Drug Development

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?

Cationic liposomes are widely used in gene therapy as a safe alternative to highly immunogenic viral vectors. Attachment of a tissue-specific ligand to the surface of the liposomes can increase specificity and reduce undesired transfection. Targeted liposomes can be categorized as either immunoliposomes or ligand-targeted liposomes. The author provides a brief review of tumour-specific and liver-targeted cationic liposomes and strategies for the development of liposome?ligand complexes.

In this article the authors examine a number of significant amendments to US policy regarding generic pharmaceuticals. These important changes could have a major impact not only on the US pharmaceutical market, but also globally. The US Food and Drug Administration (FDA) implemented new regulations, effective from 19 August 2003, that promise to benefit generic pharmaceutical companies in several ways. Significantly, they seek to prevent multiple 30-month stays and resolve much of the uncertainty regarding which patents may properly be listed in FDA's Orange Book.1,2

This article describes the use of a one-pot processor for the cleaning and cleaning validation of two drug compounds - water-soluble theophylline and water-insoluble mebendazole. Both substances were produced using wet granulation and microwave drying, after which the processor was cleaned using its clean-in-place (CIP) system. Swab samples were taken from areas considered critical during processing and analysed for remains of active ingredient. It was concluded from the results that the processor's CIP system is capable of removing both moieties to a level well within accepted regulations.

The authors examine the development and performance of coprocessed excipients, including testing them for flowability, compressibility, amd dilution potential.

This article reflects on the challenges that predicting powder flowability currently pose to the pharmaceutical manufacturing industry and considers some of the benefits that can accrue when companies overcome these issues.

Based on a German initiative, an international standard on quality management systems for the primary packaging materials of medicinal products is discussed in this article. This new directive will help to standardize the production of primary packaging materials by defining global requirements.

The influence of light on the rate of moisture gain was investigated in 36 drug substances and 18 excipients.

The author provides a brief review of tumor-specific and liver-targeted cationic liposomes and the strategies for the development of liposome-ligand complexes.

When implementing computerized systems, it is important that both purchasers and vendors ensure that each stage of the process (from planning through operation to modifying) is properly validated. This article looks at some of the issues that arise when switching from traditional document-based procedures, and at the benefits that computerized systems can bring.

The importance of calibrating instruments used in manufacturing processes is well known, particularly for highly regulated industries such as pharmaceutical production. This article discusses software applications used to support calibration management, and the potential economic gain to be had by replacing a standalone software application with a capable enterprise system.

The Six Sigma approach would appear to be ideally suited to pharmaceutical processes, yet the industry has been very slow to adopt it. This article looks at the possible reasons for this, and suggests an alternative methodology that takes advantage of Six Sigma tools and techniques, backed by good statistical principles.

The use of solid dispersion technology to increase the bioavailability of poorly water-soluble drugs has always been limited by processing and scale-up difficulties. A new approach may help to overcome some of the problems.

One of the greatest challenges facing biopharmaceutical manufacturers has been the primary recovery of recombinant materials from transgenic sources. As an alternative to existing methods, vibrating membrane technology, which is widely used in food and beverage processing, recently has been adapted to biopharmaceutical applications involving transgenic biosolutions.

With the advent of regulations such as 21 CFR Part 11 and the introduction of the electronic common technical document, it is becoming increasingly important to be able to enhance and fully utilize data management systems. Document change management is a vital tool in the construction and organization of valuable information, and can play a key role in the all-important process of getting a product to market.

Until specific audit trail requirements are available from the US Food and Drug Administration, manufacturers must define their own parameters for software system compliance and decide for themselves how to meet those requirements.

This case study describes how a major pharmaceutical manufacturer was equipped with four filling lines, for metered dose inhalers, supplied with a nitrogen cooling system to prevent spontaneous vaporization of the propellant gas. By doing so, a cost-effective and environmentally friendly solution was provided to a hazardous situation, which also complied with regulatory directives.

