Ten Things You Should Know Before Contracting a Custom Synthesis Project

WHITE PAPER

By James M. Schmidt, EAG Senior Scientific Advisor

Companies often need to arrange for the synthesis of test substances to support research and development efforts.

There are a number of important decisions to consider before proceeding with a contract for synthesis. An adaptation of the “Five W’s” for gathering information and problem solving—Who, What, When, Where, and Why—provides a good framework for decision-making:

Who. Who do you need to talk to about your synthesis project? That depends very much on your specific needs and scale, which can range from small quantities of a reference standard to support a bioanalytical project to much larger amounts of API to support a clinical trial. The quality agreements, production systems, and contracting arrangements are quite different across that range.

For large scale projects, you will want to consult with a large-scale Contract Manufacturing Organization (CMO).

This white paper provides advice and guidance to those with the responsibility of procuring the milligram to multi-gram amounts of reference standards, internal standards, impurities, or radiolabeled materials produced by custom synthesis vendors.

What. What kind of material do you need? 14C or 3H for a metabolism study? 12C for a reference standard? 13C, 2H, or 15N for an internal standard?

When. It’s important to allow sufficient lead time for the procurement of starting material, the actual synthesis, and any other deliverables (such as a Certificate of Analysis). As the complexity of a synthetic scheme increases, whether in chemistry or steps, so does the time required. Timing also will depend on the regulatory approach: for example, CGMP synthesis will take significantly longer than a non-regulatory project.

Where. For radioactive materials, it’s especially important to decide where on the molecule the label should be incorporated. This can sometimes require the design of a new synthetic pathway. Depending on the molecule, radiolabeling in multiple positions—or the strategic use of multiple isotopes—may assist in defining the metabolic pathway.

Why. It’s last in the Five W’s, but this should always be the first question you ask before proceeding with a custom synthesis. Good study design should always come first to avoid complications later. Is the test substance to be used in humans or in preclinical species? Is the material needed for tracking degradation in plants, animals, and/or environmental matrices? Answers to these questions have important implications for regulatory requirements and material needs.

In this white paper, you will learn:

  • Why good study design should always come first to avoid complications later.
  • Why it’s important to allow sufficient lead time for the procurement of starting material, the actual synthesis, and any other deliverables (such as a Certificate of Analysis).
  • Why your specific needs and scale can have a big impact on quality agreements, production systems, and contracting arrangements.

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