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Advances & New Frontiers in Sterile Manufacturing Technology

17th & 18th April 2020, Mumbai, India

S u s: NAVIGATING THE EVOLVING REGULATORY EXPECTATIONS

Swapnil Ballal Member, Disposables COP- ISPE, Partner CRAMbridge E-learning & Q-Exl Partners

Use of single-use components and systems for manufacturing therapeutics is witnessing a boom especially for small batch size finished product manufacturing. The single-use technology, with its origin in the upstream processing of biotherapeutics, has matured and its adoption has transitioned from clinical batches to commercial GMP manufacturing. Evolving regulatory framework and industry standards, involvement of multiple suppliers and limited experience of the end user presents new challenges in both science and GMP compliance.

This session will provide:

  • Overview of existing and upcoming regulations related to qualification/validation of Single-use system
  • An update on key areas of regulatory concerns and observations
  • Risk assessment and qualification of product contact components
  • Approaches to reduce the compliance burden and leveraging vendor data 

  

Swapnil Ballal is a seasoned quality assurance professional with multi-functional background and experience of over 23 years in bio/pharmaceutical industry. 

He has served in some of the leading biopharma companies in India including Biocon, Intas, Dr. Reddy’s and GE Healthcare in leadership roles. 

As an active member of ISPE he has contributed to ISPE Good Practice Guide- Single Use Technology and ISPE Baseline Guide: Biopharmaceutical Manufacturing Facilities, 2nd Edition. He was also a Co-Chair of ISPE’s Disposables COP. 

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Proper Use of Extractables Data for Single Use Systems

Dr. Armin Hauk Lead Scientist at Sartorius Stedim Biotech GmbH, Goettingen

  

This presentation describes an approach to establish a methodology based on basic physical principles to scale and combine extractables data of SUS/SUT and to extrapolate extractables towards potential leachables in risk assessments.

Extractables protocols and methods for components of single use devices have been intensively discussed and several proposals for standardized methods are available today; but two major questions, which cannot be solved by means of analytics alone, were not appropriately addressed so far:

1) How can extractables data be obtained for entire devices of different sizes and for even complex device combinations?

2) How can extractables be extrapolated toward potential leachables, and be finally used in a risk assessment of downstream processing?

The first aspect is critical, as devices in different sizes and assemblies - even as device combinations of various suppliers - are on the market, requested by the industry. Considering the vast number of available SUS, it is easily conceivable that it is impossible to conduct extractables studies for each and every possible device and device combination.

The second aspect is critical, because no quantitative approach exists today, which would allow to estimate potential leachables concentrations in products after downstream processing. For the risk assessment of downstream processing only the vague, non-quantitative phenomenological concept of “proximity to patient” is currently available as mitigation tool.

The author will discuss that the commonly applied empirical methods to extrapolate extractables based on intuitive “worst case” assumptions are not sufficient to describe an extraction in a depletive/comprehensive way. Instead of that a concept will be discussed to describe extraction experiments solely based on physical-chemistry principles (i.e. partitioning, phase-transfer and diffusion). This concept is used to establish a methodology, which allows to scale and combine extractables data for components, entire devices and complex assemblies. This methodology can be extended to be used in risk assessment exercises of parts or entire down-stream processes to provide a quantitative mitigation tool. In this context it will be discussed that an estimation of leachables in a down-stream processing requires not only to consider sources of leachables but also to take sinks of leachables into account.

Examples will be given on how extractables data can be used heuristically in scaling and combination exercises. Conventional scaling methods are compared with equilibrium and/or diffusion calculations and with respect to the prediction of potential process related leachables.

The author will conclude that in future extractables experiments shall not only measure extractables as a snapshot analysis but to get access to phys.-chem. parameters relevant for the extraction system. These phys.-chem. parameters together with the knowledge of sinks of leachables will in future allow to set up mathematical models to calculate the “Fate of Leachables” in real down-stream processes.

Audience take home messages:

  • Current empirical methods to extrapolate extractables data in scaling and combination exercises and in risk assessments are not sufficient
  • Understanding the physical-chemical principles behind an extraction allows developing a powerful methodology for extrapolation of extractables data.
  • An extension of the methodology by considering not only sources but also sinks of leachables allows the prediction of process related leachables levels and opens the possibility to establish quantitative risk mitigation concepts and mathematical modeling of entire down-stream processes 

Dr. Armin Hauk Lead Scientist at Sartorius Stedim Biotech GmbH, Goettingen 

armin.hauk@sartorius-stedim.com

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The current state and future prospective of integrity test

Dharti Pancholi, Co-Chair, ISPE Disposable-COP, Founder, Omni Consulting, COO at Advent Engineering

  

The presentation will summarize the current stage of testing integrity for single use technologies including strategies and controls, as well as where the world is progressing with respect to integrity testing of such products and components.

Integrity Testing has become a topic of concern owing to the potential to impact intrinsic (and consistent) robustness of single-use systems and leading to concern contamination. The integrity control of all stages of the manufacturing process is essential aspect of a consistent GMP process. Controlling integrity of single use containers under real conditions of usage is a key prerequisite before designing the system. Thus, analyzing the risks prior to designing the test method by QbD is essential for a reliable and consistent integrity control system. Various scientific approaches and testing methods are used to test integrity of single use systems based on 2D or 3D single use systems as well as the container closure type and usage. Establishing CCIT (Container Closure Integrity Testing) strategy continues to gain attention in recent years. BioPhorum Operations Group (BPOG) and the International BioPharm are among organizations investigating on integrity control methods. 

This presentation will describe

  • Some of the challenges associated with ensuring robustness for disposable systems
  • Overview of major integrity control methods for different type of single use systems
  • Several approaches being used to build disposable systems’ integrity controls
  • An update on some of the future progression with respect to integrity testing

At the end of the presentation, the attendees will posses more understanding on importance of integrity testing to avoid contamination concerns and enhance robustness in the bio-pharma manufacturing process when using single use technologies. They will also be familiar with current and future methods and approaches being utilized in the industry in considerations of utilizing single use systems. 


Dharti possess Masters’ degree in chemical engineering with emphasis in biotechnology and ~20 years of biotech and engineering focused experience. 

Dharti’s early career for ~10 years includes being employed with three user side public and private companies, where she successfully led multiple biotech, vaccine and API processes from late stage R&D to clinical and commercial manufacturing. 

For past ~10 years, Dharti has been involved with providing consulting services to many bio-pharma companies primarily within USA. Dharti has also provided engineering and consulting services in Europe and Asia. 

Her technical expertise spans from process engineering, process development, engineering and project management, operations, change management, process automation, quality, compliance, and CQV; and working from all project phases including capital projects. 

Having led single use bioreactor (SUB) for one of her employers in 2006, MedImmune (AstraZeneca) and working on many single use technology projects afterwards, disposable technologies remains her personal interest area. 

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