Usually, the first step of a Drug Substance process consists of some form of chemical reaction or production process (like a fermentation). The initial raw materials and intermediates will be transformed into the desired API or Intermediate.
Drug Substance Manufacturing Process
Overall, an end-to-end manufacturing process consists of 3 main steps: Drug Substance, Drug Product, and Finished Good. We will start by looking at the Drug Substance. This is often referred to as the API of a product and is always the first step in a pharmaceutical manufacturing process.
Let’s take a deeper look at the Drug Substance process and the 3 primary steps that make it up!
Reaction & Production
Purification
Once the desired API or intermediate is created as part of the Reaction/Production, it needs to be purified such that other impurities and undesired molecules are removed, leaving only the desired drug substance. These Purification steps play critical roles in ensuring the final drug substance will meet all required specifications!
Isolation
Once the final desired drug substance is created and purified, it is necessary to isolate it to be used in other drug substance processes or to be carried into drug product production.
Stages
To make a Drug Substance, it can sometimes require multiple sets of separate processes one after another to reach the final desired drug substance. We call these ‘Stages’. For example, the first Stage may be made at one site, and the next Stage at a different site!
Drug Substance Example
On the previous page, we talked through the 3 primary steps within a Drug Substance process: Reaction/Production, Purification, and Isolation. Now how does that play out in a manufacturing setting? What does that look like within our plants? Let’s look at a simplified example below!
Goal
Trying to make an imaginary Drug Substance “DS-A2”. It has 2 separate stages, Stage 1 and Stage 2.
Stage 1
The raw materials for the process are reacted in a reactor to make the desired intermediate ‘DS-A1’ still dissolved in the liquid in the tank.
The reaction mixture is then crystallized, causing the ‘DSA1’ to become a slurry of solid in the liquid in the tank.
The slurry is filtered with the isolated wet solids being put in a dryer. Once the ‘DSA1’ is fully dried, it is taken out of the dryer and placed into drums to be shipped to another site for further processing!
Stage 2
The raw materials and ‘DS-A1’ are reacted to make an intermediate.
The reaction mixture is then reacted again to make ‘DS-A2’
The liquid is then distilled to lower the volume and remove impurities.
The liquid in the tank is transferred to a lyophilizer where the liquid is sublimed off, leaving the final powdered product of ‘DS-A2’, the desired Drug Substance! This material will then be shipped to another facility for the drug product production.