The aim of this study was to validate the automated clean-in-place (CIP) system installed on a capsule filling machine to determine its ability to adequately eliminate contaminants. The results obtained from the proposed cleaning validation trial showed that all the soluble tracer was removed after the washing procedure. At the end of the CIP procedure, the discharged water had the same pH, phosphate content and total organic content as the supplied water. Lack of cross-contamination in the product was also demonstrated and a recovery trial highlighted the complete elimination of the tracer from the machine.

Previous articles have presented a general review of the different types of spheres that can be obtained with a rotary fluidized bed process.1,2 This two-part study focusses on lipid spheres that can be prepared using hydrogenated castor oil, as well as examining the feasibility of the process and the main characteristics of the spheres obtained.

Erythritol is a bulk sweetener polyol that is suitable for a variety of reduced-calorie and sugar-free foods. It has been part of the human diet for thousands of years because of its presence in foods such as fruit, mushrooms and fermentation-derived products including wine, soy sauce and cheese. This article investigates the properties of erythritol and describes how it can be used as a pharmaceutical excipient.

Pharmaceutical science & technology news.

The study presented in this article used a controlled-porosity osmotic pump, which was prepared in the form of a bilayered tablet containing a drug compartment and an osmogen layer for the delayed release of diltiazem HCI.

More than 6 years have elapsed since the US Food and Drug Administration's (FDA's) 21 CFR Part 11 regulations regarding the use of electronic records and electronic signatures came into effect.1 In February 2003, FDA issued new draft guidance concerning the scope and application of Part 11, which describes how the agency intends to interpret and enforce the requirements during its ongoing re-examination of the regulations.2 Many people in the pharmaceutical industry have welcomed this new guidance and see it as a positive development that will lead to a simplified FDA approach to Part 11 and a significant reduction in the industry's compliance burden.

Paper batch records have been used for decades to record procedures, the type and quantity of each material used, and the status of each step in the manufacturing process for both pharmaceuticals and medical devices. Although paper batch records are less complicated to implement than their electronic counterparts, and the controls required for data recording and archival are well understood, a paper batch record system is laborious to maintain and prone to human error, which increases the compliance risk. Additionally, batch records have become bulky and more time consuming to prepare and review, particularly as manufacturing operations become increasingly complicated. Advances in technology and science have created a more competitive climate in life science industries than ever before, causing the need for manufacturers to reduce costs and time-to-market, and improve their ability to satisfy the compliance requirements of US Food and Drug Administration (FDA) regulations. The use of electronic batch recording systems (EBRS) and electronic batch records (EBR) offers one solution.

Part I of this article was published in the March 2003 issue of 21 CFR Part 11: Compliance and Beyond. In this issue, Part II discusses the potential advances and changes that must be made for computer validation to remain innovative and relevant to the industry.

In an interview earlier this year (Bio-IT World, April 2003), Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), stated that "The original intent of the rule (21 CFR Part 11) was to facilitate the introduction of electronic technology to the process of the US Food and Drug Administration (FDA) submissions, as well as manufacturing and production. Part 11 was created to provide common-sense guidelines on how to do in the electronic world what was previously done on paper. During the last 5 years, however, confusion regarding what is included in the regulation and how to enforce it was impeding the introduction of new technology. The rule had created exactly the opposite of what was intended."

European expert opinions regarding pharmaceutical process validation were collected and studied by performing an Internet Delphi survey. In total, 36 experts from 10 countries representing the pharmaceutical fields of industry, regulation and academia participated in the survey. The overall attitude to process validation appeared to be positive; however, a number of concerns were raised. More education, better use of prioritizing tools and increased evidence of cost-effectiveness is needed to further develop and facilitate process validation.

In December 2002, FDA notified DMV International that its pharmaceutical lactose manufacturing facility in The Netherlands had passed inspection. It was only 3 years earlier that DMV had started an ambitious programme to implement cGMP for API production conforming with ICH Q7A guidelines.

New research has led to significant advances in formulations and inhalation systems for pulmonary delivery.