Part Four – Container Integrity Testing – Capping, Residual Seal Force & Laser Diffraction| Whitehouse Laboratories

PartFour_Thumbnail(1)Part Four – Container Integrity Testing – Capping, Residual Seal Force & Laser Diffraction | Whitehouse Laboratories

Author: Brian Mulhall – Managing Partner, Director of Container Testing

In part four of this series on CCIT, two commonly used methods – Residual Seal Force and Laser Diffraction – will be reviewed.

Parenteral Vial Capping and Residual Seal Force Testing

Residual seal force testing of parenteral vials is often performed in conjunction with helium leak testing or vacuum decay testing. Residual seal force is not a leak test, but is an indirect measure of the compressive force exerted by the stopper on the vial’s land surface. A slow, constant rate of strain is applied to the top of a capped vial and the resistance to compression is monitored and reported. The appropriate amount of compressive force is required to ensure a quality seal. Vials capped at an insufficient force may leak from the sealing surface. On the other hand, vials capped at an excessive force may experience cracking and bulging, also risking the integrity of the closure system. When used in conjunction with leak test methods such as helium mass spectrometry or vacuum decay, an optimal range of residual seal force values may be determined that correlate to a reduced risk of leakage resulting from improper capping force.

This type of testing is of value to clients aiming to establish optimal sealing parameters or those who wish to implement a sampling procedure during product production.

Laser-Based Headspace Analysis

Gas headspace analysis via laser-based analysis techniques provides a quantitative, nondestructive measure of oxygen content, nitrogen content, water vapor content, or low internal pressure in a nonporous, rigid or non-rigid package headspace.

A near-infrared diode laser light is passed through the gas headspace region of the sealed package. Light absorption, measured using frequency-modulated spectroscopy, is indicative of gas concentration and pressure. Gas headspace analysis, as a function of time, provides a quantitative measure of the total leakage rate of the test sample.

This technology is especially applicable when verifying the integrity of packages that must maintain a specific gas headspace content such as low oxygen, low water vapor, and/or low pressure. For testing, packages only need be either transparent or semi-transparent material, either amber or colorless; test samples require a minimum headspace volume and headspace path length. Vials, syringes, cartridges and bottles are all amenable to this approach.

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Part Three – Container Integrity Testing – Helium & Mass Extraction| Whitehouse Laboratories

PartThree_Thumbnail(1)Part Three – Container Integrity Testing – Helium & Mass Extraction | Whitehouse Laboratories

Author: Brian Mulhall – Managing Partner, Director of Container Testing

In part three of this series on CCIT, two commonly used methods – Helium and Mass Extraction – will be reviewed.

Helium Mass Spectrometry

Helium mass spectrometry, based upon ASTM F 2391-05 “Standard Test Method for Measuring Package and Seal Integrity Using Helium as the Tracer Gas” is applicable to non-porous packaging such as vials, syringes, and cartridges. Even flexible packages can be tested by helium mass spectrometry using appropriate test fixture.

Helium-filled samples are placed in a test chamber, where a vacuum is created by the instrument’s internal pumps. Leaking samples allow helium to escape, enter the test system, and be detected by an analyzer cell. The stream of helium ions hitting the analyzer cell target is proportional to the partial pressure inside a sample. From this, a specific leak rate can be calculated and reported to the user. Results can be reported quantitatively (as a leak rate), or qualitatively (Pass or Fail) if method development is performed.

This type of testing may be of interest to clients looking to accurately assess the performance of an established package or analyze the effect of processing variables, such as capping force, closure materials, etc., on the performance of a package system.

Mass Extraction

Mass extraction leak detection operates by drawing vacuum on a sample enclosed in a chamber. Once vacuum is established, the instrument monitors the amount of airflow required to sustain a specific vacuum level. The amount of flow required to keep the vacuum steady is equal to the amount of flow escaping from leaks in sample under testing. Specific test parameters must be set after adequate method development. Results are reported quantitatively, as flow rates, as well as qualitatively (Pass or Fail) according to acceptance criteria established in method development.

