This article continues from an earlier one discussing the cleaning of formulation labware.  Part 1 in this series is entitled “Glassware Cleaning: The most argued over topic for all formulations”.  View part 1 here.

 

 

We left off in our last article on the question of how to know if your labware is really clean.  What experimental techniques and analytics are needed to establish cleanliness?

 

The starting point is determining what the acceptable level of cleanliness actually is.  This may already be established for you in a standard operating procedure (SOP), policy, or safety document.  For example, if your formulation has a radioactive component, your safety department may mandate that all labware be cleaned down to an established baseline level of radiation (i.e. counts per minute).  You as the formulation scientist have little to no input in this example, and you are simply executing based upon the rule handed to you.

 

Alternatively, if your formulation contains a novel compound or if your formulation is itself completely novel, you may be asked for your opinion on cleaning.  This again will be you executing upon company policies.  The general thought process is as follows:

 

  • Identify what about the formulation needs to be cleaned.  Usually there is some component that is hazardous, can cause a problem with a future batch, can damage equipment if left as a residue, etc.  Basically, you need to identify what the component is that must be cleaned at all costs.  Usually this will come down to 1 or 2 compounds with the rest being relatively easily cleanable and harmless.  If you are truly unlucky, you may find that all compounds in a formulation require extensive cleaning.  At this point, you may need to look into alternative approaches such as single-use disposable labware, and we will cover these in a future article.

 

  • Identify the best way to remove the harmful residue.  In some cases, you may have to determine if total removal is even feasible.  For example, very intricate fluid paths (especially turbulent fluid paths) may never be able to be cleaned fully due to irregularities in the fluid flow.  In cases where total removal isn’t feasible, you still have a few options, but they are complex.  Such situations will be the subject of a future article.  For now, we will cover a basic situation where the residue can be removed with a simple cleaning solution.

 

  • Gather data with your identified approach in an idealized lab setting.  This will help you show that your approach is feasible, and will also allow you to work out the specifics (soak time, # of soaks and rinses required, work required to remove the cleaning solution, etc.)  It is important that your experiment reasonably mimics the actual cleaning situation.  For example, if you are cleaning at a temperature of 2° C, your lab experiment should be carried out at 2° C.  Experiments at higher temperatures may or may not be valid (these would require the extra work of a bridging study to show validity).  We will discuss these experiments in more depth later on in this article, but the devil truly is in the details when it comes to these studies.

 

  • Last but not least, an “engineering run” may need to be carried out on the at-scale equipment to show feasibility of the approach.  By this time you should be fairly confident in your approach, but also have a contingency plan in the even that the cleaning fails or needs revision when scaled up.  It is not uncommon for multiple engineering runs to be necessary to fully develop the cleaning plan.

 

An illustrative example is shown below to get the beginning scientist familiar with these concepts.  Give some examples that you have encountered in the comments below!  Or better yet, share a problem that you are wrestling with and need input on!

 

Example: Cleaning of a simple, ideal formulation from metal equipment

Formulation: 1N NaOH (Sodium Hydroxide) in H2O (Water)

Harmful residue: NaOH, can cause corrosion of metals over time

 

Chosen Approach: Rinse equipment with H2O until harmful residue is no longer present.

Why was this approach chosen?  NaOH has high solubility in water, water is not harmful to personnel, and water is not expensive to use.  Additionally, the water will leave no residue on the metal that must then also be cleaned.

 

Experimental design to demonstrate approach:

  1. Experiment 1 — Demonstrate a reduction in NaOH residue on metal coupons by rinsing with RO water.
  2. Experiment 2 — Determine the minimum # of rinses needed to get NaOH residue down to acceptable levels.
  3. Experiment 3 — Demonstrate reliability and repeat-ability of the method on metal coupons; possibly with multiple people performing the cleaning method.

Let’s discuss the exact details of these experiments in the comments.  Please share what you think the specifics of each experiment should be!

 

Coming soon in our next post in this series:Glassware Cleaning Part 3 — In-depth Look at Defining Clean