Automated loading and unloading systems for lyophilizers: autoloader systems can greatly reduce the risk of product contamination and are a cost-effective choice for many applications

/Home/Lyophilization Articles & Reports

Automated loading and unloading systems for lyophilizers: autoloader systems can greatly reduce the risk of product contamination and are a cost-effective choice for many applications
February 2004
by William Roedel
Pharmaceutical Technology
FindArticles.com
Autoloader systems can greatly reduce the risk of product contamination and are a cost-effective choice for many applications.
The goal in aseptic manufacturing is to provide a safe, cost-effective, high-quality product. With this thought in mind, leading drug manufacturers began purchasing lyophilizer automatic loading systems in the 1980s. Before that time, the manual loading and unloading of products in trays was the only method.
Operators who load a lyophilizer in Class 100 rooms are a major source of contamination. Activities in laminar airflow must be closely monitored to ensure product safety. Typically, operators place trays onto a cart (see Figure 1) and then push the cart from the fill line to the lyophilizer. In addition, the repeated gowning of operators requires time and other resources, thus reducing productivity and increasing costs. Moreover, the exposure of operators to potent products can be hazardous. Therefore, there are concerns about how to protect the product as well as the personnel in the aseptic core.
Because of the need for sterility and safety, the solution for many new applications is to automate the process. An autoloader can reliably execute the load and unload functions. Because an automated process is reproducible and can be validated, a more-consistent quality of product is delivered.
The latest versions of autoloaders can move vials without the need for trays and bands. These systems eliminate the costs attributed to cleaning, sterilizing, and storing trays, bands, and carts. In addition, because no bands are needed to contain each module of vials on the shelf of the lyophilizer, these spaces can now be filled with additional vials. A batch increase of 8-10% is possible.
To buy or not to buy
Given process improvements and cost reductions, one must carefully consider whether an autoloader should be purchased for a production line. Process equipment costs are a major part of a project, as high as 50% (1). Therefore, acquiring an auto-loader may not be an attainable goal for all companies. Currently, auto-loader systems are most frequently used in the largest companies because of cost factors.
Another powerful driving force also is playing a role in whether a company decides to purchase an autoloader system. Changes in manufacturing strategies to compete globally continue to drive manufacturers to the highest standard (2). Autoloaders make sense for CGMP compliance and for firms that must meet the highest standards in the markets they serve. An autoloader provides a competitive advantage: it greatly reduces human involvement and can ensure a reliable and quality supply of product to the markets.
Furthermore, global competition requires that manufacturers build facilities that provide the flexibility to manufacture many products (3). Autoloaders are multimission units that can process various products. This characteristic is particularly important for contract manufacturers and companies that offer a range of different products.
Applications
A favorable scenario for the use of an autoloader is the manufacturing of a new product in a new facility. In the conceptual phase, designers consider the process requirements and then determine the best system. However, if the drug product is the first or only product to be offered by the firm, the timing of the product to market must be taken into account. Including an autoloader in a project can add tinge because of systems integration, testing, and validation.
Another favorable application is the manufacture of a new product in an expanded area of an existing facility. In this case, the manufacturer has production in process and the new line is part of a profitable family of products. Thus, the manufacturer is more likely to have the resources in-house to support the project and assimilate new technology.
Contract manufacturers often consider adding an autoloader because it provides a process advantage that they can offer to their clients. Customers will perceive it to be cutting-edge technology, thus giving the contract firm an edge against those that do not have it.
The least likely scenario is the manufacture of a current product in an existing facility. In this case, the return on investment is the key hurdle. Changes in a validation plan may also weaken the justification for the purchase.
Successes and failures
Early adopters of autoloader technology deserve thanks for their courage to be first. Some projects were successful, but others became endless horror stories. The first examples were large, complex designs. Some early systems could load only trays, and others were trayless operations. Problems included unreliable controls and poor integration of the loader to the lyophilizer. Integration of motion controls and the sequencing of steps were problematic as well.
