Background information:
Due to cost reasons, the client decided to change the vaccine adjuvant.
Challenges:
During the bench scale development, the initial protocol was to emulsify the vaccine until the mixture reached 37ºC, which developed a perfect emulsion, however the water phase of the product (antigen) was temperature sensitive, which made temperature one of the PCP process critical parameters, hence a new development must be performed using a different emulsification process without heating the mixture until 37ºC.
Solution:
Formulate the product, heating the surfactant and mineral oil mixture before the emulsification process and to developed an emulsification process based on time and not on temperature.
Results:
Successful scalation of the process development.
Table Emulsion characteristics:
| Formulation type | Water in oil emulsion |
|---|---|
| Adjuvant | Polymeric |
| Volume | 16.000 liters |
| Antigen | Inactivated virus |
| Time to formulated | Under 8 hous |
Background information:
The client used a commercial ready-to-use adjuvant with “guaranteed” low local reactions in the animals and high potency.
Challenges:
The product, during development, resulted in severe local reactions in the animals, with several failures in the animal trials.
Problem:
The ready-to-use adjuvant is not compatible with the antigen produced by the client.
Solution:
To change the adjuvant and produce a potent emulsion with a low local reaction.
Results:
Thousands of animals have been successfully vaccinated using this adjuvant with minimal reaction and high potency, making it a reliable option for commercial scale production.
Table Emulsion characteristics:
| Formulation type | Water in oil emulsion |
|---|---|
| Adjuvant | Mineral oil and surfactant |
| Volume | 12.000 liters |
| Antigen | Inactivated virus |
| Time to formulated | Under 8 hous |
Background information:
Client use heat to sterilize the oil phase of the water in oil formulation.
Challenges:
The oil phase on the adjuvant plus surfactant is sterilized using heat, causing manufacturing delays and limiting capacity.
Problem:
Productivity decreases by heating sterilizing the oil phase before the emulsification process.
Solution:
Product filter sterilization
Results:
The client gained 20% more productivity and scalability by filtering the oil phase instead of heat sterilizing.
Table Emulsion characteristics:
| Formulation type | Water in oil emulsion |
|---|---|
| Adjuvant | Mineral oil and surfactant |
| Volume | 4.000 liters |
| Antigen | Inactivated virus |
Background information:
The vaccine uses a recombinant virus and polymeric aqueous adjuvant with pH-critical parameters.
Challenges:
The formulation uses pH in the formulation process, and the antigen is sensitive to pH variations.
Problem:
Antigen sensitive to pH variation and adjuvant
Solution:
The challenging formulation process was resolved by scaling up the process and defining CPM (Critical Production Parameters) and CQP (Critical Quality Parameters). Validation and manufacturing batches were successfully produced once parameters were established.
Results:
Successful scalation process and product commercially available with robust steps.
Table Emulsion characteristics:
| Formulation type | Aqueous solution |
|---|---|
| Adjuvant | Water polymeric adjuvant |
| Volume | 500 liters |
| Antigen | Recombinant vaccine |