A Digital HPLC Flowmeter Makes System Calibration Easier

Meeting tough FDA standards for HPLC system IQ OQ PQ validation as well as ongoing PV (performance verification) calls for properly installed, calibrated, and maintained equipment. A digital liquid hplc flowmeter such as the FlowCal 5000 is proven to be a convenient and accurate tool to calibrate HPLC pump flow rates, simplifying the calibration and validation procedures. Pump flow rates from 25 mL/min down to as low as 0.05 ml/min can be measured with an accuracy of ± 1 % of the flow rate. This type of tool saves time and labor compared with using a timer while manually collecting the effluent for measurement by weight or volume. In addition, the data collected is independent of operator technique and is therefore both more accurate and more precise.

When checking into digital HPLC flow meters laboratory technicians should determine if the models being considered will deliver accurate data at the flow rates typically used and have a traceable calibration certificate. In addition, the flow meter must be compatible with all brands of HPLC systems used in the lab. All wetted parts should be able to safely handle common HPLC solvents. The flow meter should have an appropriate interface such as an RS232 port for connection to a printer or PC for printing and archiving in accordance with good laboratory practices (GLP).

Installation and Maintenance

Although they are highly accurate, digital flow meter performance is adversely affected by improper mounting and poor maintenance. Citing the FlowCal 5000 as an example, several mounting configurations are available and supported by hardware supplied with the unit. Regardless of the mounting method, the unit must be within 10 degrees of vertical and with suitable space available for placing the collection vessel below the flow meter. Wall mounting, free-standing and stack system options are the most commonly used although in some instances an adapter kit can be employed to mount the unit on wide necked reagent bottles.

While GLP requires annual recalibration, flow meter accuracy can quickly deteriorate with improper use.

For example, dirty sensing tubes can trap bubbles and create false readings. In cases where bubbles are observed during operation the quick remedy is turning the meter off and letting it drain, then return it to operation. This suggests that the number one rule is to keep the sensing tube clean using supplied equipment for this important function. Another good practice is to institute a standard operating procedure specifying that flow meters be cleaned every two weeks when they are in constant use. Flow meters such as the FlowCal 5000 are shipped with a cleaning kit and directions for carrying out this function, a procedure that is usually completed within 15 to 30 minutes. If flow meters are not to be used over a week or more they should be flushed with ethanol to prevent algae growth.

Record Keeping

One method to archive data in order to properly respond to FDA inquiries involves connecting the flow meter to a PC using the RS-232 interface. This allows operators to record flow meter readings electronically, such as in an Excel document using the Windows HyperTerminal program. The process collects data and displays it using HyperTerminl.exe, copies it on a clipboard and pastes it into Excel for analysis. Step-by-step details for this process are available from FlowCal equipment providers such as Tovatech.

PROCEDURE FOR CLEANING AND SANTIZATION OF SAMPLING ROOM

• PROCEDURE:

o        PROCEDURE FOR CLEANING AND SANTIZATION OF SAMPLING ROOM

·         Procedure for preparation of cleaning and sanitizing solution, schedule of disinfectants and record of consumption of Teepol solution and Sanitization solution Refer Annexure – 1 & 2.

·         For Sanitisation, Mop / clean with wet duster, soaked with appropriate disinfectant solution. Allow to air dry.

After Sanitization update the Sanitization record for sampling room

Two-Bucket System  (for Cleaning): 

i)        Fill the required quantity of 0.1% Teepol solution in a bucket and DM Water in another bucket

ii)       Dip the mop stick in Teepol solution bucket and squeeze to remove excess solution. 

iii)     Apply the mop stick on the surface of the area to be cleaned.  Squeeze the mop.

iv)     Dip the used mop stick in another bucket containing DM water.  Wash the mop stick in DM water and repeat from step No. ii.

Two-Bucket System  (for Sanitisation): 

i)        Fill the required quantity of Appropriate Sanitization solution in one bucket and DM Water in another bucket

ii)       Dip the mop stick in Sanitization solution bucket and squeeze to remove excess solution. 

iii)     Apply the mop stick on the surface of the area to be Sanitised 

iv)     Dip the used mop stick in another bucket containing DM water.  Wash the mop stick in DM water, squeeze the mop and repeat from step No. ii.

·         Floor

·         Clean the entire floor by using Vacuum cleaner. Then mop the floor by using 0.1% Teepol solution followed by mopping with D.M. Water (2 bucket system). Allow the floor to air dry.

·         Door / Walls / Partitions / Cupboard / Ceiling

·         Mop with 0.1% Teepol solution followed by wet mopping (soaked in DM Water).

·         Clean the glasses (from Inside & Outside) by using Colin solution followed by wiping with dry duster. Allow it to air dry.

·         Sampling Devices / Utensils

·         Wash the sampling devices with plenty of DM water by using scrubber / nylon brush. Then wash and clean thoroughly with 0.1% Teepol solution and DM water and then with Isopropyl Alcohol and finally rinse thoroughly with DM water.  Ensure no traces of material are visible. Wipe it with dry lint free duster and dry it with IR Drier. Keep it in the sampling room and place it in laminated cupboard/ S.S. hanger with individual polybag with “CLEANED” status label for every utensil.

·         Balance

·         Wipe the platform of balance with damp duster soaked in 0.1% Teepol solution to remove deposited dust followed by wet duster soaked in DM Water. Allow it to air dry. Also clean the bottom side of balance by applying same procedure. Clean the display board gently with dry duster.

·         Reverse Laminar Air Flow

·         Clean the following area with the vacuum cleaner followed by wet mopping: -

a.       Ceiling of  LAF, all along the filters and grooves

b.       Front panel of  LAF

c.       Side panel of  LAF

d.       PVC Curtains.

