Disposable Filling Methods

Today, medical and pharmaceutical companies are faced with producing products and devices that are safer, more efficient, and have alternate points of administration. They must accomplish these tasks while, at the same time, reducing costs. One key concern faced by pharmaceutical and medical device companies is how to accomplish these goals while improving product quality, sterility, and consistency in the manufacture of the product.

One current trend is the adoption of disposable medical devices and fluid transfer systems in the pharmaceutical industry. This trend is growing because disposable products provide the manufacturer with cost savingsby reducing cleaning time and lowering the costs involved in the disposal of cleansing agents, which are required for traditional stainless steel containers. Prior to using disposable devices and systems, stainless steel was the primary material used to transfer and contain pharmaceutical media. However, the utilization of these reusable containers presented the risk of cross contamination as well as biological contamination. Additionally, disposable products are far easier to validate and to maintain that validation.

For example, many pharmaceutical manufacturers purchase disposable plastic tubing, cut it, apply the required components, and then autoclave it. These tubing sets are then utilized to transfer the fluid from large stainless steel cylinders into smaller containers. The costs accrued by pharmaceutical companies to assemble, sterilize, and validate these sets in house are significant with labor and materials topping the list of expenses. The cost of purchasing these sets pre-assembled, pre-sterilized, and pre-packaged from a contract medical device manufacturer offers a much more costeffective alternative.

By adopting disposable devices such as fluid transfer sets, bags, or containers into the production process and replacing their stainless steel predecessors, the risk of cross and biological contamination is greatly reduced. This reduction is the result of the gamma pre-sterilization of the disposable devices, in addition to the fact that these devices are single-use items. Since single-use components are used for each new batch, the possibility of cross contamination is virtually eliminated. All of this allows companies to focus on their core competencies while saving operating expense and improving manufacturing processes.

Disposables and aseptic filling
Aseptic filling is a process in which fluid is transferred from one container to another in order to prevent potential contamination without the use of terminal sterilization. Typically, aseptic filling is the final packaging process for a developed fluid. The media is clean and sterile going into the container using an aseptic connector with a 0.22 micron final filter. This eliminates the need for post sterilization. However, companies may use "terminal filling." Terminal filling is a process that requires the container (e.g. bag), once filled with the media, to be sterilized via autoclave after it has been filled. This process presents a huge increase in both production time and costs when compared to aseptic filling.

Companies that fill aseptically use various methods to ensure the sterility of the finished product including:
• Operating in a classified clean room (Class 100 or better)
• Utilizing barrier technologies (disposable components where applicable)
• Filtering of the media Aseptic filling and automated technology



Aseptic filling via an automated machine
offers a convenient and safe method of infusing sterile media into a container-bag, vial, plastic or glass bottle-efficiently. It is important to note, however, that automated filling machines often differ in filling capabilities. The PDC automated aseptic filler machine (AF1000) starts with a pre-gamma sterilized bag, designed with a standard length of tube dedicated for filling. This standard tube is covered to ensure the sterility of the fluid path. The tube is inserted into the classified environment where the cover is removed and the bag is filled. The tube is then sealed using RF sealing technology. The completed bag is removed from the Class 100 filling area and is ready for use. The machine can be easily set to fill different volumes (100 ml to 20 l). The bags have been designed with a standardized filling tube port which is used on all size bags thus eliminating the need to change tooling or nozzles in order to accommodate the various bag sizes.

Software can also be customized to assist the manufacturer in validation, maintaining that validation, and improving production as the manufacturer sees fit.



Automated verses traditional filling
Many media manufacturers that fill bags aseptically use manual methods. One such method employs the use of a hood that provides a Class 100 environment. The operator makes the connection within the hood, fills the bag to a pre-determined weight, and clamps the flow.

The bag is then handed to a second operator who makes the final seal. At this point, the process is complete. The many times that the bag is exposed to the environment, in addition to the multiple handlers, significantly increases the risk of contamination. The aseptic filler machine reduces the number of operators to one and eliminates handling. It also has a small footprint, reducing the amount of area that needs to be classified. Furthermore, the filling machine reduces the risk of contamination while increasing production efficiency.

What's ahead?

The benefits of aseptic vs. terminal filling are going to be a major focal point of investment to those companies who require this type of technology. With the addition of more disposable items, this technology will facilitate the development of systems that are far safer and easier to validate while reducing costs and increasing efficiency of filling production.

As the healthcare industry moves towards alternate site administration with nontechnical people involved with the care given, aseptic filling alternatives offer unique opportunities for satisfying shorter production runs with different medications. The combination of medical devices with aseptic filling appears to be a trend that will help the manufacturers, care givers, and patients improve the cost and quality of care. The convenience of user friendly devices combined with new found pharmaceutical compounds that are packaged for point of use administration opens up new horizons that will benefit all.

Aseptic filling allows for boutique compounds to be used in the targeting of various illnesses researched by the biotech companies with better and more cost effective outcomes. It gives the manufacturers flexibility that they have not experienced before-the possibility of quick changeovers, better return on capital, and small production run capabilities.


For additional information on the products and technologies discussed in this article, see Medical Design Technology online at www.mdtmag.com and www.advancedscientifics.com.

Carl Martin Martin is the president of Advanced Scientifics Inc. He can be reached at cmartin@advancedscientifics.com.

Handling Validation A manufacturer must comply with the 10 to the -6 rule regarding validation, which states that there cannot be more than one contaminated piece for every million-a very high standard. A filling machine can control the environment to negate the possibility of contamination. Since a company cannot perform a test on a million pieces to find the one contaminated unit, a different method is used for validation. The filler will start with a known amount of contaminant. The machine is then tested to see how effective it is at keeping the contamination out of the piece. Some machines use steam to clean the piece and environment, which lessens or negates that contamination. Another option is for the machine to control that contamination using a process to keep the contamination from reaching the piece.