Drug Product Manufacturing Process: Technology Transfer by Ajay Babu P., Sanjay Sharma; Joe Paul P.

PROBLEMS ASSOCIATED WITH THE ANFD (AGITATED NUTSCHE FILTER DRYER) USED IN PHARMACEUTICAL, CHEMICAL, AGROCHEMICAL AND OTHER INDUSTRIES

ANF and ANFDs are widely used in the Industry majorly because of their superior filtration and drying performance in terms of filtration time, drying time, quality of the product and minimalistic utilization of the energy. However, there are a few limitations, which can hamper the overall productivity of a manufacturing plant or unit badly. Let's discuss them in brief.




DESCRIPTION OF THE TYPICAL OPERATIONAL STEPS IN ANF/ ANFDs:

In a typical scenario (rather in majority of the cases), an ANF or ANFD operates  as per the following operational sequence viz.

1. Boot Cycle or Pressure Test Cycle: Here the ANF/ ANFD is pressurized by Air or Nitrogen gas to check if any of the valves or joints are leaking or not.

2. Charging or Feeding Cycle: The slurry type material (to be filtered and/or dried) is added to the ANF/ ANFD either manually or with the help of a flexible/rigid chute (gravity flow of the mass) or pumped in.

3. Filtration Cycle: The slurry fed to the ANF/ ANFD undergoes either Air/ Nitrogen gas pressure from the top Or vacuum from the bottom valve Or undergoes both simultaneously (pressure from the top and vacuum from the bottom) with an intent of expediting the filtration of the mass and thereby draining out the mother liquor as fast as possible.

4. Squeezing Or Pressing Cycle: The so called wet cake (formed after pressurized or vacuumized filtration as explained in the step above) is pressed with the help of the agitator by rotating it in the clockwise direction such that the blades touch the cake surface and gradually push the cake downwards while the agitator is in rotory motion (at a low rpm).

5. Washing Cycle: The cake formed after Filtration and Squeezing cycle many a times needs to be given a water-wash or a solvent-wash with an intent of diluting and removing impurities if any. For this purpose, a separate liquid (say water or solvent or any other liquid) is added to the cake from the top and the same sequence of charging-filtration-squeezing is repeated.

6. Mother Liquor Or Wash Liquid collection: It may be possible that the mother liquor (also referred to as ML) is of use to the businesses. Sometimes, ML contains major amount of solvent which can be recovered and re-used. ML is usually collected in tanks and vessel and can be stored or treated further as per the business requirements.

7. Cutting and/or Mixing Cycle: The wet cake (nicely squeezed and ready for drying) at times needs to be mixed well with an intent of increasing the cake volume so that the drying process can become more effective. The agitator is forcefully penetrated inside the cake while rotating it in the anti-clockwise direction at a low rpm.

8. Drying Cycle Or Vacuum Drying Cycle: The hot utility circulated in the limpet or jacket of the ANFD, as well as (optionally) in the agitator shaft and blades brings out the drying action in the ANFD. Under the desired vacuum (inside of the ANFD), the vapors generated are pulled and condensed inside of the shell and tube type heat exchanger and solvent or condensate is collected in a receiver tank in series.

9. Discharge Cycle: Majorly dried cake or dry powder is discharged from a dedicated nozzle (usually placed laterally on the shell of the ANFD).

10. Cleaning, CIP/ SIP and Changing of the Filter Cloth: As a part of operational sequence Or preventive maintenance, cleaning and changing of the filter cloth needs be carried our periodically.


LIMITATIONS ACCOCIATED WITH EACH OF THE OPERATIONAL STEPS (DISCUSSED ABOVE):

Typically the problems faced or limitations observed during ANF/ ANFD operations w.r.t. the operational sequence discussed above can be illustrated as follows:


1. Boot Cycle or Pressure Test Cycle

# All valves needs to be closed and only the Air or Nitrogen valve needs to be open.

# There needs to be adequate pressure available in the header.

# No leakages (at any valve or instrument joint etc) are permitted.

# Since pressure needs to he held for a while (few mins to few hours as per operational SOP), it should be ensured that so much amount of pressure is available.

# Usually its a manual operation and consumes a lot of time.


2. Charging or Feeding Cycle: 

# Usually charging is done from a reactor or a crystallizer, which produces and holds the volume of mass which is multiple times of the volume of that ANF/ ANFD. So, administering and charging the adequate amount of feed to the ANF/ ANFD is a challenge.

