When designing the manufacturing process for a new pharmaceutical, the first topic that should be considered is the potency of the product. High potent drugs are classified as drugs in the occupational exposure band (OEB) of 5 or 6, with an occupational exposure limit (OEL).
Blockchain technology is already used in the Bio/Pharmaceutical industry and can be classed as an enabler for Pharma 4.0. Today, clinical trials can use this technology as a beneficial solution, while education is required to promote Blockchain applications across organizations.
This presentation will cover the consequences of variability and benefits of reliability for sterile manufacturing. Learnings from recent inspections will also be briefly summarized.
The world has come together during these unprecedented times to respond to the COVID-19 pandemic. Health authorities and regulatory agencies are working closer than ever with industry in an effort to expedite and make available COVID-19 medical countermeasures globally. Public-private partnership demonstrates that the steadiness and resolve of the public sector coupled with the innovation and agility of the private sector can move mountains to save lives.
The use of Isolators technology in the production of ATMPs has been recently developed. For this reason, we need to set transfer of protocols initially developed for grade B. Habits need to change and procedures carefully tuned to avoid bottlenecks and to ensure smooth running. Introduction of raw and starting materials needs a careful evaluation. Containers study and procedures for cleaning and disinfection must be defined and validated. Evaluate the need of an initial package of consumables when starting a batch and what can be introduced using the pass box. Limit the materials introduced in one shot. Special attention deserve waste disposal, cells cultivation and finished product; Different solutions can be applied, like canisters, continuous tubes, dedicated waste containers. All the points above call for detailed procedural approach, good workbench organisation and optimized space management. Space is limited and every item should be considered and studied in details. Despite this great and careful work, it is worthwhile to do, so given the advantages offered by isolators. SSCB Swiss Stem Cells Biotech, a year ago undertook the tech transfer of the Adipose-derived SVF (Stromal Vascular Fraction) production from clean room to isolators. We now produce ATMPs only using isolator technology.
This presentation is part 2 of the Oxford biomedica Oxbox project case study presenting a combined Formulation-Fill-Finish platform for ATMPs including a lentiviral vector for CarT Cell therapy. The presentation covers an inventive approach to remote-virtual FAT through the Covid 19 crisis, the development of a Contamination Control Strategy (CCS) for Annex 1 compliance that also covers an Aseptic-Containment strategy to manage cross contamination control. The processing platform combines manual and highly automated processes for vial filling with consideration to IV Bag filling. Processing is fundamentally applied with use of pre-sterilized containers and single use systems with aseptic processing applied with limited glove interventions into the barrier to a minimize risks yet provide flexibility for processing different ATMPs. The Oxbox project also follows Scale out rather than Scale up principles with modular yet flexible cleanrooms and barrier technology.
The ISPE Student Chapter (SC) Munich is currently working on an industry project named "Biosafety Project" together with all other ISPE D/A/CH Student Chapters. The aim is to develop a guideline on how to define organizational and technical measures for keeping the operator and environment safe when manufacturing cell and gene therapies (CGT) - whilst fulfilling GMP requirements at the same time. In the first presentation the current work of the team regarding Biosafety requirements and implementation is presented, current obstacles are discussed, and future steps are shown. Operator Safety was one of the major goals to combine the flexibility to handle liquid and lyo products with fully isolated equipment, to guarantee the highest degree for a BSL 2 Viral Vaccine Fill and Finish Facility. The major hurdles from a project execution perspective will be presented from Bavarian Nordic/CDMO.
The design and implementation of a state-of-the art fill finish facility for viral vaccines faces numerous challenges. Besides the right facility design with focus on BSL2 aspects, this project had the challenge of a very short timeline (fast-track project) combined with facility space limitations. One major goal was to combine the flexibility to handle liquid and lyo products with fully-isolated equipment, to guarantee the highest degree of operator safety . Besides that, the presentation covers also insights into the background for handling of viral vaccines as well as the major hurdles from a project execution perspective.
The ISPE Student Chapter (SC) Munich is currently working in an industry project named "Biosafety Project" together with all other ISPE D/A/CH SC's. The aim is to develop a guideline on how to define organisational and technical measures for keeping the operator and environment safe when manufacturing cell and gene therapies (CGT) - whilst fulfilling GMP requirements at the same time. In this presentation the current work of the team regarding Biosafety requirements and implementation is presented, current obstacles are discussed and future steps are shown.
