Process Development

The senior director of Oracle's Life Sciences Business Unit tackles some of the technical issues regarding regulatory standardization, software integration, and the trend toward visualization, among other things.

To monitor and control processes or products, analytical methodology must be fit for purpose. An approach to apply quality by design principles to the design and evaluation of analytical methods has therefore been developed to meet these needs. This article features a downloadable template on which to conduct a failure mode effect analysis (FMEA).

High performance liquid chromatography has become an efficient technique at the production scale, and simulated moving bed chromatography provides several benefits during processing.

The recently published Orange Guide 2007 contains significant changes to the GMP requirement placed on pharmaceutical manufacturers, but there have been additional changes to good distribution practice that should not be overlooked.

The authors discuss how companies facing ever-evolving regulatory requirements can address and assess compliance risk in their operating practices.

The Active Pharmaceutical Ingredients Committee (APIC) - a sector group of Conseil European des Federations de l'Industrie Chimique (CEFIC) - first voiced the need for EU GMP API legislation in 1993 to help ensure the safety of medicines. In 2000, the International Conference on Harmonisation (ICH) finalized the harmonized API GMP Guideline Q7, which became legal in the US and Japan in 2001. The EU adopted a directive in March 2004 that includes the requirement for APIs in medicines for the EU market to comply with ICH/Q7A. Member States are transposing the directive into their national law: about half of them have completed this process, seven more are well on their way to completion, while seven others are still in earlier stages of adoption.

Missed or late calibration dates can accumulate, and even if the equipment is labelled appropriately, it can suggest poor management of resources and priorities.

EFPIA's 'Mock P.2' document aims to show how the role of 'quality risk management' and process analytical technology as an enabler for quality by design can be presented in a common technical document format. This article summarizes the main features of this document, and explains the key concepts and principles used.

Clean rooms are critical areas in bio/pharma facilities, and it is essential that users are responsible for their care and upkeep, and familiarize themselves with the relevant regulations.

Developed in the 1950s as a means to survive and compete against the giants of the automotive sector, lean manufacturing helped Toyota evolve from a small-volume producer (with little capital) to become a high-volume manufacturer in a process-rich environment. Toyota achieved this by using developments such as total production maintenance (TPM), just-in-time (JIT), Kanban, value stream mapping and Kaizen events.1 A summary of some of the lean terminology is shown in Table 1.

Companies must create a risk-based framework for developing and manufacturing drugs, and acquire the scientific knowledge and technological skills to create more complex products.

All sectors of manufacturing are under continual pressure to bring new products to market quicker, stealing a march on the competition and maintaining their revenue stream.

In applying a visually clean standard, any residue related to the cleaning process that is visible on the surface should constitute a failure.

Performing studies to mathematically 'correlate' swab and rinse sampling values does not add any value. What's more, do not expect them to mathematically correlate.

The European Commission has released its second report to the Council and European Parliament addressing the developments and implications in patent law concerning biotechnology and genetic engineering. The study, which centres on the patentability of inventions relating to stem cells, concluded that those capable of developing into human beings, totipotent stem cells, are to be excluded from patentability on the Directives' grounds of human dignity.

The question of pharmaceutical pricing is going to be resurrected by the European Commission, despite French President Jacques Chirac's rejection of the new EU treaty. Günther Verheugen, the Commission vice president, made this announcement at the annual meeting of the European Federation of Pharmaceutical Industries and Associates in Brussels (Belgium) responsible for competitiveness.

Reading the good automated manufacturing practice (GAMP 4) guide acquaints you with the now classic and almost famous V-model.1 The V-model, originally used for describing a validation workflow of IT and automated systems, is easy to understand and very good at ensuring that the requirements and design are built into the final solution. It is also extremely versatile and can be used for almost any type of validation task you could meet in a development phase.

The author describes strategies for analytical method development that are helpful in achieving quality by design and efficiency.

Defenders of the research-based industry are hoping for an early Christmas present from the European Court of Justice (ECJ). All the signs are that a small but significant victory is on the way against parallel importing. Right at the end of October, a senior judge responsible for a leading case at the court made clear his view that international drug firms do not necessarily have to make life easy for parallel importers. The formal ruling on the case at issue is expected within weeks.

The implementation of a total organic carbon (TOC) method into the United States Pharmacopeia (USP) has its origins in the early 1990s, when the Water Quality Committee (WQC) of the Pharmaceutical Manufacturers Association (PMA, later renamed PhRMA) debated improvements in the testing of purified water (PW) and water-for-injection (WFI). The resulting inclusion of modern analytical techniques replaced much older methods - some of which had been listed in the USP for more than 150 years. Finally, two new regulations were put in place: Chapter for conductivity, which replaced a series of individual ion tests; and Chapter which replaced the oxidizable substances test with a TOC method.

The author argues that information technology solutions will play a major part in confirming-by experimental and statistical validation-that bioprocesses may be interchangeable and therefore generic. The bioprocessing ANDA will define both in-house and contract manufacturing.

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.

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.

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 ....

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.

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?