Susan Haigney

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FDA published a draft guidance document on Jan. 2, 2025 that provides considerations for complying with 21 

) 211.110 (1). This specific section of the CFR focuses on production and process controls for sampling and testing of in-process materials and drug products. The guidance, 

Considerations for Complying With 21 CFR 211.110, Guidance for Industry, Draft Guidance, 

applies to human drug products and biologics, but not to the manufacture of APIs. The guidance document also discusses how process models can be incorporated into commercial manufacturing control strategies.

Batch uniformity and drug product integrity current good manufacturing practice requirements state that manufacturing processes must be designed and controlled to ensure that in-process materials meet predetermined quality requirements. In the document, FDA states robust product and process development are crucial for establishing and maintaining control strategies throughout the product’s lifecycle so that quality attributes are obtained.

“To ensure conformance to drug product quality requirements, the manufacturer should identify which critical quality attributes and in-process material attributes to monitor and control,” FDA states in the document (1). “Section 211.110 allows flexibility in the in-process controls, and testing, or examinations that are employed to ensure that processes deliver in-process materials and drug products with the appropriate quality attributes. To ensure that drug products have the properties that they are represented to possess, the in-process materials used throughout the manufacturing process should be of consistent quality.”

In addition, the guidance details quality considerations for drugs manufactured using advanced manufacturing technologies (AMTs). “All manufacturers, regardless of whether they are using advanced manufacturing, should apply a scientific- and risk-based approach to controlling processes and ensuring drug product quality,” FDA states in the guidance document (1). “This approach should be based on robust product and process understanding. Manufacturers must maintain the process in a state of control over the life of the process to ensure drug product quality, even as materials, equipment, production environment, personnel, and manufacturing procedures change. Planning and executing a system that monitors process performance and drug product quality helps ensure that a state of control is maintained. An effective monitoring system helps maintain a state of control in multiple ways, which include helping manufacturers: ensure that processes and controls are continuously capable of producing a drug product of desired quality; and identify areas for continual improvement.”

Additional guidance on advanced manufacturing was also published by FDA in January, explaining requirements for those in industry that wish to participate in the agency’s Advanced Manufacturing Technologies Designation Program (2). The Advanced Manufacturing Technologies Designation Program was required under section 506L of the Federal Food, Drug, and Cosmetic Act to provide a framework for those requesting designation of a drug manufacturing method as an AMT. The program provides early interaction opportunities before application submission as a way to encourage adoption of AMTs (3).

Considerations for Complying With 21 CFR 211.110, Guidance for Industry, Draft Guidance

https://www.fda.gov/media/184825/download

Advanced Manufacturing Technologies Designation Program, Guidance for Industry

 (CDER, CBER, December 2024).
3. Haigney, S. FDA Publishes Final Guidance on Advanced Manufacturing Technologies. 

Articles

The draft guidance document provides recommendations for complying with 21 CFR 211.110.

FDA Releases Draft Guidance on Sampling and Testing of In-Process Materials and Drug Products

In an interview with Pharmaceutical Technology Roger Viney from ICE Pharma highlights the importance of sustainability for the bio/pharma industry and some important future considerations for companies.

Creating a Sustainable Approach

Sustainability in the pharmaceutical industry has increased in the past few years as a significant initiative for regulators and many pharmaceutical companies. Sustainability practices may include investment in renewables, zero emission buildings, and greener manufacturing practices (1). ICE Pharma has adopted a sustainability strategy that includes fighting illness through product innovation, caring for people, accelerating sustainable operations, and building strong relationships (2).To gain more perspective on sustainability in pharma, 

spoke withRoger Viney from ICE Pharma about what pharmaceutical companies should consider when developing a sustainability strategy.

Viney stresses that the healthcare industry, which is responsible for approximately 5% of global emissions, must be aware of the impact the industry has on the environment. “I think it's important to recognize that what we manufacture is biologically active,” says Viney. “So, in that case, it has a bigger environmental impact than some other products. I think in terms of the regulations that we have to comply with, you know, or the quality compliance regulations, I think the pharma industry is relatively slow to change, and we're slow to introduce new manufacturing technologies. We have difficulty adapting to new technologies which would lower our environmental impact. So, I think we've been slower than we would have liked. It's the nature of our industry. But I think, of course, there's a very big expectation from our customers, whether it be governments, businesses, or patients, that we do make progress in this area.”