·         Periodical cleaning of Pre-filters of LAF shall be cleaned by Engineering Department

·         Pallets & Trolley:

·         Wipe the surfaces & all sides of pallet / trolley with damp duster soaked in 0.1% Teepol solution to remove deposited dust followed by wet duster soaked in DM Water. Allow it to air dry. Also clean the bottom side of pallet & trolley by applying same procedure.

·         Fixed equipments

·         Wash the fixed equipments with damp duster (soaked in 0.1% Teepol solution) first and then with wet duster (soaked in DM water). Allow to air dry.

·         Tube lights & fixtures

·         Switch ‘OFF’ the electrical fixtures and wipe the surface thoroughly with damp duster (soaked in 0.1% Teepol solution) first and then with wet duster (soaked in DM water). Allow to air dry.

·         S. S. Sink / Drain Trap

·         Wash the S. S. Sink& Drain trap with 0.1% Teepol solution first and then with DM water at the end of the day’s operations.  After cleaning, disinfect the S.S. Sink / drain trap by using double concentration of disinfectant. Fill the drain trap with appropriate disinfectant solution as per schedule given below and keep it overnight.

Disinfectant solution preparation for S.S. Sink / Drain

Sr. No.	Disinfectant	Concentration	Preparation	Schedule
1	Dettol	2.5%	Take 125 ml of Savlon and make up the volume up to 2500 ml with DM water.	1st week
2	Iteol	1.0%	Take 125 ml of Dettol and make up the volume up to 2500 ml with DM water.	2nd week
3	Savlon	1.0%	Take 50 ml of Combatan DS and make up the volume up to 2500 ml with DM water.	3rd week
4	Virosil	5.0%	Take 100 ml of Triple 256 and make up the volume up to 2500 ml with DM water.	4th week

o        Put proper status label on the container of the Cleaning solution / disinfectant solution (Refer Annexure- 1)

o        AHU Grills (Supply & Return Duct)

o        Clean all the AHU grills with vacuum cleaner to remove dirt and deposits. Then wipe it with damp duster (soaked in 0.1% Teepol solution) first and then with wet duster (soaked in DM water). Allow to air dry.

o        PVC Curtain

o        Clean the PVC curtain with vacuum cleaner.

o        Clean it with wet duster soaked with 0.1% Teepol solution manually followed by damp duster soaked in D.M. Water. Allow it to air dry.

 

o        Vacuum Cleaner

o        To clean the Vacuum cleaner for its dust collection and its interior and exterior surfaces, the following steps are to be carried out:  

o        Move the Vacuum cleaner to the de-dusting area.

o        Open the lid of the Vacuum cleaner carefully.

o        Dismantle the disposable bag carefully from the vacuum cleaner, cable tie it, then transfer it into a polythene bag and again cable it.

o        The dust collected in the polythene bag shall be sent for its disposal to scrap yard.

o        Clean the lid, outer surface and pipe of vacuum cleaner, with wet duster soaked in 0.1% Teepol solution followed by damp duster soaked in D.M. water. Allow it to air dry.

o        Precaution should be taken to avoid water splashing on electrical points.

o        Place a new disposable dust collector bag to its position in side the container of Vacuum cleaner.

o        Put the lid back to its position & tighten with the clamps, which are attached there.

o        Move the Vacuum cleaner to its designated place.

o        Spillage of Materials

o        In case of any spillage of material, cleaning must be done immediately once noticed without awaiting for the schedule of cleaning, as follows:

·         Collect the material in polythene bag and label it properly.

·         Clean and sanitize the affected surface (floor, wall, equipments etc.)

·            Report Head of the Department and Quality Assurance (QA) about spillage and further necessary action for disposition of spilled material.

·         Waste Collection & Disposal in Sampling Room

·         House Keeping Supervisor shall arrange to collect the waste from different locations within the sampling room. 

·         Collect all the wastes in a polythene bag and cable tie it properly.

·         All the collected polythene bags shall be transferred to scrap yard for disposal.

·         The concerned sampling room personnel shall ensure, the labels on empty containers and           solvent / liquid drums shall be defaced before disposal.

·         House keeping Supervisor shall ensure, that collected waste from all places within the sampling room every day and disposal.

·         Any abnormality observed shall be investigated along with the Head of the department and corrective steps shall be initiated.

·         FREQUENCY FOR CLEANING & SANITISATION:

·         Follow the given below schedule for cleaning & Sanitization.

           

Sr. No.	Cleaning Points	Frequency for Cleaning	Frequency for Sanitization
Daily Cleaning & Sanitisation
1.	Floor	Daily once & after each sampling	End of the Days operation
2.	Pallets & Trolley	Daily once & after each sampling	End of the Days operation
3.	Sampling devices & Utensils	Daily once & after each sampling	End of the Days operation
4.	Balances & Fixed equipments	Daily once & after each sampling	End of the Days operation
5.	LAF	Daily once & after each sampling	End of the Days operation
6.	PVC curtain	Daily once & after each sampling	End of the Days operation
7.	S.S. Sink & Drain Trap	End of the Days operation	End of the Days operation
Weekly Cleaning & Sanitisation
1.	Doors	Weekly & on need basis	Weekly & on need basis
2.	Vacuum cleaner	Weekly & on need basis	Weekly & on need basis
3.	Walls	Weekly & on need basis	Weekly & on need basis
4.	Ceiling	Weekly & on need basis	Weekly & on need basis
5.	AHU Grills (Supply & Return Air Duct)	Weekly & on need basis	Weekly & on need basis
6.	Tube lights & Fixtures	Weekly & on need basis	Weekly & on need basis