The FDA requires all drugs in direct contact with sterile tissues or the bloodstream to be safe, effective, and fit for their intended usage. These drugs are manufactured in aseptic facilities that can do sterile fill-finish manufacturing to prevent contamination.
However, the increasing shift from large one-dose batches to smaller batches of personalized treatment options means the old sterile fill-finish method of washing, drying, and sterilization isn’t always viable anymore.
Instead, contract manufacturing organizations (CMOs) rely on ready-to-use components to simplify manufacturing and packaging processes. In return, it reduces their overall cost and the time it takes for drugs to reach the market.
This post explains what ready-to-use components are, their use, and the pre-sterilization methods.
What Are Ready-To-Use Components (Pre-sterilized Components)?
Ready-to-use (RTU) components, also known as pre-sterilized or ready-to-fill components, are packaging materials that are already sterilized for use. These containers help preserve a drug’s efficacy and quality during market distribution.
Furthermore, pre-sterilized components eliminate the need for extra steps (like washing, sterilization, and drying) when preparing to fill containers. They also guarantee compliance with regulatory standards and allow drug manufacturers to better serve their clients by providing quality and timely products. As a result, RTU components have become popular in the pharmaceutical industry.
What Are Ready-To-Use Components Used for?
RTU components are mainly used for packaging injectables. They comprise syringes, vials, and cartridges made of plastic and glass.
When it comes to injectables, product sterility during aseptic manufacturing and administration to the end user is key. RTU components are relied upon to protect a drug from contamination, oxidation, or leakage, ensuring its quality and shelf-life.
Different Sterilization Methods for Ready-to-Use Components and When They’re Used
Drug manufacturers get pre-sterilized components from suppliers, who ensure the RTU components are sterilized. Below is a description of some of the sterilization methods that ready-to-fill components undergo in line with the current FDA cGMP requirements and guidance:
Sterilization in a Dry Heat Oven
In this sterilization method, packaging materials are placed inside an oven with an insulated stainless steel chamber and perforated shelving for the circulation of hot air.
Once inside, the outer surface of the materials absorbs the heat from the oven until it reaches the last layer. The components are heated to the temperature and time points required for sterilization and the death of microorganisms.
As such, dry heat sterilization often requires a continuous supply of electricity and may take some time to complete. It’s only suitable for sterilizing ready-to-fill glass components, such as ready-to-use vials, since other materials can melt under dry heat. Dry heat is also used to depyrogenate the glass components. Depyrogenation is the process used to remove pyrogens (typically bacterial endotoxins). Dry heat depyrogenation/sterilization is the traditional method to prepare components used in commercial drug manufacturing.
Steam Sterilization in an Autoclave
Autoclaving is a sterilization method that involves using pressurized steam to heat the RTU components to be sterilized. Steam is the most effective in carrying thermal energy and relaying it to the material being sterilized.
Pressurized steam also has a higher latent heat than water. The intense heat from the steam is used to coagulate even the most resistant cellular proteins and kill microorganisms faster than other sterilization methods. This method is typically used for closures such as stoppers and seals. While a steam autoclave will sterilize the components, it is not an effective method for depyrogenation. Stoppers need to be depyrogenated through a validated washing cycle prior to sterilization.
Gamma Sterilization
Gamma rays carry electromagnetic radiation that can severely damage the DNA of microorganisms. They make excellent sterilizers for ready-to-fill vials, syringes, and other injectable RTU components.
In terms of effectiveness, gamma sterilizers are great at penetrating different surfaces, especially for large-scale sterilization of plastic materials used to manufacture sterile components. Depyrogenation is possible through gamma sterilization. However, there are some downsides to this sterilization method. The gamma rays can cause cosmetic defects in glass and plastic, such as discoloration. it’s also possible that some grades of plastics and glass can be weakened.
Ethyl Oxide or Chemical Sterilization
Chemical sterilization using strong disinfectants such as ethyl oxide can be used to sterilize ready-to-use components. In this method, ready-to-fill components are soaked inside the chemical solution for a minimum of 10 hours. The prolonged exposure to the chemical kills endospores and unwanted microorganisms.
Generally, chemical sterilization is used when RTU components can be damaged by dry heat or high-pressure steam sterilization. This method can also be used when equipment to undertake dry heat and high-pressure sterilization aren’t available.
Traditional Sterilization Methods for Commercial Products
Out of the sterilization methods available, these two are the most common and readily available for commercial products:
- High-pressure, saturated steam in an autoclave: High-pressure steam sterilization is the most effective sterilization method. Here, high-pressure steam fueled by electricity, fuel, or kerosene sterilizes the components.
- Dry heat in an oven: Dry heat sterilization involves placing RTU components in an oven and sterilizing them using moisture-free heat. The high temperatures create an oxidative environment inside the oven that kills off any microorganisms and pyrogens present.
Keep in mind that for any sterilization method to be effective, it requires time, temperature, contact, and high pressure (for steam sterilization). Other factors that can influence the effectiveness of a sterilization method are:
- Microorganism type – Some microorganisms are difficult to kill, while others die off easily.
- The number of microorganisms present – The more microorganisms present in a ready-to-fill component, the harder it is to eliminate them than if it were one organism.
- Type and amount of organic material protecting microorganisms – Tissues, oil, blood, or other materials in a ready-to-use component can shield microorganisms during sterilization, complicating the process further.
- The number of weaknesses in an RTU component – Cracks, scratches, and crevices on packaging can harbor microorganisms, making them more difficult to remove during sterilization.
It’s important to thoroughly clean materials to remove organic matter from the ready-to-use components that could protect microorganisms when sterilizing. This way, you will have a greater chance of success.
Know More About Ready-to-Use Components
Ready-to-use components are pre-sterilized packaging materials used in the fill-finish manufacturing of drugs. These sterile packaging materials preserve the efficacy and quality of drugs until they reach the final consumer.
Most CMOs and contract-development and manufacturing organizations (CDMOs) today rely on pre-sterilized components, including sterile vials and syringes, to minimize cost and reduce the downtime of products reaching the market.
The main methods used to sterilize RTU components are dry heat sterilization and high-pressure steam sterilization, but nonconventional sterilizers, such as gamma rays and chemicals, can also work.
Remember, the effectiveness of sterilization methods depends on how to clean your ready-to-fill components before sterilizing them. If you wish to learn more about sterile components, visit our website. You can also reach out to us to talk to one of our representatives.