Name: Defining Patient-Centric Specification in a Risk-Based Control System
Start: 2024-10-28T14:00:00Z
End: 2024-10-28T14:02:00.000Z
Location: BrightTALK
Rating: 0

BioPharma Webinars aims to keep its global audience abreast of all developments in the areas of Drug Development, Manufacturing, Quality Assurance, Outsourcing and Regulatory Affairs, with only the highest quality webinars, presented by the most respected people, working with companies in Pharmaceutical, Biopharmaceutical, Biologics and Biotech Industry.

Full title: Evaluating Analytical Strategies to Quantify Capsid Titre: Towards a Platform-Method Approach to Accelerate AAV Drug Product Development

Traditional capsid titre methods rely on ELISA which commonly suffers from long turnaround times, low throughput, and large volume sample requirements. This limits the application of ELISA-based methods to routine analysis, thus requiring development of alternative high-throughput (HTP) capsid titre methods. We have performed a comprehensive assessment on currently available orthogonal capsid titre methods using multiple serotypes at concentration range relevant in IND-enabling preclinical and first-in-human (FIH) clinical studies.

Evaluating Analytical Strategies to Quantify Capsid Titre...

The advancement in technologies and innovative thinking are profoundly changing biopharmaceutical drug production industry holistically, giving rise to “the factory of the future.” What will the factory of the future with respect to its structure, technologies, processes, and drug product delivery to the patient be? What enablers will manufacturers need in terms of strategy, leadership, employee skills, IT/OT infrastructure, regulatory oversight, and suppliers to make this a reality?

The factory of the future is an innovation vision on how manufacturers should enhance production by transforming manufacturing in three dimensions: plant structure, plant digitization, and plant processes.

Having a holistic vision of the process

Designing and implementing a flexible framework

Evaluating and implementing proper technology and skill

Emphasizing safety, quality, purity, efficacy and regulatory mandates

The bottom line – delivering ROI

The Factory of the Future

Medical device chemical toxicological risk assessment is challenging because the risk assessor often needs to consider the many types of device intended uses, many types of materials used in design and manufacturing, and many types of intentional and unintentional chemicals that are or could be present in the final finished device. Medical device intended uses include the type of tissue contact, the contact frequency and duration, and the susceptibility of the device user to chemical exposure. Material factors include the material type (e.g., alloy, polymeric, ceramic, or natural), material properties (e.g., alloy surface characteristics, polymer plasticity, or polymer manufacturing process), and material chemical composition (e.g., chemical formulation, potent toxicants (if present), and the rate and duration of release). How to apply these considerations is described in the U.S. Food and Drug Administration (FDA) 2023 guidance Use of International Standard ISO 10993-1, “Biological evaluation of medical devices: Part 1: Evaluation and testing within a risk management process,” International Standard Organization (ISO) 10993 series, and ISO 14971. This presentation will describe how chemical toxicological risk assessment fits into the overall medical device biological risk management process (i.e., risk analysis, risk evaluation, or risk control). Additionally, what medical device use and chemical toxicological information to consider from the U.S. FDA 2023 guidance and ISO documents when estimating chemical toxicological risk will be covered, such as: approaches for characterizing the applicable chemical specific harm(s), estimating an exposure dose, deriving a tolerable intake (TI), and other critical factors to consider that could be useful in the determination of whether exposure to a medical device chemical presents a tolerable risk or could present a possible toxicological risk.

Medical Device Chemical Toxicological Risk Assessments...

Full title: Established Conditions in Analytical Procedure: Overview, Regulatory Examples and an FDA Laboratory Study

Established conditions (ECs) are manufacturing and control elements considered necessary to assure product quality (e.g., ECs in manufacturing process) and to help assure method performance (e.g., ECs in analytical procedures). ECs in analytical procedures help to maintain reliable results that can ensure the efficient product control strategy during the product life cycle. Changing ECs in analytical procedures may necessitate a certain level of regulatory activity and the level of regulatory activity can be different depending on the strategy defining ECs and the extent of changes. The presentation will first provide a high-level overview of harmonized scientific risk-based approaches for identifying ECs and determining the corresponding reporting categories based on scientific principles described in ICH Q12 and Q14 guidelines. Then, two regulatory examples involving ECs in analytical procedures will be discussed. It is noteworthy mentioning that both parameter and performance-based ECs in an analytical procedure are defined in these two examples. The last part of the presentation will be an FDA laboratory study on a mass spectrometry method for a recently identified NDSRI (Nitrosamine drug substance-related impurity). In this case study, analytical variables and method robustness were investigated according to recommendations from the ICH Q2R2 (draft) Guideline. Based on the impact of each variable on method performance, categorical and numerical ECs were proposed.

