Hi [[ session.user.profile.firstName ]]

Risk Assessment of Extractables and Leachables...

Full title: Risk Assessment of Extractables and Leachables in Different Phases of Development.

As the knowledge on the manufacturing process evolves during the development of a drug product or medical device, it is advised to include learning cycles into the development program to avoid existence of critical E&Ls. These learning cycles offer the opportunity to increase the knowledge on E&L associated with the product over its development time. Initially, chemical information should be collected on the materials used. First extraction studies will guide concerns, followed by simulation studies which are designed to mimic reality. At the end, the leachable study has to meet regulatory requirements and must cover real use conditions until end of product shelf-life, and these leachables need to be covered by a thorough toxicological risk assessment.
Recorded Apr 22 2021 127 mins
Your place is confirmed,
we'll send you email reminders
Presented by
Presented by Dr Clemens Günther, Senior Expert Nonclinical Safety, Director at Bayer AG, R&D Pharmaceuticals
Presentation preview: Risk Assessment of Extractables and Leachables...
  • Channel
  • Channel profile
  • CCAB: A universal tool to address the risk of microbial impurities... Jan 26 2022 6:00 pm UTC 120 mins
    Dr Friedrich von Wintzingerode, QC Lead iNeST (individual Neoepitope Specific Therapy), Roche
    Full Title: CCAB: A universal tool to address the risk of microbial impurities in parenteral drug manufacturing including ATMPs

    For parenteral drugs such as monoclonal antibodies, injectable oligonucleotides, and RNA- or DNA-based ATMPs, filtration using pore sizes ranging between 0.02 and 0.2 µm is the method of choice to reduce bioburden and ensure terminal sterilization of the drug product. While filtration efficiently removes intact microbial cells it does not remove subcellular microbial components like toxins, lipopeptide/lipoproteins, flagellin, bacterial and fungal DNA, cell wall polysaccharides, extracellular proteases or endoglycosidases. These microbial impurities can have a significant impact on product quality and patient safety when critical loads are exceeded during a contamination event. The CCAB approach described here enables a comprehensive assessment of these risks.
  • Single Use Process for Production of AAV Gene Therapy Products Jan 26 2022 3:00 pm UTC 120 mins
    Lance Marquardt, Associate Director -Upstream Processing Gene Therapy, Hopewell Biologics Manufacturing at PTC Therapeutics
    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.
  • The Importance of Women Leaders at Merck KgaA Darmstadt, Germany? Nov 30 2021 3:00 pm UTC 60 mins
    Eileen Martin Merck KGaA, Darmstadt, Germany, Global Director of Diversity, Equity and Inclusion
    At Merck, we aim to recruit, retain and promote the best talent around the world to support our drive for innovation and growth. This includes ensuring balanced representation of women across all levels in the organization. Our leaders are committed to fostering a culture where women can thrive, because we believe gender equity helps our business and our patients.

    Our global strategic diversity, equity and inclusion plan has a particular focus on gender. We aspire to increase representation of women in management and leadership positions across our healthcare, life science and electronics sectors. The leaders at Merck will track progress of women in leadership roles, along with other key metrics, including gender balance in our development courses, succession plans, and the sponsorship of women. In a world where women make up 50 percent of the population, we want to make Merck more reflective of the countries in which we do business and better reflect the customers we serve.
    We believe that a diverse workforce paired with a respectful and inclusive company culture is fundamental to our ability to innovate and contribute significantly to our business success. Curious minds make Merck better.
  • Integrity Assurance for Single-Use Systems: End-User Perspective Nov 15 2021 10:00 am UTC 120 mins
    Charlotte Masy, Senior Manager in Manufacturing Science and Technology GSK Vaccines
    Single-use technologies are more and more used in critical sterile applications, e.g. close to final manufacturing steps handling Drug Product, leading to increasing concern related to integrity. In this presentation, we make a review of the regulatory environment and present key elements to consider to defined and apply a sound integrity control strategy.

    The regulatory environment has significantly evolved in last years, with the publication of new guidance and standards and additional ones in preparation.  Current draft of EU GMP Annex 1 illustrates the increased scrutiny of regulatory authorities on this topic.  

