Selection of the method of sterilisation to be used for a medical device occurs during product development and is an important decision that has significant implications throughout the lifecycle of the product. Once the sterilisation method has been selected, it drives decisions further down the supply chain including choosing whether the product will be sterilised in-house or whether an external sterilisation facility will be required.
The selection of a sterilisation process is driven by the materials and construction of the medical device; the product has to meet the requirements for safety and performance after sterilisation and so compatibility is the key driver. A company will focus on:
- employing proven technology; wherever possible one with
- which it is familiar and in which it has expertise
- compliance with regulatory expectations, including complying with international standards that are accepted for regulatory purposes.
Sterilisation using ionising radiation - gamma ray, electron beam or X-rays - and ethylene oxide are the most widely employed sterilising agents for medical devices. Moist or dry heat sterilisation presents other options. Other terminal sterilisation processes using, for example, hydrogen peroxide, chlorine dioxide or ozone, are available but not widely used on an industrial scale. Aseptic processing might be necessary, particularly for products that combine medical devices and pharmaceutical or biologic products.
With the selection of the sterilisation method, decisions on whether the process will be delivered in-house or using an external partner can be made. A range of commercial organisations offer a sterilisation service employing ionising radiation and ethylene oxide. There are also potential partners for heat sterilisation and specialist contractors for aseptic processing in the pharmaceutical sector. Other sterilisation processes have niche applications that are more likely to be delivered in-house.
If it is decided to use an external partner, factors that come into play include those related to:
- product requirements
- quality and compliance
- commercial relationships.
These factors are summarised in and discussed in more detail below.
1. Factors for selection of an external partner
Ideally, a product, including the packaging system, would be designed to be able to fit into an existing sterilisation process. If not, it would be preferred that it is compatible with a sterilisation technology that is understood and widely used in the company. Furthermore, the product should be designed to tolerate a wide range of sterilising conditions to allow maximum flexibility in the choice of sterilisation partner. A narrow range of sterilisation conditions can severely limit options.
A key determinant in selection of a sterilisation partner is location. The relationship to the intended manufacturing site and distribution centre(s) can be critically important in managing supply chain logistics. The location drives transportation time and the method of transport from manufacturing to sterilisation and from sterilisation to distribution. Long freight distances increase the manufacturing cycle time, the amount of work in progress and the levels of inventory.
The expertise, capability and capacity of the potential partner are key determinants. The partner has to be able to deliver the required process, within defined tolerances, reliably and reproducibly. They must have the capacity to deal with current and forecast demand, and also have the flexibility to respond to changes in demand, either if forecasts are exceeded or if demand is not as strong as projected.
Quality and compliance
In considering an external partner, it is important to address a number of questions related to quality and compliance to regulatory expectations.
- What is their historical performance in terms of reliability of service and equipment?
- What is their compliance profile? Consideration should be given to the partner's compliance history, profile with local and national regulatory authorities, as well as with authorities in international markets to be supplied. Their ability to comply with the relevant standards for their activities is an important consideration. This will include the status of their quality management system (compliance, for example with ISO 13485 and the US FDA Quality System regulation) together with the relevant standards for the development, validation and routine control of the sterilisation process to be employed. Other compliance aspects to be considered include compliance with environmental legislation, health and safety requirements and treatment of employees.
- What are their capabilities in validation of the process? This would include the status and quality of the documentation and records of the installation qualification and operational qualification, and their ability to be an effective partner in delivering the necessary performance qualification for the product.
All these aspects would be subject to assessment prior to commencing operations with the partner and subject to regular review throughout the lifetime of the partnership. It is important that the relationship allows the communication of compliance information between both parties, and should form part of the quality agreement established between both parties.
In reviewing the commercial aspects of a relationship with an external partner, factors to be addressed would include:
costs - the costs for routine processing, initial validation and periodic revalidation
business relationship - this would include any past history of working with this partner, whether the goals of both parties are aligned and whether there is a common business philosophy that will be sustainable
inventory - consideration of the turnaround time at the sterilisation facility and how much work in progress will need to be held
business continuity - plans for back-up capacity in the event of facility, equipment, capacity or compliance issues arising
business security - the financial stability and capability of the external partner to support current and future business needs have to be considered.
2. How to carry out the selection process
When selecting an external provider for sterilisation, the selection process should follow the company's supplier selection procedures and subsequently the supplier monitoring procedures.
Define product requirements
Within the product design process, the method of sterilisation will be determined. The selected sterilisation method will be built into the design of the product packaging and also, potentially, determine the carton and shipping case configuration. Where possible, this should be determined early in the product development lifecycle to facilitate the development of the sterilisation process parameters for the commercial product.
Identify potential partners
The next step is to identify potential partners for product sterilisation. Where an internal process is possible this could also be rated against the capability of potential external service providers. The initial selection may consist of a list of those that are able to provide the selected sterilisation method. The list of potential partners could include any current sterilisation service providers, but consideration may also be given to alternate providers or new providers to the business.
In selecting the most appropriate sterilisation service provider data should be gathered for all potential partners to allow comparison and also to document the decision process for the finally selected provider. It may be appropriate to use a supplier selection tool, such as a 'prioritisation matrix'. Initial data may be gathered from the supplier by way of a questionnaire, and may include (but is not limited to) requests for information on items such as capacity, resource levels, quality system processes, change control and process validation. It is also important to request copies of any certification to relevant external standards. During the data-gathering period it is good practice to make a visit to the potential candidate(s); the nature of such a visit may be detailed within the supplier selection procedures, and may take the approach of a quality audit, a technical visit or maybe a business review. Whatever the type of visit is conducted, this is important in establishing the future business relationship with the service provider and will facilitate the way in which future business is conducted.
Select partner of choice
Following the collection of all the relevant information from the potential sterilisation partner, the data should be reviewed to allow the final selection of the partner. The review of the data may be conducted by a team approach, with participants from quality, supply chain, purchasing, operations and R&D, thereby obtaining a consensus of the most appropriate service provider with which to work.
At this point, the development of the relationship with the service provider begins in earnest. The ground rules for the ongoing partnership should be established and documented. In the interest of both parties, agreements should be put in place to detail all aspects of the business relationship. Agreements should be reached on the ongoing monitoring requirements including frequency of validations and on-site audits.
Monitor relationship and control
As the sterilisation process is established and the validation processes completed, data should be shared and reviewed by the company sterilisation specialists and quality assurance personnel. With the establishment of the commercial process, ongoing monitoring is essential as the accountability for sterilisation remains with the originating company, and supervision is a regulatory requirement. Process control parameter information along with batch specific data should be provided. Additionally, metrics may be established for quality and business parameters, for example, processing cycle-time adherence. As the relationship evolves over time, the level of monitoring may decrease, based on experience; however, the management supervision must be maintained for this critical process. Periodic audits of the sterilisation contractor should be carried out as specified in the supplier monitoring procedures.
Selecting a commercial partner to provide a sterilisation service is a strategic decision that has far-reaching implications. In making such a partnership decision, factors to be considered include: product requirements, logistics, capability, quality and compliance, and commercial arrangements. All these need to be balanced and appropriately weighted in order to ensure the long-term success of the partnership.
This article was first published in our sister publication Medical Device Developments.