1.0 Purpose: The standard procedure; Aseptic Handling, Operation and Aseptic Connection apply to the aseptic technique which refers to the system of working while performing procedures that are to be carried out under sterile conditions. The aim is to prevent microbial contamination while media simulation, manufacturing products, blending procedures, and aseptic connection.
2.0 Applicable: This Standard Operating Procedure is applicable during dispensing of approved active raw material (ARM) and raw material; filtration of solutions required for the formulation of the batch; aseptic connection carried out during addition of solution to blending vessel and filling of PFS/ vials and all other operation requiring aseptic handling at pharmaceutical.
3.0 Responsibility: 3.1 officer/Executive & line coordinator shall execute this SOP.
3.2 Department head to ensure overall compliance adhere to this procedure.
3.3 Head-Quality Assurance shall be responsible for ensuring compliance with this SOP.
4.1 Note: Ensure that only authorized personnel should have access to the controlled area.
4.2 Ensure personnel entering the controlled area are wearing the appropriate sterile protective clothing and gowning in an appropriate manner as per Gowning Procedure.
4.3 Personnel entering the controlled area should be in a good hygienic state and should not have any open wounds or cuts and physically fit to carry out the operations.
4.4 Check the validation and calibration status of the LAF before the start of the operation. The pressure differential of the LAF should be within the range so as to ensure that all the sterile activities are done under positive pressure.
4.5 Ensure the cleaning status of the area & LAF prior to dispensing & take line clearance for the start of dispensing process.
4.6 Before the start of dispensing of active raw material check all the materials used for dispensing are present and sterilized as per the SOP “packing of material for sterilization“.
4.7 Environmental monitoring testing should be carried out of the area and operator during sterile operation including viable and non-viable particle count, and surface swabs.
4.8 Appropriate technique to be used for the transfer of sterile packed material to the clean room environments.
4.9 Material transfer from the uncontrolled area to the controlled area should be avoided. It should be surface sterilized by mopping with 70% IPA if required to be transferred to a controlled area.
Related: Preparation of 70% IPA
4.10 Aseptic technique General considerations:
• Vertical laminar airflow should be used for all those connections where the working place is horizontal.
• Horizontal laminar air flow should be used for all those connections where the working place is vertical.
4.10.1 Wipe all the internal working surfaces of the cabinet with 70 % IPA.
4.10.2 Spay gloves with 70 % IPA at the start and then periodically throughout the sterile handling operation.
4.10.3 Sterilized packed material should be surface wiped with 70% IPA before taking inside the Laminar Air Flow.
4.10.4 While carrying out the sterile connection to the glass bottles, hold the sterile end of the tubing/ SS siphon to avoid direct contact with it.
4.10.5 Sufficient quantity of the required material should be present inside the working area.
4.10.6 Person carrying out the aseptic handling should not take out his hands outside the LAF. Material required for the operation should be provided by the supporting staff.
4.10.7 Take the material one by one so that airflow inside the cabinet is not disturbed.
4.10.8 Do not use any materials that have been dropped outside the cabinet.
4.10.9 Remove the waste from the cabinet and transfer it to the waste bins.
4.10.10 At the end of the session carry out the cleaning of the cabinet as per the given SOP and the area as per SOP ” Area cleaning“.
4.10.11 The tank under formulation should be under LAF cover while doing an aseptic connection.
4.10.12 All the formulation tanks should be under positive air pressure of sterile air during the incubation period.
4.11 Aseptic handling during formulation Tank connection:
4.11.1 All the connections should be done under the LAF cover.
4.11.2 Clean the outer surface of the nozzle/ sampling port where a connection is to be done. Before connecting the tube / sterile end of the connection to the nozzle of a tank in the headspace of the addition port, flush the nozzle with sterile air from inside the tank for 2-3 seconds and then connect the tube/ sterile end of the connection.
4.11.3 Sterilization of the sampling port should be ensured before making any connection.
4.11.4 Attach a sterile side of the vent filter to the nozzle before and after sampling.
4.12 Aseptic handling during connection of bottles:
4.12.1 Any sample which is to be collected in closed condition should be collected in a bottle with a siphon assembly.
4.12.2 The siphon assembly should have a straight connector in the tube from which the sample will be flowing in the bottles.
4.12.3 One end of the tube connected to the straight connector should be loosened without touching the inner & outer sides of the straight connector and remove the tube.
4.12.4 For addition to the bottle, the ‘Y’ connection should be used in the addition port of the siphon assembly. Step 4.12.3 should be repeated for addition from one connection of the ‘Y’ portion with one point closed with an arterial clamp.
4.13 Line-to-line connection:
4.13.1 For connecting two lines either a ‘Y’ connection or a straight connector assembly should be used.
4.14 Aseptic handling during filling of formulated bulks:
4.14.1 Carry out the aseptic handling while fixing of Piston pump and Needles during the filling of formulated bulk.
4.15 Aseptic handling during media fill activities:
4.15.1 Aseptic handling during media fill should be done for respective operations as defined in point no. 4.1 to 4.14.
4.16 The no. of aseptic connections for each activity should be done as defined during the media simulation activities.
SOP: Standard Operating Procedure
QA: Quality Assurance
ID No. : Identification number
LAF: Laminar air flow
VLAF: Vertical laminar airflow
IPA: Isopropyl alcohol