Sterile manipulation techniques and medium simulation
The following are the points for attention related to aseptic operation technology and medium simulation filling for your reference:
Bags containing filling equipment (for example filling needles) were opened by tearing the bag which presented a risk of introducing fibres to the equipment/line and subsequently the product.
Bags containing dispensing equipment (e.g. dispensing needles) are opened by tearing, which poses a risk of fiber contamination to the equipment/production line and products.
The innermost bag containing the stopper track was damaged prior to loading into the filling line which presented a risk of fibres being transferred to stoppers and subsequently the product.
The innermost bag containing the rubber stopper track is torn before being placed in the dispensing line, which poses a risk of fiber contamination to the rubber stopper and the product.
There was insufficient evidence documented to demonstrate that the number of aseptic connections after sterilisation had been minimised.
There is insufficient documentary evidence to prove that the amount of sterile contamination after sterilization has been minimized.
There is no sanitisation of hands after each individual garment is touched and put on.
Employees did not remove their hands after touching and putting on clothes
Operators wore outdoor clothes under aseptic gowns in the Grade B zone.
Class B operators wear outdoor clothing and wear sterile clothing.
Gowning procedures required operators to remove their shoes when entering grade D and C areas. The nature of the foot coverings used would not prevent microbial contamination passing from the operator’s feet onto the clean room floors.
The changing procedure requires employees to remove their shoes when entering Class D and C areas. However, the foot covers used are not made to prevent microbial contamination from employees' feet onto the clean area floor.
In the main office of Block B manufacturing operators appeared to be allowed to wear flip flops, shoes with over-shoes or socks.
In the B-block office, employees are apparently allowed to wear flip-flops, shoe covers and socks.
During gowning into the manufacturing area the bench was not sanitised prior to sitting on it.
During changing into the production area, the benches were not sterilized before being seated.
While donning sterile gloves prior to entering a grade B area an operator was observed touching the outside of sterile gloves on several occasions.
While wearing a B-grade sterile suit, an employee was found to have touched the outside of the suit several times.
Only the surfaces which are touched by the operator or are in contact with components on the compounder are sanitised before manufacture, rather than all surfaces as expected.
The mixer is disinfected before production only on surfaces that are touched by employees or that come into contact with the product, rather than on all surfaces as required.
The hooks used for hanging bottles and bags were not cleaned appropriately as they were held together with the operator’s hand and sanitised as a group rather than individually to ensure that all surfaces are sanitised.
The hooks used to hang the bottles and bags were not properly cleaned because they were held in the hands of the operator and disinfected in groups, rather than one by one, to ensure that all surfaces were disinfected.
The wipes used for sanitisation did not appear to be wetted sufficiently as only the area in the centre appeared to be wet rather than the whole area to ensure effective surface coverage.
The sanitizing rag doesn't look moist enough, only the middle part is wet, rather than the entire area to ensure effective surface coverage.
A gap between the hood and mask was seen for some operators resulting in exposed skin at the side of the face with the potential for product contamination especially when working in a LAF cabinet.
Some employees have exposed skin at the edges of their faces visible in the gaps of their hats and masks, leading to the potential for product contamination, especially when working within a laminar flow hood.
There are currently no drawings or diagrams which define the positioning of components in the laminar air flow (LAF) cabinet or isolators to ensure that unidirectional airflow is maintained.
There are no diagrams or diagrams defining the position of the sub-packaged components within the laminar flow hood or isolator to ensure that unidirectional flow is maintained.
Operators do not wear goggles even though compounding is conducted in an open LAF cabinet and ampoules may be used in the compounding process which is an open rather than a closed manipulation.
Employees did not wear blindfolds, despite the fact that they were dispensing in an open laminar flow hood, and the dispensing process may have used ampoules, which is an open rather than closed operation.
Sanitised rather than sterile googles were permitted to be worn in EU Grade B areaswww.gbw.org.cn.
The goggles worn at Class B are not sterilized, but only sterilized.
The sequence of installing the filling needles and connecting tubing did not minimise contamination risks; the sequence used resulted in contact between fingers of the restricted access barrier system (RABS) glove and the exposed tops of needles on several occasions.
The connection process between the dispensing needle and the hose failed to minimize the risk of contamination; resulting in repeated contact between the finger of the RABS glove and the exposed end of the needle. Goggles worn at Class B are not sterilized, only sterilized.
The investigation into the media fill failure did not include a full chronology of events and did not include full details of all the corrective actions taken at each event. e.g. operator assessments, re-training of operators.
The investigation of the simulated packaging failure did not include a list of incidents, nor did it include full details of the corrective actions taken for each incident, such as operator evaluation, operator retraining, etc.
A sample of the contaminated bag was not kept and therefore the contaminating organism was not able to be identified to species level which would have aided any investigation.
No contaminated samples were retained, and the contaminated microorganisms were not identified at a specific level that could assist in the investigation.
The media fill batch size was 60 bags, however these were not labelled in the order of filling and therefore the position of the contaminated container could not be determined.
The batch of simulated media filling was 60 bags, but they were not labeled in the order of dispensing, making it impossible to determine when the contaminated sample occurred.
The media fill and process validation studies did not capture the full complexity of the aseptic manufacturing processes used and therefore did not closely imitate the production process and were not representative of worst case.
mediumThe simulated filling and process validation studies did not capture the full details of the aseptic production process used, making it impossible to closely simulate the production process and not representative of worst-case conditions.