Established Conditions in Analytical Procedure: Overview, Regulatory Examples

Full title: Fully Continuous Purification Platform Using Nanoparticles With Ligands and Ultrafiltration

We present on a truly continuous purification technique with potential to reduce costs-of-goods for mAbs, over conventional chromatography-based separations.

We demonstrate the development and proof-of-concept application of a self-assembling affinity nanoparticle to enable affinity ultrafiltration of mAb from an impure mixture.

This technique leverages counter current flow ultrafiltration, concentration gradients between feed and product, in a series of filters representing the phases of the process. Impurity clearance can remain high while minimizing overall buffer consumption and consequently PMI for water.

Overall, these data represent an early advancement toward the development of a truly continuous, counter-current, and column-free method to capture and purify mAb without expensive conjugated resins. We envision further expansion of commercially available nanoparticles towards modality and application specific designs to enable PMI savings across therapeutic areas, delivering lower cost medicines to patients.

Fully Continuous Purification Platform Using Nanoparticles...

Full title: Analytical Assessment of Leachables in Biological Drug Products: FDA Approach and Experience in Reviewing Information

Biological drug products (biologicals; such as therapeutic proteins, vaccine-, gene-, and cell therapy-based) are produced via multi-step processes involving multiple materials contacting intermediates and sourcing numerous leachables into final drug products (DP). Such steps involve (i) purification of intermediates using chromatography, centrifuging, dialysis, filtering, and filling in final container closure system, etc., (ii) shelf-life storage and (iii) in-use hold of DP. The respective contact materials involve chromatography resins, filtering/dialysis membranes, tubing, collecting bags/tanks, gaskets, valves, final container closure systems, etc. By these, the assessment of leachables risk in biologics is the most challenging compared to other types of DPs. However, current guidances are generally focused on assessment of the leachables only from single manufacturing components, scored to be high-risk for leachables, and by this, underestimate other components scored to have the lower risk. Following these directions, manufacturers typically perform the assessments only for the high-risk components and by this, underestimate the contribution of other materials to the overall (cumulative) leachables profile in final DP. Other typical issues involve (i) non-validation of analytical methods, resulting in ambiguity in Analytical Uncertainty Factor (AUF) used for calculation of the Analytical Evaluation Threshold (AET; reporting limit in an assay), (ii) missing the assessment of elemental (ionic) leachables, or (iii) incorrect leachables study design; altogether also resulting in potential underestimation of the leachables risk. These issues usually cause multiple back-and-forth communications between the FDA and Sponsor during the applications’ (BLAs and supplements) review, typically ending up with post-marketing requirements.

Analytical Assessment of Leachables in Biological Drug Products: ...

Full title: Development of a Blending Design Space Model to Control Uniformity in a Mini-Batch Direct Compression Line

Presented by Manel Bautista, Senior PAT Expert, Principal Scientist at Roche, Sebastian Sowinski, Key Account Manager at Sentronic and Bernhard Meir, Head of Continuous Manufacturing (OSD) at Gericke

Blending is a common manufacturing unit operation for oral solid forms that is typically evaluated during formulation and process development with the aim to ensure proper distribution of the drug substance in the formulation, which is ultimately assessed during drug product release by means of the uniformity of dosage units by content uniformity. A common approach on how blend uniformity is controlled (but not tested) during commercial manufacturing consists in establishing appropriate blending conditions during the scale up from pilot to commercial scale. Those conditions are determined with a reduced number of experiments that usually do not provide the necessary process understanding on blending. 

Another alternative is to define the Design Space for blending, where a surface response curve allows setting the boundaries of the critical process parameters and critical material attributes by means of a multivariate process model.

The current webinar explores the development and verification of a design space model around blending on a Mini-Batch continuous Direct Compression line. This approach allows ensuring blend uniformity within specification for all Mini-Batches that are blended within the obtained design space. The approach brings flexibility to adjust changes in API particle size or fill level while ensuring proper blend uniformity.

Control Uniformity In A Mini-Batch Continuous Direct Compression Line

Presented by Dr. Parthasarathy Sampathkumar, Head, Group Center for Operational Excellence at Biocon Biologics and Sara Jane Bresee, Managing Director of APAC at MasterControl

This presentation will cover The Opportunity Landscape & Methodology utilized at Biocon to drive OE, The Group Level Structure & glimpses of The OE Framework.

Opportunities Landscape & Methodology

At Biocon, we believe that the most fundamental way of identifying Opportunities is by virtue of “The 3Ms.” These being Mura, Muri & Muda. These are Japanese terms that stand for as Un-evenness or variability, Overburden or Under-capacity and Wastes, respectively.

