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Article 08-01-06
Package Integrity Testing (Leak Testing)
Fernando Díaz Matos, PE, MBA, CFEI, CVFI, EPA
In testing packaging for leakage of all kinds, insensitive tests or inspections with low repeatability can have devastating results. At the least, failure to detect and remove defective packages could result in a product recall. In the extreme, the product could result in a catastrophic failure that produces life-threatening conditions for the end user, or may even cause death. Recalls have been on the rise in recent years, due primarily to poor component quality, poor seal quality, processing and handling errors and, above all, improper use or absence of packaging integrity tests.
Contrary to common belief, United States and European Union regulations do require package integrity testing. For example, referring to inspection of container closure
systems, the current 2004 FDA Guidance for Sterile Drug Products Produced by Aseptic Processing (cGMP) clearly states: “Any damaged or defective units should be detected, and removed, during inspection of the final sealed product. Safeguards should be implemented to strictly preclude shipment of product that may lack container closure integrity and lead to nonsterility.”
What package integrity test can help the manufacturer detecting these failures? Can such a test be incorporated on the production line? In order to answer these key questions, we must understand the basic concepts of package integrity:
Definitions
- Assurance – the “quality or state of being safe” is a key word in the manufacturing world today. Package leak detection is one of the key control measures to ensure the end user that the product was examined and is in compliance with or exceeds standard testing procedures.
- Leaks – a gap or a hole in the package wall.
- Leakage – a mass flow of gas through a leak
- Leak rate – a function of time and pressure differential across the gap. Leakage is
measured in units of mass or volume of gas per unit of time ((P x V)/ t).
- - Std cm3/s (ccs)
- – Std cm3/min (ccm)
- – Pa·m3/s (SI units)
When talking about leak testing, it is common to refer to a hole size that can be detected by a piece of equipment (eg. 5 microns). Although this reference is used to help visualize
the leakage, it is not technically correct. Natural leaks are not perfect holes, and the leak rate for a given “hole” size may vary depending on pressure, volume and other features of the package. It is also important to realize that all packages leak.
Permeation is an interaction through the package wall itself. Several factors must be considered in measuring this effect: Concentration differences, solubility of the barrier material and a product’s ability to migrate through the package material.
Permeation is measured in units of mass / (area * time)
- - g/m2·day (films)
- - mg/day/liter (bottles)
Note that permeation and leakage are different, and it is important to consider each separately. Permeation is most likely the culprit if the manufacturer is faced with loss of inert gas headspace, loss of product solvent or ingredients, or moisture sorption or loss.
A package leakage prolem is likely if there is loss of product or microbial or environmental
contamination.
Microbial contamination is one of the main reasons for leak testing, and there are several factors that indicate the possibility of this kind of contamination: package porosity and material, leak size and tortuosity, humidity and air pressure differential, microbial characteristics and concentration in air, time and temperature, liquid carrier viscosity and surface tension. Notice that critical size for airborne microbes to penetrate into a package is not yet determined. Liquid-borne microbials will only occur in leaks that allow a liquid carrier. It is important to understand that sterility does not constitute package integrity. Since a small number of samples are tested, and false positives are possible, sterility tests are not considered reliable final indictors of package integrity.
To ensure packaging integrity, the correct technology must be chosen, based on the package’s integrity database.
Leak Testing Technology
Numerous destructive leak testing technologies have been used through the years, and some, such as testing with dyes, helium or water, or peel and burst tests, are still in use. The search for simple, cost-effective, repeatable tests that are non-destructive and that can be validated has led in recent years to an increased use of pressure decay tests, airborne ultrasound and laser-absorption technologies. There is also an emphasis on incorporating the leak tester as part of the production line rather than having a separate sampling or laboratory unit.
In the case of pressure decay, the package is placed in a chamber where, depending on the product, pressure or vacuum is applied. This set pressure is then re-measured after an established interval. From a set volume, time and internal and initial pressure, the pressure change is then compared to a previously determined threshold, the results determining whether the package is accepted or rejected. The pressure decay method is used for all kinds of packages, from drums to blisters, from bottles and cans to vials and ampoules.
Some features of this process are a defective b lister cavity with vision technology (E.g. PTI 225 BLV), dual test and auto cleaning process (E.g. Bonfiglioli Pharma) and inline testing up to 1200 bpm (Bonfiglioli Pharma). Precision can be down to 5 microns (for easy visualization), depending on actual package characteristics and line speed. It is the end user’s responsibility to determine the minimum acceptable leakage, based on the package integrity database. This method can be used for all kinds of material: from aluminum to Tyvek.
Airborne ultrasound, primarily used to detect and prevent leakage in pouches and other flexible packages, registers changes in sound speed through different mediums. A seal should be uniform in medium and thickness. Sound changes speed as it travels through a change in material or air in a seal. An operator can see the changes on a screen and opt to discard a package, or the equipment itself accepts or discards a package based on these anomalies. This method of leak detection has the advantage of detecting other kinds of seal defects such as peeling, abrasion, blisters, compressed seals and others, and it can performed off or on the production line. This test can be performed off- as
well as on-line.
Laser absorption spectroscopy technology is the newest technology in moisture content and vacuum detection. (Until recently freeze-dried (lyophilized) products were checked for vacuums using spark tests, which made the glass glow in the presence of vacuum, but this test was unsuitable for high-speed applications.) In general terms, laser absorption spectroscopy directs a laser beam with a wavelength similar to the internal vibrating frequency of oxygen or water through the headspace of a vial. Oxygen or moisture molecules absorb part of the energy. The reduction in total energy is proportional to the quantity of molecules with similar vibrating frequency in the headspace and proportional to the vacuum in the area. Moisture reading has certain advantages over oxygen, as it does not require nitrogen gas to purge air and is able to read through dark glass or different vial materials and dust, and gives better reading at low pressures. Bonfiglioli Pharma has manufactured equipment with this technology at speeds of up to 500 cpm.
Leak-testing technology is one of the methods of reducing catastrophic incidence in packaging, and as the packaging line speed is increased or equipment gets older, major emphasis should be placed on establishing control procedures. The starting point for selecting the technology or particular equipment to be used for leak-testing is first a sound knowledge of the package integrity database, then a determination of whether a production line or off-line application is needed.
Are you addressing this concern? Is your company? Your product is your reputation …You certainly don’t want it to leak!
Biographical Note
Engineer Fernando Díaz Matos is a machinery and equipment appraiser who is an engineering consultant for major insurance companies in Puerto Rico and the Caribbean and founder of NCM International, one of the leading manufacturer representatives for packaging and process equipment.
Bibliography:
D. Guazzo, “Package Integrity Testing,” Parenteral Quality Control,
2nd Ed.,Marcel Dekker, NYC, 1994
Carroll, et al, “Tech Report 27,” PDA J Pharm Sci & Technol, 1998
Carroll, et al, Tech Report 27, PDA J Pharm Sci & Technol,1998 Relevant Pharmaceutical Industry Guidance Documents
• PDA Tech Report No. 27, Pharmaceutical Package Integrity
USP <1207> Sterile Product Packaging – Integrity Evaluation
FDA Guidance and DRAFT Guidance for Industry EMEA Manufacture of Sterile Medicinal
Products (cGMP)