Mass extraction testing is applicable to any package containing headspace, including parenteral vial packages, screw-capped bottles, and flexible bags or pouches. In some cases, liquid-packages can also be leak tested by this approach if the product formulation poses no threat of clogging leak paths.

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Part Two – Container Integrity Testing – Vacuum Decay and HVLD | Whitehouse Laboratories




Part Two – Container Integrity Testing – Vacuum Decay and HVLD | Whitehouse Laboratories

Author: Brian Mulhall – Managing Partner, Director of Container Testing

In part two of this series on CCIT, two commonly used methods – Vacuum Decay and High Voltage Leak Detection – will be reviewed.

Vacuum Decay

Vacuum Decay leak testing is based upon ASTM F 2338-09 “Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method”. This nondestructive test facilitates the identification of package leaks that may not be visibly detectable. It operates on the principal of vacuum decay. A test package is placed into a chamber that is subsequently exposed to vacuum. Sensitive pressure transducers monitor changes in chamber pressure; a result of package headspace being drawn through any leaks present. Using acceptance criteria established through method development, quantitative test results are qualitatively judged as pass or fail.

This type of testing is applicable to any package containing headspace, including, but not limited to, parenteral vial packages, screw-capped bottles, auto-injectors, and flexible bags or pouches. Vacuum decay is generally not recommended for liquid filled packages, as proteinaceous product has the potential to clog and mask leaks. However, if vacuum decay is the preferred method, alterations can be made to the method development and validation process to accommodate liquid filled packages.

Electrical Conductivity (HVLD)

The electrical conductivity leak test, also called high voltage leak detection (HVLD), or “the spark test”, is an approach for detecting leak presence and potentially the location of a leak(s) in the wall of a nonporous package, rigid or flexible, containing liquid product. The principle of leak detection is based on quantitative electrical conductance measurements. The presence of a leak path in the proximity of electrically conductive liquid results in a drop in test sample electrical resistance, as evidenced by a spike in current above a predetermined pass/fail limit. This highly sensitive method even works to detect package defects clogged by product formulation proteins or salts. Stability studies by clients have supported the use of this technology for nondestructive leak testing a variety of product formulation types. This should be considered, however, on a product-by-product basis.

Package systems that may be tested by HVLD include parenteral vials, pre-filled cartridges and syringes, plastic containers, and plastic bags or pouches.

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Part One – Current State of Container Integrity Testing | Whitehouse Laboratories


Part One – Current State of Container Integrity Testing | Whitehouse Laboratories

Author: Brian Mulhall – Managing Partner, Director of Container Testing

This series of articles will review the state of Container Closure Integrity Testing (CCIT) today and the various methods currently available, the factors for choosing the most optimal method and current regulatory guidelines under development.

Dye and microbial ingress testing have long been employed for assessing the integrity of container closure systems. However, research and experience as shown such tests are limited in their ability to provide accurate, sensitive and reliable data for definitive container closure integrity verification, especially for packages that demand the highest degree of product protection.

With the advent of new technologies, various sensitive and data-producing test methods have been developed to bring package integrity testing into the 21st century. The development of these new and improved methods over the past 10 years has led to regulatory agencies taking a fresh look at how to best guide industry. Within the next few months the United States Pharmacopeia will publish new General Chapter 1207 that deals specifically with container integrity and will outline in detail the various methods that industry can use. These new and improved Container Closure Integrity Tests have been successfully used to

  • characterize packages and materials,
  • optimize sealing parameters,
  • evaluate package storage temperature impact,
  • replace sterility tests for product stability batches,
  • screen production lots for faulty packages, and
  • support regulatory submission applications for product commercialization around the world.