Integration between filling lines and isolators also was challenging. Important lessons were learned about the flow of product, floor flatness, shelf flatness, and precision of shelf positioning to the loader (4). The qualification of systems and the effective transfer of the technology to operations also were major hurdles. Project timelines were too long.
But much has been learned since the early days, and new systems reflect the lessons of the past. Today it is smart to consider this technology for new applications. These systems offer many process advantages over manual methods.
System configurations
There are three types of autoloaders. The first is the batch loader, which consists of a stack of shelves equal in capacity to the shelf stack in the lyophilizer. Vials discharge from the filling line and accumulate onto the shelves of the loader. Once full, the vehicle travels on tracks to the front of the lyophilizer. When the door is fully open, the loader docks and pushes the vials onto the shelves. To remove the vials, the vehicle retrieves them one shelf at a time. When full, the vehicle travels to the capping station for discharge of the vials.
A more common type is the shelf loader (see Figure 2). This system is a vehicle that moves on the floor or a track. Shelf loaders are suitable for loading a product onto a cold shelf through a subdoor. The vehicle docks to an accumulation station and then transfers a module of vials onto the transfer platen of the vehicle. It then undocks and moves to a position at the front of the lyophilizer. As the shelf stack moves one shelf into the loading position, the subdoor opens. Vials transfer onto the product shelf. The system can load one shelf per cycle. The vehicle then returns to the accumulator station. This cycle repeats until all shelves are full.
After the lyophilization cycle is complete, the vehicle moves to the docking position. The subdoor opens, and the vehicle docks to the first shelf. A retrieval mechanism (cage) slides into the chamber and extracts the vials onto the transfer platen of the vehicle. The subdoor then closes, and the vehicle moves to the discharge station. This cycle repeats until the lyophilizer is empty.
For applications in small rooms or within an isolator, the row loader is the appropriate design (see Figure 3). The system is suitable for loading a product onto a cold shelf hrough a subdoor. Row loaders use a conveyor to transport vials from the filling line. Typically, the unit is fixed in front of the dryer, but some units are mobile. An indexing starwheel counts and accumulates a row of vials equal to the width of a shelf. A transfer platen extends through the subdoor and docks to the shelf. A pusher moves the row forward toward the shelf, thus creating space for the next row to accumulate. This cycle continues until the shelf is full. The process repeats to fill each shelf.
Row loaders use a front-mounted extraction mechanism, or for some applications a pusher is built into the rear of the drying chamber. In either case, the system extracts vials from a shelf and onto a conveyor that feeds the capper. The next shelf indexes into position, and the process repeats until all shelves are empty.
Production flow
Production-flow requirements weigh heavily in the selection of a loading system. A few common scenarios are as follows:
* One filling line feeding to one lyophilizer: A solution is a row loader, which requires less space and lower capital investment.
* One filling line feeding multiple lyophilizers: Either multiple row loader units or one shelf or batch loader are likely solutions.
* Two filling lines to multiple lyophilizers: This is a typical application for a shelf loader. It requires the loader to move and dock to multiple filling lines and lyophilizers at various locations.
Many variations of autoloaders are available to match specific layouts and flows. Vendors can customize their designs.
Materials of construction
Materials of construction follow the latest standards for filling systems in the aseptic core. Frames and metal covers are 316 stainless steel. Ultra-high molecular weight (UHMW) polyethylene is a common material for starwheels, guiderails, and so forth. Materials are low-particle generators.
Cleaning and sterilization
Automatic cleaning and sterilization in place is a feature for the most complex systems. To thoroughly clean and sterilize surfaces, component designs must address the issues of dead spaces and occluded surfaces to allow for effective clean-in-place and steam-in-place operations (5). Common practice is to sterilize and aseptically attach the parts during machine setup. Product-contact parts must be acceptable for steam or vaporized hydrogen peroxide sterilization and for cleaning with commonly used solutions.
Codes and standards
All autoloaders must comply with n