Quality in aseptic services
‘Quality’ in aseptic services means making sure that injectable medicines are right for patients. They must be
- free from microbial, particulate and chemical contamination
- of the correct content throughout their shelf life
- available to patients when and where they need them
Aseptically prepared medicines cannot be analytically tested for content or contamination without destroying the product, so there is no product-specific test data available to provide assurance of quality. Confidence of quality at the point of release can only be achieved from evidence that products have been made correctly, have not become contaminated during preparation, and will remain stable for the duration of their shelf life.
For staff and the service to thrive, a strong quality culture is essential. Senior staff should ‘lead from the top’ by actively committing to continuous improvement and investment in the service to ensure patient safety.
Quality and safety in aseptic services don’t happen by chance; they must be built into every stage of the process. By focusing on design, control, and continuous improvement, aseptic services can deliver medicines with confidence in their safety and suitability for patients not just now, but in the future. This approach can be referred to as Quality by Design (QBD); for more information refer to International Council for Harmonisation (ICH) Technical Requirements for Pharmaceuticals for Human Use Q8 part 2.
Pharmaceutical Quality Systems
A pharmaceutical quality system (PQS) is not a document or a piece of software: it is everything that we do to ensure that medicines we make are safe and effective when administered to patients.
Quality must be embedded into all aseptic service activities, from facility design and validation, through aseptic processing and all its related activities. These must be underpinned by routine monitoring, robust management and clear governance arrangements.
The PQS provides assurance of compliance with quality standards, and ensures any potential patient risks are identified and acted upon in a timely manner. Evidence of compliance is essential for the person responsible for product approval who must make an informed declaration of the product’s fitness for use.
The ICH Q10 guideline on quality systems provides more information on the PQS.
Establishing an effective PQS
When implementing a PQS it is often helpful to consider the ‘4Ps’ – people, premises, processes and products, to be sure that all factors are considered.
Premises and equipment
A well-designed, fully validated and well-maintained environment provides a stable foundation for consistent, efficient and safe practice.
Design of facilities and equipment should
- be compliant with current regulatory guidance
- consider new and emerging technologies
- minimise the risk of ingress of microorganisms
- facilitate easy cleaning and decontamination
- accommodate current and anticipated future products, and should not be limited by current production activities
The layout should prevent bottlenecks and cross-over of process stages to minimise the risk of confusion and errors and to improve efficiency.
The articles on contamination control (SPS page) and design, build and maintenance of pharmacy aseptic units (SPS page) provide more information.
People
Delivering a safe and effective service depends on a sufficiently skilled and resourced workforce and strong leadership. Competence must be routinely monitored and reassessed, and skill mix actively managed.
To be able to perform their role, everyone working within the aseptic service should be
- suitably qualified
- knowledgeable
- trained
- competent
- experienced
- clear about their roles and responsibilities
Evidence of competence status should be readily available to the person responsible for product approval.
Succession planning, deputising and contingency arrangements are essential for service resilience, to maintain continuity and minimise risk during staff changes or unexpected absences.
Processes
All processes must be standardised, validated, monitored and clearly defined in Standard Operational Procedures (SOPs). This means every step, from prescription or order receipt to final product release, can be consistently performed with confidence and control.
Where possible, processes should incorporate built-in controls designed to detect and prevent errors. If this is not possible, active supervision is needed to detect errors and deviations from defined SOPs, good aseptic practice and good comportment.
Contemporaneous batch manufacturing records and worksheets should be designed to drive consistent, compliant practice. They should include a documented declaration that each step has been performed correctly. These records provide evidence for the person responsible for product approval that SOPs have been followed, that in-process checks have been made and that supervision was in place.
Products
Many medicines made in aseptic services are highly susceptible to rapid temperature-dependent degradation after reconstitution. A full understanding of the individual medicine’s characteristics is essential so that the impact of preparation at room temperature, considering the chilling time after preparation, and subsequent storage and distribution can be assessed.
Monitoring and review
Effective systems to monitor the facility, the workforce, the processes and product quality provide evidence that the aseptic service is operating under a state of control. They detect early warning signs before product and service quality are affected.
Monitoring
Systems of monitoring will include, but may not be limited to
- end of session media fills
- sterility testing
- routine physical and microbiological environmental monitoring
- operator and process validation
- facility and equipment re-validation
- daily facility and equipment checks
- evidence of compliance with supporting processes, for example cleaning records
- error and deviation monitoring and trending
- workload and capacity data
Review
Out-of-specification results must be investigated. Results of all monitoring and on-going validation must be reviewed, trended and evaluated. Findings should be shared across the team for learning, and escalated to the Chief Pharmacist for oversight and intervention where required.
Governance
A quality culture facilitates rapid and safe introduction of new products and services for patients whilst driving continuous service improvement and ensuring patient safety.
Management oversight and review is essential to assess service performance against quality objectives, identify risks, and set priorities for improvement.
Resources
A well-led, responsive and resilient service requires sustained investment in people and premises to meet patient demand whilst maintaining quality and responding to emerging risks. Without this, even the best systems cannot deliver safe and reliable services.
Premises and equipment will age, so they require planned preventive maintenance (PPM), servicing and lifecycle planning. Plans for replacement should be made well before failure occurs, using business cases to secure investment early. Waiting until something fails risks contamination, error and service disruption.
The workforce must be supported by a training and development infrastructure that accounts for staff turnover rates. Robust deputising and succession planning is essential for key personnel.
Risk and deviation management
Routine, proactive risk and impact assessment can prevent errors and failure. When deviations and near misses occur, thorough investigations should identify root causes, not just symptoms, and enable effective Corrective and Preventive Actions (CAPA).
Detailed guidance on risk management can be found in the International Conference on Harmonisation (ICH) guideline Q9 on quality risk management (QRM).
Change management
All changes with the potential to impact on product or service quality, including significant staffing changes, must be managed through a formal change control process. This ensures that improvements are implemented safely without introducing new risks.
Audit and self-inspection
Self-inspections and external audits both assess aseptic units against the standards and can provide assurance of compliance.
Self-inspection enables units to understand their own strengths and weaknesses so risks can be identified and addressed in good time.
Periodic external audits and inspections also assess compliance with standards and identify risks to patient safety. However, if the internal audit programme is effective, units will already be aware of their areas for improvement: nothing the auditor identifies should be a surprise.
Product approval
The person responsible for product approval does not have product specific test data to inform their decision, so must rely on evidence of compliance with the PQS to provide evidence of quality.
Recent results and trends from microbiological monitoring provide evidence that the contamination control strategy is effective. Facility and equipment logs demonstrate that the facility and all equipment are working within specified limits, and cleaning records show that the facility has been correctly cleaned and decontaminated.
Evidence should be available that all staff involved in preparation or any other related activity are competent to undertake the task.
Worksheets and batch manufacturing records should provide a positive, contemporaneous declaration of compliance with all procedures associated with product preparation, and details of any deviations.
After reviewing the evidence, the person responsible for product approval can make an evidence-based professional judgment about whether the medicine is
- free from microbial, particulate and chemical contamination
- of the correct content
This informs the decision to approve or reject the medicine for use.