Like a carton of milk, biological drugs can change over their lifetime and eventually go bad. Such changes have the potential to induce an immunogenic response, according to Northeastern’s chemistry and chemical biology chair Graham Jones. With a chemical drug, he explained, “if it goes off, degrades, it’s just not going to work very well, you’ll need to adjust the dose. If biological drugs go wrong, they can kill you.”
Because of this variability and their overall complexity, Jones said analysis of biologics and their generic counterparts, biosimilars, can be extremely challenging. The standard techniques used to analyze small-molecule drugs — the standard in today’s health-care system — are not sufficient. Instead, companies and researchers must adopt more nuanced techniques that couple multiple analytic protocols.
In a paper released Friday in Nature Reviews Drug Discovery, Jones and chemistry professor John Engen assess the various techniques currently available for accurate biosimilar analysis. Biologics have a broad definition, Engen said. They could be proteins, antibodies or even living cells, all with one common feature: They are produced using biological methods, not synthetic chemistry. Unlike small-molecule drugs, biologics and biosimilars contain several thousand atoms and have complex 3-D structures.
With dozens of biologic drugs coming off patent in the coming months, the industry for biosimilars is expected to quickly swell, making efficient and manageable analytical techniques crucial. In early February, the Food and Drug Administration released regulatory guidelines stating three modes of biologic drug variation that could pose a health threat to patients and thus require precise screening. Two years of negotiations included testimony from Jones, who is also involved with the Barnett Institute of Chemical and Biological Analysis.
The institute, with its history in genomic and proteomic analysis, is uniquely situated to address the various analytical challenges now facing the field. For example, Engen has developed an instrument that turns a difficult and time-consuming biosimilar analysis process into an automated protocol.
Recognizing this advantage, Waters Corporation has provided Northeastern and Barnett Institute with specialized instrumentation to assist in a broad-reaching program that will make biosimilar analysis a manageable and efficient process. The program includes a state-of-art research laboratory housing dozens of analytical instruments, a master’s degree focusing on the area of biosimilar analysis and a training program to teach industry users and regulatory agencies how to achieve accurate characterizations of their materials.
Still, Jones said, “we need to go beyond this and look into the consumer side. What techniques can we develop that are very easy, rapid and inexpensive and [that can be used] at the pharmacy level.” As he explained, since biologics and biosimilars can go bad at any point in the supply chain, eventually what will be needed is something as simple as the sniff test used on old milk for when they reach the market.