Sustainability in the Pharmaceutical Industry

 (accessed Dec. 16, 2024). 
2. Lavery, P. 

ICE Pharma Touts Fully Recyclable Booth at Its CPHI Milan Exhibit

Roger Viney, PhD, is the chief commercial officer for ICE Pharma and is responsible for the global commercial functions. Roger has a 30-year career, starting in R&D and then moving across to sales, marketing, key account management, and business and product management for the pharma market.

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FDA published a final guidance on Jan. 2, 2025 for those interested in participating in the agency’s Advanced Manufacturing Technologies Designation Program, which was developed to facilitate drugs manufactured using advanced manufacturing technologies (AMTs). The guidance, 

Advanced Manufacturing Technologies Designation Program

, is the final version of the draft document issued on Dec. 13, 2023.

Early adoption of AMTs that improve the reliability and robustness of manufacturing processes is encouraged by FDA. AMTs can reduce drug development time and may increase the supply of critical drugs, according to the agency. FDA defines “advanced manufacturing” as an “an innovative pharmaceutical manufacturing approach or technology that has the potential to improve the reliability and robustness of the manufacturing process and supply chain and increase timely access to quality medicines. Advanced manufacturing can integrate novel technological approaches, use established techniques in an innovative way, or apply production methods in a new domain where there are no defined best practices or experience” (1).

The Advanced Manufacturing Technologies Designation Program was required under section 506L of the Federal Food, Drug, and Cosmetic Act (FD&C Act) to provide a framework for those requesting designation of a drug manufacturing method as an AMT. The program provides early interaction opportunities before application submission as a way to encourage adoption of AMTs.

The guidance document details FDA’s Advanced Manufacturing Technologies Designation Program and provides the eligibility criteria for AMT designation. The submission and assessment process for requests is also provided in the document, as well as the benefits related to drug development and application assessment. Details about key concepts for program utilization are available in a Q&A section of the guidance.

“Before submitting an AMT designation request, persons or organizations seeking designation of a method of manufacturing as an AMT (hereinafter requestors) should familiarize themselves with the data requirements described in section 506L of the FD&C Act, the recommendations outlined in this guidance, and other publicly available sources of product development information,” FDA states in the guidance. “Any technology can be considered for AMT designation provided that the technology meets the eligibility criteria described in section 506L(b) of the FD&C Act, the requestor has sufficient data and information to demonstrate eligibility, and the technology is mature enough to consistently and reliably manufacture product in the context of use for which AMT designation is sought.”

Request for AMT designation should include a brief description of the method and why it is a novel method; the context in which the AMT will be used; a description of how the method meets criteria established in section 506L(b) of the FD&C Act; potential regulatory, technical, or other challenges with implementation; anticipated timelines for drug development using the proposed AMT; among other requirements.

“FDA acknowledges that requestors who are not also applicants may not have data about a specific drug to include in their AMT designation request,” the document states. “In these cases, FDA recommends that requestors include data generated using a model drug to provide the agency with a clear understanding of the proposed AMT’s parameters, limitations, and context of use.”

The guidance provides recommendations for those interested in participating in FDA’s Advanced Manufacturing Technologies Designation Program.

FDA Publishes Final Guidance on Advanced Manufacturing Technologies

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

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

For more peer-reviewed articles, please visit 

https://www.pharmtech.com/topic/peer-reviewed-research

. 
For the latest on drug development, please visit 

https://www.pharmtech.com/topic/drug-development

. 
To read in-depth manufacturing articles, visit 

https://www.pharmtech.com/topic/manufacturing

. 
A variety of quality-related topics can be found at 

https://www.pharmtech.com/topic/quality-gmps

. 
And the latest analytical technologies are discussed at 

https://www.pharmtech.com/topic/analytics

For information on how to submit technical and peer-reviewed articles to 

®, please view our submission guidelines at 

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

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