Introduction to the conference

Emily Cheah, Chair, Conference Committee

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  Emily Cheah

  Managing Director of Charles River Laboratories (Singapore)

This presentation will cover some current microbiological hazards relating to sterile drugs, with emphasis on aseptic processing issues. It will also discuss the role of robust manufacturing equipment design and vigilant quality risk management in assuring reliable sterile drug production. The presentation will emphasize strong supplier controls, including lifecycle management and quality assurance. It will also note that the knowledge of the body of the literature and current research findings provide important inputs to the risk management decisions. Finally the presentation will emphasize the value of leveraging of modern, highly capable technologies.

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  Rick Friedman

  Deputy Director, Office of Manufacturing Quality at US FDA

Moderator: Dinesh Khokal
Panelists: Rick Friedman and Jessica Teo

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  Rick Friedman

  Deputy Director, Office of Manufacturing Quality at US FDA
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  Dinesh Khokal

  Director, External Affairs, JAPAC and Intercontinental - LatAm of Amgen
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  Jessica Teo

  Division Director, Audit and Licensing Division, Health Products Regulation Group of Health Sciences Authority Singapore

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  Tracy Moore

  Expert GMDP Inspector at Medicines and Healthcare products Regulatory Agency (MHRA)

The presentation describes the requirements, the approach and integration of processes and the documentation structure and case studies that are being developed.

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  Di Morris

  Clinical Auditor at AstraZeneca

Opening Remarks by the Moderators

The inclusion of PUPSIT in Annex 1 have challenged operations with regards to wording and interpretation; particularly with regards to when and why a risk assessment should be used.

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  Lisa Bennett

  Senior Quality & Compliance Specialist at Cell Therapies
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  Bruce Loxley

  Senior GMP Compliance Advisor at GlaxoSmithKline Vaccines

In December 2017 the PDA and BioPhorum came together and formed the SFQRM consortium (Sterile Filtration Quality Risk Management) to respond to specific needs from regulators and end-users to determine when and why a risk assessment would require the use of the Pre-Use/Post-Sterilization Integrity Testing (PUPSIT) for sterilizing grade filters. The main concern was voiced in a Q&A document of 2007, which mentioned the potential of filter flaw masking, which would mean a flaw is not detected with the post-use integrity test. This concern raised, started the sporadic enforcement of the implementation of PUPSIT, respectively the urgent need to determine whether there is such masking propensity. Moreover, the risk of masking, filter handling, transportation etc also had to be weighed against the risk of a PUPSIT implementation since it is adding significant complexity and therefore risk to the sterility assurance of the process. This meant science-based tests and evaluations had to be performed to create a solid data base for such appropriate risk assessment.
To better understand the use of PUPSIT, the SFQRM consortium issued the PUPSIT failure survey to provide a clear and well evidenced argument with data that reflects the reality of implementing PUPSIT and the impact it has on time, costs, and effort. The PUPSIT failure survey was completed by the consortium member companies in 2017, 2019, and again in 2021. The questions in the survey are around media fill, sterility and other failures linked to PUPSIT. With the most recent 2021 survey, the goal was to refresh the 2017 and 2019 PUPSIT survey and to give it a special focus on the use of the SFQRM consortium deliverables, implementation of risk assessments, and regulatory interactions on the topic of PUPSIT.
The current presentation will provide a high level overview on the work of the SFQRM consortium with specific focus on the PUPSIT failure survey including the background, purpose, and high level conclusions.

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  Marjo Peters

  Director Drug Product Technical Steward Europe of AstraZeneca

Moderators: Bruce Loxley and Lisa Bennett
Panelists: Hal Baseman, Marjo Peters and Somasundaram G.

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  Hal Baseman

  Chief Operating Officer at Valsource Inc
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  Lisa Bennett

  Senior Quality & Compliance Specialist at Cell Therapies
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  Somasundaram G.

  Senior Consultant Asia Pacific, Process Solutions at Merck KGaA
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  Bruce Loxley

  Senior GMP Compliance Advisor at GlaxoSmithKline Vaccines
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  Marjo Peters

  Director Drug Product Technical Steward Europe of AstraZeneca

Opening Remarks by the Moderators

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  Sok Tiang Koh

  Vice President - Scientific Affairs & Technical Services at West Pharmaceutical Services
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  Bruce Loxley

  Senior GMP Compliance Advisor at GlaxoSmithKline Vaccines

The evaluation of air patterns (under all conditions) is a very important part of a modern Contamination Control Strategy (CCS) as well as a regulatory requirement. Airflow visualization (AKA Smoke Studies) provides a visual representation of a cleanroom or barriers system’s overall contamination control effect. It is important to understand air patterns in both unidirectional, non-unidirectional cleanrooms as well as the interface between areas (i.e., doors, airlocks and pass-throughs).

This requirement does not change for isolators; these studies must be performed simulating all conditions, including operating, set-up, assembly, and monitoring. Unfortunately, many companies are hindered by a common isolator design oversight that did not consider the importance of “in situ air pattern analysis”. This oversight prevents a comprehensive evaluation of air patterns that could influence product quality. A common complaint related to isolator design is the inability to conduct a smoke study that simulates unassisted or automatic operations such as filling and closing while it is a regulatory expectation to have smoke studies documenting airflow patterns during simulations of manufacturing operations.

