Name: Quantification and Control of Amorphous contents by Raman, Application and Case
Start: 2020-10-02T14:00:00Z
End: 2020-10-02T15:18:24.000Z
Location: BrightTALK

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Full title: Variability, Limits, and Other Considerations for the Next Generation of Pyrogen and Endotoxin Testing 

The Limulus Amebocyte Lysate (LAL) test has been the “gold standard” test for endotoxins since the 1980s.  In 2023, we find ourselves at an exciting crossroads.  We are thinking “outside of the box” with respect to using recombinant and cellular based technologies that promise to make improvements to the existing lysate-based methods.  But as technology evolves, should we also be evolving in our thinking regarding assay capability/variability?  Given the clear benefits of the LAL test in process control and the statistically irrelevant final sample size for drug product testing, should we consider parametric release?  How do we think about setting appropriate endotoxin limits for complex or combination drugs or drugs used in infusions?  Is 20EU/device an appropriate limit for all medical devices?  Given ongoing research into microorganism adaptation and microbiome, what is the appropriate role of the current purified E. coli calibration standard?

Can we be content with 2023 technologies that are mired in 1980s thinking?  This webinar describes the events and thinking that got us here and poses some food for thought moving forward.

Variability, Limits, and Other Considerations for the Next Generation...

Full title: Process Analytical Technologies – Advances in Bioprocess Integration to Transition to Digital Manufacturing

Process Analytical Technology (PAT) instruments include analyzers capable of measuring physical and chemical process parameters and key attributes with the goal of optimizing process controls. PAT probes and sensors are intended for understanding bioprocesses with a goal to control quality and consistency at all stages of product manufacturing to achieve quality-by-design (QbD) and real-time release. The advantages and challenges, and the future development will be discussed

Process Analytical Technologies – Advances in Bioprocess Integration...

Leachable risk management continues to be of regulatory interest. However we continue to rely on experimental extractable studies as predictors of leachable risk. These are complex to design and implement, and do not always offer the answer to what is the leachable risk for a drug product or medical device. We hope to show that mass transport modelling provide an alternative or a complementary element to testing the leachable risk. There are relatively simple mathematical models which can be developed which might provide an estimate of maximum leaching in a system. These can estimate factors such as solubility, partitioning and diffusion if successfully constructed and in combination these can estimate leaching. There are several ways which these might be modelled and this presentation will discuss each one. The presentation will illustrate where modelling might replace or support current approaches which rely upon experimental study. Results from modelling is complementary to risk appraisal, as predictive modelling gives quick insight into effects of storage time, temperature and other kinetics of leaching. This could be used to screening different materials and predict their leaching characteristics perhaps more effectively and efficiently than current extractable test protocols leading to better leachables studies to confirm these models.

Mass Transport Modelling in support of leachable risk management.

Full title: The Importance of Accurate Chemical Characterization of Medical Devices Extractables

The Importance of Accurate Chemical Characterization of Medical Devices...

Full title: Utilizing Cell Culture Platform and High-Throughput Bioreactors to Streamline Upstream Process Development and manufacturing scale up 

Discuss how to accelerate the clone selection with using the bioreactor systems
Understand how to implement the bioreactor systems e­ffectively with a minimal resources    
Know how to scale-down model definitions suitable for design space, QbD, or other BLA-enabling activities.

Utilizing Cell Culture Platform and High-Throughput Bioreactors to Streamline...

Full Title: Commercial Cell Therapy Experience Using Mycoplasma NAT For Product Release: Five-Year Review

Commercial Cell Therapy Experience Using Mycoplasma NAT For Product Release...

Presented by Dr Clemens Günther, Senior Expert Nonclinical Safety, Director at Bayer AG, R&D Pharmaceuticals

Safety Evaluation on Extractables and Leachable

UNICAN: Dual capability in single use bioreactors

Disposable technology is being used more each year in the biotechnology industry. Disposable bioreactors allow one to avoid expenses associated with cleaning, assembly and operations, as well as equipment validation. However, one of the biggest challenges for single use technology including single use bioreactor is single sourcing of consumables. Typically, the consumables are tied to the hardware eliminating the flexibility and interchangeability among existing systems, which ultimately forces the end user to rely on a single vendor’s supply chain. In order to address to this challenge, a 200L bottom mounted single-use bioreactor was converted into a universal can, or “Unican”, which supports the use of both bottom mounted agitator and top mounted agitator single use bioreactors. The implementation of Unican increases flexibility for cell culture operations, improves assurance of supply, allows handling of any bag film changes/issues in future and reduces the dependence on single suppliers. As part of the project, mass transfer and cell culture experiments were performed to ensure optimal performance of both bags in the Unican. Cell Culture data and mass transfer was shown to be comparable in both top and bottom mounted bags with historical data. Additionally, the modification of system was performed such that no hardware requalification was required post modification. The system has been successfully implemented in pilot plant for bioprocessing.

