Fill-Finish

The authors describe the origins of single-use components and explain their application to aseptic processes. They also show how disposable devices have changed over time and offer a glimpse of the future.

Drugmakers have many incentives to avoid overfilling their containers, including the scarcity, and correspondingly high cost, of certain cells and ingredients. These concerns highlight the need for techniques that can fill small volumes of product with great accuracy. Many strategies are available to the industry, but which one works best?

What have been the key innovations that have shaped current aseptic practices and techniques?

Each sector of the pharma industry is fraught with challenges and weighty regulations; aseptic processes and techniques are no exception.

Closed vial technology has been designed to address the challenges - potential contamination, counterfeiting and process complexity - associated with the aseptic filling of injectable drugs.

The author details the factors in formulation design, requirements in facilites and equipment, and validation criteria for aseptic formualtions.

The author discusses the risks involved with aseptic processing, methods and tools used to identify and control risk, and regulatory guidelines relevant to the risk-management process.

Why correctly calibrating a drug with its packaging is the key to success.

The authors discuss current and future disposable technologies and outline the validation and qualification steps that would be required for a possible disposable process stream.

The authors review the role of automation in aseptic processing and describe their experience in implementing advanced technologies, including the use of isolators and robotics.

The author discusses the key issues to consider when using isolators such as containment, protection of personnel, the efficiency of biodecontamination cycles, sterility assurance levels, barriers and their integrity, and environmental impact.

A comparison of conventional cleanrooms, restricted access barrier systems, and isolators, shows the benefits of using isolators in high-potency drug manufacturing.

The US Food and Drug Administration issued a rule that clarifies its requirements for current good manufacturing practices for aseptic processing, water standards, and verifications standards.

This article presents a study of an aseptic environmental monitoring system for surface contamination at critical areas using a robot.

Aseptic processing has advanced over the past several decades, yet the pharmaceutical industry is still accepting of its limitations, particularly as it relates to human intervention as a source of contamination. The authors explain the importance of further diminishing the role of operators in aseptic processing and the approaches and technologies needed to achieve that goal.

This article summarizes changes to the Akers–Agalloco aseptic processing risk analysis model (first presented in Pharmaceutical Technology's November 2005 issue) as well as some of the underlying thinking behind the revision. The simplified model makes the method easier to use because of its greater flexibility of environmental control practice. It maintains the emphasis on human activity as the primary consideration in risk management for aseptic processing.

Any aseptic processing technology that allows intervention by gowned personnel during operation cannot be considered an advanced technology. Although a standardized definition of restricted access barrier systems has been developed, these systems fall well short of being classfied as advanced technologies.

The industry has acknowledged only recently the significance of the contamination risk posed by humans. The authors assert that this realization, together with technological advances, will lead to the elimination of human intervention and, hence, improved sterility.

There are few, if any, valid reasons not to install an isolator in a new aseptic processing facility.

The authors focus on the effects of cellulosic materials during the performance qualification validation of a transfer barrier isolator used for the purpose of sterility testing.

A ready-to-fill closed vial can improve aseptic filling quality and reduce process complexity.

The complete elimination of human-derived contamination is possible only with the elimination of human intervention.

The appropriate barrier system should be selected using a logical, risk-based approach, with awareness of all the possible sources of contamination.

Study results show that the state of a cleanroom clothing system–new or much used–influences the protection efficacy of the system.

The authors argue that chlorine dioxide (CD) is a safe and effective decontaminating agent that can be used for challenging applications.The effectiveness of CD gas for sterilizing complex isolator systems is studied.

This article outlines a comprehensive approach for organizing a firm's aseptic operations, including planning for routine and nonroutine interventions, establishing effective process simulations, and determining which vials to incubate.

A discussion of the validation and operation of two commercially available vapor-phase hydrogen peroxide decontamination systems is presented, based on a hands-on examination of both systems.

The authors review current industry practices and regulatory expectations for the aseptic processing of sterile drugs. They compare and outline critical issues in current manufacturing technology and capabilities with regulatory requirements.

The authors suggest a design strategy for an aseptic process simulation that focuses on the basic repeating unit of the process, establishing alert and action criteria for the unit itself, and using worst-case simulations to establish routine operational parameters for the manufacturing process.

The limitation-of-risks (LR) method can be used as an engineering tool in risk assessment work for the identification, minimization, and evaluation of potential airborne risks, and for the identification of adequate monitoring points.