Medical Device Link.

The highly competitive thermoplastic industry is constantly expanding its capacities and developing new products. Additionally, resin manufacturers periodically institute formulation changes due to the availability of raw materials or to enhance manufacturing value and efficiency. Because most disposable medical devices and solution containers are composed of thermoplastic materials, this environment of constant change provides challenges to the medical device manufacturer.

As mandated by regulatory requirements, the medical device manufacturer must evaluate whether a change impacts the product's safety and efficacy.^1,2 FDA requires that medical manufacturers institute a process to identify and validate material or design changes.³ These evaluations require varying degrees of time and resources; while some changes occur quickly, others can take years to validate. In addition, an ongoing awareness of process changes enables the medical device manufacturer to have better understanding and control of the materials being used.

If change occurs without the medical device manufacturer's knowledge, the potential arises for mechanical failures, toxicological reactions, or FDA design control violations. In addition, the consequences of a medical device manufacturer failing to be ready to implement a change on time may be loss of production and additional material purchasing costs.

It is important that device manufacturers obtain a commitment from their suppliers regarding immediate notification of any process or material changes.⁴ Changes that must be approved by the manufacturer include changes in composition or source of raw materials; methods of production, processing, or testing; and manufacturing sites. ISO requirements have forced thermoplastic manufacturers to become more diligent about notifying their customers of changes.⁵ Nevertheless, each manufacturer should obtain a written supplier commitment to change notification (see Figure 1). Such an agreement solidifies the supplier's intention to work with the device manufacturer.

Figure 1. An example form for a supplier notice of change.

Once notified of an impending change, the challenge to the medical device manufacturer is to validate the change with minimal financial impact. For large, multiple-division medical device manufacturers, communication across divisions is critical to eliminate redundancies and delays in approval. Traditionally, gathering sufficient resources and using them effectively has been an obstacle to resolving process change notifications (PCNs).

To address these challenges, medical device manufacturers should develop a team equipped to handle all aspects and implications of a change. The keys to success are to centralize the approval process, maintain a consistent core team, and apply structured design controls.

THE TEAM APPROACH

One technique for addressing PCNs from thermoplastic suppliers is for the medical device manufacturer to form a resin process change team (RPCT). This team meets to facilitate communication between the firm's purchasing, engineering, manufacturing, and quality personnel and with suppliers. Additionally, the team tracks project milestones during the approval process and keeps all divisions informed of the project schedule. The engineering function provides centralized testing to be used throughout the company. The flowchart in Figure 2 illustrates the entire procedure.

The RPCT should be organized into three teams: core, divisional (or product group), and plant. A communication network including all three teams is critical to success.

The Core Team. The core team is the central conduit for communicating change notices and validation progress to the company. It is made up of representatives from purchasing and product engineering for each division, and from corporate quality, toxicology, and materials R&D, as well as the RPCT coordinator. Quarterly meetings provide the platform to ensure that each process change is being properly addressed, including the development of action plans and the assigning of responsibilities. Written summaries are then distributed to the divisional and plant team representatives.

The Divisional Team. The divisional team reviews proposed resin changes to determine if performance or safety of the finished product is influenced. Each division establishes its own criteria based on the end-use application. Participants should include the core team members and representatives from product engineering, quality, marketing, regulatory, and purchasing.

The Plant Team. The plant team consists of one representative from each manufacturing location. An individual from inventory control is usually best suited to fulfill this role. The plant team verifies whether or not the plant uses the material in its processes and coordinates the validation activities until the change is resolved.

Once the teams are established, PCNs can be handled more efficiently. Anyone in the company who receives a PCN immediately forwards the information to the RPCT coordinator. If the change could result in a supply interruption, an emergency meeting of the RPCT is called to develop and implement an action plan. For PCNs that would not interrupt supply, the action plan is developed at the next quarterly RPCT meeting. Planned process or material enhancements should be structured to provide sufficient lead time for the RPCT to handle the project on a routine basis. For ongoing PCN projects, the quarterly meeting is used to provide status reports, which are distributed to all three team levels

CENTRALIZED ENGINEERING LEADERSHIP

Divisional Participation. The divisions function essentially the same under both systems. This system does not have a divisional team assembled, however; instead, participants are selected on a project-by-project basis.

The Plant Team. The role of the plant team is the same for both the team and centralized systems.

In the centralized system, the focal manager determines the significance of the PCN and identifies the divisions affected. The focal manager then works with those divisions to complete the validation.

ACTION PLAN

Once notified of a possible change, manufacturers should immediately develop an action plan. The action plan will determine the following:

• Whether to accept the proposed PCN or change to a different material.

• The time needed for the change to be both approved and implemented.

• All of the components and products affected by the change.

