Plastics and Human Health
By Nancy D. Lamontagne
Plastics are used for a wide range of medical applications such as tubing, implants, bioresorbable scaffolds, drug delivery, and medical devices. New manufacturing equipment and processes are helping medical plastics meet a variety of complex requirements while keeping costs and material use low. New materials are also upping the performance of medical plastics.
Preventing infection is important for this market. New materials and novel applications of plastics are helping prevent infection during medical procedures, and alternative techniques are giving manufacturers new options for sterilizing plastic devices. Packaging is also important for ensuring that devices stay sterile throughout their shelf life and during use.
Medical Tubing Extrusion
The Conair Group makes downstream extrusion equipment for medical microbore tubing (less than 0.060 inch in diameter) and for larger commodity medical tubing. Microbore tubing is used in products like heart and brain catheters, and properties such as ovality, concentricity, and burst strength are key. “For extrusion of microbore tubing, speed isn’t an issue, but these specialty materials are expensive, so manufacturers want to use the least material possible while maintaining precise properties,” says Bob Bessemer, Conair sales manager, Medical Extrusion.
Bessemer explains the benefits of using vacuum sizing, rather than free extrusion, to accomplish the high level of precision necessary for microbore tubing extrusion. “With free extrusion, if the draw-down ratio is not correct, then more air is needed to create the desired tube size,” he says. “Since air is compressible and variable, this creates more fluctuation in tolerance. At Conair, we teach the use of vacuum sizing as a process.”
Conair’s MedVac vacuum sizing/cooling tanks have chambers that can range in length from 3 to 18 feet with temperature-controlled water. They use differential pressure to expand the tube, and the vacuum is applied over a specific length for consistency. “However, it is still essential to pick the right tooling to make the tube and to use the vacuum to accomplish roundness rather than to grow the tube,” he says. “Let the tube tell you what size it wants it to be, because if you push the size, then you push the tolerances.”
Precision is also needed in maintaining the water temperature, as heat-transfer rates directly affect material properties. At the end of the line, a Med-Line puller/cutter servo-drive speed controller maintains consistent pulling. “We also work with blade manufacturers to get thin and sharp blades that cut tubes without particulates or collapsing,” Bessemer adds.
Manufacturers of commodity tubing must make it at high speeds without sacrificing precision, and they are reducing wall tolerances to minimize material use. In addition, because the extrusion is performed in clean rooms, space is a major issue. Conair has a multipass tank that includes a vacuum-sizing section, a conventional cooling section, and horizontal rollers to guide the tubing back and forth through the tank. A servo-driven wheel in the tank serves as the primary puller to increase tubing precision. This configuration saves one-half to two-thirds of the space compared with conventional sizing and cooling tanks and minimizes stretching of the tubing during cooling. The system also has OD/ID wall gauging and monitoring, which is important for documenting process conditions for customers and the U.S. Food & Drug Administration (FDA). “It is key to make changes in a very controlled and automated manner,” Bessemer says.
He says that manufacturers are gradually moving away from using flexible PVC for commodity tubing because of consumer concerns about possible toxicity. However, alternative materials tend to be much more expensive, so it is even more important to keep production rates up and tolerances tight. “The goal is to accomplish high speed with tight precision while limiting the material used,” he says. “We are consistently pushing processing to tighter tolerances and faster speeds.”
Putnam Plastics Corp. of Dayville, Connecticut, USA, has developed a new process for making oriented, large-diameter fibers. These fibers are lightweight and yet strong, making them ideal for replacing metal in minimally invasive medical devices. They are also compatible with medical imaging because of their X-ray transparency and nonmagnetic properties. “The convergence of minimally invasive devices and medical imaging technologies are increasing the demand for nonmetallic components made from high-performance materials. These emerging device solutions are custom by definition,” says Ray Rilling, general manager at the company.
When making large-diameter medical monofilaments, the increased extrusion volume and substantial draw-down required for orientation can make it challenging to control diameters, maintain strength performance, and manage setup time and costs. Putnam developed a proprietary process for manufacturing large-diameter custom monofilament fibers (0.025 to 2.54 mm) from polypropylene, nylon, polyester, polyurethane, thermoplastic elastomers, and other materials. The new process controls voids and diameters to create fiber with consistent performance.
