Susan Haigney

Industry Outlook for 2025—Real World Data

The use of real-world data (RWD) and real-world evidence (RWE) has become a focus of pharmaceutical regulators in recent years. In December 2024, FDA’s Center for Drug Evaluation and Research announced a new Center for Real-World Evidence Innovation that will coordinate and promote the use of these data in regulatory decision making (1). The agency also published a number of guidance documents on data in 2023 and 2024 (2,3). The European Medicines Agency is also working to promote the use of RWD and RWE (4).

To gain more perspective on these data and other trends impacting the industry, 

® spoke with Sujay Jadhav, CEO of Verana Health. “We're seeing exponential changes in both of those particular components,” says Jadhav. “[F]rom an approach perspective, particularly in clinical research, we're seeing sort of external control arms becoming more mainstream. Part of [this is because] of [FDA] and their guidance of late, which [is about] helping facilitate the leveraging of real-world data and external control arms in the overall drug discovery process. But a key component is that this is an incredible source to help improve sort of efficiency and the quality of our research overall.”

“One of the other trends that we are also seeing is predictive analytics and AI [artificial intelligence], and how this can help predict disease progression and assist with early detection to support patient recruitment and retention … AI and these technologies, they can identify trends for data, [and lead to] informed decisions across the drug life cycle.”

Click the above video to watch the interview.

1. Haigney, S. FDA Creates CDER Center for Real-World Evidence Innovation. 

Guidance for Industry, Data Standards for Drug and Biological Product Submissions Containing Real-World Data

Guidance for Industry, Real-World Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Making for Drug and Biological Products

 (CDER, CBER, July 2024).
4. Barton, C. Using RWD in Non-Interventional Studies. 

Videos

Pharmaceutical Technology® spoke with Sujay Jadhav, CEO of Verana Health about trends in real-world data and the impact these trends will continue to have on the pharmaceutical industry in 2025.

Industry Outlook for 2025—Real-World Data

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On Dec. 23, 2024, the World Health Organization (WHO) provided an update on COVID-19 vaccine antigen composition, pointing to the continued evolution of variants of the virus. A review of data has resulted in the recommendation that the current COVID-19 vaccine antigen composition, monovalent JN.1 lineage variant(NextStrain: 24A, GenBank: PP298019, GISAID: EPI_ISL_18872762), be used to enhance neutralizing antibody responses to JN.1 and its descendants. Vaccine antigens from more recent variants or alternative formulations is also a possible approach.

WHO’s Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) has been monitoring genetic and antigenic evolution of SARS-CoV-2 variants and the performance of COVID-19 vaccines against these variants. WHO then advises manufactures of vaccines and regulatory authorities on implications of updates to the vaccines.

In December 2024, the TAG-CO-VAC met to review the evolution of SARS-CoV-2. Also discussed were the immune responses to the infection and vaccination. Currently approved COVID-19 vaccines were evaluated by the advisory group, which then provided an update on antigen composition. Previously, in April 2024, the group recommended the use of a monovalent JN.1 lineage vaccine antigen in response to JN.1 and its descendants. Manufacturers responded by updating their COVID-19 vaccine antigen composition to monovalent JN.1, with some of these approved by regulatory authorities.

The TAG-CO-VAC reviewed evidence that included the SARS-CoV-2 genetic evolution, antigenic characterization of previous and emerging SARS-CoV-2 variants, immunogenicity data on antibody responses seen in approved vaccine antigens, preliminary immunogenicity data on immune responses, vaccine effectiveness estimates of approved vaccines against XBB.1 and JN.1 lineages, and preliminary preclinical data and clinical immunogenicity data on candidate vaccines. The evidence, according to WHO, show that SARS-CoV-2 continues to circulate globally, resulting in severe disease and death, especially in people 65 years and older and/or with existing conditions, and current variants are all derived from JN.1. Based on data using antisera, it appears thatcirculating JN.1-derived variants (JN.1, JN.1.16.1, KP.2, KP.2.3, KP.3, KP.3.1.1, LB.1 and XEC) are antigenically closely related. Data from vaccination frommonovalent JN.1 or KP.2 antigens showed a significant increase in neutralizing antibody titers that cross-reacted with all JN.1 descendent lineages tested.

“The weekly proportion of XEC sequences among all SARS-CoV-2 sequences submitted to GISAID continues to increase, while the weekly proportions of all other Variants of Interest (JN.1) or Variants Under Monitoring (KP.2, KP.3, KP.3.1.1, JN.1.18 and LB.1) are now declining,” WHO stated in a press release (1). “There are other JN.1-derived variants that are currently in low proportions, but which have mutations that may give them an advantage over XEC: currently LP.8.1, NP.1, LF.7.2 are variants being monitored and/or characterized.”

