providing exemplary oxygen barrier properties, are now available. According to TekniPlex, the market is shifting away from conventional food-grade materials to higher-grade resins. “These high-leverage materials are then used for cleanroom-produced films and bags manufactured in accordance with GMP [good manufacturing practice] guidelines,” the company stated in a press release (1).

In addition to these increases in capacity, the company will also be showcasing its range of sustainable blister packages at Pharmapack Europe, including a pharma-grade blister film with 30% post-consumer recycled content on a mass balance basis. A fully transparent recyclable mid-barrier blister package will also be exhibited by the company. The package features a polyolefin blister film paired with a barrier polypropylene lidding film. According to the company, this is the first time a formed blister plus lidding combination with moisture barrier has been made recyclable.

The company will also exhibit its pharma rubber compounding and manufacturing solutions. “Manufactured to precise dimensional tolerances to ensure proper fit and function within packaging or medical devices, the company’s pharma-grade rubber substantially minimizes the risk of migration-associated impurities [such as] extractables and leachables,” the company stated in the release. Additionally, the company’s Flexapharm SBC series of PVDC (polyvinylidene chloride) coated PVC structures and Aclar laminates will be on display.

TekniPlex can be found at Stand E97 at Pharmapack Europe, Jan. 22–23 in Paris, France.

Earlier in 2024, the company unveiled the HPC74 Series, a reinforced paper for medical device packaging applications, at Pack Expo 2024 in Chicago (2). The paper is breathable, has several coating formulations, a clean peel, and has the highest puncture and tear strength of all of the company’s previous reinforced papers.

TekniPlex. At Pharmapack Europe, TekniPlex Healthcare to Tout Expanded Capacity for Injection Blow Molded Bottles and Five-Layer Blown Film. Press Release. Dec. 12, 2024.

Lavery, P. TekniPlex Healthcare Announces Offerings on Display at Pack Expo 2024. 

The company will be showcasing its injection blow molded bottles and five-layer blown film at the packaging event in Paris on Jan. 22–23, 2025.