Diamond rings

I was looking at a diamond ring the other day. Like most people, I quickly learned that the most important factor influencing a diamond’s worth and beauty is its purity. The top three purity indicators are:

• Inclusions

• Transparency

• Blemishes

Each test is an important purity indicator, is mostly independent of the others, and has its own scale with generally accepted thresholds that make a diamond “good.” There is no single overall “purity” value that can be assigned to a diamond. Instead, diamonds come with a formal certificate that lists the tests performed and the measured values.

To have a single diamond with very good purity in all categories is very expensive. But what about a ring with two diamonds? Each diamond would have its own purity profile and could be selected for having very high purity in a specific category. For example, one diamond might score well for inclusions, while the second diamond might be the purest for blemishes. Could two diamonds in the same ring be better than one?

And this got me thinking about radiopharmaceuticals.

For those new to radiopharmaceuticals, there are three tests (for biologics, there are four) that must be completed to fully evaluate the purity of every batch of the drug product:

• Chemical purity

• Radiochemical purity

• Radionuclidic purity

Like a diamond, each test is an important purity indicator, is mostly independent of the others, and has its own scale with generally accepted thresholds that define what is acceptable.

Chemical purity evaluates the purity of only the chemical portion of the molecule (small molecule, peptide, or protein). Are there any unexpected molecules, or significant degradation of the molecule that makes up the drug product? The specification depends on many factors, but it is not unusual to set the specification at >95%.

Radiochemical purity evaluates the purity of the molecule (small molecule, peptide, or protein) that has been labeled with the isotope. Are there any unexpected molecules, or significant degradation of the molecule that makes up the drug product? The specification depends on many factors, but it is not unusual to set the specification at >95%.

Radionuclidic purity evaluates the purity of the isotope itself. Are other isotopes present, and in what amounts? The specification depends on the isotope (and the production process), but it is not unusual to set the specification at >99%.

Even for early-stage clinical programs, including first-in-human studies, these are purity thresholds that are reasonable to set and relatively easy (if you have done the work ahead of time) to achieve.

And, just like a diamond, there is no overall “purity” value that can be assigned to the drug product. Instead, the certificate of analysis lists the tests performed and the measured values. From the summary of all the test methods, the drug product is very pure—as would be expected for any drug tested in humans.

But the interesting thing about a radiopharmaceutical drug product is that it is not truly “pure,” in the sense that it is not a single molecule. There is a mixture of molecules that make up the drug product. In its simplest form, it is a mixture of two molecules:

• The molecule with the isotope (this is the active pharmaceutical ingredient)

• The molecule without the isotope

And it gets a little stranger.

On a percentage basis, the molecule with the isotope (the active pharmaceutical ingredient, the one that provides therapeutic efficacy or enables imaging) makes up only a small percentage of the overall mass. The active pharmaceutical ingredient in a radiopharmaceutical drug product is, depending on how you define it, an “impurity.”

The mixture of molecules in the drug product is not a problem (with apologies to my friends in the quality control department). In fact, it is essential. An effective radiopharmaceutical therapy requires both types of molecules to be present in the drug product. So much so that the ratio of molecules with isotope to molecules without isotope has its own term. We call it specific activity. Specific activity is a very important design parameter for radiopharmaceuticals. It is…....a post for another time.

As for the two-diamond ring, I have been informed on good authority—and in no uncertain terms—that diamonds are not like radiopharmaceuticals.

In summary

• One diamond for the ring

• Two molecules for the radiopharmaceutical drug product

• Beauty is in the eye of the beholder