Manufacturing update

Great news! It appears we have the manufacturing process nailed down, which is pretty exciting. We have the drug substance manufacturing set (that is the actual drug, also referred to as active pharmaceutical ingredient). We know the recipe for making the tablets in the doses we need (including the extra ingredients, called excipients, that keep the tablet together, allow it to dissolve when in the stomach and assure that it dissolves consistently). In parallel with proving the tablet recipe works, we had our manufacturer working on a big batch of drug substance for the clinical trial. They've been responsive, detail oriented and efficient. And it helps too that they have an efficient set of steps to make the drug. The next step is to use the tablet recipe, make tablets from the big batch and do another round of testing for purity, potency, stability and a whole bunch of other stuff that we need to validate before we can submit our application to the FDA to conduct the first clinical trial.

While I knew the manufacturing process would be demanding to manage and exacting in its requirements, I did not appreciate how much so. But isn't that usually the case with big projects?

Drug manufacturing requires expertise in chemistry, engineering, regulation and project management, with success more likely with a bit of paranoia thrown in. That last part is so crucial because this process leads to the administration of the chemical to a person - so any errors cannot be accepted.

As alluded to above, the process works in two stages, making the drug (referred to as drug substance, which you can visualize as the powder-like chemical) and then the final product (referred to as drug product, essentially the tablets or capsules). Each needs to be conducted by moving from testing potential prototypes to formalizing a specific set of steps with proper documentation and oversight. With completion of drug substance (DS) and drug product (DP), a series of tests are performed to assure that the process produces the desired drug every time without unanticipated and undesirable by-products. The rate at which the DP dissolves in the stomach, which allows for it to be absorbed into the body, are tested in machines that simulate the human stomach.

I expect I am describing this in more detail than is interesting to you. But this is a very, very small amount of detail. Our DS manufacturer (Suven Pharmaceuticals, a.k.a., Cohance Lifesciences) figured out the process and validated each step. The documentation that they filed with the FDA is over 1.5GB and over 6,000 pages. They figured out a more efficient synthetic plan (less steps) that produced drug at high yield and with high purity.

We decided to use tablets for our final drug product form, rather than the capsules used for the currently available, high dose form of the drug. A major reason is that we may learn that people will be taking high doses of the drug and we did not want to require a very large capsule or taking more than one capsule. To form a tablet, we are compressing the DS and so we can fit more drug into a smaller form.

Our partner FreeThink Technologies is expert in formulating drugs into tablets and capsules. And if you are wondering, they work as a wonderful mix of how their name sounds (creative free thinkers) and what their work requires (science-driven regulatory compliance).

With the technical support from the experts in this field at BioPharmaWorks, we refined our needs, identified partners and watched them closely to assure ourselves that the proper controls are in place. After all, this drug will be administered to people so we can't afford any lapse in quality.

And that quality is assured by submission of these materials to the FDA for their review. Traditionally that was a fairly quick process, requiring only a couple of months, but we anticipate more time will be required for the review owing to the changes in work force and work environment at the Agency. If there are delays, we will fill that time with preparations to start the trial that much quicker once the FDA approves us to start. We know time is the enemy, and also that sloppiness is, so we'll balance such factors as we move forward as quickly as is possible.