BoNT Quality Control and Lot Release Testing
The use of natural products as novel therapeutics in medical and cosmetic indications has increased in recent years. One such product is Botulinum toxin, a protein produced by the bacterium Clostridium botulinum that is used to treat muscle spasms, chronic pain, hyperactive nerves, eye muscle disorders and other emerging therapeutic indications. Because of the toxicity of botulinum toxin, it is crucial for that the potency of the product is very accurately determined. The gold standard for botulinum toxin potency testing is the in vivo mouse botulinum toxin bioassay.
Since 1990, Pacific BioLabs has been working with botulinum toxin developing and offering a variety of in vivo and in vitro testing paradigms in support of research and clinical development efforts by private and commercial entities. PBL’s experience performing the in vivo mouse botulinum toxin bioassay is unmatched. Pacific BioLabs is registered, and works closely, with the Federal Select Agent Program at the CDC ensuring compliance with federal regulations associated with handling of botulinum toxin.
Botulinum toxin use is highly regulated by both the Food and Drug Administration (FDA) and the Centers for Disease Control (CDC) given its potent biological mechanism of action. Pacific BioLabs is registered with the CDC’s Federal Select Agent Program which means that we are capable of working with large amounts of botulinum toxin.
Pacific BioLabs has an experienced and dedicated staff with expertise in botulinum toxin testing offering the following assays:
- Botulinum Toxin Identity, Dose Concentration Verification and Purity Testing
- Botulinum Toxin Bioassay – In Vivo Lot Release Assay
- BoNT In Vivo and In Vitro Immunogenicity Assays – Patient Serum Testing
- BoNT Cell Based Potency Bioassay Development
Botulinum Toxin Identity, Dose Concentration Verification and Purity Testing
Pacific BioLabs supports manufacturing related activities for botulinum toxin lot release, which includes identity and dose concentration verification by ELISA and purity testing by SDS-PAGE or HPLC. Purity, identity and dose concentration verification methods can be validated per both ICH and FDA guidelines.
Botulinum Toxin Bioassay – In Vivo Lot Release Assay
Each therapeutic preparation of botulinum toxin is required by the FDA to be tested for potency and stability before being released for use. Pacific BioLabs supports testing of both the active pharmaceutical ingredient (Drug Substance) and the final formulated product (Drug Product) for potency and stability.
BoNT In Vivo and In Vitro Immunogenicity Assays – Patient Serum Testing
Patients undergoing treatment with botulinum toxin may develop antibodies that make the toxin ineffective, or less effective, against the indication for which they are being treated. Therefore, during the course of treatment a physician may want to determine if a patient has generated antibodies against the toxin. Patient serum samples can be submitted by physicians to Pacific BioLabs for testing in an in vivo assay that will confirm the presence or absence of antibodies to botulinum toxin. If a patient has developed botulinum toxin antibodies, the test assay will be positive for toxin activity. If no antibodies are present, the test assay will be negative for toxin activity. In a similar manner, patient serum samples submitted to Pacific BioLabs can be subjected to an in vitro ELISA test method that will confirm the presence of antibodies against botulinum toxin.
Both test methods may be used to support developmental activities, including ongoing clinical trials and post market clinical surveillance programs.
BoNT Cell Based Potency Bioassay Development
There is an increased awareness in drug development for the implementation of cell based assays for the determination of botulinum toxin potency, which has already been initiated by several pharmaceutical and biotechnology companies. There are many compelling reasons to develop cell-based assays, not the least of which are high throughput testing and long term cost savings when compared to in vivo testing. Furthermore, cell based assays have the advantage of evaluating key biological processes that include binding of the toxin to its receptor, internalization-translocation of the receptor and subsequent catalytic activity that may benefit potency optimization efforts that in vivo assays cannot support. Given the extensive experience working with botulinum toxin and bioanalytical expertise, Pacific BioLabs scientists are exploring cell based bioassay methods for botulinum toxin potency determination in order to support customer needs.