The Group COE (Center of Excellence) Structure

The purpose of The COE Structure is to identify, exploit and translate the opportunity landscape into viable improvements under the umbrella of Business Excellence Framework providing Centralized Governance and driving Institutionalization of OE Leveraging Digital Transformation.

Operational Excellence Framework – An Introduction

The OE Framework is an Agile, Scalable, Holistic yet Flexible Model with a capability to Balance, Integrate and Assimilate all existing and any future initiatives under One Umbrella including Digital Interventions. This encompasses the Strengths of tried and tested International Excellence Frameworks with high internalization & contextualization to The Biocon Group in totality. The individual elements of The Framework will enable seamless delivery of Business Objectives with a strong linkage to robust Business Processes.

Leveraging Digital Transformation To Deliver Operational Excellence

Full title: The role of the pre-use post-sterilization integrity test (PUPSIT) in a contamination control strategy.

The recent revision of EU GMP Annex 1 positions the need for a pre-use post-sterilization integrity test (PUPSIT) in the context of Quality Risk Management and highlights that this is a natural component of the contamination control strategy (CCS). In this webinar, we discuss the relationship between the CCS and PUPSIT, highlight the role of sterilizing grade filtration in the control strategy, and talk about how this can change throughout the product life cycle. We review the risk assessment process as a precursor to developing an effective CCS and provide guidance on PUPSIT and other filtration-related contributions to the strategy. Throughout the webinar, we will share the perspectives from Cytiva’s experienced scientific and application teams and guidance for its successful implementation.

A medical laboratory from Spain, Reig Jofre, will also share their industry standpoint and showcase their journey of PUPSIT adoption and compliance, using both manual and automated solutions.

The Role of the Pre-use Post-sterilization Integrity Test (PUPSIT)...

The newly revised Annex 1 emphasizes Quality Risk Management (QRM) and highlights how this can inform and direct a contamination control strategy (CCS). The CCS is not a new initiative. The intention of Annex 1 is to use this as a single point of reference that helps define critical control points through data-informed risk assessment, and ultimately to demonstrate a state of process control. But this is not a static state, and the CCS is expected to be a living document, with periodic reviews that drive continuous improvement to further reduce the risk of contamination. 

Sterile filtration plays a critical role in aseptic manufacturing. As innovation in new therapeutic modalities evolve, it is important that end-users understand how to implement a CCS throughout the product lifecycle. Here we outline regulatory expectations for sterile filtration at each stage of product development, and how those feed into the CCS. We also show how shared responsibilities between the end-user and supplier help ensure compliance to Annex 1. Finally, we provide a perspective from a Contract Development and Manufacturing Organization (CDMO) on best practices to ensure compliance with Annex 1.

Building an Effective Contamination Control Strategy for Sterile Filtration

Presented by Lindsey Silva, Ph.D. Director, Microbiology in Analytical Sciences at Genentech, Evelyn Der, Senior QC Scientist at Genentech, Kevin L. Williams, Endotoxin Sr Scientist at bioMérieux and Allen L. Burgenson, Global Subject Matter Expert, Testing Solutions Lonza Walkersville, USA

The webinar will provide insight into the regulatory landscape for recombinant Factor C (rFC) implementation as a sustainable endotoxin test method. A range of considerations for method validation activities to ensure health authority acceptance will be covered in the webinar including rFC method validation requirements as an alternative non-pharmacopeial method, rFC method implementation considerations for pharmaceutical water and product testing, and rFC method transfer strategy for QC network adoption.

RFC Implementation Strategy For Endotoxin Testing

Sterility Assurance is an essential component of a contamination control strategy for aseptic processes and manufacturers of sterile products. With the recent revisions to Annex 1 heavily emphasizing the importance of a contamination control strategy for manufacturers, Takeda sought to enhance sterility assurance for aseptic production sites, as well as aseptic practices for low bioburden manufacturing sites. The program was developed via design thinking methodology with quality and manufacturing subject matter experts from global sites coming together in a workshop approach to define current challenges and potential opportunities for the sterility assurance program. The program was designed to be a collaboration between global and local functions to support standardization, harmonization, and implementation of best practices across aseptic manufacturing sites. Ultimately, the program will offer training and capability building on sterility assurance and aseptic practices throughout the network.