UNICAN: Dual capability in single use bioreactors

Downstream protein purification and product concentration is known to be the most challenging part of the process development. It is also known that the Downstream process development is critical to ensure protein drug’s quality, safety & efficacy meet regulatory expectations. When initiating the development, the Chemistry, manufacturing and controls considerations for process development and manufacturing must include molecule complexity. Raw materials, process development. Equipment and manufacturing, Quality and Regulatory affairs. The critical factors for development and manufacturing is performing stage-wise assessment on Product development, analytical and process development and not the least, the manufacturability assessment. The expected qualities of a superlative process shall include increased capacity, flexibility, cost-effectiveness, controllability, scalability, and efficiency. However, general challenges exist in downstream process development involving,

Balancing higher cost chromatography resins and solvents
Constrained purification space for molecules prone to degradation at wide range of pH and temperature
Process fit to multi-product facility,
PAT availability to accelerated processing
Adaptation of new technologies one of smarter way to address the challenges:
Non-Protein A process
use of next-generation chromatography resins
Continuous processing for capture, intermediate purification, Viral clearance

Best Practices of Downstream Protein Purification and Product Concentration

Full Title: Annex 1 and Environmental Monitoring Program - Implementation And Justification of The Best Practices In Routine

What is new? How to implement the changes?
EM program and Contamination Control Strategy
Example of Risk Analysis Methodology
EM program and Data Management
 

Presented by Benoit Ramond, Head of Microbiology & Sterile Technology at Sanofi

Benoît Ramond is a Doctor in Pharmacy at the University of Paris XI in France and obtains a PhD in Microbiology. He has more than 30 years of experiences in the Pharmaceutical Industry. Since 2016 he is Head of Microbiology and Sterile Technology Expertise in Sanofi Group including Aseptic Processing, Barrier Technologies, Environmental Monitoring Program, Cleaning and Disinfection, Visual Inspection.  In his function he has also a leading role in the Annex 1 implementation program within Sanofi.

Annex 1 and Environmental Monitoring Program - Implementation And Justification.

Digitally Transforming Pharmaceutical Process Development and Manufacturing: Enabling Technologies for a Sustainable Future

The focus on accelerated development of new modalities for advanced therapies and challenges with complex drug candidates has driven adoption of novel concepts and technologies in pharmaceutical development and manufacturing. The active substances have become more structurally complex and R&D timelines continue to be compressed, the technologies necessary to provide safe, robust and economical access to these molecules needs to keep pace. Enabling technologies such as automation and associated information management systems are increasingly being used in the development and manufacturing of therapeutics across the pharmaceutical industry to collect, analyze, and interpret an immense amount of advantageous process data that would otherwise be inaccessible. This combination provides many additional benefits, such as enabling processes, ability to safely handle highly reactive, unstable, and toxic reagents. All these aspects help to minimize the time and cost associated with development and manufacture of drugs and bring medicines to patients more effectively. The importance of such concepts has become even more evident in recent Covid-19 pandemic crisis, different organizations are actively thinking of implementing these paradigms to their benefit. In order to fully leverage and integrate the larger organization, end-to-end automation and information management strategy and vision is necessary where there is seamless workflow for automated route screening to optimization and scale-up of robust process is established. This presentation will share AbbVie’s strategy and experiences in integrating such end-to-end technologies into process development and manufacturing facilities and discuss the challenges and opportunities associated with our approaches.

Digitally Transforming Pharmaceutical Process Development and Manufacturing

Presented by Dr. Markus Zeitz, Head of Global Quality Digital Transformation at Boehringer Ingleheim

Quality Analytics –How to Leverage Quality Data for QMS 2.0

Batch to Continuous Technology: The Journey from Laboratory to Pilot Scale for DS Manufacturing

The presentation outlines a case-study in establishing the operational space of a Grignard reaction in a series of continuous stirred tank reactors (CSTRs). The development of a laboratory scale continuous flow process for the manufacture of a key intermediate of the pharmaceutical product Ipatasertib for the treatment of metastatic castration-resistant prostate cancer and triple negative metastatic breast cancer involves flow and batch unit operations. In a head-to-head comparison between the continuous and batch processes, the former was clearly superior as it gave a higher yield (81% vs 63%) of the product and better reaction control for handling the unstable reaction intermediates. Short residence times, accurate temperature and pH control and steady concentration profiles enabled the synthesis of product in excellent and invariable purity The gathered data and experiences from this study was crucial for guiding the decision making process in order to design a suitable pilot setup for the subsequent cGMP campaign.

