The main goal of the aseptic filling process in manufacturing is to give patients medical products that are free of contaminants and as beneficial and safe as possible.
Aseptic Filling Process in Manufacturing
The aseptic filling process in manufacturing uses the fill-finish mechanism. Fill-finish is a procedure that sterilizes the medicinal product, container, and container lid separately before combining them. The phase of mixing the product, container, and closure is performed in a clean facility and often uses sterile special equipment.
We use vaccines, ear, and eye drops, nasal sprays, and other medications daily. Thus we want them to be completely sterile and clean. Add anything non-sterile to your eye, nose, or injected into your muscle, skin, or vein, and you risk major unpleasant effects like fever and infection. Aseptic processing, also known as fill-finish manufacturing, is a specialized manufacturing method used for this purpose. It eliminates potential contamination and contamination sources through a series of sterilization, isolation, and cleaning steps.
Aseptic processing is the process of making a formulation, pouring it into a vial, syringe, ampoule, or cartridge, and then inspecting, labeling, and packing it in a sterile environment. This method is also popular as “fill-finish manufacturing.” But this phrase better describes the last steps of the aseptic process. No matter what terms are, the end result is the same: consumables that is free of harmful microorganisms and other impurities.
What Is the Difference Between Aseptic and Sterile Manufacturing?
It’s essential to tell the difference between aseptically manufactured goods and those just sterilized. The term “aseptic” describes a manufacturing procedure designed to ensure that no living organisms are present at any time throughout the production cycle. The term “sterile” refers only to the absence of living organisms in the final product.
Regulations say that any product should be sterilized at the end. Aseptic preparation is used when the drug can’t handle the thermal cycle of terminal sterilization. This happens when the medicine is filled. What gives? To make safe products using modern aseptic techniques, you need a better level of design and operation. Instead, it is much easier and cheaper to reduce the number of bacteria along the way and then use heat to kill any remaining bacteria. Like most biologics, vaccines, and cancer drugs, many drugs can’t stand up to a step of heat sterilization.
Terminal Sterilization
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Diluent solutions and IV standard bag solutions
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Small-molecule drugs that don’t break down in the heat
Aseptic Processing
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Antibiotics, biologics, vaccines
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Monoclonal antibodies, antibody-drug conjugates
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Molecules with short, medium, and long chains that are sensitive to heat
Operational Members
It takes careful cooperation and a detailed relationship between the following for the aseptic filling process in manufacturing to be successful:
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Cleanroom and support structures
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Equipment and cleaning systems
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Pre-sterilized and sterilized products
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Support members
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Personnel
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Transfers
Regulation Monitoring
Injectables, eye drops, and nasal drops are subject to tight rules. Fill-finish activities are carefully regulated because they risk contamination or drug deterioration and their technical nature.
Aseptic Filling Process in Manufacturing Requirements
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Manage viable and non-viable space pollution.
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Bioburden control protects the product.
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Clean to control viable and non-viable particles.
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Optimize GMP by covering important areas with a risk-based strategy.
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Train and follow aseptic protocols.
Managing Biologics
Small, medium and long-molecule API medications are expanding to fulfill patient demands. Biologics provide five challenges:
1. Steadiness
Most biopharmaceuticals are delicate, and processing and filling may influence protein structure, activity, and stability. Many biopharmaceuticals are watery. Proteins are also unstable in liquid. Thus their 3D design must be preserved throughout the aseptic procedure. Temperature control maintains stability.
2. Filling
Like a vial filling machine, filling equipment is ideal for precisely filling each biological dose. As patients must have correct doses. The automatic filling and packaging equipment lowers the risk of contamination at every step, from making the biologic to storing it, shipping it, and giving it to the patient.
3. Inspection
Biologics inspection problems include looking at clear and cloudy solutions in amber vials, telling the difference between foreign and product-related particles, and finding contaminants even when they look clean or sterile. There must be strong QA controls to keep patient products from contamination.
4. Risks
Product loss is possible. Pharmaceutical manufacturing requires time, effort, supplies, and labor before filling the final container. Any bacterial or human contamination at the last phase might harm patients and cost manufacturers financially.
