Biologics have provided solutions to the 3R paradigm since the inception of recombinant human insulin (Lilly’s Humulin®) in 1982.  Because the insulin gene could be cloned and inserted into microorganisms and produced in cell culture reactors, there was no need to further harvest extensive tissue from cows and pigs (bovine and porcine insulins were animal insulins prior to r-insulin).  

Biologics as a model are not entirely new, but what is a recent development is their recombinant production. 

Historically old biologics existed (rabies vaccine, horse sera, etc.), but today “biologic” mostly refers to the following:

• Large, complex molecules that must be produced in living organisms
• Produced via recombinant methods
• Often based upon immune modulation
• Sometimes bring adverse immunological reactions
• “The process is the product” in terms of a QC vantage
• Consist of different classes that include monoclonal antibodies, coagulation factors, cytokines, vaccines, fusion/chimeric proteins, and cell therapy products

In terms of “refinement,” the biologics revolution has allowed for the recombination of molecules, including insulin, which now allows diabetics to utilize insulin varieties that do not occur in nature (e.g., “fast-acting”, “slow-acting” and “ultra-long acting” etc.).

Utilizing recombinant technology for rFC manufacture means that no horseshoe crabs (HSC) are needed, and the entire process is more ecologically friendly and infinitely sustainable.  HSCs are listed as “vulnerable” in the US (a pre-endangered status) and “endangered” in Asia (as defined by the IUCN(5)).  Many shore birds, like the Red Knot,⁵ who depend on HSC eggs for food on their migratory journeys, are now endangered from the loss of egg mass on the shores, particularly in Delaware Bay.

Sanctuaries have been created thanks to the importance of the species for medical purposes, but their vulnerability on the extinction scale exposes them more to other environmental impacts. It seems underappreciated that recombinant Factor C (rFC) is a non-animal-derived reagent produced in a biotechnology manufacturing facility used to detect bacterial endotoxins in pharmaceutical products.  Since it is not harvested from wild animals as is LAL, . the rFC assay helps alleviate pressures on its ecosystem derived from a growing demand for LAL. Additionally, because it is produced in an industrial lab, it is an inherently more reliable resource, ensuring greater supply chain security.

Global drug manufacturers are increasingly seeking to employ rFC to avoid the potential pitfalls of LAL’s (a) isolated geographical location of production, (b) the inherent variability of its batches that are naturally sourced, and (c) the risk of increasing costs given a global climate influx. They are prompting governmental authorities to revise outdated guidelines and add rFC in the texts.⁶