Tag: ASTM

Best Practices for Managing the Life-Cycle of Single-Use Systems

Single-use systems (SUS) have become increasingly prevalent in biopharmaceutical manufacturing due to their flexibility, reduced contamination risk, and cost-effectiveness. The thing is, management of the life-cycle of single-use systems becomes critical and is an area organizations can truly screw up by cutting corners. To do it right requires careful collaboration between all stakeholders in the supply chain, from raw material suppliers to end users.

Design and Development

Apply Quality by Design (QbD) principles from the outset by focusing on process understanding and the design space to create controlled and consistent manufacturing processes that result in high-quality, efficacious products. This approach should be applied to SUS design.

ASTM E3051 “Standard guide for specification, design, verification, and application of SUS in pharmaceutical and biopharmaceutical manufacturing” provides an excellent framework for the design process.

Make sure to conduct thorough risk assessments, considering potential failure modes and effects throughout the SUS life-cycle.

Engage end-users early to understand their specific requirements and process constraints. A real mistake in organizations is not involving the end-users early enough. From the molecule steward to manufacturing these users are critical.

    Raw Material and Component Selection

    Carefully evaluate and qualify raw materials and components. Work closely with suppliers to understand material properties, extractables/leachables profiles, and manufacturing processes.

    Develop comprehensive specifications for critical materials and components. ASTM E3244 is handy place to look for guidance on raw material qualification for SUS.

    Manage the Supplier through Manufacturing and Assembly

    Implementing robust supplier qualification and auditing programs and establish change control agreements with suppliers to be notified of any changes that could impact SUS performance or quality. It is important the supplier have a robust quality management system and that they apply Good Manufacturing Practices (GMP) through their facilities. Ensure they have in place appropriate controls to

    • Validate sterilization processes
    • Conduct routine bioburden and endotoxin testing
    • Design packaging to protect SUS during transportation and storage. Shipping methods need to protect against physical damage and temperature excursions
    • Establish appropriate storage conditions and shelf-life based on stability studies
    • Provide appropriate labeling and traceability
    • Have appropriate inventory controls. Ideally select suppliers who understand the importance of working with you for collaborative planning, forecasting and replenishment (CPFR)

    Testing and Qualification

    Develop a comprehensive testing strategy, including integrity testing and conduct extractables and leachables studies following industry guidelines. Evaluate the suppliers shipping and transportation studies to evaluate SUS robustness and determine if you need additional studies.

      Implementation and Use

      End users should have appropriate and comprehensive documentation and training to end users on proper handling, installation, and use of SUS. These procedures should include how to perform pre-use integrity testing at the point of use as well as how to perform thorough in-process and final inspections.

      Consider implementing automated visual inspection systems and other appropriate monitoring.

      Implement appropriate environmental monitoring programs in SUS manufacturing areas. While the dream of manufacturing outdoors is a good one, chances are we aren’t even close yet. Don’t short this layer of control.

        Continuous Improvement

        Ensure you have appropriate mechanisms in place to gather data on SUS performance and any issues encountered during use. Share relevant information across the supply chain to drive improvements.

        Conduct periodic audits of suppliers and manufacturing facilities.

        Stay updated on evolving regulatory guidance and industry best practices. There is still a lot changing in this space.

        Voluntary Standard Organizations and You

        A consensus standards organization, also known as a voluntary consensus standards body, is an entity that develops and publishes technical standards through a collaborative, consensus-based process involving various stakeholders. Here are the key characteristics of consensus standards organizations:

        1. Voluntary participation: Involvement in the standards development process is voluntary for interested parties.
        2. Consensus-based approach: Standards are developed through a process that seeks general agreement among participants, considering the views of all parties and reconciling conflicting arguments.
        3. Openness: The procedures and processes for developing standards are open to interested parties, providing meaningful opportunities for participation on a non-discriminatory basis.
        4. Balance: The standards development process aims to achieve balance among different stakeholder groups, ensuring no single interest dominates.
        5. Due process: The organization follows established procedures that include provisions for appeals and addressing objections.
        6. Transparency: The procedures for developing standards and the standards themselves are transparent and accessible.
        7. Non-profit status: Many consensus standards organizations operate as non-profit entities.
        8. Diverse stakeholder involvement: Participants typically include industry experts, government representatives, academics, and consumer groups.
        9. Accreditation: In some cases, these organizations may be accredited by national bodies (e.g., ANSI in the United States) to ensure they follow proper procedures.
        10. Wide range of applications: Consensus standards can cover various fields, including product specifications, testing methods, management systems, and more.

        Examples of well-known consensus standards organizations include:

        • International Organization for Standardization (ISO)
        • American National Standards Institute (ANSI)
        • ASTM International (formerly American Society for Testing and Materials)
        • British Standards Institution (BSI)

        These organizations play a crucial role in promoting quality, safety, and interoperability across various industries and sectors by developing widely accepted standards through collaborative processes.

        The Unique Role of Inter-Governmental Agencies in Pharmaceutical Standards

        While discussing consensus standard organizations, it’s important to highlight a distinct category that operates similarly but doesn’t quite fit the traditional mold: inter-governmental agencies like the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S).

        These organizations share some key characteristics with consensus standard bodies:

        1. They focus on harmonization efforts in the pharmaceutical industry.
        2. They operate internationally, involving multiple countries and regulatory authorities.
        3. They provide frameworks for collaboration among stakeholders.

        However, ICH and PIC/S differ from typical consensus standard organizations in several ways:

        • Membership: They primarily comprise regulatory authorities rather than a broad range of industry stakeholders.
        • Authority: While not legally binding, their guidelines and standards often carry significant weight with regulatory bodies worldwide.

        These organizations play a crucial role in shaping global pharmaceutical regulations, bridging the gap between formal regulatory requirements and industry-led standards. Their work complements that of traditional consensus standard organizations, contributing to a more cohesive and harmonized global regulatory environment for pharmaceuticals.