One alternative method of resolving a PCN is to negotiate with the supplier. Some nonmedical material suppliers are not always fully aware of the impact a change can have on intricate medical devices. A simple explanation of the potential impact may provide the material supplier with ample reason to suspend the PCN or to continue to make the current formulation as a special product. If sufficient time is not available to validate the change, one final production run should be initiated using the original formula.⁶

The RPCT may decide to change to a different material or supplier rather than approve a process change. The decision to change suppliers is usually made in an effort to move to more "medical-friendly" suppliers or to consolidate material suppliers.

When a PCN requires engineering evaluation, it provides an opportunity to determine if the resin change project could have synergy with another program (e.g., conversion to gamma- grade material, supplier consolidation, or grade consolidation). Combining a PCN resolution with a cost-savings project can actually result in a financial advantage rather than a cost impact.

If the supplier's implementation date will occur before the change can be validated, a medical device manufacturer has options beyond shortening its company's time to approval. Often, the supplier's implementation date can be negotiated. This approach is usually most successful for medical-grade plastics, and least successful for commodity-grade plastics. Another option to increase the timeline for implementation is to stockpile material either with the supplier or within the manufacturer's own company. The medical-friendly supply companies are generally open to work with customers to assist in managing the challenge of a PCN.

The lead division is typically determined after the RPCT coordinator has identified all parts affected by the PCN. The division using the material in the most applications becomes the lead division. Management in that division is responsible for selecting a project leader.

Since most PCN projects require quick turnaround, the project team must emphasize the design control system within the company to ensure quality decisions. The same design controls that apply to new product development must be applied to resin process change projects.

THE ENGINEERING PLAN

For both approaches, maintaining centralized engineering for PCN evaluation is more cost-effective than if each product group (or division) completes independent evaluations. This conclusion is not as apparent as it initially seems, however. Each different product group may be using a material in significantly different applications. Therefore, the challenge is to generate enough data to understand the practical impact of the process change without performing excessive testing of each application.

Centralized engineering gives a larger perspective on the project. By examining the corporate-wide applications that are affected by a PCN, a manufacturer may be able to identify opportunities to reduce the quantity of testing. Many lower-stress applications can be validated with data derived from higher-stress applications.

To capture properly all of the mandatory steps involved in the design control of a project, a checklist should be made to ensure each requirement is completed. The checklist can include aspects such as material selection rationale, requirements definition, clinical appropriateness review or market trial, risk analysis, and design review and verification.

A key to the successful management of PCNs is a reliable, searchable database of product components, with links to the materials used for each component. Obviously, to understand the impact of a PCN, a company must start by identifying all components affected. Identifying components within a purchased assembly or those components molded from an in-house blend of resins can pose a significant challenge. For a PCN that impacts large numbers of plastic components, it is wise to confirm database search results with all locations using the material.

TIPS FOR SUCCESS

When implementing or validating a process change, manufacturers must pay careful attention to several areas of concern.

Toxicological Testing. When implementing an RPC, toxicological testing often is the portion of the project with the longest lead time. It is one of the key areas where the cost impact can be minimized by combining all applications into one project. Before testing begins, a representative from each division should agree to the toxicological test plan.⁷

Supplier and Regulatory Approval Initiation. It is vital that manufacturers obtain regulatory and supplier approval as early as possible. Supplier approval may be needed to confirm that the resin is manufactured at an approved site or that the manufacturing process has met internal quality requirements. A new regulatory approval may be required for each product or product group, depending on how the original filing was completed.

Protocol. Manufacturers should obtain protocol concurrence from a representative for each division or product group before initiating the test plan. Common protocol oversights include failure to test the worst case for each sterilization method and failure to include regrind.

Final Review. After toxicological, regulatory, and validation requirements are completed, the project leader prepares a final review that incorporates a letter summarizing the evaluation results, recommendations, scope, and limitations.

An example better illustrates the PCN system. The following example resulted in savings of both time and money over former methods of resolving process changes. This representative process change impacted 19 formulation and color variations and over 100 components. The change also affected five product groups within the manufacturer's operation. The time required to complete testing for all components would have greatly exceeded the resin supplier's timeline for implementation.

Using the RPCT procedure in this scenario, the product group with the most components affected became the lead division. The project leader identified four worst-case components to be tested, and design control documentation was completed. A rationale was established to significantly leverage toxicological testing. Additionally, supplier-generated toxicological test data were used.

All product groups used the test data from four components that were functionally tested to approve conversion to the new formulation. Implementation was completed without any interruption to manufacturing or product quality. Cost avoidance by using these systems exceeded $1,000,000.

CONCLUSION

Because formulation and process changes will always be a factor in the dynamic thermoplastic industry, it is imperative that medical manufacturers develop a process change system to meet their customer and regulatory requirements.

The negative impact of material-related changes can be minimized by formalizing communication and developing a corporate-wide cross-functional team. An established product design control procedure can be followed to confirm a changed material's continued efficacy. As with any other supplier-manufacturer relationship, an effective communication loop helps manage change and improve the validation process. By applying these strategies, device manufacturers will be prepared to manage inevitable future process changes.

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