Quality Takes Control: Sterility Assurance for Packaging Parenteral Drugs

Injectable, or parenteral, drugs are particularly susceptible to contamination from materials such as silicone and cellulose, as well as from airborne particulates. In order to ensure the most sterile materials possible, manufacturing must be tightly controlled, with every part of the process strategically monitored to prevent entry points for potential contamination.

Manufacturers should ensure that personnel receive rigorous safety training as well as proper PPE equipment, and that facilities offer proper air flow.

It is instructive to review the various techniques for sterilizing components used in parenteral drug packaging. These methods can be divided into physical and chemical processes.

1. Heat
Steam sterilization is a common and accepted method for many parenteral drug components and has no measurable effects on a rubber compound’s physical or chemical properties. However, because steam often results in residual moisture, subsequent drying steps are required that may affect rubber properties. Steam’s residual moisture also makes it a less desirable sterilization choice for certain drug products which are reactive to any moisture.

2. Irradiation 
An alternative physical technique, Gamma irradiation, offers higher penetrability through electromagnetic wave properties, making it more suitable for dense bulk sterilization, even for full pallet configurations. This is a popular option for manufacturers because it is considered reliable and cost-effective. It is also clean, leaves no residuals and operates at low temperatures. While the chemical properties of elastomers are not altered by gamma irradiation, there could nevertheless be alterations in the physical properties of the rubber.

3. Chemical 
EtO sterilization is widely used in the biopharmaceutical industry; its effectiveness, however, depends on variables such as pressure, time, gas concentrations, temperature, and relative humidity, requiring careful monitoring.

Because rubber typically absorbs EtO residues, sterilization should only take place with dedicated rubbers that have high EtO permeability. Importantly, EtO is not suitable for certain compounds like butyl rubber because of chemical byproducts that are created. EtO has also received some unwanted scrutiny from the EPA over environmental concerns.

One of the significant challenges of sterilizing parenteral drug products is the fact that they are made up of different components, and each component has its own unique material properties.

Given these complexities, it is important to consult a supplier who has a thorough understanding of the material science of packaging components, and the impact of different sterilization techniques on specific drug formulations being packaged. This can help determine the best method to sterilize all components within a packaging system.

New sterilization techniques being introduced to the market may offer manufacturers some options to optimize their operations. One example that manufacturers are eyeing is chlorine dioxide (ClO₂), a water soluble yellow-green gas that acts as a biocidal agent against bacteria, fungi, viruses, and bacterial spores. It has been EPA registered, found to be competitive with traditional techniques, and possibly more effective compared to gamma irradiation or EtO chemical sterilization.

Another technique under review is the use of X-ray. Its penetration is superior to that of gamma rays, and it enables easy full pallet sterilization. It requires a shorter exposure time and works on electricity, not on radioactive materials. X-ray does not require specialized facilities and may be a more cost-effective and easier option for pallet irradiation. However, like gamma irradiation, the use of X-ray can cause physical alterations in rubber properties.

Drug manufacturers can take advantage of ready-for-sterilization (RfS) and ready-to-use (RTU) products available on the market that can help simplify the complexities of sterilization.

Currently, RfS products are available that are compatible with steam or gamma sterilization methods, and suitable for companies with pre-existing equipment and sterilization processes, or who use trusted third-party sterilization vendors. RTU products sterilized with gamma irradiation are currently available for manufacturers and can be incorporated into fill-finish operations with no additional washing or sterilization needed.

Manufacturers can also consider enhancements to primary packaging such as restricted access barrier systems used in the production of drug and biologic products.

The universe of parenteral drugs is expanding, as is their complexity. Manufacturers have an ongoing need to enhance and ensure the safety and sterility of their processing and packaging operations. To keep up with the array of sterilization options, it is best to develop a partnership with your packaging supplier which you can leverage to navigate these complexities. Ensuring best practices in sterilization can enhance public health and protect a company’s corporate reputation.