Design of a Global Sterility Assurance Program

Full title: Insights into Practical Issues Associated with Extractables Testing of Medical Devices

It is a well-known adage that “the devil is in the details.” As authoritative texts and regulatory guidelines that address the chemical characterization of medical devices usually present concepts and generalities and lack granularity, sponsors seeking to design and implement extraction studies for medical devices occasionally struggle to establish and justify critical experimental details that are scientifically sound, practical, achievable, and regulatorily compliant.

This presentation provides insights into several of these critical experimental details, addressing concepts that include:

The “It all comes out at Once” Paradox

Exhaustive Extractions as a Source of Kinetic Release Data

Predicting Exhaustive Extractions with a Minimum Number of Extraction Steps

A Rational (?) Approach to Quantitation and Managing the AET

Accurate versus Protective Quantitation

What exactly is a “Semi-polar” Solvent?

Insights into Practical Issues Associated with Extractables Testing...

Full title: Leveraging Development and Commercial Knowledge for Root Cause Analysis of Commercial Near-infrared Methods

Presented by Brendan Lyons, Senior Scientist, Forensics and Innovative Technologies group in Global Quality at Bristol Myers Squibb and Followed by Joseph Andrew, Innovations Engineer at Optimal Industrial Technologies

Bristol Myers Squibb manufactures a high-volume drug product which is tested for release primarily by Near-infrared spectroscopy (NIR) assay and content uniformity analytical methods. Due to the large testing volume, the performance of these NIR methods has been challenged with respect to system suitability, reference method comparability, statistical control limits, and release specifications. These events trigger investigations or proactive initiatives, which require root cause analysis. The determination of root cause for these NIR based methods is very different compared to the deviations and investigations typically encountered with traditional HPLC release methods. For example, NIR method performance events are rarely associated with laboratory error. Also, the multivariate calibration models and associated diagnostic metrics are abstract mathematical concepts, which can be difficult to interpret or assign to specific risk factors. However, within the appropriate context, the additional details available from these multivariate models can be leveraged to determine root cause. Appropriate context can be adopted from historical knowledge available either from the quality by design strategy used for NIR method development or from method robustness trends during commercial operations. This talk will discuss actual examples of leveraging these knowledge sources for root cause analysis of atypical NIR method performance events.

Leveraging Development and Commercial Knowledge for Root Cause Analysis...

Full title: A Digital Transformation Journey in Process Development – Building Automated Data Flows, from Equipment to eLN to Advanced Analytics
Sanofi CMC/Process Development is implementing a comprehensive Digital Transformation program to improve our productivity and reduce our development timelines. We are deploying a standardized digital workflow across our development sites globally (target: 2,000 users) and building automated data access to ensure scientists can document, visualize, and analyze their experimental work. We will discuss the progress, successes, and pain-points encountered by the development teams as we progress towards our digital ambition.

A Digital Transformation Journey in Process Development...

Presented by Dr Clemens Günther, at Bayer AG, R&D Pharmaceuticals and Susanne Becker at Intertek

Toxicological Risk Assessment on Extractables and Leachables

Presented by John F. Cipollo, Ph. D. Team Lead and Senior Principal Scientist, Global Biologics and Khaled Yamout, Senior Director, Analytical Services and Quality Control at TriLink Biotechnologies.
Following the rapid and successful deployment of mRNA vaccines during the COVID-19 pandemic, over 150 mRNA vaccines are in development, with further therapeutic applications in oncology, cardiovascular and genetic diseases and forecasts predict a high level of growth in products using this drug manufacturing platform. USP engaged with stakeholders in government, drug development, pharmaceutical companies and other experts to build consensus on relevant quality attributes for mRNA-based products and appropriate analytical methods. As part of this effort, USP worked with vaccine experts to generate draft guidelines (Analytical Procedures for mRNA Vaccine Quality) and solicited feedback from stakeholders to update and evolve the guidelines. This presentation will provide an overview of USP updated guidelines and plans for further assessment and qualification of analytical methods presented therein. Physical, chemical, and structural elements of drug substance and drug product and how they relate to product quality attributes will also be discussed.

mRNA Quality Assessment and USP Guidelines

Defining limits for analytical method outputs is a central element of a control strategy. Traditional approaches usually focus on ensuring process consistency, while in more advanced approaches the understanding of structural-function relationships are utilized. This enables definition of patient centric limits that focus on controlling the impact of CQAs on product efficacy and patient safety. In certain cases, those limits and can be defined independent from a specific analytical method and where indicated can extend beyond a therapy specific clinical history. Process consistency control and change management are an integral part of the patient-centric specification and risk-based control strategy approach. The presentation will provide some practical examples for the definition of patient-centric specifications and process consistency control.

Defining Patient-Centric Specification in a Risk-Based Control System

control strategy

analytical methods

CQAs

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