Biosimilars: They May Look the Same, but One is a Real Stinker

Biosimilars by nature look much like their comparator products, but they sometimes behave quite differently. That’s because the two products often originate from different cell lines or expression systems. And no matter how hard you strive for parity in the way they’re cultured, minor differences in manufacturing can lead to sticky variations in primary amino acid sequence, glycosylation chemical modifications and protein folding issues. The FDA understands biosimilar products sometimes behave differently than their name-brand counterparts. But, they do expect you to understand why those differences occur, and to demonstrate that they have no clinical significance. That’s where ABC Laboratories comes in.

Choosing the Right Analytical Partner May Be the Most Economically Important Decision You Make

FDA guidance calls for a “complete and thorough” CMC section that begins with extensive comparative characterization of the biosimilar and... click here for more.

Gene Editing - A New Frontier

By Glenn Petrie, Ph.D.
Senior Scientific Advisor
ABC Laboratories
www.abclabs.com

A new technology for “editing” genes has scientists excited about an entirely new method for treating disease. The CRISPR technique, along with other gene-editing technologies (TALENS, zinc finger nucleases) allow for the precise deletion of specific DNA sequences. CRISPR involve a Cas9 protein linked to an RNA strand. The RNA sequence serves to target the specific DNA sequence of interest and once bound the Cas9 enzyme cleaves both strands of the DNA.

Above graphic credit (link) to Scitechweb.com 

Since RNA synthesis is relatively cheap and easy this technology has exploded in the last 2 years. Feng Zhang and Eric Lander at MIT have created CRISPR libraries that target essentially the entire human genome. The promise of the technology is to delete genetic mutations and replace them with the correct genes.  Initial targets involve only a single mutation, e.g. sickle-cell anemia, progressing to diseases involving multiple mutations.

As with any new technology there are calls for caution. Chinese scientists reported attempts to repair defective genes in human embryos. This held up the specter of future “designer babies” enhanced in their embryonic stages. Others warn that this technology could be used to “weaponize” bacteria or viruses. Several prominent scientists have proposed a complete moratorium on gene editing until proper safeguards are in place.

Despite these concerns several biotech start-ups have been founded in the last 2 years including Intellia Therapeutics, Editas Medicine and Crispr Therapeutics. Successful in vitro results have been reported for the repair/modification of clinically important genes in hematopoietic stem cells, fibroblasts and T-cells. A quick internet search yields a number of companies offering their services to utilize CRISPR to perform gene editing in both cell lines and whole animals. Based on the extremely rapid advances in this area, gene-editing using CRISPR and other technologies promises to revolutionize our ability to manipulate the genome and attack genetic diseases.

Biosimilarity: Can You Spot the Differences Between the Bunnies? Now Can You Spot When the Differences are Clinically Significant?

Attempting to create an exact duplicate of the comparator product would be a fool's errand. Variations such as primary amino acid sequence, glycosylation chemical modifications and protein folding issues are common. Your challenge is to determine whether those differences have clinical significance—and when they do, to make well informed mid-course adjustments to keep development moving forward.

Choosing the Right Analytical Partner May Be the Most Economically Important Decision You Make

Recent FDA guidance calls for a "complete and thorough" CMC section that begins with extensive comparative characterization of the biosimilar and reference products. This information is used to substantiate chemical, physical and bioactive similarity, which ultimately will influence the scope and number of animal and clinical studies that will be required to demonstrate interchangeability. In other words, a deficit in analytical characterization expertise can equate to a great deal of...

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