Susan Haigney

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Astellas Pharma US announced on Dec. 23, 2024 that it is voluntarily recalling one lot of PROGRAF 0.5mg (tacrolimus) and one lot of ASTAGRAF XL 0.5mg (tacrolimus extended-release) capsules because some bottles may contain empty capsules. PROGRAF and ASTAGRAF XL are immunosuppressive drugs used to prevent organ transplant rejection.

The recalled lot information for PROGRAF—which is used in kidney, heart, liver, or lung transplants—is as follows:

Product: PROGRAF (tacrolimus), 0.5 mg capsules, 100 capsules per bottle

National Drug Code (NDC) Number: 0469-0607-73

Recall information for ASTAGRAF XL—which is used in kidney transplants—is as follows:

Product: ASTAGRAF XL (tacrolimus extended-release capsules), 0.5 mg capsules, 30 capsules per bottle

The recalled lots were distributed nationwide to wholesale and retail outlets. Other product formulations or doses are not impacted by the recall. Astellas is notifying customers about the recall so that arrangements to return the product can be made.

According to Astellas, patients who receive empty capsules of the recalled product may have limitation of rejection of the transplanted organ, tissue, or cells. “In the case of life sustaining organ transplants such as a heart transplant (for which there is no permanent substitute such as hemodialysis in the case of a failed kidney transplant) if the transplant fails, the consequences of rejection initiated by ingesting empty capsules may be fatal,” the company stated in the press release (1).

While the company states that, as of the date of the press release, no adverse events have been reported in association with the recall, adverse events may be reported to FDA via its MedWatch Adverse Event Reporting program.

FDA also announced a recall of Systane Lubricant Eye Drops Ultra PF, Single Vials On-the-Go, 25 count by Alcon Laboratories on Dec. 23, 2024 (2). The eye drops are used to sooth burning and irritation from dry eyes. The company voluntarily recalled one lot—Lot 10101,NDC 0065-1432-06—because of foreign material found by a consumer inside a sealed single-use vial, which was determined to be fungal. The recalled lot has an expiration date of 2025/09. No adverse events had been reported as of the date of the recall notice.

“Fungal contamination of an ophthalmic product is known to potentially cause eye infections. If an infection occurs, it may be vision-threatening, and in very rare cases potentially life-threatening in immunocompromised patients,” the company stated in the press release (2).

1. FDA. Astellas Pharma US, Inc. Issues Voluntary Nationwide Recall of One Lot of PROGRAF 0.5mg (Tacrolimus) and One Lot of ASTAGRAF XL 0.5mg (Tacrolimus Extended-Release Capsules) Because Bottles Shipped to U.S. May Contain Empty Capsules. Press Release. Dec. 24, 2024. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/astellas-pharma-us-inc-issues-voluntary-nationwide-recall-one-lot-prografr-05mg-tacrolimus-and-one


2. FDA. Alcon Laboratories Issues Voluntary Nationwide Recall of One (1) Lot of Systane Lubricant Eye Drops Ultra PF, Single Vials On-the-Go, 25 count (Lot 10101), Due to Fungal Contamination. Press Release. Dec. 23, 2024. 

https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/alcon-laboratories-issues-voluntary-nationwide-recall-one-1-lot-systane-lubricant-eye-drops-ultra-pf

Articles

The company is recalling one lot of PROGRAF 0.5mg (tacrolimus) and one lot of ASTAGRAF XL 0.5mg (tacrolimus extended-release) capsules because some bottles may contain empty capsules.

Astellas Pharma Recalls PROGRAF and ASTAGRAF XL Capsules

 publishes independent, science-based articles and peer-reviewed papers from bio/pharmaceutical professionals working in the development and manufacturing of pharmaceuticals. In 2024, 

via print issues, ebooks, and our website, 

 published articles on topics ranging from development challenges, to manufacturing best practices, quality considerations, analytical approaches, and more.

The following are our picks for the ‘best of’ technical and peer-reviewed articles published in 2024, in no particular order:

Legal and Regulatory Perspectives on 3D Printing: Drug Compounding Applications


This paper explores the legal and regulatory framework around 3D drug printing, particularly for personalized medicine, considering regulatory compliance, business concerns, and intellectual property rights.


https://www.pharmtech.com/view/legal-and-regulatory-perspectives-on-3d-printing-drug-compounding-applications

The Quest for Quality: Challenges and Strategies in Raw Material Selection for Biopharmaceuticals


Biopharmaceutical production faces the challenge of ensuring the quality of raw materials due to a lack of specific guidelines. By implementing effective risk assessment strategies and working with reliable, selected solution providers, biopharmaceutical manufacturers can minimize these challenges and improve product quality.


https://www.pharmtech.com/view/the-quest-for-quality-challenges-and-strategies-in-raw-material-selection-for-biopharmaceuticals

Data Governance, Data Integrity, and Data Quality: What’s the Connection?


Nomenclature is important. Data governance, data integrity, and data quality are all widely used terms, but what do they actually mean and how are they connected? The purpose of this article is to provide a structured model for these terms with their definitions and their relationships in the context of analysis and testing within a pharmaceutical quality system.


https://www.pharmtech.com/view/data-governance-data-integrity-data-quality-whats-connection

Application of Validation Principles to the Training Quality System: Part 9, Quality Risk Management Hazard Identification


Pharmaceutical training programs are enhanced by integrating ICH quality risk management considerations.


https://www.pharmtech.com/view/application-validation-principles-training-quality-system-part-9-quality-risk-management-hazard-identification

Accelerating Discovery and Development with Advances in High-Throughput Screening


Automation, miniaturization, and new software algorithms are improving throughput and accuracy.


https://www.pharmtech.com/view/accelerating-discovery-and-development-with-advances-in-high-throughput-screening

Validating Pharma 4.0 for Smart Manufacturing


The drug manufacturing ecosystem Pharma 4.0, a term coined in 2017 by the International Society for Pharmaceutical Engineers, promises a revolution across drug discovery, manufacturing, and supply chain logistics, ensuring drugs are delivered precisely when needed, and improving overall patient care.


https://www.pharmtech.com/view/validating-pharma-4-0-smart-manufacturing

Understanding the Value of Excipient Grade


Greater collaboration and understanding are needed to ensure the correct grade of excipient is used in drug products.


https://www.pharmtech.com/view/understanding-the-value-of-excipient-grade

Determining Low PPB Levels of Nitrite in Polymeric Excipients


In this paper, the authors introduce a method that combines ion exchange chromatography with an easier-to-perform, simpler one-step post-column derivatization that is selective to nitrite and visible spectrophotometric detection to allow high sample loading volumes without affecting resolution.


https://www.pharmtech.com/view/determining-low-ppb-levels-of-nitrite-in-polymeric-excipients

Increasing mRNA Product Stability with Lyophilization


Developing freeze-drying processes requires patience and deep product and process understanding.


https://www.pharmtech.com/view/increasing-mrna-product-stability-with-lyophilization


A greater understanding of molecular and cellular biology and technological advancements are revolutionizing the field of biologics.


https://www.pharmtech.com/view/biologics-on-target-for-the-future

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To read in-depth manufacturing articles, visit 

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https://www.pharmtech.com/view/pharmaceutical-technology-submission-guidelines-and-editorial-calendars

The PharmTech Group editors present our most popular technical articles from 2024.

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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

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 

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.