Regulatory Affairs

Evaluating Biosimilars: A View from the Small-Molecule World

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…

Bioassay Evolution: Finding Best Practices for Biopharmaceutical Quality Systems

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…

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

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…

eBook: Biologics Stability — Lifecycle Management of Drug Products

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…

eBook: Speed to IND — Balancing Risk and Reward

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…

Addressing Regulatory Requirements for Filter Integrity Testing

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…

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

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…

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

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…

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

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…

A Harmonized Approach to Data Integrity

Data integrity is achievable when data collection is complete, consistent, and accurate (1). Failure to maintain data integrity compromises a company’s ability to demonstrate the safety and efficacy of its products. Escalation of serious regulatory actions related to data integrity violations has prompted the need to assess data integrity compliance and implement systems designed to guarantee it. Comprehensive measures must be taken to ensure that data are attributable, legible, contemporaneous, original, and accurate (ALCOA) (2). Preventive measures need to be…