Putnam also has a new continuous-manufacturing technology for producing catheter shafts. Today’s vascular procedures reach further into the body with longer, thinner catheters. The proximal end of these catheters must be more rigid to give them pushability and torque without kinking or buckling, while the distal end must remain flexible enough to navigate through blood vessels. Catheter shafts with variable stiffness from the proximal to distal end are traditionally made by manually assembling segments with varying flexibility, but this approach can be costly and sometimes produces performance problems in bonded regions or segment unions.
Putnam’s new variable pitch braid and coil reinforcement manufacturing methods eliminate assembly labor costs and the weak or abrupt bonded joints that are typical of medical shafts assembled manually. These new methods can also be used with geometric tapering or sequential polymer extrusion of distinct materials.
Making Small Parts
Wittmann Battenfeld recently introduced its MicroPower 15/10 for high-precision injection molding of micro-sized parts. The system offers cost-efficiency, process reliability, and speed. The two-step injection unit consists of a screw and a plunger and has a shot volume of 0.05 to 4 cm3. It injects thermally homogeneous melt and produces high-quality parts with stable production and short cycle times. All the MicroPower’s peripheral equipment is adapted for producing small parts.
The MicroPower 15/10 provides gentle elaboration of the material and quality control via a camera, and is ideal for medical applications because it is very clean. There is no oil used in the machine, and the clamping unit is capsulated, which means that the toggle system does not transport any dirt into the production area. The injection unit is also capsulated, and outgoing air of the dryer can be channeled away from the inner side of the machine. Because of the capsulated design of the whole machine, it can be installed in a clean room. The parts can be packaged in the machine, which avoids an intermediate station where parts could get dirty.
The modular system has a basic platform that can be extended according to the customers’ needs, and it has a rotary disk, partsremoval handling, and is extendable up to a complete production cell. The unit has a clean-room module that provides ISO Class 6 air. When using this module, the parts are injection-molded, inspected, and then deposited in the clean-room compartment.
New Materials
Teknor Apex Company is now offering the Medalist® MD-200 Series of thermoplastic vulcanizate (TPV) elastomers. They come in a wide range of hardness levels, and their high purity and resilience make them ideal for replacing rubber in medical applications such as syringe stoppers and vial gaskets. Like all thermoplastics, they process more easily and quickly than rubber, offer greater design freedom, and are recyclable.
The elastomers don’t need pre-drying because they are nonhygroscopic, and their light natural color means they are easily colored. All grades are certified to pass ISO 10993-5 and are Drug Master File listed with the U.S. FDA. They have lower oxygen absorption than non-vulcanizate thermoplastic elastomers, which means they better protect pharmaceutical contents when used for vial seals or gaskets.
Keith Saunders, senior market manager for the Thermoplastic Elastomer Division, explains that the company manufactures its own TPV compounds by starting with polymers and basic ingredients, rather than using a masterbatch intermediary. This allows Teknor Apex to create compounds that meet demanding requirements. The new elastomers are more resilient than other thermoplastic elastomers and can be sterilized in steam, autoclave, or gamma irradiation processes.
The company also has a new family of calendered PVC films for medical applications. Called MF-165-J3R-79NT, these PVC films incorporate a non-phthalate citrate plasticizer that is stable when sterilized by gamma irradiation. Calendering gives the film uniform thickness, consistent physical properties, and thermal stability. To produce the calendered film, the company fuses flexible vinyl compound and passes it through a series of synchronized nip rolls.
The new PVC film comes in various embossed finishes and thicknesses from 0.15 to 0.5 mm, widths up to 1525 mm, and slitting down to 51 mm. According to the company, this new film gives medical manufacturers PVC’s advantages while meeting requirements for plasticizers to be phthalate-free.
A new material from Clariant Performance Packaging helps keep moisture away from diagnostic test strips, pharmaceuticals, and medical devices, which are often extremely sensitive to moisture. Too much humidity can lead to false readings and affect diagnostic accuracy or efficacy of pharmaceuticals. Clariant Performance Packaging, formerly Süd-Chemie and now a member of the Clariant Group, offers an anti-dusting Advanced Desiccant Polymer (ADP®) with improved adsorbent capabilities that can be integrated directly into the thermoplastics used in packaging or the device itself.