5. Shipping/Transferring
It costs a lot to keep and ship parenteral formulations in a cold chain. This causes companies to think of new ways to fill medicines at the end, which helps reduce the need for cold chain storage and transportation. When filled vials are lyophilized, the cold chain costs decrease, and the product stays stable.
The aseptic filling process in manufacturing depends on the equipment, controls, and detailed procedures. It has more dangers than processes that aren’t clean. So, it needs more expertise and assessment than other pharmaceutical procedures, like dosing with oral solids.
Failures during the “fill-finish” phase that cause microbial contamination, problems with formulation, and dosage problems may result in:
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Product loss
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Negative effects on production
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Patients’ possible health risks
When the filling process in manufacturing is done right, it makes the factory more productive. Every business case is different, and every facility has its own set of problems that need solutions dependent on size, risk, and product pricing, among other things. When designing a facility, you have to think about line speeds, transfer times, and even how to clean. To find the best solution, you must do a cost-of-goods analysis and a risk assessment to lower both.
Another thing to think about is how flexible you want to fill lines. The flexibility of a fill line can be measured by the product profile, the value, or the type of container. For instance, your facility may find it helpful to be able to handle vials, syringes, and cartridges all on the same line. Other facilities might want to be able to make different kinds of products on the same line, such as monoclonal antibodies, cell therapies, and gene therapies. How much flexibility a company needs will depend on what it wants to do with its filling lines.
Today’s Aseptic Processing
Even before the pandemic increased the need for pharmaceuticals, the aseptic processing industry was under a lot of pressure. The aseptic filling process in manufacturing new products was already hard to come by because CDMOs were already running at 95–98% volume. If a firm wanted to sell a new medicine, it had to wait in line for a long time. Many pharm companies were already setting up new places to make their products so they could be final-filled.
When the COVID-19 vaccines were prepared to be made, much of the CDMO’s manufacturing capacity was quickly redirected. This means that most ATMP businesses need to arrange to have their own fill-finish resources. Concerns about fill-finish, timeliness, and medicine shortages are significant concerning biologics, biosimilars, and generics.
As more small-batch, targeted biologics come onto the market, the difficulties of aseptic processing will keep getting harder. Automation advancements and cleanroom technology, such as isolators and restricted access barrier systems, will make it possible for fill-finish operations to become more flexible and handle more than one product.
Automating Aseptic Processing
There will be more and more automation in manufacturing industries, from simple tasks to those that are fully automated. Automation is essential in every industry, and a manufacturing facility can benefit from it. Using automatic filling machines can make it easier to follow GMP rules and reduce contamination. In any clean room process, operators are a major source of contamination, so reducing the number of operators can lower the overall level of contamination. In the end, this leads to a higher level of productivity. As the chances of contamination go down, product safety and, by extension, patient safety go up.
One significant advantage of using an automatic filling process in manufacturing is that it cuts down on the number of repetitive work that the operators have to do. Automatic filling machines are made to do repetitive tasks, so if you use them to do repetitive tasks, you’ll need fewer operators. Overall, a higher level of automation can help reduce human mistakes and make a big difference in how many daily batches a facility can make.
It is possible to have a fully automatic aseptic fill-finish process without taking medicine out of its lyophilization environment. A lyophilizer is automatically loaded with filled vials. Then, stoppers connect to vials while the lyophilizer shelves are automatically lowered. The whole process requires a very accurate setup since vials must be made in batches with their caps sitting on the vial edges. It takes place in isolation inside a barrier system.
With automatic systems, they must be carefully programmed to do fill-finish steps a certain way until they are told to do something else. Automatic systems also may not have all the tools they need to handle unexpected events or changes. Even in the most automatic aseptic processing facility, humans will always to keep an eye on things. Data integrity is another critical part of automation that you should pay attention to. For instance, the FDA wants control over logins and passwords to keep information, and avoid stealing. Online information needs to be safe. Possible data breaches are being closely watched and have led to citations.
Future Aseptic Facilities
As the fill-finish industry grows, it will be more important to work together, manage risks, and follow the rules about aseptic processing. To meet the growing demand for fill-finish services, it’s important to have:
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skill and knowledge
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relevant tools
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both upcoming technology and business model advancements