Best Practices for Qualifying Single-Use Assemblies

Section Overview

• Implementing Single-Use Technologies: Considerations for Suppliers and End Users
• Quality by Design (QbD) Ensures Fit-for-Use Components 
• Quality Risk Management (QRM) in the Production of Single-Use Assemblies
• Operator Handling and Training to Ensure Quality
• The Emprove^® Program – Your Technical, Regulatory and Supply Information
• Related Products
• Reference

Implementing single-use technologies: considerations for suppliers and end users

The recently updated ICH Q9 guidance¹ has reinforced a framework for biopharmaceutical development that relies on quality risk management. Implementing single-use technologies into the workflow requires close interactions between a biomanufacturer and single-use supplier, with each sharing responsibilities in managing potential risks (Table 1).

The supplier must apply best practices for qualifying single-use assemblies against a long list of requirements related to particulates, endotoxin, bioburden, extractables and leachables, sterilization, shelf life, packaging and transport, and integrity testing. The biomanufacturer, as the end user, is expected to audit the supplier’s manufacturing process, equipment used for manufacturing, in-process testing, and leak and/or integrity release testing practices. This information can then be incorporated into the biomanufacturer’s risk management process to assess the risks and mitigation actions needed to safely incorporate the single use system in their bioprocessing workflow. The Emprove^® Program provides convenient access to reliable quality and testing information for our broad portfolio of high-quality products and includes single-use assemblies. This program was designed to help biomanufacturers accelerate risk assessments and make agile, risk-based decisions to maintain compliance and control.

This technical article highlights our approach to single-use assembly qualification and includes:

• Quality by Design (QbD) Ensures Fit-for-Purpose Components
• Quality Risk Management (QRM)
• Operator Handling and Training
• The Emprove^® Program – Your Technical, Regulatory and Supply Information
• Related Products

Quality by Design (QbD) Ensures Fit-for-Use Components 

QbD provides a framework for assuring that all components are suitable for pharmaceutical manufacturing. This is mainly achieved with manufacturing design and controls, along with selected testing of components, when appropriate, using standard industry methods. 

Single-use assemblies are offered with different certification levels to meet different requirements in the bioprocessing workflow (Table 2). Certification levels reflect differences in the type and frequency of testing. The highest-level assembly certification includes Helium Integrity Testing (HIT), designed for assemblies used in the most critical applications. By contrast, Bronze certification would be appropriate for assemblies in less critical applications.  

Components are qualified and tubing connections are validated to ensure quality of the system. Failure Modes and Effects Analysis (FMEA) is used to identify and evaluate risks of component failure.

Quality Risk Management (QRM) in the Production of Single-Use Assemblies

QRM encompasses environmental control, in-process and release testing, sterilization, packaging, shelf-life determination, and point-of-use testing, if preferred by the end user.

Cleanrooms and Environmental Monitoring

Our single-use assemblies are manufactured in an ISO Class 7 environment with continuous monitoring of cleanrooms for particulates and routine cleaning of all surfaces. This eliminates the need for gears, mitigates particle risk, and ensures there is no disruption to HEPA airflow within the cleanroom. Operators gown-in within an ISO Class 8 environment that is connected to the ISO 7 cleanroom via interlocks.

In-process and Release Testing of Single-Use Assemblies

As there is no industry guidance for integrity testing single-use assemblies used in biopharmaceutical manufacturing, integrity testing during assembly production is guided by risk management. In-process leak testing, along with standard manufacturing leak and integrity tests, are routinely performed throughout the production process. Specialized release testing can be performed as needed. End-users may also choose to perform point-of-use testing as part of their qualification.

• Leak testing generally detects gross leaks in a system and may be correlated to the size of an orifice.
• Restrained plate integrity tests, with a sensitivity of 20 μm, and HIT, with a sensitivity of 2 μm, offer a higher level of confidence in system integrity and are recommended for critical applications.

