Originally published September, 1996
Along with injection molding and extrusion, thermoforming is one of the major manufacturing technologies for polymer-based medical devices and packaging. The essence of the thermoforming process is that a sheet of plastic is heated to a working temperature and then formed into a finished shape by means of vacuum or pressure. For the production of thermoformed medical packaging, however, this simple description refers to a variety of complex processes demanding superior technical finesse with extremely tight control and stringent documentation.
This article will review some of the internally developed practices commonly employed by thermoformers conversant with medical applications, with the intention of offering device manufacturers an overview of the level of expertise and kinds of procedures and techniques they should encounter when dealing with a quality medical thermoformer.
A well-organized system for product development that conforms to GMPs and the requirements of ISO 9001 is essential for effective medical thermoforming. A typical product development process can be divided into six steps or phases: (1) new-item phase; (2) planning phase; (3) equipment, tooling, and material phase; (4) trial phase; (5) R&D to production validation phase; and (6) final-packet-specification approval phase. Once a project is under way, progress can be categorized in the appropriate phase according to guidelines set up by the thermoformer to optimize work flow.
New-Item Phase. It should be the goal of the thermoformer to be as familiar with the product to be packaged as is the customer requesting that package. Accordingly, at the start of any new medical packaging application, the thermoformer should provide the device manufacturer with a product development questionnaire seeking essential facts about the project. Information should encompass product specifications for all components to be packaged, details of the manufacturing and distribution environments, and drawings. For example, it is important for the thermoformer to know as much as possible about the lidding material, sealing equipment, and sealing processes to be used, as these will directly impact thermoforming flange tolerances. Other critical information includes the test criteria that will be used to validate the package and, especially, the chosen method of sterilization.
When the product information has been received, the thermoformer files it in a computerized logbook that will serve to track the phase and status of the project from start to finish.
Planning Phase. The decision to proceed with a project should come only after a careful feasibility study has convinced the thermoformer that it can design and manufacture the package with quality and consistency. This will include checking the material availability and verifying the capacity of its current equipment. Once the customer has approved the thermoformer's engineering part prints and issued a purchase order specifying price, quality, and delivery time, prototype molds can be designed. A software design program such as ProEngineer (Parametric Technology) can be used to generate solid models that can be plotted or reproduced with a thermal wax printer, which enables minor modifications to be made quite rapidly. The solid models can then be downloaded to a machining-center computer for manufacture of prototype molds via Smartcam and Freeform Surfacing software.
The preparation of prototype molds is an essential step in the planning phase of developing a thermoformed medical device package, allowing for close sampling and analysis of the finished part. Part fabrication with prototype molds enables the
thermoformer to stage preliminary sealing, sterilization, and mechanical stability tests, and permits changes to be made at minimum cost before production tools are built.
Equipment, Tooling, and Material Phase. Also known as the build phase, the next step in the development process represents the point at which the plan becomes tangible and the equipment, tooling, and material are ordered. A build phase can actually occur more than once during the development cycle; for example, when the design of a prototype is altered or when production tooling is modified during the trial phase.
Trial Phase. During the trial phase, the thermoformer conducts a trial run of the prototype tooling and sends prototypes to the customer for evaluation. If they are accepted, final approval can then be given for the procurement of production tooling, material, and equipment. If modifications are required, the thermoformer
returns to the planning phase and repeats the process until trial runs of the modified mold produce new prototypes for the customer to evaluate.
R&D to Production Validation Phase. When the device manufacturer approves the prototype package, the thermoformer is ready to enact a complete validation run of the production tooling. All of the conditions normally present during actual production--personnel, procedures, work environment, inspection--should be in place for verification. A report on the validation run should be reviewed and signed by managers responsible for engineering, production, and quality assurance, and by the thermoformer's general manager or president. The parts, along with a summary specification document, are then sent to the customer for final approval.
Final-Packet-Specification Approval Phase. The last phase of the development process is when the end result of the validation run is officially designated as a production item and is registered as part of the thermoformer's product line in a master record. From this point on, the product can only be modified through an official "request for process change."
A review of all of the material considerations for the wide variety of available medical packages would require a presentation beyond the scope of this article. Therefore, the discussion that follows will concentrate on materials used in the thermoforming of rigid medical device trays that undergo postsealing.
