Parenterals

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.

Big Pharma is ramping up capital spending in parenteral manufacturing at the same time that contract manufacturers are completing their own major investment programs.

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.

The role of microbial testing to ensure the sterility of aseptically filled sterile products is explained, from the product development phase to in-process monitoring to finished product testing.

FDA's draft guidance on aseptic processing contains some inherent difficulties, including unrealistic expectations of sterility and microbial quantification, an absence of harmonization with international rules, and failure to support new technologies or a risk-based approach. The authors propose a science-based alternative.

In spite of regulatory uncertainties, the industry continues to develop improved aseptic processing technologies.

FDA's aseptic processing draft guidance and the industry's state-of-the-art isolator technologies prepare manufacturers for the next generation of contamination control solutions.

Isolator technology can be used in clinical product formulation and filling facilities to ensure environmental control and reduce contamination risk in aseptic processing.

Members of FDA, industry, and academia formed a working group within PQRI to openly discuss topics from a scientific perspective and provide formalized clarifications and recommendations to FDA to be considered and incorporated into FDA's draft guidance on aseptic processing.

The authors describe the solicitation of industry input for the guidance through a process that included a 2002 meeting of the Advisory Committe on Pharmaceutical Science and the subsequent formation of the PQRI Aseptic Processing Working Group.

Training for aseptic processing cleanrooms must be a dynamic process to meet job requirements and industry demands. The author discusses various approaches that may be taken to ensure a successful training session.

The recently issued FDA concept paper about aseptic processing shows how the current guidelines could be expanded and makes recommendations for alternatives to traditional cleanroom installations such as isolator-equipped aseptic filling lines and blow?fill?seal equipment.

As parenteral drug delivery becomes more complex and sophisticated, excipients that can facilitate drug (or gene) delivery to specific therapeutic targets will be required. An overwhelming majority of these excipients are derived from natural sources.

When FDA reviewed PDA's Technical Report No. 34 about isolator systems, significant differences of opinion between the organizations came to light.

The development of a successful powder for injection formulation requires careful study of preformulation parameters, packaging and process parameters, and the elimination of particulate matter.

Two types of hydrogels used in parenteral protein-delivery systems offer opportunities for achieving a variety of prolonged- and delayed-release patterns.

Significant advances have shaped the past 25 years in the pharmaceutical industry, and the next 25 years will be no exception.