การศึกษาเทคโนโลยีที่เหมาะกับการตรวจสอบรอยรั่ว Leak Detection ของ 1ml and 2.25ml Albumin Prefilled Syringe

Tags: leak detection, albumin, prefilled syringe, pfs, รอยรั่ว, ตรวจสอบ

Leak Detection of 1ml and 2.25ml Albumin Prefilled Syringe (PFS)

Container Closure Integrity (CCI) สามารถทดสอบได้โดยใช้วิธีการทดสอบที่หลากหลาย ซึ่งไม่สามารถตรวจจับรอยรั่วในแพ็คเกจได้จากวิธีการทดสอบที่กำหนดใน USP 1207 ซึ่ง 2 วิธีสำหรับ Container Closure Integrity (CCI) ที่ใช้กันทั่วไปสำหรับผลิตภัณฑ์ Albumin (อัลบูมิน) คือการ Vacuum Decay และการตรวจจับการรั่วไหลแบบแรงดันสูง (HVLD) โดยการศึกษาต่อไปนี้มุ่งเน้นไปที่การทดสอบ Container Closure Integrity (CCI) โดยใช้เทคโนโลยี MicroCurrent HVLD และระบุข้อจำกัดของการตรวจสอบรอยรั่วแบบ Vacuum Decay ของ Albumin (อัลบูมิน) และผลกระทบของการอุดตันของผลิตภัณฑ์

การศึกษากับหลอดแก้วขนาด 1 มล. และ 2.25 มล. ที่ประกอบด้วยน้ำหรืออัลบูมิน (Albumin) ตัวอย่างที่ทดสอบประกอบด้วยชุดของตัวควบคุมเชิงลบ (non-leakers) และตัวควบคุมเชิงบวกที่ได้รับการรับรอง (leakers) วิธีการทดสอบ Vacuum Decay ที่เรานำมาใช้ใน Container Closure Integrity (CCI) ในการตรวจจับการควบคุมในเชิงบวกที่มีน้ำ แสดงความน่าจะเป็นที่ลดลง และความสามารถในการตรวจจับการควบคุมในเชิงบวกของ Albumin เป็นศูนย์ ชุดตัวอย่างเดียวกันภายใต้เทคโนโลยี E-Scan MicroCurrent HVLD

ซึ่งแสดงให้เห็นว่าเทคโนโลยี HVLD สามารถตรวจจับได้เกือบ 100% ของผลิตภัณฑ์ที่มีการเติมน้ำหรืออัลบูมิน (Albumin) ในขณะที่ vacuum decay ให้ผลไม่ค่อยดีนัก เนื่องจากรอยรั่วขนาดเล็กอาจถูกอุดด้วยตัวอย่างสินค้าทำให้เซนเซอร์ไม่สามารถตรวจจับได้

Vacuum Decay vs. HVLDmc Test Methods.

Container Closure Integrity (Container Closure Integrity (CCI)) can be challenged using various test methods, not all of which are equally capable of detecting leaks in the package. Of the test methods listed as ‘deterministic’ in USP 1207, two methods for Container Closure Integrity (CCI) commonly used for parenteral products are Vacuum Decay and High Voltage Leak Detection (HVLD). The following study focuses on Container Closure Integrity (CCI) testing using the MicroCurrent HVLD technology, and tangentially addresses limitations of Vacuum Decay with protein filled products, and their clogging effects.

The study was done with 1 mL and 2.25 ml glass syringes containing either water or Albumin. The samples tested included a series of negative controls (non-leakers) and certified positive controls (leakers). The Vacuum Decay Container Closure Integrity (CCI) test method shows a reduced probability in detecting positive controls containing water, and zero capability to detect positive controls with Albumin. The same sample set subjected to the E-Scan MicroCurrent HVLD technology showed nearly 100% detectability of either water or Albumin filled products.

The study addresses the common concern that Vacuum Decay is not a suitable test solution for detecting micro leaks in parenteral containers if the product contains large molecule or proteinaceous liquids. The data further supports and confirms that a wide range of liquid parenteral products can reliably be tested for Container Closure Integrity (CCI) using MicroCurrent HVLD to detect micro leaks in the critical leak range.

