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.