    We will position integrity tests in the more global picture around integrity strategy. Concepts such as QbD and QRM, as well as close collaboration between supplier and end-user are required to build a good strategy and enhance the integrity assurance for processes using single-use systems. A defined integrity control strategy is very important for critical applications where single use systems are used after last sterile filtration step or in a process where no sterile filtration is possible.

    We will discuss the different technologies available on the market to control integrity of single-use systems and key parameters that are affecting integrity measurements, at supplier’s and at end-user’s side.

    Several case studies will be shared, illustrating how integrity concerns can be practically addressed for cGMP manufacturing applications, and what are the results observed after a few years of use.
  • Advances in the Purification of Antisense Oligonucleotides Oct 27 2021 2:00 pm UTC 120 mins
    Robert Gronke, Ph.D., Senior Principal Scientist, Technical Development, Biogen
    Following on the commercial success of Spinraza® (the first successful treatment for patients with spinal muscular atrophy), antisense oligonucleotides (ASO) are now an important part of Biogen’s drug portfolio that enables us to better treat neuromuscular diseases. Development of the ASO process employs orthogonal chromatography to achieve industry high purities while maintaining good yield along with detritylation and UF/DF steps.  This purification platform process is all aqueous based on green chemistry principals that easily fits into our existing biologics manufacturing facilities. To date, we now leverage this ASO platform process to purify 13+ ASO molecules that contain different sequences, chemistries, and most recently incorporating conjugation reactions.

    Having completed process characterization for our lead ASO candidate, we have achieved a greater understanding of the process, its capabilities to clear process and product related impurities and understand the mechanisms that control the chromatography. On the manufacturing side, Biogen recently completed at scale PPQ validation batches of an ASO clinical candidate.  Cases studies and learnings will be presented on results from characterization studies and PPQ batches.
  • Application of Next Generation Sequencing (NGS) Based Methods... Oct 21 2021 2:00 pm UTC 120 mins
    Jurgen Mulberg Associate Director at Bristol Myers Squibb and Audrey Brussel at PathoQuest
    Full Title: Application of Next Generation Sequencing (NGS) Based Methods for Detection of Viral Contaminants in Biomanufacturing

    Contamination of a biological product with viruses, potentially harmful for humans, is of concern for therapeutics derived from human and animal sources, i.e. plasma, and for protein therapeutics and vaccines produced in mammalian cells.  More recent “Advanced Therapeutic Medicinal Products (ATMPs)”, such as gene and cell therapies, share the same concern.  Tests for viral contaminants are performed at several stages of manufacturing.  Current tests for detection of viruses are lengthy; cell culture based assays and animal experiments are required.  Alternative molecular tests, such as “next generation sequencing (NGS)”, provide faster results, and can eventually replace in vivo animal studies.  It is noteworthy that identification of a viral contaminant that evaded detection in classical tests, by NGS, has been demonstrated.  In addition, due to the fast turnaround time, application of targeted NGS for “in process” detection of viral contaminants can be envisioned.  Current efforts for development of unbiased and targeted NGS based viral safety assays will be discussed
  • Overcoming Antibody-Drug Conjugate (ADC) Process Development... Sep 30 2021 8:00 am UTC 120 mins
    Dr. Jincai Li, Vice President of WuXi Biologics
    Full Title: Overcoming Antibody-Drug Conjugate (ADC) Process Development & Manufacturing Challenges

    Presented by Dr. Jincai Li, Vice President of WuXi Biologics
  • Sanofi’s Journey & Strategy for Continuous Processing for Small Molecules Sep 27 2021 2:00 pm UTC 120 mins
    Flavien Susanne, Head of Chemical Development Engineering at Sanofi
    In the past decade, there has been a growing interest in the application of continuous processing in the pharmaceutical industry with 100s millions of investments and several products delivered to the market using this technology. 

    Continuous processing demonstrates several value propositions for the Pharmaceutical industry. Amongst them we can name, access to better chemistry, product quality enhancement, reduction of CoGs but mostly speed to market where phase 3 to launch is drastically accelerated. 

    Sanofi R&D is building capacities to perform future GMP clinical batches using this technology. The first investment was completed last year, and we are in the process of expansion. It is a really changing time for science at Sanofi.  

