What Are the Influence Factors of Filling Precision In the Filling System?

1.What Is the Filling Precision?

Filling Precision - Sourced: assetpackaging

The precision control of filling volume is one of the important indexes of the filling machine. When conducting PQ (Performance Qualification) of filling machines, the precision of the filling machine should be confirmed, in order to ensure the operating status of the packaging line meets the requirements of the Good Manufacturing Practice for Drugs (2010 Revision) and production needs, ensuring that the filling volume meets the requirements.

Aseptic filling is not only to meet the strict hygiene requirements, but also to complete the liquid filling with high quantitative control precision to achieve the required filling precision. The precision of a filling machine is not only related to its own specifications, quality, and performance, but also to external interference factors.

2.What Are the the Influence Factors of Filling Precision?

The precision of the filling system is influenced by both systematic and random errors. Systematic error arises when performing repeated measurements on the same item under specific conditions, and it exhibits a discernible pattern. While this type of error can be controlled or corrected, it typically cannot be mitigated solely through repeated measurements.

On the other hand, random error stems from a variety of unpredictable and incidental factors. During multiple measurements, the magnitude and direction of random errors change unsympathetically, yet they tend to conform to statistical principles. This means that the occurrence of random errors cannot be anticipated, but their behavior can be analyzed and understood through statistical methods.

3.What Are the Systematic Error of Filling Precision?

(1) The Setting of Filling System

Penicillin Vial - Sourced: fresenius-kabi

The whole filling process is controlled by the filling system. Before filling, the formula should be corrected and downloaded, and the target filling capacity, warning value and correction value can be set.

Meanwhile, the parameters such as pump speed, suction, the distance between the filling needle and the bottom of the penicillin vial as well as the detachment distance are also included in the formula. These parameters are of great significance to the filling process and product quality.

Filling Needle - Sourced: americanlaboratory

In the production process, accurately injecting the drugs into the vials involves the acceleration and deceleration of the pump, as well as the movement trajectory of the filling needle.

If the needle of filling needle is relatively far away the bottom of the bottle at this stage, the liquid receives a downward pump to the force coupled with its own gravity. When the liquid comes into contact with the bottom of the vial, it will produce a reaction force, which will lead to liquid splashing, and even the liquid may fly out of the vial, and stick to the filling needle.

(2) The Setting of Online Weighing System

Online weighing is one of the important means for controlling the in-process IPC of aseptic filling equipment. The hardware of the online weighing control system mainly includes IPC weighing, wireless communication module, server, high-precision scale, level conversion module. The weighing module should be regularly confirmed and calibrated, and its performance will have a crucial impact on the weighing results.

Plunger Pump - Sourced: mpaitaly

Usually, the filling precision of a plunger pump is relatively stable, but uncertain factors such as the increase of bubbles and liquid level changes in the liquid drug bag, long-term wear of the hose connecting the filling pump, and the operating speed of the liquid drug filling machine can lead to the inaccurate filling amount of the plunger pump after running for a period of time.

If the program correction parameters are executed well, and the piston displacement of the plunger pump can be stabilized within a reasonable range after adjustment, the precise filling of the plunger pump will be achieved. This can ensure the precise filling of each batch of drugs.

(3) The Wear of Filling Pump

Metallic Materials - Sourced: refractorymetal

In the daily production process, if non-metallic materials are not selected for aseptic filling equipment, the pump rod comes into contact with the metal material during sterilization, and the metal material stick to the pump rod, which will easily cause pump rod wear, poor airtightness, and bubbles during the filling process.

Bubble - Sourced: airproducts

At the same time, when cleaning the packaging equipment after each production shift, when assembling the plunger pump and filling needle, mixing occurs when the pump body and pump rod are not assembled according to the label, the gap between the pump body is not matched, and the placement of the needle and filling pump collides, which can easily cause wear on the pump rod or filling needle, resulting in poor airtightness, bubbles or dripping during the filling process. The longer the filling pump is used, the greater the wear and tear will be.

