FINISHED PREFILLED SYRINGES INTEGRITY TESTING METHOD DEVELOPMENT, VALIDATION AND 100% IN-LINE HIGH SPEED SOLUTION

 

The application of Vacuum Decay Method for 100% In-line high-speed Container Closure Integrity Test to pre-filled syringes is a technological innovation that allows pharmaceutical companies to increase their quality assurance for sterility and stability. Main reasons are linked to the high control given by such a very sensitive tool to identify possible leakages linked to imperfect assemblies and pinholes that also gives the possibility to be validated in a simple, reliable and repeatable manner by means of calibrated leakers. An established technology, based on ASTM standard F2338, FDA consensus standard since 2004, applied on most pharmaceutical containers can now be used also with high performances in terms of throughput and sensitivity for PFS’s.

 

Prefilled syringes have become very popular in pharmaceutical industry as a parenteral drug delivery device, in fact, many are the benefits of this format including eliminating dosing errors and reducing accidental needle sticks by hospital staff. Since its introduction, several methods have been developed and applied for the performance of Container Closure Integrity Test (CCIT), both as in process control and in line.

Stringent requirements from the industry have brought to the development of different technologies and implementations by pharmaceutical companies both as in-process control and as in-line control; up to now all the available methods presented limitations either from the aspect of 100% usability or from the aspect of reliability.

The innovative technical solution, here presented, which utilizes Vacuum Decay Method, compliant with the ASTM F2338 “Standard Test Method for Non Destructive Detection of Leaks in Packages”, recognized as a Consensus Standard by the US Food and Drug Administration is able to perform a reliable and efficient CCI test in a 100%high speed in-line pharmaceutical manufacturing environment.

Vacuum Decay Method is included, just like Electrical Conductivity and Capacitance, Laser-Based Gas Headspace Analysis, Mass Extraction, Pressure Decay and Tracer Gas Detection, in the list present in USP between the suggested deterministic leak test technologies. Being this the most up-to-date reference that clearly suggests pharmaceutical world to move towards this type of methods instead of probabilistic ones more commonly used, such as Microbial Ingress or Dye Ingress. It also specifically addresses the maintenance of the microbiologically integrity of sterile product packaging until the time of use of its contents, by defining:

  • Package Integrity Testing in the Product Life Cycle.
  • Test Method Selection Criteria.
  • Test Instrument Qualification, Method Development, and Method Validation.

The limits of the dye ingress test method, for example, like high risk of inaccuracy and above all its being a destructive procedure, have been largely eliminated thanks to the development of non-destructive techniques, limiting this traditional method to In Process Control and lab procedures.

 

In particular, when dealing with PFS’s, the CCI testing is performed while the PFS itself is held within a hermetically sealed test chamber, connected to external vacuum source and designed to minimize residual volumes. Once the test chamber is loaded, the VDM process comprises 3 phases:

  1. a) Vacuuming: the period of vacuum setting within the test chamber
  2. b) Stabilization: the time necessary to get a homogeneous vacuum distribution within the test chamber
  3. c) Testing: the time frame in which the vacuum level is monitored by means of a dedicated transducer.

During testing, two measurements are taken respectively at the beginning (1st reading) and at the end (2nd reading) of this phase in order to compare the vacuum decay delta (“Δ”) to a predetermined threshold (THR).

 

 

The advantages of VDM include:

  • Complying with a FDA consensus standard.
  • Being applicable to most package systems.
  • Being able to test the overall package systems.
  • Being reliable and repeatable.
  • Including a barometric compensation system.
  • Being convertible: it can test vacuum or pressure without need to change any components.
  • It’s a technical solution capable of prevent syringe stopper movement.

But there are also some disadvantages, such as being not appropriate for proteinaceous or highly viscous content that can be, in some cases, cope with using Pressure Decay Method instead.

 

A more comprehensive showcase on the machinery that carries out vacuum decay testings, is available in this webinar that we recently broadcasted.

<iframe width=”620″ height=”348″ src=”https://www.youtube.com/embed/uj-VuatCh90″ frameborder=”0″ allow=”autoplay; encrypted-media” allowfullscreen></iframe>

 

This article was created by Giovanni-Benedetto Golinelli and was initially published in the latest issue of PHARMA HORIZON magazine [vol. 2(2) 2018]. You can download the full article here: http://www.bonfiglioliengineering.com/uploads/files/Golinelli_PH2.pdf

 

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