Drug Substance (DS) or Drug Product (DP): a different approach during batch review ?

Confusing? Allow Selly Van Parys, our QP/RP Associate, to explain the difference between both and the impact towards batch record review.

 Let’s start with a Drug Substance (DS). This is any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of … the drug product … exactly. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the body. It is also known as Active Pharmaceutical Ingredient (API).

So, that‘ll make it easier to explain the term Drug Product (DP). This is a finished dosage form, for example, a tablet, capsule or solution that contains an Active Pharmaceutical Ingredient, generally, but not necessarily, in association with inactive ingredients.

Thus, in summary, a DS is the starting point for the manufacturing of a DP, while a DP might contain additional inactive ingredients that enhance the general performance of the DS in the DP.

What does this implicate for a batch record of a DS versus a batch record of a DP?

The DS manufacturing process generally consists of a numerous and diverse set of unit operations (reaction, work-up, crystallization,…), making the process time consuming and complex. In addition, the manufacturing process often ends with batch filtration, washing and drying, resulting in several sub-batches. This in combination with the amount of different filters, reactors, tanks,… makes it challenging to follow and understand the overall process.

The DP manufacturing process on the other hand is more predefined than the DS manufacturing process. For example, there are three different techniques for tablet manufacturing: wet granulation, dry granulation or direct compression with fixed steps for each. Direct compression is the easiest and most cost-effective process since it compresses powdered materials directly into tablets without modifying physical properties.

In Belgium, during the advanced master in Industrial Pharmacy, the emphasis is mainly on DP manufacturing techniques and less on the DS manufacturing process steps such as crystallization, chemical reactions… The latter for example are mainly taught during the first study years of the Pharmaceutical Sciences program. Since the manufacturing process of DS is more complex, it might thus be challenging to find your way in the batch record…

Let me give you some advice

What may help or what helps me in practice when reviewing batch records of drug substances is creating a flow of the process including each different step. This way you can keep track of where you are in the process step by step and you know what follows. An additional option is listing all the different filters, reactors, tanks,… with their corresponding use in the process. This way you can approach your review in a structured way, which benefits the quality of your work! And let this just be what we are aiming for during our daily tasks!

Do you need some support in the review of DS or DP batch records, don’t hesitate to contact us!

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