(4) The Size and Shape of Filling Needle

Selection of inner diameter of filling needle

Inner Diameter of Filling Needle - Sourced: mpaitaly

The inner diameter of the needle is matched with the inner diameter of the dosage pipeline to avoid the increase of resistance caused by a small inner diameter of the needle, resulting in a small flow rate and expansion at the end of the hose where the needle is connected. During the intermittent filling process, due to the natural resetting of the expansion part, the medicine liquid is squeezed out of the needle, causing liquid dripping; At the same time, it is also necessary to avoid excessive needle inner diameter, which may cause natural dripping of the medication at the end.

Selection of filling needle shape

Filling Needle Shape - Sourced: esiultrapure

In actual production, commonly used flat mouth needles and trident needles are often chosen. The advantage of flat mouth needles is that they are easy to manufacture and have good suction effects. The disadvantage is that the impact force of flat mouth needles is large, which can cause liquid splashing during the filling process.

The advantage of trident needles is that the filling pressure is small, which can effectively prevent liquid splashing. However, the disadvantage is that the processing of the needle mouth is relatively difficult. If the opening is uneven, it can cause liquid dripping and hanging, resulting in natural dripping of the end liquid and affecting the filling precision.

4.What Are the Random Error of Filling Precision?

(1) Pipeline Length and Hose Deformation

Filling Pipeline - Sourced: packagingdigest

A complete filling pipeline in the penicillin vial filling line includes: filling bag (buffer tank), filling pipeline, filling needle, plunger pump and other structural components. When installing the pipeline system, the swing arm will drive the hose to swing back and forth when the length of the silicone tube is too long, causing excessive shaking and affecting the slight shaking of the filling needle, resulting in dripping.

And then, the shape of the hose connected to the filling needle changes. As the frequency and time of use of the hose increase, the circumference of the hose increases, the wall thickness becomes thinner, and the inner diameter increases due to compression, resulting in an increase in flow rate and higher filling precision.

(2) Changes in Liquid Level and Pressure

The installation positions of the storage tank, dispenser, filling pump, and needle holder, have a significant height difference compared to the installation position of the filling pump. If the filling pump is subjected to too much pressure from the liquid, it is easy to cause needle dripping.

Liquid Pressure - Sourced: atmo.arizona

Changes in inlet pressure. As the liquid level at the filling inlet decreases, the inlet pressure decreases and the flow rate decreases.

According to the Poiseuille formula, it can be concluded that:

Q=ΔPπd⁴ /（128μL） (1)

In the formula: Q - volumetric flow rate, m3/s; ΔP - pressure difference, Pa; d - pipeline inner diameter, m; L - pipeline length, m; μ - dynamic viscosity coefficient, Pa·s.

During the process from the beginning to the end of production, the type of liquid, the diameter of the pipeline, and the length of the pipeline cannot be changed. During the filling process, the liquid level in the storage tank will decrease, resulting in a decrease in inlet pressure and flow rate.

The average flow rate also decreases, resulting in a smaller filling volume and affecting filling precision.

(3) Liquid Characteristics

Liquid Drug - Sourced: Bruker

The viscosity of liquid is the main factor affecting the filling precision in liquid properties.

According to the formula, fluid viscosity   v=μ·ρ  (2)

In the formula: μ- dynamic viscosity coefficient, Pa·s; ρ - density of liquid, kg/m3.

The combination of formulas ①+② yields Q=ΔPπd⁴ρ/（128μL), which means that from the beginning to the end of production, the density of the liquid, the diameter of the pipeline, and the length of the pipeline cannot be changed.

The viscosity of the liquid will affect the dynamic viscosity coefficient, thereby affecting the flow rate of the pipeline system and causing changes in flow rate, resulting in differences in filling quantity and thus affecting filling precision. And the viscosity of the liquid can also affect its fluidity.