Sterilization

Validation of single-use system sterilization follows harmonized international standards and is described in the common document ANSI/AAMI/ISO 11137.² Quarterly dose audits of sterilization processes are typically performed to monitor the irradiation dose on an ongoing basis. Single-use assembly suppliers should provide comprehensive documentation on their assembly sterilization procedures which should include a Certificate of Quality stating that the product is sterile after irradiation, a summary sterilization validation report, dose mapping report, the most current quarterly dose audit report, and a Certificate of Irradiation for the system lots in the batch, certifying the minimum dose recorded by the batch dosimeters.

Packaging and Transport

Following sterilization, single-use assemblies are shipped to the end-user using a transportation method validated to properly protect the single-use component materials. Resistance to shipping stress is demonstrated based on International Safe Transit Association (ISTA) protocol.  

Dependent on the risk assessment, the end-user may conduct point-of-use testing on the assemblies to detect gross leaks that may result from improper transportation, handling, or storage.

Operator Handling and Training to Ensure Quality

Following successful transportation, the integrity of single-use assembly must not be compromised in the end-user facility. Particular care must be taken during receipt, unpacking, and during use. Operator training is essential to ensure incoming receipt, inspection, and storage procedures match supplier release procedures to secure integrity of the assembly through to the point of intended use.

The steps outlined below may help identify areas where damage could occur; if necessary, the end-user and supplier should collaborate to optimize procedures to minimize risk to system integrity:

Receiving

• Incoming procedures
• Damage from shipping

Warehouse storage

• Orientation of boxes
• Storage in original packages

Transportation to point-of-use

• What types of carts are used?
• Where/how are assemblies removed from boxes?

Storage at point of use

• Types of shelving used

The Emprove^® Program – Your Technical, Regulatory and Supply Information

The Emprove^® Program provides convenient online access to comprehensive documentation needed for implementation of single-use systems in pharmaceutical manufacturing. Detailed product information contained with Emprove^® Dossiers enables more agile, risk-based decisions to support cGMP compliance and reduce the time and investment typically needed to gather and/or prepare documentation. The Emprove^® Program includes single-use components, filters, connectors, and film, as well as a wide range of other products used in bioprocessing such as chromatography resins, cell culture media, and chemicals. The description for the filter and single-use dossiers are below.

• The Emprove^® Material Qualification Dossiers (MQD) include product test specifications, release criteria, and regulatory information for the components as well as materials used for component qualification.
• The Emprove^® Quality Management Dossiers (QMD) includes quality and validation information including site qualification, irradiation sterilization process and packaging validations and site qualification. 
• The Emprove^® Operational Excellence Dossier (OED) includes extractables data following BioPhorum and USP <665> guidance to support patient safety evaluation. OED’s are available for individual filters.
• The Emprove^® Component Extractable Reports includes extractables data following USP <665> guidance to support patient safety evaluation. The reports are for single-use component made by third-party suppliers.

Special considerations for single-use assemblies

As single-use assemblies are comprised of multiple components, qualification can be more complex.  Extractables, which are compounds migrating from the fluid contact layer of polymeric plastics used in single-use assemblies into the process stream, are a key consideration during qualification of single-use systems for manufacturing. USP general chapter <665>, effective in May 2026, is the first regulatory guidance for plastic components and systems used to manufacture pharmaceutical drug products and biopharmaceutical drug substances and products. This data is the first step in evaluating patient safety and Table 3 provides an overview of a workflow.   

The Emprove^® Advanced Qualification Dossier (AQD) was developed to provide biomanufacturers with the information they need to support risk assessments on single-use assemblies containing multiple components. This first-of-its-kind dossier supports custom and configurable assemblies and includes:

• All available component qualification information along with extensive USP <665> extractables data for all the components in the assembly.
• Information on extractables, bills of material, regulatory statements, component surface area information, original manufacturer information, shelf-life statements, and customer-approved drawings of the assemblies.
• The data needed for end users to conduct risk assessments and patient safety evaluations of their assemblies.  

If you are interested in Emprove^® premium content, Demo dossiers are available to download including data for custom assemblies.