Resin Types and Grades. Materials currently employed to produce rigid medical trays include copolyesters (PET, PETG, APET), polystyrene (HIPS), polypropylene, polyvinyl chloride (PVC), polycarbonate and other engineering resins, and acrylic multipolymers.
PETG offers good clarity and rigidity, and has become something of a favorite among medical device manufacturers for their thermoformed trays. Though PETG is more expensive than some other resins, the added cost is often justified by the material's desirable properties. One disadvantage of PETG used for postsealed packages is that a silicone coating must be added as an antiblocking agent to aid in denesting stacked trays.
High-impact polystyrene (HIPS) provides many of the same properties as PETG. It is also less expensive, and does not require an antiblocking additive. However, one cannot achieve the same degree of clarity as with PETG. This is an important consideration in the medical market, where it is almost always required that a product be clearly visible and where a tray serves not only as a sterile barrier but also as a logical means of presenting a device in settings such as the operating room.
The use of PVC in thermoformed trays has declined somewhat in recent years. One reason is that the material will sometimes develop pinholes in deep-draw applications. Some hospitals are also disinclined to consider PVC as a material of choice for incineration or recycling.
Polycarbonate is an excellent material for high- temperature applications, although it is somewhat expensive. Like other engineering resins, it can also be rather difficult to thermoform and is generally reserved for specialty applications.
Acrylic multipolymers feature good forming and barrier properties. They also offer excellent mechanical strength, but are less than ideal for recycling.
Material Specifications and Inspection. Material purchase specifications should be prepared by the thermoformer in coordination with the material supplier, in a joint effort to satisfy customer requirements. To procure the best available material, it is advantageous for the thermoformer to know as much as possible about the quality of the resin and the sophistication of the material supplier's manufacturing process. Whenever feasible, the resin producer and converter should be experienced in meeting the demands of the medical packaging market. The purchasing specification should be controlled as a master-record document and have a revision and approval log.
Incoming material inspection can be quite time- consuming during the initial qualification of a resin supplier. Once a vendor has met the qualification requirements, however, it should be relatively simple for the thermoformer to control quality as a standard operating procedure without spending an undue amount of time inspecting.
Quality molds and dies are a critical part of any thermoforming project, and are especially important in medical applications. For many thermoformers, the preferred material for making prototype molds is an aluminum-filled epoxy resin. Stable and capable of being polished or filled for modification purposes if required, this material works well for resins that do not require mold temperatures above 180°F, such as polycarbonate or polysulfone. At higher temperatures, however, the considerable expansion ratio of the epoxy needs to be taken into account.
When building production molds, a thermoformer should always select the highest quality material that is feasible for the part being formed--which means using machined 6061 aluminum whenever possible. This material polishes well and is extremely predictable and stable. Because good mold-temperature control is essential, flood-cooling designs that maintain temperature to ±2°F are recommended.
Steel-rule dies are the least expensive and most common form of tooling used to trim thermoformed trays. Shortcoming of steel-rule dies include less-than-optimal accuracy, die life, and punch-through ability, along with a tendency to produce "angel-hair" scrap that must be vacuumed off the parts. The dies of choice for an increasing number of thermoformers are forged high dies, which cost about twice as much but require minimal cleaning and offer accuracy approaching what can be achieved with matched metal punch dies, along with good punch-through ability and a die life at least three times longer than that of a steel-rule die. Matched metal punch dies are the cleanest and most accurate and long-lasting dies, as well as the most expensive--five to six times more than forged high dies. The press used for matched metal punch dies must be flat and parallel and capable of holding tight x- and y-axis tolerances.
The integrity of a medical package is greatly influenced by the quality of the tooling and by the degree of care taken in applying proper thermoforming design principles. Any modification to the tooling must be controlled by a request-for-process-change document in the master record file so as to ensure that proper validation and testing are performed and that all personnel involved are notified.
Widespread advances in thermoforming equipment have contributed to the production of more accurate, cost-efficient packages. Device manufacturers should consider whether a thermoformer works with the most recent technology, which can help to enhance product reliability and cleanliness.
Controls. The increasing demand for innovative plastic parts has led to part designs that require sophisticated and accurate process control. In the last 20 years, process controls for thermoforming machines have improved by an order of magnitude, with development of the microprocessor sparking a veritable chain reaction in peripheral device improvements. For example, the advent of microprocessor control has led to interfaces between computers and programmable logic controls that can signal or monitor the response of motors, relays, and timers; and to the deployment of servo- controlled stepping motors with encoders on in-line thermoformers that can index thermoplastic sheet to within ±0.015 in. Tool and setup menus can be stored for fast downloading, and reports documenting running conditions can be generated automatically to ensure consistent processing from setup to setup. With the aid of a modem and a telephone line, diagnostic technicians from the equipment manufacturer can help determine problems and reprogram machinery.
