Fumigation and fogging are commonly used in pharmaceuticals to control microbial contamination in a controlled area. Fumigation is the process of gaseous sterilization, that kills microorganisms and prevents microbial growth in the air or on the surface of the wall/floor.
Fumigation agents, including the chemicals or solutions like formaldehyde and potassium permanganate, are commonly used to control the micro-organism. The fumigation technique also helps to remove lizards, cockroaches, cobwebs, rodents, flies, and insects from the area. However, Nowadays, fumigation with formaldehyde and potassium permanganate usage is illegal by different regulatory agencies in pharmaceutical firms.
Why is formaldehyde banned in Pharmaceuticals?
Being banned is because of its carcinogenic property ( cancer-causing) and the risk of cancer associated with it. This may be to the personnel who is handling formaldehyde. Formaldehyde also irritates the eyes and nose.
De-Fumigation in Pharmaceuticals
There are requirements for de-fumigation of the area by operating AHU ( air handling units) continuously for a few hours without any activity. Defumigation must be done to remove residue from the air, and equipment cleaning is also required after the fumigation process.
Difference between fumigation and fogging?
Fumigation
Fumigation is the process of spraying formaldehyde and potassium in the form of liquid
Principle of fumigation:
Formaldehyde chemically (H-CHO) in its pure form. Formaldehyde is a gas at room temperature, and its boiling point is -19 ℃. However, it readily polymerizes at a temperature below 80 ℃ to form a white solid. Its important polymer is paraformaldehyde, a colorless substance that rapidly yields formaldehyde on heating. Its bacteriocidal power is super but weak penetration power.
For an effective fumigation process, the gas has been dissolved in the surrounding environment of bacterias. For this reason, fumigation in pharma industries is recommended at a temperature above 22℃ and a 75% relative humidity.
Advantages of fumigation:
- Fumigation controls all life stages of microorganisms because of its toxic nature.
- It is a quick way to control microorganisms, saving money and time.
- Fumigation is easy to process and reach in all areas where aerosol and spray can not reach.
- No residue problems.
Mode of action:
The mechanism of fumigation is the production of a cross-link between the proteins which interact with RNA and DNA. It acts as a mutagenic and alkylating agent that reacts with carbonyl, thiol, and hydroxyl groups.
75% relative humidity is required For more effectiveness ( humidity limit 60-80% and temperature 22 ℃) because gas has to dissolve in the film of moisture surrounding the bacteria.
Method and concentration;
Steam can use to increase humidity and temperature in a room up to the required limits.
- Use 500 ml formaldehyde and one liter distilled water for 28 cubic meters of area for four hours or overnight.
- Use 170 gm potassium permanganate and 500 ml formaldehyde for 28 cubic meters for four hours or overnights.
This concentration may be changed after proper validation.
Fogging:
Fogging uses a mixture of hydrogen peroxide and silver ion solution; for this fogging machine is required.
Fogging is used in pharmaceutical industries to control microbial contamination in controlled areas, and Hydrogen peroxide and silver are used for Fogging purposes. These are non-toxic, eco-friendly, chlorine-free, non-mutagenic fumigating agents. Various formulation of H2O2 is available in the market having a concentration of 10% H2O2 with acidic pH and odorless.
It is water-miscible and does not cost material. The required solution for 1000 ft3 of the area is 20% (i.e., 200 ml of solution in 800 ml demineralized water). Spray it with the help of a fogger for 30 minutes. Fogging may be done at a 130ml/minute rate. The contact time shall be at least one hour.
Mode of action:
It is a strong oxidizing agent. It oxidizes the bacteria and makes them inert. virosil is a preparation available in the market with a 10% hydrogen peroxide concentration. The recommended concentration for the same are below;
- Surface disinfection (5%).
- Instrument disinfection (10%).
- Resin and filter disinfection (1 to 3%).
- Strong tank disinfection (5%).
- Laundry disinfection (10%).
But in the case of H2O2 and silver ions. It is supposed to be a safe solution for personal use. There is no requirement for de-fogging in fogging areas because no residues remain left after fogging as they decompose into the water and nascent oxygen. So there is no requirement for cleaning and mopping on equipment.
Precautions During the fumigation and fogging process
- Stop the process of operation before fumigation or fogging.
- All materials, raw materials, finished goods, intermediates, and in-process goods related to products should be removed.
- All personnel follows entry and exit procedures.
- Windows and doors should be closed. AC and AHU should be switched off before starting fumigation or fogging.
- The status label ‘Area under fumigation or fogging, Do not enter’ shall be fixed on either side of the entrance.
- Intimation of fumigation and fogging and additional rounds should be given to security.
Cleaning after fumigation:
After Fumigation Use 70%v/v IPA solution and lint-free cloth for cleaning, the wiping of external parts of equipment should be done. Clean the floor and drain point as given in the respective SOP “Cleaning and sanitization in pharmaceutical. “
Scheduling of fumigation should be done after any prolonged shutdown or during weekends and the plant’s start-up.
Validation of fumigation in Pharmaceuticals:
Validation requires verifying the effectiveness of fumigation in pharmaceutical companies. For this, indicator-like strips of Geobacillus stearothermophillus ATCC 7953 are used.
These strips are marketed with the name BIO NOVA (these are perforated s.s. coupons with spores.)
These indicators place at different locations, mainly in critical locations like corners and behind the instruments. After the fogging process, these strips are incubated in the MC20 growth medium provided with the biological indicator at 60±2°C for twenty-four hours.
What are the validation criteria for fogging?
If the color of the MC20 growth medium change to yellow after incubation at 60±2°C. It indicates the presence of microbes even after fogging in the strips. If no change in color. It shows the effective fumigation of the area.
Related: SOP on Fogging at the Production Floor and Service Floor
Conclusion:
Fogging is a safe and better method to control microorganisms over fumigation in pharmaceuticals. Fogging is preferred over fumigation because it is safe for personal and has no requirement for cleaning and defogging.
It kills bacteria and fungi quickly. There is no need to take extra care of residues, but in fumigation, there are requirements of regular care and keeping the area and handling equipment safe; therefore, fogging is the best choice for fumigation.
