Aseptic Processing in the manufacture of Pharmaceutical and Biotech products course objective is to explore the role of aseptic filling to assure that manufactured product will retain the sterility assurance level prescribed by GMPs
Sterile products may be broadly classified into two main categories based on their production mode -- those that are terminally sterilized following the filling and sealing of the container and those that are aseptically sterilized, that is, filter sterilized as a bulk product, filled, and then sealed. Aseptic Processing play a critical role with large molecules that cannot be terminally sterilized. The verification of the process to produce sterile product is evaluated through the demonstration of various media fill process simulations that will vary in both numbers and size of the containers as well as the volumes filled over a defined period.
Aseptic Processing involves risk assessment on an on-going basis because of the inherent risks due to consequences of management and process failure and challenges within the detection, isolation, control, and management of product contamination. Within aseptic processing, the severity of the consequences of a failure can be severe to the end user while detection through sterility testing remains rather limited because of the small number of final products tested.
The FDA and EMA require that any product that may be terminally sterilized be managed in that fashion. However, almost all large molecules and some small molecules can only be sterilized by aseptic processes, i.e., membrane filtration.
With membrane filtration, it is essential to establish acceptable levels of microbiological contamination to ensure both product safety and compliance. Meeting sterility claims for Phase 1, 2, 3 and commercial products in a timely and effective manner is important in avoiding costly delays. In addition, since aseptic processes are associated with endotoxin control, it too, must be managed to acceptable levels.
A variety of variables can impact sterility assurance and the accompanying endotoxin level. These include the personnel, process, equipment, components, sterilization, depyrogenation as well as facilitates and utilities that impact the management and processing of the ultimate products. Issues that need to be considered include the monitoring of environmental areas and personnel, water sources, media, and media fills, gowning and sanitization.
Products that have historically been aseptically filled have relied upon the use of USP <71> Sterility Tests to demonstrate sterility. However, since no more than 20 containers are tested per media (TSB and FTM) regardless of the production lot size, the use of sterility tests does not provide a high degree of sterility assurance (SAL). Thus, media fills are now utilized to simulate the actual fills and to demonstrate at least a 10-3 sterility assurance level of no contamination. If the facility uses RABS or isolators to meet their filling requirements, a SAL of 10-5 to 10-6 is possible since the interactions with personnel and the environment decrease markedly.
Media fills are required during the commissioning of an aseptic operation within a new facility, when a new container configuration (volume or neck size) or other unique activities associated with aseptic filling occur. Following the on-going performance of a new aseptic filling line, a requalification is required at six-month intervals.
It will review the issues regarding preparing media and setting up the “filtration train”, environmental monitoring, interruptions that may occur during the operation of the Clean Room (planned and unplanned) and the cleaning of the room and its equipment. Equipment used to monitor the equipment and personnel will also be reviewed along with gowning issues that periodically arise. The seminar will also discuss media failures and how to “work through” them. Because of the sensitivity and importance of media fills, this live, interactive training seminar is a MUST for anyone in your organization that is involved in aseptic filling in general and media fills in particular. Please plan to attend this as part of an interactive group project.
Seminar participants will learn the following:
- Gain an understanding of the fundamental principles and skills necessary to conduct Aseptic Processing of Sterile Drug Products with minimum risk
- Analyze issues impacting Aseptic Processing to include the environment, personnel, gowning and sanitization
- Acquire the skills necessary to control the process environment
- Minimize media fill failures to permit production throughput
- Determine how to develop media fill simulations to include the "worst case" scenarios
- Learn best practice techniques for determining media fill sizes
- Understand the "critical factors" required to maintain compliance
- Decrease inspectional observations
- Avoid Warning Letters and Consent Decrees
Join the conversation 7:45 -8:00 AM
- Aseptic Processing - Introduction
- The Sterile Dosage Form
- Maintenance and control of critical environments
- Development of procedures for operation, calibration, Preventive Maintenance, CAPA, etc.
- Training of operators to include gowning
- Documentation and evaluation of changes
- Contamination Sources in Aseptic Manufacturing
- Particle Content Controls, Cross Contamination Risks
- Cleaning Process and Agents for Sterile Production
- Developing Media Fill Requirements in An Aseptic Environment
- Form FDA 483s
- Equipment set up
- Sterilization process
- Media fills
- Smoke studies and their emphasis in Aseptic Production (ISO Class 5 facilities)
- Endotoxin sources
Dr Barry A. Friedman, Ph.D,
Cambrex Bio Sciences
Dr. Friedman possesses over 30 years of industrial managerial experience in various aspects of biopharmaceuticals and medical devices to include regulatory compliance, expert witness testimony, GLP/GMP, quality control, auditing, sterility assurance, microbiological/analytical validations and fermentation technology.
Prior to becoming an independent consultant, Dr. Friedman was associated with Cambrex Bio Sciences, a contract manufacturer of GMP bulk biopharmaceuticals located in Baltimore, Maryland. As the Director of Quality Control, he managed a multi-shift Department of thirty one individuals involved in client management, the receipt and testing of raw materials, environmental monitoring and microbiology, analytical chemistry and QC compliance for the production of Phase 1, 2, 3 and commercial products manufactured from bacteria, yeast and mammalian cells. In this capacity, Dr Friedman enjoyed many client and regulatory interactions, both domestic and international.
Prior to 2000, Dr. Friedman was the Laboratory Director for Chesapeake Biological Laboratories, a contract Aseptic Fill n’ Finish manufacturer located in Baltimore, Maryland. In addition to the professional history listed above, other associations have included W.R. Grace, Sigma Chemical Co., Sherwood Medical, Becton Dickinson, American Cyanamid and Union Carbide.
Dr. Friedman received his B.S. degree in Microbiology from Ohio State University, his M.S. from Michigan State University in Microbial Genetics, and his PhD from Ohio State University in Microbiology.
Who Should Attend
- Aseptic Processing
- Quality Control
- Quality Assurance
- Regulatory Compliance
- Project Management
- Process Chemistry
- Analytical Chemistry
- Preformulation and Formulation Development
- Scale-up and Technology Transfer
- R&D/technical writing/quality management/original and postapproval submissions in pharmaceutical companies,