Tech Transfer Blog #10 – Engineering runs – Just an expensive Insurance policy?
An Engineering Run can be also called many other names such as an engineering trial run, engineering lot or practice runs or demonstration runs but they are usually non-GMP runs used to demonstrate that the manufacturing equipment and processes work as required and that the end product can meet the required quality specifications.
Engineering batches do not have to use the actual API but may just simply be run with simply media, buffer, and other components, often called a “water batch.”
However, the term “engineering run” can also be used for any non-GMP trial, for example commissioning runs following the installation of new equipment or the installation of a new manufacturing line. It should be noted though that all validation runs must be run under full GMP conditions and are thus not engineering runs.
The scale of an engineering trial can vary according to the purpose and complexity of the trial; however, engineering runs are not mandatory, just a good idea in most situations.
From the Technology Transfer point of view, engineering runs can be used for:
- Demonstrating that the manufacturing equipment itself works, such as being able to fill 2ml. vials at the speed required. A water run can be used in this respect although the use of product is recommended to demonstrate viscosity or foaming issues would not be a problem. If the actual product cannot be used due to scarcity, cost or toxicity concerns, then a substitute with close physical or chemical properties could be used.
- Demonstrating that individual process steps or unit operations work as required and that the process step produces product to the right quality.
- Demonstrating that individual process steps work as part of an integrated process.
- Optimizing process equipment.
- Developing or optimising manufacturing parameters.
- Optimise sampling regimes.
- Finalising the process control strategy.
- Identifying and resolving any potential issues before the formal cGMP documentation and activities. Challenges will inevitably be encountered before or during manufacturing and addressing these in a non-GMP situation is easier, an engineering batch run can help avoid many predictable and unpredictable issues.
Quite often a transferred process will be new to both operators and engineers, and an engineering run allows for familiarisation and training of operational staff. And don’t forget that quality staff will also need to become familiar with sampling methods and actual product to use for analytical process and verification activities.
Rarely are such process related Standard Operating Procedures (SOP) and manufacturing documentation such as batch records complete, error free and ready for use prior to GMP use, and engineering batches are often used to “red line” these documents prior to being used in anger.
Engineering batches can be of any scale, from “pilot” scale up to full scale depending on what aspect of the process is to be studied and the full process or only part of the process.
In fact, an engineering run can be run at any time before or after the product has been launched such as for process improvement purposes.
As stated before, engineering runs are not mandatory, but form part of the company’s risk assessment process, it’s a risk assessment thing with the balance depending on project costs and timelines versus confidence in the GMP production process and brand reputation.
It’s a Risk Thing
If something goes wrong with the GMP run, the consequences could be severe but there is no easy way to attribute a hard number to the amount of time or money that could be lost, it partially depends on the stage of the process the error occurs. Moreover, if you are using a CMO then remember that many CMO’s book GMP slots back-to-back, so if an organization misses its scheduled GMP run, another slot may not be immediately available.
If you have a lot of confidence in the process development work and you already have experience with this process in other plants and at other scales, and that the product is easy to work with then the risk may be in your favour. However, it is a mistake to assume that a particular drug product will run the same as similar drug products. One common issue is viscosity, where mixing or filling systems must be adjusted to accommodate the characteristics of the product.
If process unit operations can be run independently then it might make sense to just execute engineering runs on the higher-risk operations particularly if they have a well-known or a relatively common process for other process operations.
Disadvantages: – Of course, there are also disadvantages associated with engineering runs in that they arerun at GMP scale and, as such, demands the same resources as a GMP run meaning that they can be costly and time-consuming.
If viable material is used to execute the run, the resulting product usually is lost, since it was not produced according to GMP standards.
Engineering runs can use scarce single-use media, an issue all to frequent during the last pandemic manufacturing operations.
Engineering runs can be viewed as a very expensive insurance policy.