Dhavalkumar Surti, an expert in aseptic techniques, continues to share his knowledge and core experience in the pharmaceutical industry. Here he deliberates on smoke study, a very important tool in injectable manufacturing. What is smoke study? Why we need smoke study during the filling setup and filling interventions? Why we need smoke study for the area qualification and equipment qualification?

What is Smoke Study?

First of all, let us understand what smoke study is. Critical airflow or what we call smoke study is used to maintain the aseptic conditions when manufacturing sterile products. When we are manufacturing sterile products, we have to maintain aseptic conditions under the laminar airflow. So, how to ensure that the airflow is proper?

We cannot see air, but we can see smoke. Smoke is used as a visual aid, a visual help, so that we can understand that really our airflow is laminar. Under aseptic conditions, the smoke study, the visualization of critical airflow is used to demonstrate unidirectional airflow and sweeping action over and away from the product.

We need to protect our product. So whatever air is coming, it should be Grade A air, and there will be no microbial contamination. The particulates are within the Grade A limits, microbial contamination within Grade A limits, and ensure that the air should come and sweep away from the product. The air should not be turbulent, it should not be bouncing back, and it should not happen that air is not coming to the working height or where the product is kept. It will not be helpful if the air is not coming up to the working height. So, we need smoke study to demonstrate that.

What is Smoke Study?

In the filling machine there will be lot many instruments, such as filling assembly, and if it is a vial filling line, we will have a stopper bowl, seal bowl, we have in-feed and out-feed, and the complete setup. How do we ensure that that setup is not disturbing the airflow?

There will be obstacles of process equipment and our operating procedures. We will be doing a lot of interventions during the aseptic assembly, lots of aseptic manipulations while we are filling the product. We have to ensure that these interventions, these aseptic manipulations are not creating turbulence and not blocking the air. 

There is a concept called first air, first air is the air directly coming from the LAF and coming into contact with the open product container, empty or filled. That container should receive the first air. That is the air which has not come into any other contact after leaving the HEPA filter from the top.

Our equipment, our operating procedure, our personnel movement, and product handling should consider basic aerodynamic requirements to prevent serious turbulence in the vicinity of the contamination source.

So, within our product vicinity, there should not be any turbulence, there should not be obstacles and physical obstruction from the equipment. This is the first and foremost requirement for filling of aseptic products. To demonstrate that we are providing Grade A air to our product, we need to do smoke study.

Regulatory Guidelines

The second question on smoke study is about regulatory guidelines. A lot of people ask, okay we need to perform smoke study, but where is the guideline requirement for that. There are guideline requirements and let us understand them.

FDA guidance for industry September 2004 states that proper design and control prevents the turbulence and stagnant air in the critical area. Once relevant parameters are established, it is crucial that air flow pattern should be evaluated.

Relevant parameters mean our air flow, air velocity, particulate counts, etc. Once they are established, it is crucial that air flow pattern should be evaluated for turbulence or eddy current. This is the requirement as per the September 2004 guidance for the industry.

Eddy current can act as a channel or reservoir for air contaminants. If the air is not going outside, if the Grade A is not positive, then outside air can come inside, whereas it should go away. That positive pressure has to be mentioned in situ air pattern analysis, which we call smoke study.

The guidance says that in situ air pattern analysis via smoke studies shall be conducted at the critical area to demonstrate unidirectional airflow and sweeping action over and away from the product under dynamic conditions. Critical area means Grade A, where we are filling our aseptic product.

The study should be well- documented with written procedures and written conclusions. We not only have to perform study, and not only have to prepare the video of the smoke study, but have to prepare a report, a written conclusion that whether our smoke study requirement has been met, and whether it is meeting the acceptance criteria or not meeting it. We have to write them down. We cannot simply say that see the video and conclude for yourself.

What guidance says is that the study should be well-documented with written conclusions and include evaluation of the impact of the aseptic manipulation. If we are performing any aseptic manipulation, example interventions and equipment design, we have to document them into written record if there is any impact of aseptic manipulation or equipment design.

Video tape and other recording mechanism have been found to be useful aids in assessing airflow initially as well as facilitating evaluation of the subsequent equipment configuration changes. So, once you set up your new line you have to perform the smoke study. Later also, if you are making any changes you have to repeat the smoke study as and when required based on your evaluation.

People say that we have a very good machine, we have imported machine, we have qualified air flow and air velocity, we have integrity, and our particulate count is within limit, so why we need smoke study? The guidance says that it is important to note that even successfully qualified systems can be compromised by the poor operational maintenance or personnel practices.

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