    Sanofi is investing in modular concept with high capability of production of API and ability of infinite reconfiguration. We are not only thinking machine; to enhance our ability to always produce best quality drugs to our patient, we are also implementing digital twin system, tracking and controlling the quality of our product at any moment of time. 

    We are ready to meet the challenges of tomorrow and produce the new APIs to help patients.
  • The Business Benefits of PAT in Continuous Drug Product Manufacturing Sep 22 2021 2:00 pm UTC 120 mins
    Steve Hammond, Independent Consultant at Steve Hammond Consulting
    It is well recognized that continuous processing requires continuous monitoring, at the “heart-beat” of the process to ensure product quality and patient safety. However, the use of PAT in the optimization of equipment and the development of processes from which a product will be manufactured is also of significant value, and justifies the investment in PAT for a continuous manufacturing. The data density and timeliness can deliver immediate feedback and exquisitely detailed information on the success of processing steps. The gathered information can aid in the establishment of an effective and robust processing regime for new or existing products.

    This paper will discuss the use of information rich PAT technologies to understand equipment and process steps during development. Examples of equipment characteristics and the effect on the product will be examined.

    An important area for PAT in continuous manufacturing is cleaning. The equipment trains to be effective must be capable of rapid change over. PAT’s designed for rapid assessment of surface cleanliness are important. Devices that allow rapid cleaning verification will be discussed.
  • Development of automated chemometric platform for accelerated... Sep 20 2021 2:00 pm UTC 120 mins
    Oliver Steinhof, PAT Scientist at Biogen and Nicolas Langenegger, Senior Associate Scientist at Biogen
    Full Title: Development of automated chemometric platform for accelerated Raman-based model optimization in biologics

    The increasing use of multivariate models both as part of the control strategy in commercial (bio)pharmaceutical production as well as for process monitoring calls for an efficient strategy for model development and model life cycle management. The traditional approach to develop multivariate models based on spectroscopy involves manual data management such as selection and transfer of spectroscopic data, import into modeling software and selection/exclusion of data. That is followed by addition of reference data, alignment of time stamps and import into the modeling software. 90% of the time required to construct a multivariate model is spent on data preparation. It was decided to develop a solution to automate these steps to prepare (stage) the data required for model development, reducing the time required to prepare a typical set of batch data to about five minutes. A second tool was developed to automatically optimize data pretreatment parameters and spectral range for PLS models. Both tools allow our scientists to invest their time into more value-added activities.
  • Vaccine Development & its Manufacturing using Integrated... Sep 20 2021 8:30 am UTC 120 mins
    Dr. S.K. Jana at Serum Institute of India Pvt. Ltd. and Vikas Revankar at Merck
    Full Title: Vaccine Development & its Manufacturing using Integrated High Throughput Technology

    The billions of doses of vaccines manufactured worldwide each year are used to vaccinate the healthy people. This is the fact which drives vaccine manufacturing to be among rigorously designed, manufactured, monitored & compliant health products. In order to produce this huge number of doses, there is a need to have a manufacturing process which strongly influence the cost effectiveness, volume, application of technologies involving ease of scale-up, flexible in nature, automated integration with different manufacturing unit operations, minimal manual intervention or hybrid for complex biologics like vaccines manufacturing. The use of integrated way of automation with different online sensors like IOTs, AI at different measurement points of processes to make manufacturing process continuous, seamless, robust with high throughput yield, higher process capability with less time or no failure is the cornerstone of a modern, advanced & powerful manufacturing system. The concept of High Throughput Manufacturing is related to time required for a product to pass through a manufacturing process converting raw materials in to finished goods involving automation, integration of several unit operations with minimal manual intervention during the manufacturing. The ability to manufacture vaccines safely and consistently must be built on the theme with consistent quality, compliance, easier regulatory authorization in order to reach the market fast as manufacturing complexity is compounded by the need for different producing strains, type of vaccines & their processes. The present talk on “Vaccine Development and its manufacturing using integrated high through put Technology” is going to address some challenges & opportunities and its full scale application to future biologics manufacturing.
  • Janssen's Real Time release: Using MSPC to enhance batch release. Sep 15 2021 2:00 pm UTC 120 mins
    Sarah Nielsen, at Janssen and Herman He, at Thermo Fisher Scientific
    The Janssen real time release strategy will be presented. Multivariate statistical process modeling is used as a way to guide batch release (either via RTR or conventional testing). The RTR strategy uses spectroscopic release tests, skip lot testing and a surrogate model for dissolution. The surrogate dissolution model was developed with a dedicated pilot scale DOE and validated with commercially manufactured product. Multivariate raw material and process “health check” models ensure that the surrogate dissolution model is used appropriately.  RTRT provides greater manufacturing efficiency, process monitoring and allows for additional sampling when compared to a traditional release strategy. The presentation will illustrate the commercial use of this technology for a batch manufactured product within Janssen
  • CONTINUOUS MANUFACTURING OF BIOLOGICS: A JOURNEY FROM CONCEPT TO REALITY Sep 15 2021 8:30 am UTC 120 mins
    Himanshu Gadgil, CSO and Whole-Time Director at Enzene Biosciences Ltd.
    Full Title: Opportunities and Challenges in Developing a Fully-Connected Continuous Manufacturing Process for Biologics

