Regulatory Affairs

Using Blockchain Technology to Ensure Data Integrity: Applying Hyperledger Fabric to Biomanufacturing

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Digitalization of manufacturing operations is a major challenge that many industries face. With the advent of smart equipment, automation of unit operations and complete processes, and digitalization of batch documentation, more data are generated now than ever before. The information must remain manageable, and data integrity needs to be ensured. The challenge for biomanufacturers will be to ensure that their entire large output of data will be attributable, legible, contemporaneous, original, and accurate (ALCOA) as defined by the US Food…

March 3, 2020

Evaluating Biosimilars: A View from the Small-Molecule World

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For many years the pharmaceutical industry was dominated by small (usually synthetic) molecules, mixed with a number of nonactive materials and encapsulated or (in the really old days) rolled into pills or pressed into tablets. Although synthesizing the active pharmaceutical ingredients (APIs), formulating the dosage forms, and analyzing the materials at every stage of a product life cycle were not always trivial activities, they were relatively straightforward. Most of the tools needed for analyzing/controlling each step of the manufacturing process…

February 7, 2020

Bioassay Evolution: Finding Best Practices for Biopharmaceutical Quality Systems

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Bioassays help drug developers determine the biological activity (potency) of their products, which has been a biopharmaceutical critical quality attribute (CQA) since long before that concept had a name. Because of their complex nature, bioassays are among of the most challenging experiments to perform reliably with dependably accurate results. Consistent assay performance requires a controlled environment and qualified reagents; skilled analysts who understand cell physiology, regulatory requirements, and the latest techniques; and assay protocols that are intelligently developed, characterized, and…

February 7, 2020

Cell Banking for Cell and Gene Therapy: Regulatory, Ethical, and Scientific Considerations

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Regenerative medicine holds great potential for human disease management, with hundreds of cell and gene therapy (CGT) products for tissue/organ reconstitution or replacement in different stages of development and clinical testing for toxicity, safety, and efficacy. For example, currently more than 60 CGTs have marketing authorization (although many with only conditional approval) from central regulatory agencies worldwide (1). Those products are treating conditions such as hematopoietic malignancies, immunological disorders, and cartilage disorders. Most of those treatments use culture-expanded autologous or…

January 31, 2020

eBook: Biologics Stability — Lifecycle Management of Drug Products

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The biomanufacturing industry’s increasing attention to risk mitigation through quality by design (QbD) and the emergence of complex therapeutic modalities have driven the need for a lifetime-management approach to assuring drug product stability. To that end, industry guidelines have been (or are being) developed to guide the industry toward a “holistic approach†to conducting stability assessments. However, not all methods are stability indicating, and many more industry concerns need to be addressed. This BPI eBook offers perspectives on ICH Q12…

December 17, 2019

eBook: Speed to IND — Balancing Risk and Reward

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With so many biopharmaceuticals obtaining breakthrough or fast-track designations, companies that use accelerated strategies to be first in human studies can be left with significant quality and manufacturing challenges that must be solved later on. Despite regulatory encouragement to create solid design spaces and define parameters according to quality by design (QbD), those may go by the wayside given the pressures of speed. The reward is the investigational new drug (IND) application itself — but if companies lock in subpar…

December 11, 2019

Addressing Regulatory Requirements for Filter Integrity Testing

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Filter integrity is a fundamental element of sterility assurance during production of biopharmaceutical and vaccine products. Integrity test results are a key foundation for drug lot release, so any external element that could affect their reliability must be viewed as a critical issue. But when should a filter integrity test be performed? This article highlights the Sartocheck 5 Plus filter integrity tester as a means to address regulatory requirements. Please fill out the form below to read the full article…

October 28, 2019

Good Manufacturing Practice in China: Equipment Strategy and Quality Management to Compete with the West

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Although the concept of good manufacturing practice (GMP) was created about half a century ago in the United States, the history of GMP biomanufacturing is relatively short in China, with the first version of GMP rules issued by the Ministry of Health in 1998. In 2010, the ministry issued its fourth version of China’s GMP rules, which came into effect in March of 2011 (1). According to a recent report from BioPlan Associates, the 2010 version raised the standards to…

June 12, 2019

Biologic Labels and Induced Patent Infringement: A Perspective on Evolving US Law

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The mechanism for proving patent infringement is changing for developers of both branded and follow-on biologics (either biosimilar or interchangeable). Here we examine how drug labeling can establish infringement, thus affecting follow-on manufacturers accused of inducing others to infringe patents on methods of treating medical conditions. Because precedent is paramount in the US legal system, judges look to small-molecule case history to help them understand alleged infringement by follow-on biologics. The classic approach to induced infringement of generic small-molecule drugs…

May 17, 2019

Risk Management of Biopharmaceutical Operations: End-to-End and Over Lifecycle

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Biopharmaceutical manufacturing processes that were developed before the implementation of quality by design (QbD) typically use control strategies that are not founded on a formal understanding of criticality. Thus, manufacturers of “legacy†products lack the understanding of critical process parameters (CPPs) and critical quality attributes (CQAs). Introducing such elements to a legacy biologic drug product filing aligns fully with expectations described in the ICH Q12 guideline (e.g., increased process understanding and better risk mitigation strategies) (1). Here we discuss how…

May 15, 2019