Process and Scaling

FDA's recently released initiative has made process analytical technology (PAT) a hot topic in the life science industry. PAT describes the application of process analytical chemistry tools, feedback process control, information management tools, and product and process optimization strategies for the development and manufacture of pharmaceuticals. In this article, the author explores the impact PAT will have on the pharmaceutical industry.

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FDA is re-engineering the CMC review process for innovator and generic drugs and backing risk-based ICH quality standards.

Pharmaceutical Science & Technology News

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.

A straightforward approach reveals how the probability of passing the USP content uniformity test can be calculated for tablets and capsules.

Customers are placing high demands on pharmaceutical manufacturers to produce sensitive, cost-effective and regulatory compliant inspection technology. This article examines how metal detection equipment suppliers can combine forces with manufacturers to provide state-of-the-art inspection systems, giving particular consideration to cleaning processes and regulatory issues.

The author describes the efforts of the standards committees to establish guidelines for PAT implementation and the impact of the guidelines on the industry.

A novel probe design can reduce the powder-sample density variance such that moisture and solvent levels can be accurately modeled and predicted in process.

FDA recently approved the first PAT applications for the introduction of rapid microbial testing of drug products and pharmaceutical-grade waters. Officials from FDA and GlaxoSmithKline worked together to ensure the appropriate scientific evaluation of the methods. Team members report on the successful validation approach and identify technical issues to be considered for the future.

The results of forced degradation studies indicate the need for alternatives to valerophenone as an internal standard calibration for quantifying ibuprofen in bulk drug and tablet assay samples.

The authors examine the VHP resistance of microbial isolates recovered from controlled environments and compared them with commercially available biological indicators under various test conditions.

Most, if not all, pharmaceutical companies today are moving towards a paperless reporting structure. This article examines FDA's 21 CFR Part 11 regulations, which relate to technical and procedural compliance for electronic records and signatures.

If an inspection reveals any shortcomings ... a manufacturer may be warned, fined, or its facility closed down until full control can be demonstrated to the satisfaction of the authorities ....

As FDA prepares for the Critical Path initiative, offices across the agency are expanding the use of the risk-based approach to regulation and applying a quality systems approach to internal operations.

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 authors outline stability studies designed to evaluate the effect of temperature excursions on product quality that may occur during distribution.

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.

Pharmaceutical Science & Technology News

A recent USP gathering generated creative suggestions for the March 2005 USP convocation.

The author describes a separation method for two active ingredients in the contraceptive pill with liquid chromatography UV detection.

Pharmaceutical Science & Technology News

Total organic carbon (TOC) analysis is a fast and effective analytical technique for cleaning validation. Understanding the various types of TOC technologies is essential for choosing the best solution.

FDA expects a firm that is subject to GxP to develop a risk evaluation of its product and to then mitigate the identified risks. Identified risks may be addressed by technical fixes that effectively eliminate the risks or reduce the likelihood of occurrence and/or severity of consequences to acceptable levels.

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.

Current microbiological methods cannot measure microbial contamination at the levels that engineers and regulators seek to establish for aseptic processing cleanrooms. New approaches for assessing data and establishing alert and action levels are advocated, and an example of one analytical tool is considered.

Following the launch of its initiative, "Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach," FDA has been looking to process analytical technology (PAT) for improvements in process efficiency and quality. This article discusses the implementation of PAT systems into production environments, its impact on quality assurance and the necessity of an integrated approach. Options for implementing PAT are also presented.

This article examines European differences in GMP requirements for the acceptance of Certificates of Tests. The authors look at how pharmaceutical manufacturers can address the issues and suggest a US-compatible framework for GMPs that could be incorporated into EU requirements.

FDA is expanding electronic data submission programmes to improve regulatory operations, and ensure appropriate and safe drug use.

Europe is debating the process by which drugs receive marketing authorization. As ever, the debating table features the EU, the pharmaceutical industry and the usual suspects among the European lobbies. The crux of the matter? Should comparative efficacy play a role in marketing authorizations?