Feature Article

Incorporating quality

Since its first use in medical devices in the late 1940s, silicone tubing has become indispensable in a range of now traditional applications, from shunts to drainage tubes, catheters to feeding tubes. With the evolution of technology, innovative and increasingly sophisticated applications continue to emerge. One such application is the use of silicone tubing in a single-use device under development for sedationless colonoscopy, which is described later.³

Regulations have also evolved, compelling device manufacturers and encouraging raw material and component suppliers to build quality and safety into their products from initial development and design and throughout manufacture and commercial launch. Medical device manufacturers place increasingly high expectations for quality and safety on their suppliers, for whom incorporating quality also includes implementing elements of continuous improvement and risk management principles. Yet even this approach can benefit from further steps. To be truly effective over the long term, scrutiny must continue after launch by maintaining systems to monitor product performance and investigate issues discovered during product use.

Defining a risk based approach

It is the medical device manufacturer’s responsibility to ensure device safety and compliance with regulations. At the same time, raw material suppliers should provide consistent, reproducible and safe materials. In general, medical device good manufacturing practices (GMPs) were developed to help ensure safety, efficacy, quality and consistency of products, achieving this in part by minimising or eliminating errors, mix-ups and contamination. Current regulations do not specify quality and safety requirements for medical device raw materials and components, including tubing. Instead, the United States Code of Federal Regulations 21, Part 820.1(a)(1) states, “This regulation does not apply to manufacturers of components or parts of finished devices, but such manufacturers are encouraged to use appropriate provisions of this regulation as guidance.”⁴ For some critical applications, device manufacturers may require their suppliers to provide materials manufactured according to medical device GMPs.

It is important to establish appropriate balance between device manufacturer requirements and material supplier capabilities. Suppliers can work towards achieving this goal by

• designing control into their manufacturing
• minimising sources of potential contamination
• developing and implementing appropriate safety testing
• managing change at all levels
• notifying device manufacturers of any change that could potentially affect the quality or safety of their product(s)
• maintaining complete process/product traceability and documentation.

The result should be a high level of assurance that the materials supplied will be of consistent quality, performance and purity.

The quality, consistency and purity of silicone tubing used in drug delivery devices can be more critical than in tubing used for the transfer of fluids in pharmaceutical manufacture. Purchasing tubing from a source that may not operate according to the appropriate level of GMPs could pose additional concerns, especially if a loss of quality event occurs and the supplier cannot identify specific batches, or if there is no record of unusual events, which makes it difficult to determine the reason for the occurrence. If the root cause is never found, there is no way of knowing for certain that it will not occur again.²

What device manufacturers need

With increased global regulatory focus on medical devices, an expanding array of standards and guidelines is intended to ensure that the devices are functional and safe. Device manufacturers should define and achieve the appropriate level of raw material and component quality, consistency and purity by working closely with select material suppliers, industry organisations and regulatory authorities.

Using this approach, silicone tubing manufactured under strict quality control standards helps minimise risk to the patient and the device manufacturer. Although the ISO 9000 group of standards is recognised globally as a quality management system that can provide a useful structure for quality, its focus remains more on the “what” rather than the “how” and the end result. In today’s medical device market, it is essential to be able to manage and trace materials used in products throughout their entire supply chain. The solution lies in adherence to appropriate GMP principles. In doing so, silicone tubing suppliers can help ensure successful production, handling and distribution of materials and thus support medical device manufacturers to successfully produce safe and effective finished products.

The chance to work closely and exchange information with their suppliers allows device manufacturers enhanced opportunity to communicate their requirements. As a result, tubing suppliers can assess how their materials are being used and react more quickly to provide input during the development process. Because device manufacturers are ultimately accountable for final product testing, a supplier with product and regulatory expertise can build the proper level of quality into its silicone tubing, beginning with the elastomer itself, and thereby contribute significantly to the quality of the finished product.

