| William Bowtle at Encap Drug Delivery describes the issues inherent in the development and manufacture of oral ‘high containment’ products in a contract environment
Many ‘high containment’ oral products such as cytotoxics and high-potency compounds are in development in companies across the industry. Their development and manufacture present issues of cost, containment and compliance with specifications. In addition, they are likely to be small-volume products and are unlikely to offer future economies of scale.
Standard encapsulation and compression routes for oral dosage units often involve dusty operations that raise problems relating to cross-contamination and operator safety. They can also be costly, due to the installation and maintenance of an expensive special plant. Operators may also be required to wear cumbersome protective clothing and use complex procedures. For high-potency compounds, there are additional issues in assuring product compliance with specifications for assay and uniformity of content. Some companies have the relevant technical resources to meet these demands. Increasingly, however, they are addressed in contract environments where speciality expertise and facilities exist. This expertise also provides for consideration of alternative technologies which may reduce the significance of the good manufacturing practice (GMP) issues, whilst meeting tight technical specifications. The experience and approach described here refer to development and manufacturing issues for such products in so-called liquidfill hard capsules.
PROJECT INTRODUCTION
The first steps in any project introduction are aimed at the development and implementation of safe handling guidelines and the establishment of equipment clean-down monitors. The former are required for dispensing, processing and other support operations, and contribute to minimising potential cross-contamination issues. Assurance of suitable post-use equipment clean-down is critical to ongoing manufacturing operations, and has to be supported by the identification of an appropriate cleaning route and related monitoring system for each product. In a contract development environment, particular issues arise from the limited nature of contemporary data, and the product-introduction system has to recognise this. The following system has been found to work well. It is based on a specific introduction sequence for each new compound, with supporting routine campaign-specific cleaning verification. |
