Scale Up

When I run a small production batch of a particular formulation with the same tablet press used to develop it, I get compressibility and disintegration issues. What am I doing wrong?

The authors share their approach and experience working in complex, multicompany environments for in-licensed products to develop successful chemistry, manufacturing, and controls packages for managing outsourcing partnerships.

The same recipe obtained in laboratory-scale equipment cannot, without modifications, generally be used to freeze-dry the product in a pilot-scale or industrial-scale freeze-dryer.

The authors highlight the need for a technology-transfer process that is efficient, cost-effective, and repeatable, stressing the importance of process understanding. Read this and other preferred organization articles in this special issue.

FDA published its long-awaited guidance titled Process Validation: General Principles and Practices this week.

This article examines the difficulties in designing lyophilisation processes that can be faithfully scaled up to production volumes and suggests the most effective ways in which this can be achieved.

The authors present three approaches that a contract development and manufacturing organization can consider when designing development and process-optimization studies that will provide useful data for scaling up a project.

The authors discuss a continuous-flow reactor that avoids parallel channels and enables economic plant setup. This article is part of a special issue on API Development, Formulation, Synthesis and Manufacturing.

If you’ve worked in the drug industry for a while, chances are good that you remember Pfizer’s Rezulin, which was produced through hot melt extrusion (HME). If you work for a major pharmaceutical manufacturer, it’s likely that your company owns a twin-screw extruder. Yet HME has not been a common way of manufacturing drugs, and many industry employees don’t understand the principles of HME or the advantages that the technique offers.

Continuous manufacturing could bring the pharmaceutical industry advantages such as improved product quality, easy scale-up, flexibility, and short cycle times. But how can a company switch from batch to continuous manufacturing?

Could flexible manufacturing change the standards for biopharmaceutical production? To find out, Equipment and Processing Report talked to James Robinson, vice-president of technical and quality operations at biotechnology company Novavax (Rockville, MD).

The authors sought to improve the productivity of protein synthesis by using a highly active cell-free extract from Escherichia coli and by optimizing buffer conditions and shaking conditions.

Recent advances in microreactor technology are improving the application and scale at which the technology can be applied.

The manufacturing process, which influences a drug's safety and efficacy, is particularly critical for drugs administered through injection, and personnel must closely supervise lyophilization to ensure product quality.

The US Food and Drug Administration?s Draft Guidance for Industry?Process Validation: General Principles and Practices provides a life-cycle approach for validating pharmaceutical processes and aims to help pharmaceutical companies achieve consistently high product quality.

A manufacturing line can be improved if technology transfer is implemented thoughtfully. Effective technology transfer helps to provide process efficiency and control and maintain product quality.

Whether you advance your technology from concept to commercialization or use a third party for parts or all of this work, the ability to do technology transfer flawlessly is essential to successful, efficient pharmaceutical production.

Specialty Pharmaceutical Company Bentley Pharmaceuticals has entered into an agreement with Cardinal Health for the scale-up of clinical supplies for Bentley's intranasal insulin product candidate.

Arlington, VA (Sept. 12)-At the American Association of Pharmaceutical Scientists meeting here, &quote;Real World Applications of PAT and QbD in Drug Process Development and Approval" (Sept. 11-12), chemical engineer and process modeler Michael L. Thompson, PhD, described how Procter & Gamble (West Chester, OH, www.pg.com) applies these mathematical tools to increase product quality and reduce development and trouble-shooting time for consumer and pharmaceutical products.

Although agitation improves drying efficiency and ensures uniformity of the final dry material, it can also affect the physical properties of the product as it dries. This study evaluates the effect of scale up and equipment selection on an active ingredient undergoing granulation during the drying process.

The author reviews dimensional analysis as a straight-forward approach to scale up.

The author points out some major obstacles to effective scale-up and describes methods available to pharmaceutical scientists for addressing scalability issues.

In the manufacture of many pharmaceutical products, dry-particle blending is a critical step that directly affects content uniformity.

This article describes a novel approach to a scale-up management system, based on a holistic view of the scale-up lifecycle and an accompanying electronic development record of the information created.

Poly(vinyl acetate) phthalate-based and acrylic-based enteric coating systems are evaluated for their performance on acetylsalicylic acid tablets in areas such as acid resistance and coated-tablet stability.

Careful planning and decision-making can circumvent possible delays in technology transfers.