Process and system for obtaining botulinum neurotoxin

A vacuum-dried or lyophilized pharmaceutical composition comprising:

• a) a substantially animal protein free (APF) drug substance comprising about 100 Units of biologically active, approximately 900 kilodalton (kDa) Clostridium botulinum toxin serotype A (BoNT/A);
• b) about 0.5 mg of human serum albumin (HSA);
• and
• c) about 0.9 mg sodium chloride;
• wherein:
• the biologically active, approximately 900 kDa BoNT/A is obtained by a substantially animal product free (APF) culture, fermentation, and purification process utilizing a plurality of chromatography columns;
• the substantially APF culture, fermentation, and purification process utilizes a Hall A strain of Clostridium botulinum;
• the substantially APF drug substance has a residual nucleic acid content of less than 1 ng per mg of biologically active, approximately 900 kDa BoNT/A;
• 1 Unit of biologically active, approximately 900 kDa BoNT/A is an amount that kills 50% of a group (LD50) of female Swiss Webster mice weighing about 18-20 grams each upon intraperitoneal injection;
• and
• the composition is reconstituted with normal saline prior to administration to a human patient.

A vacuum-dried or lyophilized pharmaceutical composition comprising:

• a) an essentially animal protein free (APF) drug substance comprising about 100 Units of biologically active, approximately 900 kilodalton (kDa) Clostridium botulinum toxin serotype A (BoNT/A);
• b) about 0.5 mg of human serum albumin (HSA);
• and
• c) about 0.9 mg sodium chloride;
• wherein:
• the biologically active, approximately 900 kDa BoNT/A is obtained by an essentially animal product free (APF) culture, fermentation, and purification process utilizing a plurality of chromatography columns, including an anion exchange chromatography (AEX) column followed by a cation exchange chromatography (CEX) column;
• the essentially APF culture, fermentation, and purification process utilizes a Hall A strain of Clostridium botulinum;
• the essentially APF drug substance has a residual nucleic acid content of less than 1 ng per mg of biologically active, approximately 900 kDa BoNT/A;
• 1 Unit of biologically active, approximately 900 kDa BoNT/A is an amount that kills 50% of a group (LD50) of female Swiss Webster mice weighing about 18-20 grams each upon intraperitoneal injection;
• and
• the composition is reconstituted with normal saline prior to administration to a human patient.