 # At times, there is a complex network of the feeding headers and sub-headers (with multiple valves in series and parallel). Therefore, the next big challenge is to manually ensure the appropriate valves in the path needs to be open only (rest needs to be closed), so that the slurry follows the right path and reaches the right ANF/ ANFD. This is not only time consuming, but can be also highly tricky and complex. Also, role of the skilled operators becomes extremely important.

# Charging of multiple ANF/ ANFDs simultaneously can be extremely challenging.

# Doing all this while strictly adhering to the HAZOP guidelines can be too challenging and time consuming.


3. Filtration Cycle: 

# Operator needs to visually monitor the changes in the physical appearance of the fed mass (which will gradually changes its form from slurry to wet cake) by physically seeing through the view-glass mounted on the top dish of the ANFD. 

# Operator also needs to physically monitor ML flowing out of the ANF/ ANFD by keeping an eye on the view glass mounted on the ML outlet header.

# During the pressure-filtration, at times the top-most layer of the cake (slightly appearing to be a dry one) cracks forming V groove like cracks. The Nitrogen Or Air pressure easily flows out, thereby diluting the pressure-filtration effect. Operator needs to keep an eye of the crack formation and manually fill the cracks with the help of the agitator. This can be too frequent and too cumbersome.

# Operator needs to always ensure that appropriate valves only needs to be open and rest all are closed.

# Too much of the manual tasks and consumes a hell lot of time.


4. Squeezing Or Pressing Cycle: 

# It's both a skill, as well as, an art where the operator needs to:

i) Decide first that he needs to start with the squeezing operation (i.e. agitator driven filtration operation)

ii) Move the agitator vertically downwards (by inching mechanism) on the surface of the cake, while the agitator is in clockwise rotations.

iii) If the cake is too soft, the agitator may get stuck inside the cake. Whereas, if the cake is hard, forceful movement of the agitator can damage the mechanical seal or cause deflection in the shaft.

# Operator also needs to physically monitor ML flowing out of the ANF/ ANFD by keeping an eye on the view glass mounted on the ML outlet header.

# Too much of the manual tasks and consumes a hell lot of time.


5. Washing Cycle

# Problems associated with the Washing Cycle are somewhat similar to those associated with the Charging or Feeding cycle. In addition, the operator needs to ensure that the Wash Liquid is coming from the appropriate tank and in appropriate volume.


6. Mother Liquor Or Wash Liquid collection

# Collection tanks can be separate for separate liquid washes (based on the SOP and process requirement) or can be a common tank. 

# Operator needs to ensure the ML after wash is getting collected at the appropriate collection tank only.

# Incase there is a network of sub-headers of ML outlet line, appropriate valves should be aligned in the open position.

# Some mechanisms should be in place Or a visual alertness is needed to ensure the ML collection tank is not overflowing.

# Manual and cumbersome operation.  


7. Cutting and/or Mixing Cycle: 

# Movement of the agitator needs to be managed manually.

# Manual and cumbersome operation. 


8. Drying Cycle Or Vacuum Drying Cycle

# As per the Process (or SOP) the adequate temperature and vacuum conditions needs to be established. Operator needs to constantly monitor that.

# Drying end point needs to be defined (be it based on the end of the receipt of condensate or be it a sudden change in vacuum or something else).

# Skillful and manual operation

  

9. Discharge Cycle

# At times, the discharge valve has a mechanical dead-plate (lock) at the end, which needs to be removed every time.

# Anti-clockwise movement of the agitator needs to be manually administered.

# Manual and cumbersome operation. 


10. Cleaning, CIP/ SIP and Changing of the Filter Cloth

# Purely manual and labor oriented operation.


CAN THESE CHALLENGES/ LIMITATIONS BE MITIGATED OR MINIMISED:

Industrial automation can be the only solution to these challenges. The level of automation depends on the complexities of the operations and the need of the process. The objective behind any of the automation should involve: 1. Ease of operations 2. Consistent Results 3. Optimization of the Process and 4. Reduction in the manual intervention (so as to get better accuracy of the outcome).


Please feel free to contact me at  shg.techo@gmail.com for more information.

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