CMOs need the flexibility to respond to ever-evolving client needs. Likewise, manufacturers who are bringing their ATMP production activities in-house have complex product pipelines and need the flexibility to develop different modalities in parallel, unsure of which will ultimately go to market. Both are united by the same challenge: they need a facility that can accommodate a pipeline of four or five product types, each requiring a highly sensitive process. But designing a bespoke production suite unique to each modality would lead to astronomical costs and a sprawling, inefficient facility. This presentation will illustrate how multimodal suites allow ATMP manufacturers to campaign between modality-specific process platforms, which raises the value of each square foot inside a facility. This level of flexibility, once considered outside the realm of possibility for such highly customized and novel processes, is now emerging as an essential feature of an efficient ATMP facility design. Each attendee will learn how to: - Protect investments with a facility built for change - Get up and running with industry-leading rapid deployment -Easily scale a facility as pipeline evolves - Understand costs and schedule Fight cancer with an mAb product. Fight a pandemic with a vaccine platform. Do it all in the same manufacturing suite, weeks apart.
Gene/Cell Therapy is a rapidly emerging novel therapeutic technology in the biotech industry. Applications for these therapies are wide-ranging from cellular immunotherapies to cancer vaccines, and new facilities are being designed and built quickly to support the production of these new drugs. Manufacturing facilities that are designed to handle cell/gene therapy unique challenges compared to traditional bulk biologics and mAB facilities as their processes/products are still in development and are subject to change. Many gene/cell therapy facilities will utilize live virus during production which poses additional design/operational considerations to ensure aseptic product handling throughout the manufacturing process.
This presentation will discuss the planning, resources, and capabilities necessary to effectively produce a client’s highly potent active pharmaceutical ingredient (HPAPI) therapeutic, while effectively controlling the risk of exposure to operating personnel. Controlling exposure is a critical factor in successfully bringing many of today’s novel highly-potent drugs to the clinic and eventually to the commercial market. Successful manufacture of HPAPIs includes containment design and installation considerations, Best Industrial Hygiene Practices vs. Good Manufacturing Practices, and the process of characterizing, challenging, and verifying isolator performance.
The processing of HPAPI's, especially ADC's faces multiple challenges in terms of equipment design ,execution as well as handling/operation. This presentation covers besides an introduction into ADC's, a realized customer project to identity the major challenges in terms of aseptic high-potent fill-finish equipment. Besides having the right Isolator and filter systems design, the focus needs to be on the filling equipment and the right cleaning and wash-in-place procedures to secure both the product as well as the operators.
Annex 1 is highly important to all involved in sterile medicinal and Advance Therapeutic medicinal products manufacturing as such clarity of requirements is essential. The targeted consultation of Annex 1 version 12 received many comments on the concern in the lack of clarity in sections for Barrier technologies and Cleanroom and clean air devices classification and qualification. The PHSS prepared alternative test to address the industry concerns and submitted to the EC in the formal targeted consultation process. The main concerns with the barrier technology section in version 12 of Annex 1 was the lack of differentiation between RABS and Isolators. The concerns with Classification and Qualification related to interpreting the generic classification requirements from ISO 14644 and application in a Pharmaceutical setting particularly handing at rest and in operation classification. This presentation considers the key points to understand clarity of regulatory expectations, how barrier technologies have developed to meet CGMP requirements and how Classification-Qualification should be applied as a phased process through Classification, environmental qualification and APS qualification into routine production process monitoring.
Decontamination of cleanrooms as opposed to Isolators present unique challenges. The volume of the room and the geometric limitations needs to be taken into account. This presentation will describe the development and qualification of a system that was developed to decontaminate RABS cleanrooms using aerosolized hydrogen peroxide. This is specifically useful for flexible cleanrooms with frequent product changeover. The details include: Design of decontamination system & cleanroom, optimization of the aerosolized amount of H2O2 selection of positions to be challenged with indicators, optimization of relative humidity, optimization of the decontamination time value of chemical indicators for validation of bio-decontamination processes.
In aseptic production using barrier systems, a variety of differing materials like packaging materials or consumables are present. Nowadays, further new technologies emerge for application of hydrogen peroxide for biodecontamination. However, hydrogen peroxide can interact with materials. This can have significant critical impact on the aseptic process or product. Especially biopharmaceuticals (as most vaccines) are highly prone towards oxidation. In this presentation a basic introduction to the interaction processes between hydrogen peroxide and materials is given, explaining the resulting possible impacts on products or processes. Approaches for practical investigation are discussed and evaluated by means of experimental data of real-life examples from pharmaceutical production. It can be concluded that careful evaluation of interactions between hydrogen peroxide and materials is inevitable when performing process risk analysis and will provide additional safety for the respective aseptic processes. As a result, the conference participant will learn which interactions may occur, how they can have impact on process or product and how to investigate this. Therefore, he will become aware of the necessity of a comprehensive assessment on interactions of hydrogen peroxide and materials.
In the new draft Annex 1 the use of automated processes and Rapid Micro Method technologies are mentioned. How can be current technologies for EM monitoring replaced through new innovative technologies.