How to Excipient selection in biologics and vaccines formulation Manufacturer

An excipient plays a significant role in the formulation of molecule pharmaceuticals as these are an integral part of pharmaceutical products. Novel excipients are used in various ways depending on several factors, such as the active ingredient, the route of administration, the dosage form, the target population, and the indication, etc.

Additionally, stabilization during processing and storage is a major challenge for the pharmaceutical industry. As a result, biologics and vaccines are vulnerable to degradation by numerous chemical and physical mechanisms. Consequently, the processing and storage of biologics and vaccines require a variety of excipients.

GRAS excipients are the most commonly used excipients in biologics and vaccine formulations.

It is important to understand interactions between actives and excipients when formulating protein-based therapeutic drugs for stabilization. The complexity of Excipient manufacture is often more pronounced for the development of high concentration antibody formulations.

Antigens based on peptides, proteins, and subunits can also be developed similarly to biologics.

Other side, vaccines for emerging markets would benefit from excipients that improve thermostability, especially if they can reduce the requirements for a cold chain during storage or distribution.

Excipient selection

The formulation process can be broken down into three distinct but interrelated stages, namely pre-formulation, formulation, and process development.

Pre-formulation involves determining the amino acid the sequence of the biologic, performing biochemical and biophysical characterization as a function of pH, ionic strength, and excipients to understand the prominent degradation pathways. 

The development of frozen or lyophilized products may be initiated if preliminary stability studies indicate that a liquid formulation will not meet the desired target product profile established early on in the program.  

An approach based on rationality during the a pre-formulation stage may also provide a basis for achieving QbD (Quality by Design) during formulation development.

Formulation of vaccines using adjuvants

Be sure to understand antigen-adjuvant interactions before choosing the type and amount of adjuvant to use, as they will have an impact on the stability and immunogenicity. Excipients that stabilize antigen-adjuvants maybe necessary if aluminum adjuvants are included to prevent physical and chemical degradation of the antigen on the surface of the adjuvant.

Conclusion

The excipients should be determined based on a comprehensive understanding of their impact on the product during multiple events that may relate to drug substance processing, freeze-thaw, time-in-solution, filtration, mixing, material compatibility, formulation/fill process, lyophilization process, long-term stability, and photosensitivity, time-out of refrigeration, in-use stability, and shipping. In most cases, biologics and vaccines are designed for parenteral administration and require endotoxin-free excipients. Before deciding on excipients, the cost and ease of sourcing pharmaceutical-grade excipients need to be considered.