Best Practice: Developing Drugs that are Highly Potent

There is an increasing number of new drugs in development that require handling of materials classified as highly potent or cytotoxic. Many of these drugs can also be highly toxic, hence, requiring extreme care and specialist knowledge. This article discusses some of the issues and challenges when developing such products.

Classification remains a challenge
The handling of highly potent and cytotoxic materials that require containment capabilities is a tricky business especially if the material is a new chemical or biological entity that has not been used in humans before. Drug substances can be categorized by their potency by using occupational exposure limits (OELs). However, if potency is not yet established because the product is only at the development stage, the first challenge can be in getting the material manufactured to understand if there is safety and efficacy in the proposed indication.

There are many challenges to handling materials that require containment for personal protection, the first of which is an understanding of what high potency actually means. This interpretation can vary depending on the different viewpoints. Moreover, there is no standard classification that is globally accepted for high potency materials. As a result, many large pharma companies have developed their own in-house classification systems for materials to try to clarify and categorize the types of controls and handling procedures required for adequate personal protection and potential for cross-contamination.  

There have been efforts across the industry to interpret these various classifications; SafeBridge is a widely recognized good example of such, but there are also many other categorization systems including the Merck system, the Roche system, and the Affygility system. Nevertheless, there remains no “one-size-fits-all” system across the pharmaceutical industry, which adds complexity to the issue. With a wider need for the industry to move away from time-heavy tasks and constant duplication of efforts to become more efficient, agreeing on and standardizing the classification of highly potent and cytotoxic materials would be a good starting point.

Hazard warning
Interpretation of the potential hazards is required by many different types of organizations for classification of potent materials for containment during handling processes. Communication and information sharing between companies developing new drugs and those seeking to handle potent materials on a contract basis are crucial. Ensuring potential hazards are identified and understood, and that risk is adequately managed for people who handle such materials in the process of manufacturing a drug product for first-in-human use, are key aspects in the product development phase.

Potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. But if the effects are not yet fully established, as in the case of a new drug to be evaluated in clinical trial, that process for assessment of the potency is less easily applied. Clearly, the potency of materials is one thing, but exposure is another. Specialist facilities are required for handling potent materials, including dedicated areas for containment and segregation. There must be clear processes for risk assessment, ensuring adequate staff training, and understanding of risks. Controlled waste-stream management is required to control materials after the main manufacturing process.

Developing and manufacturing highly potent and cytotoxic drugs tend to be more complex than most products, with challenges in terms of classification, handling, and selecting the right contract manufacturing organization. A more collaborative approach in supply-chain management, information sharing, risk identification, and agreed standards would go a long way in helping overcome these challenges.

About the Author
Colin MacKay is CEO of Symbiosis Pharmaceutical Services