Manufacture of the first FDA-approved batches of 900 kilodalton crystalline type a botulinum toxin for clinical use: a personal remembrance.

Type A crystalline 900 kDa botulinum toxin (BTX-A) was first approved in December 1989 by the US Food and Drug Agency (FDA) as an orphan drug for treatment of strabismus and blepharospasm associated with dystonia in patients twelve years and older. This approval opened a new industry of pharmacology and therapeutics of botulinum toxins. Spanning treatment over 30 indications and 10 medical fields, BTX-A has become invaluable for numerous patients and physicians alike. To this day, BTX-A sales is a multibillion dollar industry and is growing annually, but BTX-A had humble beginnings with Edward J Schantz and my need to overcome difficulties in manufacturing and evaluation of BTX-A for FDA approval and for Alan B Scott to develop his strabismus primate model. Crystalline botulinum toxin was first injected into rhesus monkeys for strabismus in 1972. This important and hands-on collaboration with my mentor, Ed Schantz, and later myself in the 1980s and 1990s, spearheaded a 17 year journey preceding approval by the FDA. This paper describes key activities in the collaboration of Ed Schantz, Alan Scott, and myself, including some of the trials and tribulations we went through in commercial preparation of BTX-A in the 1980s and 1990s at a public university.