There are limitations to the data that were available for review, however, according to WHO. Gaps have been seen in the reporting of cases, hospitalizations, and deaths from WHO Member States. It is also hard to predict the timing of mutations and emerging variants, the organization said in the statement. Immunogenicity data against current variants are also not available for all COVID-19 vaccines. In addition, there are limitations in the number and geographic diversity of studies.

“Although neutralizing antibody titers have been shown to be important correlates of protection from SARS-CoV-2 infection and of estimates of vaccine effectiveness, there are multiple components of immune protection elicited by infection and/or vaccination,” said WHO. “Data on the immune responses following JN.1 descendent lineage infection or monovalent JN.1, KP.2 or XBB.1.5 vaccination are largely restricted to neutralizing antibodies. Data and interpretation of other aspects of the immune response, including cellular immunity, are limited.”

The TAG-CO-VAC is encouraging the generation of more data and the further development of COVID-19 vaccines. “The TAG-CO-VAC will continue to closely monitor the genetic and antigenic evolution of SARS-CoV-2 variants, immune responses to SARS-CoV-2 infection and COVID-19 vaccination, and the performance of COVID-19 vaccines against circulating variants,” WHO stated in the release. “The TAG-CO-VAC will also continue to reconvene every six months to evaluate the implications for COVID-19 vaccine antigen composition.”

1. WHO. Statement on the Antigen Composition of COVID-19 Vaccines. Press Release. Dec. 23, 2024. 

https://www.who.int/news/item/23-12-2024-statement-on-the-antigen-composition-of-covid-19-vaccines 

Articles

Pointing to the continued circulation and evolution of COVID-19, WHO published a statement on the COVID-19 vaccine antigen composition to respond to variants of the virus.

WHO Provides a Statement on COVID-19 Vaccines

The European Medicines Agency (EMA) announced on Dec. 18, 2024 that the agency, along with the Heads of Medicines Agencies (HMA) have revised their guidance on identification of commercially confidential information (CCI) and personal data used in marketing authorization applications as part of their commitment to transparency in the disclosure of information in response to access-to-document requests and the publication of data for authorized medicines.

The original 2012 guidance document offered, for the first time, a common approach for European regulators to use in order to identify parts of an application dossier that can or cannot be released publicly. EMA and national competent authorities have gained experience since then in the handling of access-to-documents requests and have applied more transparency when data is released. Therefore, EMA stated in a press release that it was necessary to review the 2012 guidance to align with current day-to-day practices and harmonize those practices across authorities. The revised guidance also applies to EMA’s 2014 proactive clinical data publication.

“As a general rule, the overwhelming majority of data in marketing-authorization applications is not considered CCI,” EMA stated in the press release (1). “The exceptions mainly relate to information about the manufacturing of a medicine, as well as information about facilities or equipment and some contractual arrangements between companies. While considered CCI at the time of the initial guidance, general information related to quality is now mostly considered releasable.”

The revised guidance considers information as “releasable by default” instead of applying a yes or no rule to an entire section of a dossier when determining which data can be released. Detailed practical orientations are provided for specific points that may be redacted or made anonymous within each section of the dossier. The guidance’s annex has also been updated to include examples of information that may be considered CCI or protected personal data.

How personal data are to be protected when it might lead to identification of a person is also detailed in the guidance. The revised guidance considers recent data protection legislation in the European Union, including the EU General Data Protection Regulation and Data Protection Regulation for the European Union. Identifying personal data of experts, staff, or patients that should be made anonymous is also addressed in the guidance.

The revised guidance went through public consultation in 2024 and report of the analysis from that consultation will be published in 2025.

The EU has been proactive over the past several years regarding data protection. In September 2024, EMA and HMA published recommendations for staff in the European Medicines Regulatory Networks about the use of generative artificial intelligence in large language models (LLMs), stating it could create potential data security risks (2). These guidelines are part of the HMA/EMA Multi-annual AI Workplan 2023–2028, published in December 2023, to be a guide for the use of AI in managing risk and maximizing benefits of AI.

1. EMA. A Common EU Approach to Data Transparency in Medicine Regulation. Press Release. Dec. 18, 2024.
2. Barton, C. Responding to the Increased Use of Generative AI. 

https://www.pharmtech.com/view/responding-to-the-increased-use-of-generative-ai

Revised guidelines published by EMA and HMA update the rules on identification of commercially confidential information and personal data used in marketing authorization applications.

Protection of Personal Data in European Medicine Regulation

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.

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.