Regulatory Affairs

Change Happens: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management (CMC Forum)

by , , , , , and

In the current global regulatory environment, management and implementation of postapproval CMC changes often can be unpredictable and inefficient. Timelines for change approval can vary from months to years, depending on regional regulatory procedures. Therefore, the challenge in postapproval lifecycle management is to maintain a constant supply of high-quality product while supporting innovation and continual improvement. This was the premise of the CASSS Chemistry, Manufacturing, and Controls (CMC) Strategy Forum held in Gaithersburg, MD, on 20–21 July 2016. The forum…

September 19, 2017

Polysorbates, Biotherapeutics, and Anaphylaxis: A Review

by

Rapidly increasing use of monoclonal antibodies (MAbs) in the treatment of neoplastic, autoimmune, and inflammatory diseases has led to a dramatic increase in hypersensitivity reactions worldwide, complicating the use of MAbs as first-line therapies and limiting patient survival and quality of life (1). The origins of anaphylaxis are not well understood, though its mechanism is fairly straightforward (Figure 1). It is usually attributed to some undefined intrinsic property or properties of a biotherapeutic — despite the fact that biotherapeutic formulations…

September 19, 2017

Emerging Markets: Current Insights into the State of Global Biopharmaceutical Manufacturing

by and

Opportunities for establishing strong biopharmaceutical capabilities are expanding across the globe. This e-book seeks to encapsulate the current state of emerging markets/countries, tracing key elements above and offering examples to show where (in the world) the biopharmaceutical industry is expanding and securing its footholds. Generally, to succeed in these markets, foreign companies must exercise efficient resource management and control, show creativity and receptiveness to cultural differences, develop new strategies, and manage expectations. Working with local partners can provide access to…

August 31, 2017

Regulation, Analytical, and Process Issues with Leachables: Toward Harmonization for Latin America with Europe and North America

by , , , , and

The pharmaceutical industry follows strict regulations regarding impurities, including process-related leachates. Plastic manufacturers use hydrophobic, nontoxic additives for manufacturing containers for use in the pharmaceutical and food industries. However, some issues about dealing with such impurities are not yet resolved. In developing countries, regulators are working on guidelines to help local companies ensure characterization of impurities. In this exclusive editorial eBook, authors from Mexico describe some issues related to plastic leachables in the context of ongoing efforts to harmonize regulations…

August 23, 2017

An Industry Proposal for Change Notification Practices for Single-Use Biomanufacturing Systems

by , , and

Current practices for change notification in the biopharmaceutical industry are neither efficient nor conducive to accelerating the adoption of single-use systems (1, 2). Drug manufacturers (end users) often observe that supplier change data packages lack technical content or detail and that the time allowed for change implementation is too short. Occasionally, customers (end users or next tier in supply chain) learn of changes after the fact, possibly even by happenstance. Suppliers, however, can find the potential affect of a change…

May 18, 2017

Opportunities and Challenges in Biosimilar Development

by , and

A biosimilar biotherapeutic product is similar (but not identical) in terms of quality, safety, and efficacy to an already licensed reference product. Unlike generic small molecules, it is difficult to standardize such inherently complex products based on complicated manufacturing processes. Table 1 describes the main differences between biosimilar and generic drug molecules. The global biosimilar market is growing rapidly as patents on blockbuster biologic drugs expire (Table 2) and other healthcare sectors focus on reduction of costs. Biologics are among…

May 18, 2017

Implementing Quality By Design in Analytical Development: A Case Study on the Development of an Anion-Exchange HPLC Method

by , and

The concept of quality by design (QbD) initially was outlined in ICH Q8 guidance for drug-product development and later in Q11 for drug-substance development (1, 2). Since then, the QbD concept was further expanded to the development of analytical methods. FDA issued a 2015 guidance on analytical procedures and method validation for drugs and biologics (3). Although the agency did not explicitly state the requirement for implementation of QbD in analytical method development, the concept is embedded in its section…

May 18, 2017

Introduction: Tackling the Technical and Regulatory Challenges of Biosimilar Development

by

In a just a few years, the biopharmaceutical industry has gone from questioning the feasibility of “follow-on biologics†(around the time of BPI’s first issues) to fearing them (when we published our first supplement on the topic in 2013) to the acceptance and strategizing of today. Perhaps because of its more socialized medicine, Europe led the way in biosimilar regulation and approved its first such product nearly 10 years before the first US biosimilar launch in 2015. In between came…

April 18, 2017

The Clinical Side of Biosimilar Development

by

Biosimilars have become common on pharmacy shelves in Europe. The first biosimilar product — Sandoz’s Omnitrope version of Lilly’s Humatrope (somatropin) — was approved by the European Medicines Agency (EMA) in 2006. In the decade that followed, more than 20 biosimilars have gained regulatory approval in Europe. The first biosimilar monoclonal antibodies (MAbs) — comparators to Janssen’s Remicade (infliximab) — were approved in 2013. The pace of approvals in the United States has been much slower. The US Food and…

April 11, 2017

Evolving Bioassay Strategies for Therapeutic Antibodies: Essential Information for Proving Biosimilarity

by

The modern age of biologics began 35 years ago with the approval of Lilly’s Humulin product — a biosynthetic form of human insulin derived from recombinant DNA and microbial cell culture (1). Today, about a quarter (27%) of the drugs approved yearly by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are biopharmaceuticals: primarily monoclonal antibodies (MAbs), but also vaccines, blood products, and (recently), advanced therapies based on genes and cells. A decade ago, the average…

April 11, 2017