    Insights through case studies for developing a fully integrated mAb manufacturing process

    Integrating upstream perfusion with a connected downstream process

    Implementing the continuous process in GMP
  • Points To Consider: Demonstrating Comparability Between Recombinant... Sep 9 2021 2:00 pm UTC 120 mins
    Karen Zink McCullough at MMI Associates, Nicola Reid at Charles River Labs and Veronika Wills, At Associates of Cape Cod, Inc
    Full Title: Points To Consider: Demonstrating Comparability Between Recombinant and Lysate Reagent For BET Testing
  • Implementing a Quality by Design (QBD) Approach In Integrated DSP In-Line PAT... Sep 6 2021 2:00 pm UTC 120 mins
    Dejan Arzenšek, at Novartis and Maryann Cuellar at Kaiser Optical Systems, Inc.
    Full Title: Implementing a Quality by Design (QBD) Approach In Integrated DSP In-Line PAT Advanced Analytical Technologies to Monitor Critical Quality Attributes

    Continuous processing technologies and connected downstream unit operations may require advanced analytical technologies for process monitoring and control Evaluation of:


    Different advanced analytical technologies with the potential to accelerate process development and facilitate continuous manufacturing control strategies. The suitability of the selected techniques at scale
    The combination of outputs from different sensors in a combined manner to increase process understanding during downstream process development and reduce offline analytics and enable prediction of future platform processes
    Results of these endeavors will be presented including a critical review of the and challenges of inline analytics and processing of large data sets to increase process understanding and enable process control. 
    The Resulting concept of using a process analytical technology (PAT) approach can ensure continuous processing with tight controls at all times and thus has the potential of integration into a new DSP continuous manufacturing platform
  • Laboratory 4.0 Digitalization and IoLT (Internet of Laboratory Things)... Recorded: Jun 10 2021 100 mins
    Terryl Kibodeaux at Regeneron Pharmaceuticals, Inc. and Aimee Balkenende at Thermo Fisher Scientific
    Full title: Laboratory 4.0 Digitalization and IoLT (Internet of Laboratory Things) Strategies to Enrich Industry 4.0

    The joining of online process automation devices and data (Operational Technology or OT level) and offline laboratory management systems and data (Enterprise Information Technology or IT level) is becoming an indispensable modernization and digital maturity aspect that needs to be realized to make the Industry 4.0 paradigm an industrial reality.  This presentation describes options for the building of a sound Lab 4.0 digital laboratory environment, which consists of laboratory informatics, automation and robotics, interconnectivity, big data, analytics and machine learning to create a more holistic and better-connected, self-monitoring smart digital manufacturing ecosystem.  The digitization of laboratories, along with the IT – OT interconnectivity, makes the availability of near real-time offline laboratory methods and results an actuality in the exercise to achieve the Industry 4.0 benchmark.
  • Latest Analytical Techniques in Extractable and Leachables Recorded: May 20 2021 70 mins
    Dr. Tom van Wijk, Abbott Healthcare Products BV
    In contrast to other impurities the control of extractable and leachables is not well defined yet. Currently guidance is provided e.g. by USP and PQRI, but there is room for interpretation. New guidance (ICHQ3E) is being developed. In general, comprehensive screening is applied, using gas- and liquid chromatography techniques hyphenated with mass spectrometry, to aim for complete coverage on E&L. Although considered to be the state-of-the -art approach, in practice this approach is not as straightforward as it may seem. Many assumptions are made and for effective approach an E&L database is deemed necessary. Moreover, the strategy is completely opposite compared to the strategy applied for potential mutagenic impurities which is highly relying on a theoretical assessment (Risk based approach). The presentation will focus on the analytical technique selection, challenges of coverage of E&L in the current strategy and finally a perspective on E&L analysis.
  • Exosome Manufacture Based on the iCELLis® Bioreactor Platform Recorded: May 11 2021 118 mins
    David Haylock, CEO VivaZome Therapuetics and Roberto Ciboldi, Scientific & Laboratories Services Pall Corporation
    Presented by David Haylock, CEO VivaZome Therapuetics