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  Morgan Polen

  Contamination Control Expert at Microrite

Pharmaceutical elastomers are commonly applied in the form of stoppers, plungers, and needle-shield for parenteral drug-delivery applications. In this presentation, we will look at different class of elastomers and how the characteristics of halobutyl elastomers allow it to be suitable for pharmaceutical use. Typical elastomer formulation, manufacturing process and the various in-process checks involved during the production of pharmaceutical elastomer will also be discussed. Participants will also gain insights into the process of pharmaceutical washing and how consistent products can be derived for use in fill-finish operations. We will also take a look at the various considerations during gamma and steam sterilization of pharmaceutical elastomers which can help to minimize variability in sterile operations. Lastly, automated vision inspection as a form of value-added processing technology will also be discussed.

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  Terence Lee

  Senior Technical Account Specialist at West Pharmaceutical Services

Opening Remarks by the Moderator

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  Emily Cheah

  Managing Director of Charles River Laboratories (Singapore)

The field of cell and gene therapy is growing rapidly. Patients depend on access to these therapies as well as strict controls to assure prevention of microbiological contamination during the life cycle from patient to manufacturing to patient. The 2020-2025 USP General Chapters-Microbiology Expert Committee is developing some new proposed content to provide foundational knowledge about microbiological control in cell and gene therapy manufacturing as well as modern methodologies for microbial contamination testing. Current USP chapters will be aligned to the autologous cell and gene therapy short shelf-life life cycle and consequently for the allogeneic therapies by valuable updates about closed systems, e.g. revisions to <1211> Sterility Assurance, <1116> Microbiological Control and Monitoring of Aseptic Processing Environments. New chapter-proposals are being developed for microbiological controls of cell and gene therapy manufacturing, alternative rapid microbiological contamination methods, and detection of other adventitious agents. Bring your questions to learn more.

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  Don Singer

  Senior Microbiology Technical Consultant at Ecolab

This seminar will cover a risk-based approach to an Aspergillus brasiliensis contamination in a Cell and Gene Therapy Cleanroom. Details will be provided on how to follow a risk-based approach utilizing a fishbone diagram and the five whys centered on using good science. The most common causes of contamination will be conveyed in case studies with fungal spore contamination. New efficacy testing data will be covered on Chaetomium and Aspergillus. A recent case study will be covered in detail as well as microbial identifications and how to utilize a risk-based approach. Solutions are going to be conveyed on how to proactively prevent fungal contamination from reoccurring.
 
Who Should Attend the Conference
Validation Managers | Quality Control Managers | Quality Assurance Managers | Lean Managers | Operations Managers | Cleanroom Managers | Regulatory Affairs Managers | Production Managers | Quality Systems Managers

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  Jim Polarine Jr.

  Senior Technical Service Manager at Steris Corporation

Moderators: Emily Cheah and Vishal Sharma
Panelists: Peter Baker, Don Singer, Jim Polarine and Ziva Abraham

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  Ziva Abraham

  CEO of Microrite
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  Emily Cheah

  Managing Director of Charles River Laboratories (Singapore)
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  Jim Polarine Jr.

  Senior Technical Service Manager at Steris Corporation
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  Vishal Sharma

  Co-Founder of Vienni Training and Consulting LLP
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  Don Singer

  Senior Microbiology Technical Consultant at Ecolab
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  Peter Baker

  Vice President at Green Mountain Quality Assurance LLC

Opening Remarks by the Moderator

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  Li Wei Chan

  Manager, Microbiology at MSD International GmbH

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  Olivier Chancel

  Quality Auditor, Sterility Assurance Expert at Boehringer Ingelheim

This presentation considers:

• What are rapid and alternative methods?
• The different categories of rapid methods.
• The commonly described advantages.
• Current sources of guidance and regulatory opinion.
• A review of some of the available types of rapid methods.
• The key validation requirements.
• Barriers to implementing rapid methods.

The presentation will consider some important philosophical questions about what we want to get from rapid methods and whether we are driving the technology or whether the technology is driving us.

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  Tim Sandle

  Head of Microbiology, Quality Risk Management & Sterility Assurance at BPL

The need to utilize rapid sterility testing is gaining momentum within our industry, especially for short-life drugs with an immediate patient need, such as advanced therapy medicinal products (ATMPs; cell and gene therapies). This webinar will explore the challenges of manufacturing and releasing ATMPs and the benefits of implementing rapid sterility test strategies. We will also discuss the global regulatory policy changes that support using rapid sterility tests for these types of products, as well as the introduction of compendial chapters providing guidance for validation and implementation. We will finish with case studies on how rapid sterility validation studies may be performed.

What Will be Covered:

• Assess the current state of sterility testing for ATMPs and the need for rapid testing solutions
• Review current regulatory policies and compendial guidance for rapid sterility testing
• Understand the required validation parameters including limit of detection, specificity, method suitability and equivalence
• Consider sampling strategies when compendial requirements cannot be met
• Discuss the impact of short-life products on detection time
• Provide examples of rapid sterility validation strategies

Who Will Benefit:

Anyone who is manufacturing and releasing ATMPs, QA/QC technicians and scientists performing sterility release testing, senior management responsible for quality and manufacturing decisions, and especially regulatory affairs personnel looking to understand the current regulatory framework for rapid sterility testing acceptance.

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  Michael J. Miller

  President at Microbiology Consultants, LLC