V – High voltage source
R – Electric resistance of the product
C1 – Capacitor 1: Glass between the inspection electrode and product
C2– Capacitor 2: Glass between the detection electrode and product
I1 – current produced when product container is sealed
I2 – current produced when product container is defective

Feasibility Study – Samples Tested

– 1 ml and 2.25 ml syringes
– Filled with H2O and Albumin (17.5%)

Summary of Results (negative controls)

– All negative samples are identified as such with both VeriPac® and E-Scan® instruments
– No false positives

Summary of Results (positive controls)

– No Albumin prefilled positive sample could be detected with Vacuum Decay
– E-Scan® identified all positive samples except one

Test Results Summary 1ml Prefilled Syringe (PFS) w/ Water and Albumin

Conclusion

The identical vacuum decay test method showed very similar results for negative control samples (good syringes) between the 1 ml and 2.25 ml syringes, with a range in absolute results from 3.8 to 4.2mbar and differential readings ranging from 10.7 to 13.9. When introducing positive (defects) controls with pure water, a discrepancy between detection of positive controls appears between the 1 ml and 2.25 ml syringe. While the vacuum test method is generally more capable of detecting samples with pure water content, the results show a greater detection capability with 1 ml syringes over the 2.25 ml syringes, all other things being equal. The discrepancy between 1 ml and 2.25 ml syringes in the ability to detect the positive controls extends into the Albumin results, with the 1 ml syringe having a higher detection capability across all defect sizes for both water and Albumin.

The discrepancy in detection capability may be a result of defect geometry and flow rate. The positive controls are manufactured laser-drilled defects, a process that is sensitive to material variations. In manufacturing the 1 ml and 2.25 ml syringe defects, a difference in characteristics of the positive control samples is evident. This difference in the quality and performance of the positive control samples may be the source of deviation when samples, where tested using HVLD and the 5 micron defect in a 2.25 ml syringe sample (K2), was not detected.

HVLDmc (E-Scan 655) technology performed the Container Closure Integrity (CCI) test satisfactorily and is the recommended Container Closure Integrity (CCI)T inspection method as per USP 1207 for liquid prefilled syringes, ampoules and vials. The Vacuum Decay method fails to detect leaks on Albumin filled syringes, or has a reduced probability of detection on water, because small leaks easily get plugged.

Leak Testing with E-Scan HVLDᵐᶜ / Container Closure Integrity (CCI)T

Off-line laboratory system to inspect liquid filled:
– Vials – Syringes – Ampoules
– Cartridges – BFS
DC with offset AC Voltage
Lower HV application
mc: MicroCurrent
Improved SNR
Negligible Ozone
Product not exposed to HV
Good for low conductivity liquids including distilled water

Micro Leak Testing of Parenteral Products

The E-Scan 655 is a revolutionary deterministic offline micro leak test instrument that utilizes a new class of HVLD technology to inspect vials, syringes, and other liquid filled parenteral products for container closure integrity. The E-Scan 655 technology is a MicroCurrent conductivity test method, HVLDmc, that is completely non-destructive to the container and product; exposing the package and product to lower voltage than other conductivity based solutions. The technology uses a non-contact and non-invasive test method that requires no sample preparation. E-Scan 655 can be used with a wide range of liquid based products including low conductivity sterile water for injection (WFI) and proteinaceous products with suspensions.The E-Scan 655 features a fast test cycle and simple operation. Additional benefits include quick changeover and easy recipe setup to accommodate a wide range of products and applications. The offline E-Scan 655 method can bemigrated from laboratory to 100% inline testing applications at high production speed.

The E-Scan testing process uses a set of electrode probes to scan a non-conductive container that is sealed. The container material can be glass, plastic, or poly laminate.The container or package must contain liquid (minimum fill 30%). If a pinhole, crack, or other defect is present, there is a resistance differential and change in current flow indicating a breach in the container. The approximate defect location can be identified. PTI’s E-Scan 655 patent pending technology uses a unique mode of MicroCurrent HVLD, applying less than 50% of the voltage used with conventional high voltage technologies. The nature of this solution allows for testing packages with extremely low conductivity liquids such as sterile water (WFI). The MicroCurrent applied to the product during the test greatly reduces the voltage exposed to the product and environment. In fact, using PTI’s MicroCurrent HVLD reduces voltage exposure to the product to less than 5% of the voltage exposure experienced when testing with comparable HVLD solutions.MicroCurrent HVLD technology is the optimal solution for all parenteral and biologic products.

สนใจข้อมูลเพิ่มเติมเกี่ยวกับการตรวจสอบรอยรั่วขวดยาฉีดแบบ Vacuum Decay และการเปรียบเทียบวิธีการทดสอบ HVLDmc ติดต่อมาได้ตามช่องทางด้านล่างนี้เลยค่ะ