Producing Biologic Drugs with Sterile Fill Finish

Choosing a sterilization tactic for a drug product that needs aseptic fill finish production is commonly determined by the drug substance stability. For terminal sterilization, stable products that include heat sterilization exposure to chemicals like vaporous hydrogen peroxide and ethylene oxide or radiation is the preferred strategy.

These methods have advantages. This is because the processes can be tracked and validated and are less susceptible to error.

However, most biologic drugs are not stable when exposed to chemicals, radiation, or heat, and they usually require aseptic fill finish manufacturing with the use of sterile filtration. A successful sterile filtration demands a drug product formulation with the right viscosity and compatibility with the shear stresses involved in fluid pumping and the contact surfaces.

Today, single-use technology is vastly used in sterile fill-finish operations. And it helps to reduce the cross-contamination risk and turnover time.

At Abbvie, we have successfully advanced and distributed drug products for over 130 years, delivering products to more than 175 countries globally. There is no basis for the question as to whether or not we are excellent at what we do. 

Factors with Formulations

The most important fact that must be considered from the beginning when developing formulations for biological drug substances that need sterile filtration includes the product’s physical and chemical stability under several conditions during the manufacturing of products, shipping, storage, and administration.

Some factors that are related explicitly to sterile filtration include the shear forces involved, contact surfaces, and the potential to induce particle formation or aggregation.

The method for sterilization of primary packaging or fill-finish equipment must be considered. This is because any residual chemical has the potential of interacting with biologics.

The method used to sterilize the fill finish equipment or primary packaging must also be considered because any residual chemicals may interact with the biologic.

Addressing the Issues

To address these challenges, some excipients can be included to reduce process loss to the filter, negative interactions between the filter, and biologic or residual sterilization chemicals that can lead to decreased rates of filtration, aggregation, or particle formation.

To make sure that contaminants are excluded and that sterile filtration will be effective, it is crucial to test every batch process.  

Because biologic drug substances can be sensitive to shear stress, the pumping and mixing during formulation need to be gentle to prevent aggregation and conformational mutations of the biologic.

In addition, drug fill finish processes need to be performed under controlled temperatures to avoid thermal degradation. A lot of biologics are lyophilized during the last fill as a result of their thermal instability.

Generally, product development must carefully consider the method of manufacturing that was intended. It is very important to evaluate whether every essential process unit operation of the manufacturing process beyond normal operating parameters will impact quality attributes.

At AbbVie, we handle your product as our own. The nature of your biologic drug notwithstanding, you can count on us when it comes to aseptic fill-finish manufacturing. We will provide reliable and safe products that patients are ready to use.