    and Overcome Exosomes Production Challenges.

    Presented by Roberto Ciboldi, Senior Scientist, Purification Team, Scientific & Laboratories Services Pall Corporation
  • Mycoplasma Testing: Past, Current, and Future State Recorded: Apr 29 2021 122 mins
    Kenneth Tai at Kite Pharma, Lori Daane at BioMerieux and Alexander Bartes at Roche Pharma
    For nearly 30 years, mycoplasma testing for biologics have been performed using cell culture-based methods.  The compendial mycoplasma detection method has been the gold standard in the biopharma industry.  Its high sensitivity (0.1 CFU/mL detection) is achieved through multiple subcultures and observations of culture media and agar plates over the course of 28 days.  While awaiting for the results of testing, CHO-derived antibody drug substances are stored in freezers; however, long storage times have contributed to an inefficient supply chain network resulting in huge costs.    

    Pressure to reduce long turnaround times (TAT) has spurred innovation through the use of nucleic acid technologies (NAT), such as real-time PCR.  With guidance from the European pharmacopeia chapter (2.6.7), multiple biopharmaceutical companies have successfully validated real time PCR methods for testing.  In addition to the benefit of reducing TAT from 28 days to a single day, cost to the patients are reduced from lowering FTE, reducing storage costs, and creating a more agile supply chain network. 

    TAT reduction becomes even more critical in the new cell and gene therapy landscape, where some of these medicinal products are customized from the patients themselves.  Furthermore, integration of testing built into the production line can improve efficiency and further expedite live saving medicines.  As innovate therapies emerge, quality control tests must also become creative to adapt to these new modalities.  That includes mycoplasma testing.
  • Risk Assessment of Extractables and Leachables... Recorded: Apr 22 2021 127 mins
    Presented by Dr Clemens Günther, Senior Expert Nonclinical Safety, Director at Bayer AG, R&D Pharmaceuticals
    Full title: Risk Assessment of Extractables and Leachables in Different Phases of Development.

    As the knowledge on the manufacturing process evolves during the development of a drug product or medical device, it is advised to include learning cycles into the development program to avoid existence of critical E&Ls. These learning cycles offer the opportunity to increase the knowledge on E&L associated with the product over its development time. Initially, chemical information should be collected on the materials used. First extraction studies will guide concerns, followed by simulation studies which are designed to mimic reality. At the end, the leachable study has to meet regulatory requirements and must cover real use conditions until end of product shelf-life, and these leachables need to be covered by a thorough toxicological risk assessment.
The Journal for Asia's Pharmaceutical and Biopharmaceutical Industry
BioPharma Asia aims to keep its 30,000 readers abreast of all developments in the areas of Drug Development, Drug Delivery, Manufacturing, Quality Assurance, Outsourcing and Regulatory Affairs, with only the highest quality articles, written by the most respected authors, associated with only end-user companies. This ensures that the information will always be guaranteed to remain timely, informative and above all totally unbiased.

Embed in website or blog

Successfully added emails: 0
Remove all
  • Title: Risk Assessment of Extractables and Leachables...
  • Live at: Apr 22 2021 2:00 pm
  • Presented by: Presented by Dr Clemens Günther, Senior Expert Nonclinical Safety, Director at Bayer AG, R&D Pharmaceuticals
  • From:
Your email has been sent.
or close