Figure 1: Single-use colonoscopy device incorporating flexible silicone tubing.

The case of developing a new medical device for potentially sedationless, hands-off colonoscopy (Figure 1) is an example of how the physical properties and biocompatibility of silicone tubing have contributed to innovative applications. Once it reaches the market place, this new device will respond to some fundamental issues associated with traditional colonoscopy, including³

• pain associated with the semi-rigidity of conventional colonoscopes
• potential cross-infection risks due to the potentially inadequate disinfection of conventional colonoscopes
• potential complications related to sedation and semirigidity of the devices.

In this device, flexible silicone tubing forms an inverted sleeve that enables the user to drive the endoscope. A hand-controlled device is used to control the motion of the endoscope in the colon without manual pushing or pulling. Coupled with the flexibility of the silicone, the controlled motion minimises potential forces on the colon wall and opens the potential for sedationless colonoscopy. The single-use device is delivered ready for use and on completion of the examination the entire endoscope is discarded. Because patients have their own individual endoscope, the potential for cross-infection is eliminated. It is clear that the quality, consistency and purity of the silicone tubing manufactured according to GMPs and incorporated in the construction of the sheath contribute to the safety of the device and the procedure.

What can suppliers do?

A number of actions on the part of suppliers form a foundation for producing and supplying silicone tubing appropriate for use in the sedationless colonoscopy application, as well as in other emerging medical device technologies. One of the most positive steps is to manufacture materials for healthcare applications in dedicated facilities that are registered and inspected by the United States (US) Food and Drug Administration (FDA). Although not required, a reliable supplier should make the conscious decision to manufacture silicone tubing for medical device applications according to the critical principles of medical device quality system regulations.

In tandem, it is critical to identify and manage appropriate quality system requirements for tubing production. These should include designing the process and product for consistent quality, establishing controls to minimise product contamination, maintaining appropriate documentation, ensuring appropriate change control, and where necessary, communicating significant change to fabricators or device manufacturers who use the tubing.

Figure 2: Summary of risk management from a GMP perspective (click to enlarge).

Another vital component of the overall quality package is maintaining full traceability for materials throughout a globally integrated supply chain. In short, this means documenting each step from raw material receipt, inspection and testing through production, to final testing, lot-sample retention, handling and distribution. Figure 2 provides an overview of risk management principles coupled with selected GMPs.

In addition, a premier supplier will think and proceed on a global scale, planning and acting to qualify and manufacture materials that comply with regulatory requirements for various countries. Device developers look to suppliers to help expedite and simplify the regulatory approval process, for example, creating and granting access to US FDA Drug Master Files and Material Application Files. For users outside the US, Technical Files can help support and expedite registration needs. Finally, suppliers can enhance their business relationships by providing copies of their most recent FDA Establishment Inspection Report, as needed, to medical device manufacturers or other regulatory authorities.

Implement the right strategy

With the level of complexity and geographic reach of today’s medical device market, it is clear that quality must be designed and built into medical device products, including into their raw materials and components such as silicone tubing. Testing alone simply cannot be relied on as the only assurance of product quality.

Silicone tubing can be an integral part of medical devices and it is therefore important to assess the intended use of each device to help define and “match” the tubing quality system requirements based on end-use. A competent supplier should develop and implement risk management strategies for its materials and also support device manufacturers as they assess, develop and implement strategies to manage their own risk.

Suppliers of raw materials and components have the best chance of success when they develop and implement appropriate risk control strategies for their products. These efforts help ensure supply chain integrity and safety of the products through delivery to the device manufacturer. By focusing on the appropriate level of GMPs, both suppliers and device manufacturers combine risk management to arrive at the best solutions that ultimately benefit patients.

Jim Curtis Senior Industry Chemist, Healthcare, Dow Corning Life Sciences, PO Box 994, Midland, Michigan 48686-0994, USA tel. +1 989 496 6809, e-mail: jim.curtis@dowcorning.com, www.dowcorning.com