Aseptic Processing in Manufacture of Sterile Products & ATMPs

Summary

This 3-day online training will cover GMP regulations and regulatory expectations in Aseptic manufacturing of sterile medicinal products and ATMPs including key points in compliance to the revised EU GMP Annex 1 that encourages increased application of Quality Risk Management (QRM) principles (ICHQ9) over the product life cycle (ICHQ12). Details will be provided of manufacturing technologies to improve efficiencies and GMP compliance together with guidance on how to prepare a Contamination Control Strategy (CCS) and if required aseptic-containment strategy. The training extends into process operations covering best practices; Good aseptic technique, good Cleanroom behaviour together with good training practices (including increased use of VR (virtual reality).

Background

The revision of Annex 1 EU GMP for manufacture of sterile medicinal products marks a paradigm shift in regulations taking a more risk based, holistic and proactive approach to managing contamination and product quality in manufacturing. To support the paradigm shift ICHQ9 QRM: Quality risk management has been revised to focus on hazard and risk knowledge before applying risk control mitigations to move away from the subjectivity of risk assessments that tend to focus on risk priority numbers (RPNs) that can lead to poor justifications of unacceptable risks. Regulators consider the full benefit of QRM is not being realised hence the revision of ICHQ9 (R1) and direct linkage to Annex 1 to engage this essential principle. Such regulatory changes impact key elements of aseptic processing and keeping current requires an understanding of these changes and impact. This essential training will cover key points to consider as result of regulatory changes and possible solutions to regulatory requirements that may be an expected or necessary process improvement.

Who should attend?

This course will cover a range of aspects in aseptic processing that will be of interest to: QA/QPs and QC, Facility and process design, Materials Science and Technologies (MSAT), Manufacturing operations, Aseptic processing technology specialists, GMP consultants and auditors

Course content and who should attend

The training content will cover all levels of interest and knowledge requirements where aseptic processing is involved in sterile product manufacturing including ATMPs and will be suitable for QA/QPs and QC involved in improvements to meet new regulatory requirements and demonstration of ongoing GMP compliance together with batch release, plus, manufacturing operatives and production management. Also, the training will be relevant to those involved in process and facility design where integrated manufacturing technologies (intensification) are applied with increasing levels of barrier separation and automation e.g. combined formulation and filling platforms, automated filling lines including robotics, open and closed processing equipment, barrier technologies (Isolators and RABS), aseptic-containment technologies, monitoring technologies and single use technologies( SUT), single use systems (SUS) and Ready to use (RTU) product containers and closures.

Training will cover key aspects of material transfers, product sterilisation by filtration (with PUPSIT), Aseptic process simulations (media fills) and data collection/ analysis as evidence of control and detection of variance/ deviation from specification and specified limits.

Key takeaways

Changes in regulations and new GMP requirements challenge all industries but also considering the growth in biologics/ ATMPs for more targeted personalised/ individualised medicines and the paradigm shift away from big ‘block buster products’ the need to understand aseptic processing and regulatory expectations has never been more current. Vaccines have become a new ‘Block buster’ manufactured at large batch scale that use biologics requiring aseptic processing with high efficiencies provided by automation.

New aseptic processing platforms are following five ‘pillars’ that characterise an advanced approach, including: Flexibility, Modularity, Intensification, Digitalisation and Automation.

• Flexibility is required for adaptive approaches as new products are developed and different dose forms and presentations may be required. Flexibility applies in process design to combine closed systems (single use systems) with barrier technologies that are required in more open aseptic processing steps e.g., Filling – container closing.
• Modularity is required to enable pre-designed modules to be configured to meet different product and manufacturing platform requirements. The pre-design element is a cost and time saving facilitating faster project delivery and reduced time to market.
• Intensification is the combination and integration of process steps to increase efficiencies, reduce manufacturing space, typically specific manufacturing platforms are intensified in one GMP Cleanroom to reduce in-process transfers and improve contamination control. Scale up and Scale out applies to facilitate commercialisation.
• Digitalisation applies through the complete process in control and monitoring. Process controls, process variables including critical process parameters (CPPs) are characterised as a ‘digital twin’ to the manually applied process and process monitoring data (EM and PM) as digital formats facilitate more real time proactive responses to deviations and efficient and assessable/ visible trend metric analysis that can drive continuous improvement.
• Automation to improve process efficiency and repeatability over manual processes (avoiding human error) and improved contamination control (avoiding interventions).
• GMP guidance cannot be prescriptive for all processes and products so applying QRM to accommodate alternative processes has become key to introduction of new technologies and methods that are developing to support new product bio-processing and manufacturing – learn about these challenges and practical experiences via case studies.

Key takeaways include

• GMP regulation changes and their impact on Aseptic processing
• QRM what this really means and how it is applied
• Contamination Control Strategy (CCS) and considerations in aseptic processing
• Barrier separation technologies, alternatives for aseptic processing of different product types e.g., Pharmaceuticals, biologicals, ATMPs and toxic products – small and large batches
• Application of single use systems, RTU: Ready to Use product containers and closures in barrier technologies considering transfers into Grade A and bio-compatibilities
• Application of large batch vial filling for liquid and freeze-dried products considering environmental zoning in transfers, application of UDAF, localised UDAF and Grade A air supply plus the surrounding environment
• Integration of automation with GMP compliance in manufacturing environments
• How to apply EM and PM as measures of collective effectiveness of contamination control measures
• Digitalisation of data, data analysis/ trending and data to support batch release.
• Future trends in aseptic processing

Key Topics

• Key points from revised EU GMP Annex 1, GMP for ATMPs and ICH Q9/10/12
• Preparation of a Contamination control (CCS) strategy (Annex 1 requirement) following QRM principles
• Encouragement of aseptic processing in barrier technologies and what processing options are available
• Key points in design and operation of barrier technologies used in aseptic processing including key points of impact from regulation changes
• Characterising risk assessments for environmental control (focus on design and technical control measures) and monitoring (focus on detectability of contamination events and adverse trends)
• Environmental and process monitoring (EM & PM) and role in collective effectiveness of contamination control measures
• Process operations: Procedural controls and best practices
• Case study 1 of integrated formulation and filling of a viral vector for ATMP CarT cell therapy; example of combining bioburden control processes with aseptic processing: Fill& Finish
• Case study 2: Bulk vial filling of biological products either liquid or freeze dried with an integrated filling line combining: Vial washer-sterilising tunnel, Filling Isolator, Transfer Isolators to Freeze dryer(s) and capper before tray off load. Bulk product supply is via mobile vessel transferred from adjacent formulation room
• Case study 3: Robotics and Gloveless cells applied to filling ATMPs – challenges and process solutions to meet GMP compliance
• Key principles and trends for new/ future product aseptic manufacturing: ‘Modularity, Flexibility and Intensification’ – how these are applied

Our online training experience includes

• Our client zone – a single source for all training materials as well as pre and post-training communication
• Live interactive format via the Zoom platform
• Direct interaction with the trainer
• Q&As, case studies, polls
• Revisit recorded sessions for 7 days
• Training in digital format
• Digital and LinkedIn certificates