According to the company, eliminating the need for separate desiccants helps streamline workflow by avoiding the need for inserting desiccant, foil pouching, or carton packaging and allows manufacturers to use the entire volume of the package for their product. In the case of pharmaceuticals, such packaging can also increase product safety compared with packaging where desiccants are added to bottles or containers. ADP desiccant kinetics can be customized to specific absorption rates. It can be molded into virtually any shape or size, including hinge-cap tubes, dosers, dispensers, inhalers, and bottles as well as caps of fertility or pregnancy test kits or complete in-vitro diagnostics housings.
Bioresorbables: What’s New?
Bioresorbable polymers, which are gradually broken down by the body, have been used for some time to make various types of closures and implants. These polymers can also be used to make tissue patches and scaffolding, meshes, and adhesion barriers, which support or separate tissue while the body is healing and then degrade when not needed anymore. Steve Coulter, a senior associate at Fallbrook Engineering, says that although there hasn’t been a great number of advances in bioresorbables in the last 30 years, he has seen a lot of interest in them lately.
Bioresorbable processing is a mature technology, but supply and demand barriers are hampering their use in medical devices to some extent. “It is hard to foster competition through small suppliers, because if the supplier doesn’t survive, then the medical-device manufacturer has to requalify the new supplier with the FDA,” says Coulter. The low number of suppliers keeps prices so high that start-ups can’t afford to license the materials. “Suppliers that can offer a full portfolio of bioresorbable materials are a plus, because customers don’t want to have to qualify multiple companies with the FDA.”
He sees a renewed interest in using composites to fine-tune properties of bioresorbable polymers for orthopedic applications. The multilayer pregnancy test cap is molded by Clariant Performance Packaging and contains its Advanced Desiccant Polymer (ADP®), which protects the strip’s reagents from moisture degradation. He notes that failure modes are important for bioresorbables, just as with other plastics. The material must be durable, can’t soften or deform after use, and must maintain properties under varying temperatures. “The companies supplying bioresorbable materials have really stepped up the reliability, which is key for implants but also benefits other applications,” he says. Coulter sees bioresorbables being used more for drug delivery because there is a higher payoff after qualifying the product with the FDA.
Researchers led by Iza Radecka, PhD, from the University of Wolverhampton (West Midlands, UK) are using a matrix made from a biodegradable polymer to protect probiotics during delivery. Probiotics contain live beneficial bacteria that, when consumed in adequate amounts, can help maintain and improve gut health, strengthen immunity, and fight gastrointestinal disorders. However, to deliver their benefits, these live bacteria must survive freeze-drying, then storage, and highly acidic gastric juices.
The new bioresorbable, edible, and nontoxic biopolymer allows a consistent number of live and viable bacteria to be administered via food products. It stays stable in a highly acidic environment, such as that in the stomach, while disintegrating in a slightly weaker acidic or neutral environment, such as that in the intestine. “Previously, solutions such as coating or microencapsulating the bacteria have been offered, but these have not been able to satisfactorily protect the bacteria in the heavy acidic conditions of the stomach,” says Aditya Bhat, a member of the research team.
The researchers’ tests of the biopolymer showed that beneficial bacteria, including strains of Lactobacillus and Bifidobacteria, could survive in simulated gastric juice for up to four hours when embedded in the biopolymer matrix. In contrast, unprotected bacteria died within two hours. Even after one hour, their viable counts were not satisfactory. The biopolymer also offers straightforward protection of the bacteria without any complicated encapsulation procedures. The researchers are now working with companies to possibly commercialize the polymer and on expanding its use to other applications.
Preventing Infection
Dhuanne Dodrill, president of Rollprint Packaging Products, Inc., says that barrier is key for plastic packaging of medical products. For combination products, such as a device that contains a drug, the appropriate barrier to gases and moisture ensures that the drug remains efficacious. “Maintaining a sterile barrier is critical,” she says. “There is now more rigorous evaluation of the effects of distribution and handling of products on sterility maintenance.”
