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By Prathap Shastri

Prathap ShastriWith an increasing interest in biologics, it is important to keep up with new innovations, emerging guidances, and advancements in the field of biotechnology. The U.S. biotechnology market has shown progressive growth dominating the global market: In 2012, it accounted for about 47% of the global biotechnology market. As the early biotech products near their patent expiration dates, biosimilars have gotten great attention throughout the industry and have led to a significant amount of investment in terms of time and research. More than 20 biosimilars are already approved in Europe and India, and the advent of biosimilars has already shown competitive pricing for the brand product. In 2007 a biosimilar for rituximab was launched by Dr. Reddy’s Laboratories in India. This led to a 63% drop in the brand product cost from $350 per 100 mg in 2006 to around $130 in 2010. The FDA is currently reviewing biosimilar applications, and soon biosimilars are expected to hit the U.S. market as well. With big pharma–including Pfizer, Amgen, Merck, and Biogen Idec–competing for the space in biosimilars, the advances in biologics research are reaching new levels. The alluring biologics market also brings multiple challenges to researchers in industry or academia during developmental phases.

Protein aggregation and stability is a common problem and a critical quality attribute of biologics that presents challenges during the product development process. This is not only a concern for the product quality but also as a potential safety concern due to the increased immunogenicity potential of protein aggregates compared to monomers. One of the ways to overcome stability issues in protein is by using protein engineering. Protein engineering combined with computational modeling has led to exciting outcomes to develop relatively stable proteins. Rilonacept, an interleukin 1 inhibitor marketed by Regeneron pharmaceuticals, is an example of an approved product that was developed using protein engineering.

Over the years, monoclonal antibodies (MABs) have contributed significantly to biotech’s growth. Antibody drug conjugates (ADCs) have shown great promise, and recent approvals include ADCetris (Seattle Genetics) and KADCyla (Genentech and Roche). One of the challenges during the development of ADCs is the ability to perform accurate or precise measurement of ADC exposure. Measurement of this exposure can be done at different levels, including measurement of conjugated or unconjugated antibodies, measurement of the antibody with one or more conjugated drugs or a measurement of the total amount of conjugated drug, and measurement of unconjugated drug in circulation. Although several assays are available for accurate measurement, overall interpretation of the pharmacokinetics of ADCs is complicated because there is no single assay that can capture all aspects of the in vivo behavior, such as rate of drug loss from an ADC, the effect of conjugation on ADC clearance, or the exposure-response relationships. Therefore, information from multiple assays must be integrated while interpreting the exposure to ADCs and pharmacological response.

The list of challenges and solutions in biotechnology grows endlessly. A remarkable amount of effort from researchers around the world has led to significant advancements. The 2014 AAPS Annual Meeting and Exposition in San Diego provides extensive programming geared towards educating attendees toward understanding challenges and recent advancements in the field of biotechnology, including:

We welcome everyone to participate in these sessions and learn from and share your knowledge with others from various sectors.

Prathap Shastri works for the ADME/DMPK group at WIL Reseach Laboratories in Ashland, Ohio. Prior to joining WIL research, he worked at Seventh Wave Laboratories working as a principal investigator for the PDM group.