BIOPHARMACEUTICAL MANUFACTURING - Risk Management Applications in Pharmaceutical and Biopharmaceutical Manufacturing

Biomedical Engineering Reference

In-Depth Information

The primary reason for testing these materials is to address the issue of suit-

ability for intended use. By testing extractables, one can generate information

about the potential of a process material to leach contaminants into the process

stream. This information can inform decisions regarding the need for further

testing of the process stream.

Extractable testing can be based on model solvents and thus data provided by

suppliers can be used to assess actual conditions. Adequate characterization of

extractables will facilitate choosing containers that contribute minimally to the

drug product over the product lifecycle. The initial materials used to formulate

polymers and elastomers all degrade during processing and may potentially leach

degradants into the drug product. Other contaminants in elastomers that may leach

into the drug product include curing agents, additives, accelerators, plasticizers,

processing aids, and reaction products.

Potential interactions between biologicals and containers are influenced by

the characteristics of the biological and the container itself. While plastics and

elastomers have the most potential for interaction, other materials, for example,

glass, metallics, etc. may also interact with biological materials.

Leachates from the package may adversely impact the safety profile of prod-

ucts and should therefore be carefully characterized. Characterization processes

include both the extraction and the identification of contaminants as well as an

assessment of the toxicological impact of the contaminants. Establishing levels

at which no or minimal toxic effect is observed provides important information

in assessing the risks associated with extractables and leachables.

Extractable/leachable testing should address several risk questions including,

but not limited to, those in Table 12.3.

Answers to these questions can be used to establish risk-based test schemes to

characterize materials from the perspective of compatibility and safety [30,31].

Such characterizations will minimize adverse patient impact.

TABLE 12.3 Extractable/Leachable Considerations