Batch to Continuous Technology: The Journey from Laboratory to Pilot Scale...

Path to Smart Manufacturing and Intelligent Development within Industry 4.0 - Building an Integrated Sensing Strategy

Over the years there have been many frames of reference on the use of process analytical technology (PAT) in the commercial manufacturing space including monitoring, closed loop control, quality control/real time release, advanced process control, quality by design, Industry 4.0, etc.  With each evolution of framing, the context we view process sensing and analysis of manufacturing processes is trending towards expanded scope and context from unit operation to production train, plant level, and up through manufacturing network, supply chain and value chain to customer. Similarly in the Development space, the frame of reference on the use of PAT continues to evolve as various capabilities become standard aspects of pharmaceutical and biopharmaceutical process technology stacks enabling the use of digital twins, modeling, and workflow automation which aim to drive more efficient and reliable development, technical transfer, and lifecycle management practices. In this talk we will present how we at Biogen are integrating PAT as part of our Digital Evolution strategy on a pathway towards realization of Smart Manufacturing and Intelligent Development.

Path to Smart Manufacturing and Intelligent Development within Industry 4.0

Industry 4.0 comes with an impressive collection of assets and capabilities. However, although the degree of applicability in Bioprocessing is high, the origin of these technological innovations is exogenous. This is not without implications and in this talk we are concerned with their identification and quantification. We commence with the onboarding of an exogenous technology problem. Industry 4.0 tools have been developed with different objectives in mind. Integrating them in Bioprocessing requires a critical a priori analysis of similarities and transferability.  We then move on to address a fundamental question: is this exogeneity positive or negative for Bioprocessing?  The answer is drawn from historical case studies, stemming from different industries. This naturally leads us to the concept of  the fallacy of division and the associated dangers of disruption. Finally, we go a step further and explore how the addition of 4.0 in Bioprocessing can alter the core business activities and what this implies for the insourcing vs outsourcing dilemma that both big and small corporations have to face.

The exogenously driven disruption of Bioprocessing

Full title: ICH Q3E Impurity Guidelines: Assessment and Control of Extractractables and Leachables for Pharmaceuticals and Biologics.

ICH Q3E Impurity Guidelines: Assessment and Control of Extractractables...

Presented by Paolo Grisostomi, Senior Engineer, Materials Science at Biogen and Donald Young, Sr. Product Manager at Thermo Fisher Scientific

Challenges In Therapeutic Biological Products

An overview of single use manufacturing for the production of AAV gene therapy products with comparisons to traditional monoclonal antibody production.  Specific challenges of scaling up AAV production and considerations to accommodate a range of demands of differing gene therapy products will be discussed.  I will review the reasons for starting and the challenges of being the inhouse manufacturing facility for a rapidly growing company.  The challenges of making non-COVID products in the era of Warp Speed along with future commercial production comparing fully single use with a hybrid facility will be explored.

Single Use Process for Production of AAV Gene Therapy Products

Full Title: Quantification and Control of Amorphous contents by Raman, Application and Case Studies in Pharmaceutical Processing

Presented by Michelle Raikes, M.S., Scientist IV and Dr. Fredrik Nordstrom, Sr Research Fellow at Boehringer Ingelheim

Amorphous regions in crystalline material can have significant impact on bioavailability, processability and stability. Conversely, crystalline material can act as nuclei for recrystallization and resulting in instability of amorphous systems. Raman spectroscopy is sensitive to polymorphic differences and amorphous content in pharmaceutical materials. This make Raman spectroscopy a powerful process analytical technology (PAT), when combined with multivariate modelling, to control the amorphous content in a pharmaceutical process. We will present pharmaceutical case studies showing process-induced amorphization of crystalline drugs across the DS and DP processing steps. In addition, we will compare the kinetics of crystallization of amorphous material when stored at various relative humidity and temperature conditions. The results clearly demonstrate that Raman spectroscopic techniques combined with multivariate methods is a powerful and effective tool for quantitation of amorphous content in crystalline material with applications ranging from API isolation, milling and to multiple unit operations in DP manufacturing. The information generated was critical to determine the root-causes and outline appropriate mitigation measures

Quantification and Control of Amorphous contents by Raman, Application and Case

Biopharma

Biologics

Crystalline Materia

Bioavailability Processability

Recrystallization

Amorphous systems

Raman Spectroscopy

Process Analytical Technology

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Quantification and Control of Amorphous contents by Raman, Application and Case

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