During the last six years, single-use systems and devices have emerged as key agents in the biopharmaceutical landscape.¹ Single-use solutions have revolutionized the Pharmaceutical and Biopharmaceutical industry due to their effectiveness in reducing the risks of contamination and allowing faster changeovers. These advantages, coupled with the significantly reduced time and costs required to establish a new manufacturing facility, have made single-use a very popular choice.
Single-use products have gone well beyond an early-stage technology, and it is likely that the popularity of these devices will continue to rise over the next few years.¹ Therefore, it is becoming increasingly important to view single-use system suppliers, not only in the context of “can they make the disposable,” but also from the perspective of “does the single-use system supplier maintain strong quality oversight to support their product from a control process and ensure regulatory compliance.” The recent 10th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production found that 65.7% of end-users of single-use devices agreed use of disposable/single use devices are factors in creating “significant” or “some” improvement to biomanufacturing performance².
Drug manufacturers — especially biopharmaceutical contract manufacturing organizations — must ensure their operations maintain a robust quality systems infrastructure to ensure production efficiency and superior operational excellence thereby driving the continuous improvement cycle. The resulting manufacturing distinction will provide customers with the confidence to withstand regulator scrutiny while providing with certainty that quality products will be available to meet the therapeutic markets demand for its therapies. The manufacture of high-quality single-use systems and process solutions requires the same from its suppliers to minimize risk and ensure safety, traceability and compliance at every stage of production. To minimize risk, single-use system suppliers similarly must control and document each production step from raw materials and assembly to final test, packaging and sterilization.
As a result, change control has become an important factor for the biopharmaceutical industry. Indeed, the FDA’s guidance for single-use system suppliers clearly reinforces the importance of implementing efficient change control procedures as a critical element in an overall quality system, and suggests the scope of a successful change control program must cover a broad set of possibilities, including changes to the supply chain and product specifications or design, as well as upgrades to facilities, utilities, equipment, computer systems, manufacturing instructions, SOPs, test methods and any changes in policy.3
WHAT IS CHANGE?
Change can be defined as a movement out of a current state, through a transition state, to a future state. In biopharmaceutical manufacturing, change can be internally or externally motivated, as well as minor or dramatic departures from what is known, anticipated or unexpected, including alterations to facilities, products, processes, equipment or computerized systems.
Change may be required due to:
• Design and development review, verification, or validation (IQ, OQ, PQ)
• Requests from engineering
• Requests by customers or suppliers
• The need for corrective or preventive action
• Safety and regulatory requirements, and
• Improvements to the function and performance of a product
Effective change control systems take time to establish and must be continuously updated. A mature change control system becomes intuitive and remains relevant. Intuitive in that it fosters a structured approach toward managing and documenting change in an environment that engenders continuous improvement, and relevant in that it stays centered on the objective and nature of pending change, and focused on the exact scope of imminent change.3
Key components of a change control system include3:
• End-to-end communication with all stakeholders from raw materials vendors to product end-users
• Documentation of the details of change, change approvals and implementation, thereby tracking changes effectively for visibility and traceability
• A consistent, structured and sequential approach toward managing change
• An automated system that provides redundant flags/alerts, the ability to search by various criteria, and requires authorization via user credentials in order to make changes
• Routing of change requests to individuals for approvals
• Easy retrieval of information
• Provision of an audit trail
• Demonstration of compliance to FDA regulations
• Speed to allow due deadlines to be met, and
• Education on change control methodology for all employees, to allow timely execution of inventory disposition and existing job orders
Incorporating these key components allows for a dynamic change control system that can help end-users implement continuous improvement and manage impending change with their own products and systems.³
In particular, a change control system must effectively accommodate supply chain interruptions, as the ability of a single-use system supplier to provide accurate raw materials data is crucial to the quality of high-value products. Raw materials changes are notoriously inconvenient for the end-user, often unavoidable and include changes to component specifications, suppliers and resins.