Scale-up is the term used to refer to the increase in the batch size of a product. For example, if a drug is successful, then it may scale-up multiple times throughout its life cycle to meet growing demand. Eventually, scaling down may also happen in response to shrinking demand for drug.
On the way from laboratory to market, scale-up is part of product research and development (R&D) and optimization. The possibility of manufacturing a drug at commercial-scale should be considered as a possibility when new formulations are in the R&D phase. Any processes involved in fabricating the drug must be scalable in terms of safety and efficacy, and economic factors must also be considered.
Understanding what scale-up is and how it happens will make it easier to incorporate into the R&D phase of a drug.
1. Know the Different Scales
Laboratory-scale batches are those that are made when the drug is still being tested from its time in the lab to clinical trials. The next level is pilot-scale which may be for the purpose of expanding clinical trials, or for mid- to later stage clinical evaluation. Pilot-scale is usually about 10% of the production-scale, which is also known as commercial scale. When a drug is approved and in demand it will be produced at the commercial-scale batch size. If demand increases, production may be expanded to other facilities and in some cases to other countries.
2. The Elements of Scale-Up
If a contract manufacturing organization (CMO) is not already involved in the pharmaceutical R&D process of the drug it will mostly likely be involved in scale up. With the CMO, the product profile must be defined including the critical quality attributes (CQA). CQA are the biological, microbiological and physical attributes that can be measured and defined for a drug so that quality can be monitored and controlled. When the product profile is defined, the appropriate manufacturing process can be designed. This includes selecting equipment and doing a Scale-Up and Post Approval Changes (SUPAC) report to ensure, for example, that the right equipment has been selected.
3. What Are the Challenges R&D Pharma Should be Aware of?
There are different approaches to scale-up including the more involved Quality by Design approach and the more minimal End-Product testing approach. Each approach poses challenges for the scale up of a drug. When those involved in R&D pharma know these challenges they are better equipped to understand how to respond to them when considering scale-up issues.
For example, if there are temperature-sensitive processes involved in making the drug, the feasibility of replicating those processes at a large scale must be considered. Similarly, if particular equipment is used at the laboratory-scale there needs to be comparable equipment available for commercial-scale batches.
R&D teams may also want to consider that manufacturing can affect the purity profile of drugs, which can pose a challenge for safety studies done previously. An experienced CMO may be able to support the approach to these challenges and will be interested in keeping processes economical and efficient.
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