PAT for vial washing machine
Natrajan S Iyer and Purva P Khot
USFDA has defined cGMP as a system for designing, analysing and controlling, manufacturing through timely measurements of critical quality and performance attributes of raw and in process materials processed with goal of ensuring final product quality. In light of this definition we will found out how a vial washing machine can satisfy all requirements of definition. According to Process Analytical Technology (PAT), quality is built in system and not in the final product checking. This is done by analysing the manufacturing process by using chemical, physical, microbiological, and mathematical and risk analysis. Risk is defined as measurement of uncertainty. The main function of vial washing machine is to clean the vials and reduce the bioburden. Vial should be devoid for particles and stains. The critical parameter for vial washing machine is cleaning of vials in various steps using different types of fluids (filtered compressed air, DM water, WFI and recycled)
The cleaning is done via jet of fluids. Experimentally, it has been found 0.3 ml to 0.5 ml/ cm2 surface area of vial is required for purified water, 100 ml/cm2 is the requirement for compressed air @ 3 Kg/cm2. Since the vial washing machine is used to wash different sizes of vials, the quantity requirement of fluids will change. That means that the compressed air and purified water should be provided with control valve and programmed through a Programmable Logic Control (PLC), which continuously monitors the flow requirement getting a feed back from a flow meter. It assures the flow all times, for specific capacity of vial.
Flow requirements are calculated as e.g. Vial volume (Size) = 10 ml Height = h = 45 mm (App.) = 4.5 cm Diameter= d = 24 mm (App.) = 2.4 cm Hence, Surface Area = pd2 + p d h 4 = (3.142 x [2.4]2) + 3.142 x 2.4 x 4.5
= 38.4580 cm2 (App.)
The water requirement is 0.4 ml /cm2 avg. Hence, water required for 38.4580 cm2 = 0.4 x 38.4580
= 15 ml / vial
In this way we can calculate air requirement. Another critical parameter is fluid coming out of jet for cleaning the vials.
The nozzle which have hallow cone and swirling, so that the wall can get cleaned in two directional fluid flow i.e. tangential and vertical.
The impact force calculation for nozzle is given
I = K X Q X v P Where I = Total Theoretical spray impact (Square inch (cm) K= Constant Q = Flow Rate
P = Liquid Pressure
The pressure of jet is directly proportional to impact. That means as the pressure decreases, the impact force will decrease, it can directly affect the cleaning of vial. Continuous monitoring of pressure is essential as this is a critical parameter which is done by a pressure transmitter, which gives out put of 4-20 Ma, this controlling the variable frequency drive (VFD) of purified water system, thereby the pressure can be maintained throughout the washing cycle.
The impact force of jet depends on the velocity of fluid at exit of nozzle as the distance of vial surface is more , the impinging velocity will decrease i.e. the impact force will decrease. To maintain same impact force for different sizes of vial, the pressure is getting converted into velocity. So to maintain same velocity impact, pressure requirements are programmed between 5-6 Kg/cm2. This pressure is required for normal vial washing. Thereby critical parameter required for vial washing is taken care of. WFI washing, temperature is critical parameter. Temperature should be 80 ºC, even though the loop maintains 80ºC, the buffer tank provided in vial washing machine temperature drops. Thereby quality washing can be a problem. Hence, special jacket heaters with controller keep water at 80oC by which temperature of WFI is maintain throughout. WFI tank should have insulation
Cleaning time for different sizes of vial will be different which will be found by performance qualification. These timings are set for washing by proving of ON/OFF timers with various stages of washing. Feedback of timer is taken to control the next step of PLC. Thereby all critical parameters are online monitored corrected (if any deviation) with goal of ensuring final quality.
The recycled water which is used for cleaning vials in intermediate steps for economical reason can be checked for conductivity (the different effective values can be taken which come out during performance qualification) which can be taken as limits beyond which it trigger an alarm and that tank will be filled with WFI, thereby quality of recirculated water can be controlled. Thereby all critical parameters will be controlled and this experiment is done on linear vial washing as well as circular vial washing machine.
(The authors are Chief Engineer and QA Executive of VHB Medisciences)