Effective medical thermoforming also requires close monitoring of the systems providing compressed air, vacuum, electricity, and water. It is important that thermoforming equipment always have a sufficient supply of air, as compressed-air "starvation" can induce difficult-to-detect product flaws that can cause the failure of a sterile package in the field. Reservoir surge tanks can be used to help ensure an adequate air supply. The air must also be kept clean through the use of dryers and oil and particulate filters equipped with moisture-discharge valves.
A well-maintained vacuum system is critical, especially with high-volume molds running at high cycle speeds. Vacuum volume rate and timing must be controlled, and pump discharge processed in a clean manner. It is a good idea for the thermoformer to use large vacuum lines with no sharp bends and to locate the vacuum supply as close to the demand as possible.
The thermoformer's supply of electricity must also be controlled, in two ways. The first, and most important, concerns the regulation of the main power- supply line that powers heaters, servo drives, and other auxiliary equipment. Capacitors used for power-factor correction should be supplemented through the addition of a tuning reactor, forming a "filter" that avoids adverse harmonic resonance points while cleaning up existing levels of harmonic currents at the tuned frequency. Second, computers should be supplied power through uninterrupted power supplies (UPSs) to protect against outages. It is critical that the thermoformer's power systems be designed by certified electrical engineers.
Consistent process control for medical-grade thermoforming requires clean heat transfer and mold cooling. A thermoformer's water supply should be treated via closed-loop processes to inhibit the proliferation of scale, corrosion, and microbial growth--all of which can impair effective heat transfer.
Although most modern thermoforming machines no longer incorporate hydraulics, any hydraulic pumps, lines, and controls that are used should always be kept below the sheet line to lessen the risk of part contamination.
Calibration and Setup. Maintaining the accuracy of thermal controls, timing devices, and mechanical actuators demands regular calibration of this equipment. The thermoformer should have in place a preventive maintenance program designed to control, maintain, and document equipment accuracy. Thorough process and product validation requires that windows for equipment capabilities and maintenance procedures be formally established as quality standards, as suggested by GMPs and required by ISO 9002 prior to certification.
FACILITIES AND PERSONNEL
One of the cardinal rules in medical thermoforming is that the manufacturing area must stay clean. Positive air pressure should be maintained, and any makeup air must be filtered. Air quality and contamination can be monitored and reported in parts per million with the aid of a laser particle counter. To reduce dust, floors should be covered with vinyl, epoxy, or urethane coatings, and walls with a two-part epoxy coating. All material handling should be done with pneumatic or electric power. In order to stabilize humidity and lessen the burden of static charge, static controls in the form of deionizing bars and air-wash systems are recommended. Clothing for personnel should be antistatic and non-lint-producing. Good lighting is also imperative if a thermoformer expects to produce high-quality parts, and lighting systems have been developed recently that minimize eye strain and facilitate on-line inspection. Cleanliness is important as well in the materials- receiving area or warehouse, which should ideally be kept at the same temperature as the manufacturing floor. Documented training programs for all personnel should accord with GMP and ISO 9002 criteria.
Thermoformers packaging medical trays for distribution are strongly urged to use black antistatic bags, which reduce contamination and guard against ultraviolet exposure that can lead to photodegradation of some thermoplastic parts. Many medical device manufacturers require that trays be delivered double-bagged and labeled. Corrugated containers used to transport finished product are a major contributor to particulates in the manufacturing environment, and should be eliminated in favor of plastic totes.
Medical thermoformers dedicated to quality consider the package to be as important as the product it is designed to protect. In the medical industry this is literally true, since a defective package can compromise the sterility and thus the functionality of a device. A successful medical thermoformer is one that can plan with intelligence and foresight, process with precision and control, and validate and document with care, objectivity, and integrity.
Brett Baker is a process engineer at Sabin Corp. (Bloomington, IN), where he specializes in the development of thermoformed medical trays and turnkey packaging systems. A member of the Cook Group, Sabin produces extruded, insert- and injection-molded, and thermoformed device components.