An Overview of Some Issues in the Licensing of Botulinum Toxins
Botulinum toxin is a protein neurotoxin produced by Clostridium botulinum. Botulinum toxin blocks neurotransmission at the neuromuscular junction by inhibiting the presynaptic release of acetylcholine (for a recent review, see ref. 1). The ability of botulinum toxin to block neurotransmission and paralyze or weaken muscles has been useful in the treatment of different neurologic disorders. A number of focal dystonias and other conditions with involuntary muscle movements currently are being treated with botulinum toxin, and it appears to be a potentially valuable therapy for many of these conditions.2 A preparation of botulinum toxin type A (trade name Oculinum, manufactured by Allergan) was approved for human use by the Food and Drug Administration (FDA) in 1989. Oculinum is approved for the treatment of blepharospasm and strabismus, and also has been used experimentally for a number of other disorders. Oculinum has also been designated as an orphan drug under the Orphan Drug Act (ODA) of 1983, which entitles the manufacturer to a seven year period of exclusive marketing for the specific indication for which the product has been approved. This exclusive marketing granted to the manufacturer of Oculinum raises questions of how additional botulinum products can be licensed, for either the same approved indications as Oculinum or for other indications. This article will review general requirements for approval of botulinum toxin by the FDA, and discuss how regulations in the Orphan Drug Act might affect approval of additional botulinum toxin products.
KeywordsBotulinum Toxin Orphan Drug Cervical Dystonia Botulinum Toxin Type Botulinum Neurotoxin
Unable to display preview. Download preview PDF.
- 1.Wellhoner HH. Tetanus and botulinum neurotoxins. In: Herken H, Hucho F, eds. Handbook of Experimental Pharmacology, Volume 102. Berlin: Springer-Verlag, 1992: 357–417.Google Scholar
- 3.Federal Register, January 29, 1991, Notice of Proposed Rulemaking Orphan Drug Regulations.Google Scholar
- 4.Ludlow CL, Hallett M, Rhew K, Cole R, Shimizu T, Sakaguchi G, Bagley JA, Schulz GM, Yin SG, Koda J. Therapeutic use of type F botulinum toxin. N Engl J Med 1992; 326: 349–350.Google Scholar