This Month’s Issue

The November issue cover is illustrated by a technician checking the high-speed filling line at IDT Biologika’s new facility in Dessau, Germany, which can handle 24,000 vials every hour. Read it Now.

November Supplement

2014-2015 Poster Hall 
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Guidance Is Lacking in the European Biosimilar Regulatory Framework: Considering the Dynamic of Quality Profiles in Development

Biopharmaceutical medicinal products (biologics) had an estimated global commercial market size of US$100 billion in 2013. Because they are more complex than small molecules — and defined by the uniqueness of their manufacturing processes — the generics approval process is not applicable for biologics. Article 10(4) of European Medicines Agency (EMA) directive 2001/83/EC was amended in 2004 in response to the industry’s desire for market access by launching a “similar” biologic abbreviated approval pathway. Leading the subsequent process, the EMA…

Figure 4:  Structural variety of FDA-approved Fc-fusion proteins is illustrated. Typical receptor ECD- containing Fc fusions exhibit single-ligand specificity in bivalent fusion constructs such as (i) alefacept, and (ii) abatacept and belatacept (black dots in denote Cys–Ser mutations in the hinge); “cytokine traps” (iii) such as rilonacept, aflibercept, and ziv-aflibercept; and “peptibodies” (iv) such as the aglycosylated romiplostim with single-ligand specificity in multivalent fusion constructs (in which peptide mimetics represented by large red ovals are attached in tandem and separated by flexible spacers at the C-terminal end of IgG Fc); etanercept (i) and clotting factor Fc (v) FIX Fc and FVIII Fc, with single-ligand specificity in a monovalent fusion construct. Shown in yellow are domains of truncated FIX. Horizontal lines indicate interchain disulfide bonds. Glycosylation sites are indicated in the ligand-binding domains (small red ovals) and Fc domain (small gray ovals). This figure is reproduced and adapted with permission from (3). 


Immunoglobulin Fc-Fusion Proteins Part 2: Therapeutic Uses and Clinical Development

The potential therapeutic value of many proteins — including enzymes, receptors, cytokines, blood factors and peptides — can be realized by fusing them to the Fc region of human immunoglobulin G. Of the 46 monoclonal antibody (MAb) and MAb-derivative products approved by the FDA to date as human therapeutics, 10 are Fc-fusion proteins (Table 2). Among approved products, several structural variations are represented (Figure 4). In BPI’s October 2014 issue, Part 1 of this review examined the structure and manufacturing…



Unwanted Immunogenicity: From Risk Assessment to Risk Management

Although vaccines and immunotherapies are designed to engage the human immune system in fighting disease, unwanted immunogenicity can be a major problem for protein-based therapeutics. Some patients produce antidrug antibodies (ADAs), which might lead to drug inactivation or adverse effects. Even human and humanized proteins have proven to be surprisingly immunogenic in some cases, suggesting that immune tolerance requires careful consideration in biologic product design. In rushing to deliver new drugs to market, some biotherapeutics developers have overlooked factors that…