Savillex’s approach to SUTs in the rapidly-growing biopharmaceutical market.
In biopharmaceutical manufacturing, the implementation of single-use technology (SUT) is growing rapidly. Offering improved flexibility and reduced contamination risk, SUTs have more appeal than their expenditure alone. Some other advantages include rapid product development, adaptability, decreased manufacturing footprint, no cleaning validation, as well as decreased process times.
Bulk drug substance (BDS) have also found a home among SUTs—utilizing fluoropolymer (PFA and FEP) bottles for the storage and transportation of BDSs (particularly for their low particulate content and wide temperature range). In addition, biopharmaceutical labs are beginning to invest in ICP-MS instrumentation and supplies with regulations on elemental impurities close to being implemented.
Needless to say, biopharmaceutical facilities don’t want to be left behind with all the SUT hype among pharmaceutical manufacturers.
“In our contact with biopharmaceutical companies, what we’ve seen is that SUT is a hot topic at the moment,” said Don Potter, Director of Sales & Marketing at Savillex Corporation—a manufacture of fluoropolymer products. “The biggest thing we see is that our customers, the biopharma companies, want to partner with the manufacturer of single-use technologies.”
Savillex manufactures SUT products, such as their PFA and FEP Purillex™ bottles, which are produced using proprietary blow molding technology.
SUTs are primarily polymers—from thermoplastics through to fluoropolymers. Polymer bags are commonly used for freezing and storage, which are made of laminated polymer film. But, depending on the intended usage of the SUTs, different selections will be preferable.
“If the BDS is unstable at typical storage temperature conditions (-25°C) and requires blast freeze (-70°C) storage, then fluoropolymer bottles are the only option, since fluoropolymers are the only plastics that can withstand this temperature (the fluoropolymers PFA and FEP are stable to -200°C),” Potter explained.
SUTs may not be optimal for every operation, however. Large scale, traditional pharmaceutical manufacturing, on the other hand, will likely continue to use large stainless steel tanks for bulk freezing and storage of drug substance.
Known for their versatility, SUTs have grown both in prominence and in their selection.
“There is now a wide range SUT products, from tubing and simple connectors to more complex, self-contained assemblies,” said Potter. “Basically, SUT manufacturers are required to produce high quality products, in most cases, that are sterilized and ready to use. Since it will come into direct contact with the intermediate, API, or bulk drug, cleanliness and quality control are critical. SUT manufacturers must partner with the biopharma end user in order to achieve successful SUT implementation.”
Convenience, as you can imagine, is critical in biopharmaceutical manufacturing (along with just about every other industry in the world). When a biopharmaceutical company selects a SUT manufacturer to work with, pre-sterilization is key—as many facilities do not have the time or capacity to sterilize SUT products in-house.
“One of the great benefits of SUT is that generally they are supplied pre-sterilized (by irradiation) which is a big benefit for biopharma companies,” said Potter. “Fluoropolymers, however, cannot be irradiated, since this breaks down the structure of the fluoropolymer and the integrity of the product may be compromised. Fluoropolymer bottles are supplied unsterilized, and then pyro treated or autoclaved by the customer.”
But, SUTs are not new to the industry.
“SUTs have been around since the 1990s and are widely used,” explains Potter. “But what is driving its greater adoption is the growth in biologics manufacturing and the progress made in standardizing testing and certification of SUTs, and in supply chain assurance by the various industry groups.”
Although there are a number of reasons as to their growing popularity, it can be said that the biopharmaceutical industry, itself, (and its demands) has impacted companies’ drive to implement SUTs.
“I think the growth in biologics manufacturing is generally driving SUT implementation,” said Potter. “Manufacturers of biotheraputic products in the form of (very high value) vaccines benefit particularly in the downstream process from the convenience in storage and transport, and flexibility in batch size that SUT can offer.
“Vaccines are probably the main use for single-use technologies,” said Potter. “Biologics is a growing areas as well.”
Not only is there a growing need for SUTs in the industry, but there is also a need for improvement in specific products to meet evolving needs and various regulations. As a result, the SUT fluoropolymer bottles have evolved over time.
“The SUT fluoropolymer bottles used until now in biopharma processing traditionally were originally designed many years ago for the shipment and storage of high purity acid and other uses in trace metal analysis,” Potter explains. “When we developed our Purillex bottle line about 7 years ago, we decided to design a bottle primarily for biopharma processing. We chose a GL45 closure which is unique in fluoropolymer bottle but commonly used in biopharma. We also wanted to manufacture our bottles in an ISO 7 clean room, since particulate control is critical for biopharma. To do this, we had to design and build our own stretch blow molding equipment, which is a cleaner technology for blow molding bottles, and small enough that it can fit in a clean room.”
Savillex, as a company, prides themselves in their willingness and ability to adapt to various needs.
“Aside from the bottle design and performance, where we have tried to differentiate ourselves is to work very closely with the biopharma companies to understand their critical requirements,” said Potter. “For example, the biggest issue biopharma users of fluoropolymer bottles face is minimizing particulate contamination—both embedded and loose, including hairs. We designed our manufacturing process to achieve this, and also consult with biopharma companies to minimize contamination during sterilization at their site.
“Biopharma companies also use large quantities of small size bottles during validation to minimize use of their very high cost BDS. We modified the design of our small bottles to match the wall thickness of the larger 2 L bottles used in biopharma production. This allowed the small bottle to more closely replicate the performance of the larger production bottle and to helps support our customers with their validation programs for the regulatory authorities.”
Since 1976, Savillex has been manufacturing fluoropolymer products, and they both design and manufacture their molding tools in-house.
“I think where we excel is our responsiveness to customer’s needs and a willingness to change our processes as needed,” said Potter. “This is especially important as the standardization of SUT evolves. On technical and design issues, our biopharma customers communicate directly with our VP of engineering. We think that is unique in the part of the business we are in.”