(4) Intervention Factors

Connect the pipeline

Connect the Pipeline - Sourced: moperry

In daily production, the installation positions of buffer bottles, separators, plunger pumps, and needle racks can have certain impacts. The height difference between the position of the storage tank and the installation position of the plunger pump is too large, which can lead to needle dripping. Loosening during assembly and connection of the filling pump, filling needle, and hose interface by the operator before filling can also result in bubbles or dripping.

Additionally, when venting the filling pipeline, the operator fails to completely remove all air from the pipeline, resulting in a small amount of bubbles in the pipeline. This can also lead to differences in filling volume and affect filling precision during the filling process.

Operation failure

Operating Failure - Sourced: eci

Taking the penicillin vial filling system as an example: The online weighing system uses a robotic arm to load the vials in both the pre and post filling states into high-precision IPC weighing each time. The controller compares and determines whether the net weight of each vial exceeds the limit.

In the daily production process, if the filling machine encounters operational failures at the vial feeding station and weighing station, such as vial explosion, glass debris from penicillin vials will splash onto the IPC weighing station. If the operator does not clean thoroughly, it will affect subsequent weighing and thus affect filling precision.

Differential pressure fluctuations

Excessive or insufficient wind pressure inside a laminar flow isolator can also affect the value of online weighing. In aseptic filling processes, the online weighing system is usually installed in an A-level environment, inside a laminar flow fan protective cover. If the frequency of the fan is too high, it will cause damage and impact to the wind pressure environment.

The fluctuation of the laminar pressure difference in the isolator will become larger, which will have a greater impact on the online weighing value of the scale. This will cause the value of the online weighing to be higher, resulting in errors in the online correction of the displacement curve of the filling pump by the controller during the filling curve analysis, which will affect the online adjustment of the filling amount and affect the filling precision.

The suction generated by static electricity

Static Electricity - Sourced: Sofamel

The magnitude of static electricity can also affect the value of online weighing systems. The penicillin vial has just undergone cleaning and high-temperature sterilization process. If the glass body of the drying vial is “rubbed” and the protective cover is blown vertically downwards by laminar airflow, it is easy to generate charges on the surface. The generated charges can be positive or negative, causing attraction or repulsion, which may result in the weighing display value being greater than or less than the actual weight.

The humidity in the filling room and the operation of the filling machine, including the online weighing of components and the rotation of molds, can generate static electricity. This leads to errors in the online correction of the displacement curve of the filling pump by the controller during the filling curve analysis, which affects the online adjustment of the filling amount and leads to filling precision.

The impact of vibration

Vibration - Sourced: gisellebaumet

The impact of vibration on high-precision weighing is self-evident, and equipment with mechanical motion is more difficult to avoid its own vibration. Especially in the area around the online weighing of the cork pot and corking station on the penicillin vial filling line.

At the same time, you should consider the insufficient rigidity of the filling servo motor itself, slight shaking of the plunger pump in the later stage of filling will have an adverse impact on the weighing results, thereby affecting quality control. To ensure accurate weighing of filling equipment, it is necessary to isolate or improve predictable vibration sources as much as possible.

(5) The Setting of Suction

The Setting of Suction - Sourced: Universal Packaging

The suction setting in the formula is also an important factor affecting the filling precision. Taking the rotary plunger pump of the penicillin vial filling line as an example, during forward rotation, the liquid is sucked into the pump body, compressed, and then discharged to the extreme, while during reverse rotation, the opposite is true.

There is a close relationship between the suction volume and the deceleration of the filling pump. However, the suction volume should not be set too large or too small. If the downtime is too long, it can cause the liquid to dry and form a drying layer near the needle, thereby affecting the filling precision.

Conclusion

For the controllable factors that affect the filling precision in the filling machine system, there are relatively perfect control measures at present. However, many factors still need to be considered. Nowadays, the liquid filling machine industry will continue to promote refined development, improve the precision, stability, and reliability of filling machines. If you want to know more information about liquid filling machine, you can contact Aipak at any time.