She says the increasing emphasis on seeing the product for inspection is leading to more use of clear barrier materials. “Nurses prefer to see the product so that they can make sure it is the right size—such as adult or juvenile,” Dodrill says. “They want to give it a quick visual check, not read a label. Packaging must be intuitive and designed for human factors.”
Sustainability is on the minds of medical-device manufacturers. They are moving from rigid packaging to environmentally friendly flexible packaging, and from double packaging to single packaging. Rollprint makes a recyclable, peelable polyester lidding known as StreamOne®. It seals and peels from APET, CPET, and PETG trays and can be recycled with the trays in the “number one” polyester waste stream. The lidding allows device manufacturers to recycle their entire waste stream.
New devices can bring complex packaging challenges. Rollprint recently developed peelable lidding for the SwabCap® from Excelsior Medical Corporation. The SwabCap is an elastomeric cap containing a sponge saturated with 70% isopropyl alcohol. The disinfection cap covers needleless connectors, protecting them from touch and airborne contamination. This protection and disinfection helps decrease the chance that the patient will get a hospital-acquired infection.
“The lidding had to seal to two different rigid materials and hold alcohol. Alcohol can be difficult to package because it is prone to wicking through peelable seals and evaporating. Peeling with the same force from different materials is also a challenge, and, to make things more complex, the lidding couldn’t stick to the SwabCap’s sponge,” Dodrill says. Rollprint used its Allegro B peelable sealant to make a peelable film that met the packaging needs of the SwabCap.
Sterilization is an important step in the manufacturing of medical products, but it can bring unexpected challenges for plastic products. Gamma irradiation can degrade or change the properties of some plastics, and using gases such as ethylene oxide can be costly and time-consuming because it takes as long as two weeks for the gas to release from the product. Noxilizer, Inc., offers an alternative sterilization technique that uses NO2 gas.
“NO2 is a well-studied gas, so its toxicity and material interactions are understood,” explains David Opie, PhD, senior vice president for Research & Development at Noxilizer. “NO2 is different than using other gases for sterilization because it is truly room-temperature, and there is very little sterilant residue on the devices.”
For manufacturers, low residues means that the products, sterilized in the primary packages, can be handled immediately after sterilization cycle is complete. This rapid aeration and relative safety of the process permits the continuous completion of small batches in-line with the manufacturing process. After which, products are ready to go into the shipping containers. This is the alternative to waiting for large batches of products to be sent out for sterilization. The company’s RTS 360 is an inexpensive sterilization unit that can process a pallet of product per shift, which is sufficient to replace contract sterilization for many medical-device product lines.
Dr. Opie emphasizes that even when the material is compatible with gas sterilization, the sterilization cycle depends on the material properties. Certain materials may interact with a sterilant gas; for example, owing to high permeability. This material-specific interaction, known as the “carrier effect,” can hinder the sterilization process. “Material compatibility needs to be tested. It is important to individually evaluate polymer blends because additives and fillers can alter the sterilization of a device,” he says.
NO2 works well for many materials and device geometries. “For products that are compatible with NO2, such as implants, biodegradable materials, and prefilled syringes, it provides manufacturers with opportunities for cost savings,” he adds. “We work with companies to implement this sterilization technique, from cycle development to validation.”
For the future, Noxilizer is also developing a sterilization unit for reusable surgical instruments and devices in hospitals.
Resistant Polymers
Hospital-acquired infections are a big problem, but scientists at the University of Nottingham in the UK have discovered a new class of polymers that resist bacterial attachment and could help reduce infections.
The researchers simultaneously screened thousands of unique polymers using a high-throughput process developed by researchers from the Massachusetts Institute of Technology (USA). The new group of materials reduced the attachment of the pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. The materials work by stopping biofilm formation, which is responsible for a great deal of hospital infections, when bacteria first attempt to attach to a device.
Although this work is still in the research stage, the investigators will next develop methods for fabricating coatings made from these materials so that their performance can be clinically tested. They are also in early stages of discussions with a number of medical-device companies.