The program topic for the September 25, 2003 Boston Area Chapter meeting was Disposable Technology. Parrish Galliher of Xcellerex and Holly Haughney of Pall Corporation were the speakers and were joined by Dennis Annarelli of Millipore Corporation for a panel discussion on this topic.
Parrish Galliher started the presentations by discussing one of the drivers of this technology: the growth of the biopharmaceutical industry. Currently there are approximately thirty unique biologics approved with over one hundred versions sold worldwide. Today there are over four hundred biologics in clinical trials and this number is growing at a rate of fifteen percent per year. The industry is approaching a phase in which the available and planned manufacturing capacity will not be sufficient to handle the number of new drugs ready to enter the clinic or approved for commercial sale. As the typical new biomanufacturing facility requires 3-4 years to plan, design, build and validate, this situation will not be alleviated soon. The speed with which a company can get its product into the clinic and to market is critical. Another factor is that companies desire to delay major capital expenditures until after drug approval, as over 80% of drugs fail during clinical trials. Currently about 40% of clinical and commercial manufacturing is outsourced.
Disposable systems have several advantages that address these issues. By reducing the amount of permanent (typically stainless steel) equipment design, delivery and installation times are reduced. The amount of equipment that needs to be cleaned, sterilized and validated is reduced; this lowers the utility requirements also. Capital costs and depreciation charges will be less. Labor savings will be realized from reduced SIP, CIP, utilities, maintenance and validation. The cost of cleaning chemicals and neutralization will also be lowered. The reduced CIP/SIP requirements will allow for faster batch cycle times and faster product changeover. The potential for batch-to-batch and product-to-product contamination will be reduced also as will the potential for operator exposure to highly potent drugs.
Disposable systems do have several disadvantages to the typical stainless steel processing system. Bag systems are currently limited to about 3000 liters in size. Material compatibility validation can be substantially increased. Although capital costs are reduced, each batch will have a significant cost for the disposable components and for their disposal. There will be a greater dependence on outside vendors. The actual manufacturing process will be more labor intensive. On-line monitoring (instrumentation) will be a challenge in a disposable system.
Holly Haughney discussed the various disposable system components currently available. The preferred current method of sterilizing disposables is by gamma irradiation at the vendor's facility. Although many common materials used in the industry can be sterilized by this method (i.e. PVDF, nylon, PES and stabilized polypropylene), there are some that cannot (i.e. PTFE, silicone and unstabilized polypropylene). Advantages to disposable filters include translucent housings and manifolds that require less space than stainless steel assemblies. Unlike vessels, sterile bags arrive completely empty and simply expand when filled and do not require venting. Disposable tubing often uses clamps instead of valves and many types of tubing, clamps and adapters are commercially available today.
The presence of an alloy with a lower corrosion resistance than 316L often increases rouge formation. An example of this is a straight chromium stainless steel component in a high purity water system.
Three methods are commonly used to make connections with disposable components. Quick connects can be used under a class 100 hood. Tubing welders are flexible and reliable, but are costly and heavy. A new aseptic connector is available that is similar to a quick connect but both the male and female ends contain a peel away strip that allows for an aseptic connection in an uncontrolled space.The connector has been validated.
An overview of biopharm operations that currently can be performed with disposables and those that will probably be available within the next few years was given.
Disposable technology is becoming more common in the biopharm industry, especially for contract manufacturers, and does have several advantages over traditional stainless steel facilities.There are limitations however, and a careful analysis should be performed to ensure that it can be implemented throughout a new facility in order to take advantage of its strengths. A new type of easy to use quick connector enables aseptic connections without other equipment outside of a class 100 hood.