An Introduction to Aseptic Fill Finish

 

One of the most crucial procedures in biopharmaceutical manufacturing is aseptic fill filling manufacturing of sterile pharmaceuticals, often known as sterile filling. This is because of its highly technical processes and the potential safety impact on the end-user, usually an already impaired patient. After the loaded medicine is stoppered and capped in the cleanroom, there are only indirect controls for its sterility.

Unlike terminally sterilized filled medications, the stability of aseptically filled drugs will be influenced by steam autoclaves, dry heat ovens, ethylene oxide, and irradiation with either E Beam or cobalt 60 gamma. As a result, certain biologicals, pharmaceuticals, and biotechnology medications must be filled using an aseptic procedure. So pharmaceutical fill finish is a term only familiar to the aseptic process field, yet not so common in the outside world. 

Historical Facts on Aseptic Fill Finish

Aseptic fill finish manufacturing has a recent history, with sterility regulations for injectables being set in the 1920s and large-scale biological manufacture of blood and plasma products occurring during WWII. Plasma products used to have, and some still have, a post-fill pasteurization process that involved a low heat treatment of 60°C for about 10 hours. Although pasteurization does not provide sterility, it can prevent fungus growth and contamination. Anti-fungicidal reagents were also added to parenteral medications to help reduce contamination caused by early aseptic processing.

The Legal Side of Aseptic Fill Finish

In 1981, the Parenteral Drug Association (PDA) issued its Aseptic Validation Technical Report in an effort to promote consistency in aseptic processing. The Food and Drug Administration (FDA) followed suit in 1987 with its Aseptic Processing Guidelines. In 1999, the International Society of Pharmaceutical Engineering (ISPE) released Sterile Facilities as part of their Guidelines Series. And then, in 2003, the FDA published its novel paper on Aseptic Guidelines.

Aseptic Fill Finish Products

What can be filled aseptically? Almost any solution, powder, or suspension that can be terminally sterilized before the aseptic fill/finish procedure can be used. Typically, sterile medications are filled aseptically in molded glass bottles, tubular glass vials, tubular glass syringes, and, in Europe more than in the United States, glass ampoules. 

To further stabilize pharmaceuticals, solutions can be lyophilized in a sterile drier. The higher the product or container's uniqueness, the greater the technical or operational issues that may arise.

The SOP in the aseptic fill finish manufacturing process is as follows: decontaminate the operational staff, terminally sterilize the drug product, fill components, replace equipment parts, and sanitize the cleanroom and in-place equipment. The simplified process maps resemble the aseptic process map when all of this is combined with good aseptic procedures.

Fill finish procedures can range from early clinical phase hand filling (clinical solution fill photo) to small volume semi-automated filling to fully automated high-volume production batches over numerous days.

Conclusion

It is common in pharmaceutical circles to collaborate with a CDMO due to complex production and limited resources. The acronym CDMO stands for "contract development and manufacturing organization" and are pharmaceutical companies that provide medication development and drug fill finish manufacturing services. Pharmaceutical companies partner with CDMOs to outsource drug development and drug manufacturing.

One such reliable CDMO is AbbVie. With a large, dependable, and high-quality industry network, AbbVie is committed to providing top-notch aseptic fill finish services. We offer two convenient aseptic fill-finish options for parenteral drug products, which are prefilled syringes and vials. Contact us to get development and manufacturing support for your product formulations.