The new USP 1207 chapter will prove to be a useful guide for companies that are in need of CCI testing. As this area of qualification is often misunderstood, the initial draft of the general chapter has taken a basic approach and will dedicate a section to each of the methods that may be employed. In addition, the chapter will discuss all the factors that must be considered when choosing the most optimal method. Key factors test method selection include package type, chemical make-up of product, type of seal and storage conditions.

With so many variables under consideration, there will not be one method that will satisfy all the CCIT needs of a company. Over time, the industry will need to have the ability to employ all the various methods if they are to insure that their products and package systems meet the stringent GMP regulatory requirements.

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Continue Learning Beyond the INTERPHEX Show Floor

INTERPHEX Free Spring Webinar SeriesJoin us for our complimentary spring webinars from the convenience of your own desk.

Schedule of upcoming webinars:

  • Single Pass Tangential Flow Filtration for Bioprocessing May 21, 2014 at 2:00pm EST Presented by EMD Millipore This webinar reviews the advantages of single pass tangential flow filtration (SPTFF), discusses applications where SPTFF adds value, provides recommendations for process development, and presents guidance for scale up and implementation. Find out more and register>>
  • Performance and Economics Analysis of Fully Automated Single-use Tangential Flow Filtration Process June 5, 2014 at 11:00am EST Presented by Pall Life Sciences Fully automated single-use tangential flow filtration (SUTFF) system, coupled with the Cadence™ single-use TFF modules brings real-time process control, monitoring, flexibility and reliability in manufacture.  The Webinar presents Pall Life Sciences’ design approach for SUTFF and the process economics analysis to show significant utilities, cost, and time savings as it compares to conventional re-use TFF. Find out more and register>>
  • Taking Life Sciences to the Cloud June 12, 2014 at 2:00pm EST Presented by Cornerstone OnDemand Life science organizations face unprecedented compliance and transparency expectations today.  In order to meet requirements, focusing on the development of your people has to be just as important as your improving upon your product. In this webinar, learn how the cloud can address compliance requirements, empower your employees and improve performance.Find out more and register>>
    INTERPHEX Webinar Series
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Day Two of INTERPHEX Recap


Day Two Wrap up at INTERPHEX 2014, sponsored by PDA
– Positive Reactions at Leading Pharmaceutical & Biopharmaceutical Manufacturing Event -

NEW YORK CITY, NY, March 19, 2014 – INTERPHEX (International Pharmaceutical Expo) the leading annual trade event dedicated to the pharmaceutical and biopharmaceutical manufacturing industry is being held this week at the Jacob K. Javits Center in New York City, NY.
This year, INTERPHEX along with premier sponsor PDA (Parenteral Drug Association) has brought together over 12,000 industry professionals and more than 650 exhibitors to learn, network and source from the latest technology, equipment, education and services. And after two days of the three-day show, companies are impressed with the quality and value of this year’s attendees and look forward to seeing what the final day will bring.
“I have nothing but good things to say about INTERPHEX,” said Suzy Arraste, Marketing Manager at Cozzoli Machine Company. “We come to the show because half of our company is in the pharmaceutical industry and this is a great way to get leads.”
IPS Technologies Floor Tours
A highlight of the day was the five Technologies Tours led by IPS-Integrated Project Services. Attendees on the Biomanufacturing tour met with top industry vendors, including EMD Millipore, GE Healthcare, Parker-Hannifin Corp., Pall Life Sciences, Thermo Fisher Scientific, and ASI Life Sciences who gave brief presentations showcasing their new manufacturing technologies, novel applications and equipment innovation.

“I couldn’t be more pleased with the titles and positions that IPS is bringing to us on the technologies tours,” said Amber Sherrick, Marketing Manager at ASI. “INTERPHEX is always a great way to premiere new products while getting to know customers and networking.”

Other Technologies Tours included: Advanced Aseptic, Inspection and Packaging, Modular Construction, and Oral Solid Dosage.

Featured events
The INTERPHEX Connects Innovation Stages also brought together crowds of industry professionals for complimentary, enriching presentations. Topics today covered continuous bioprocessing and manufacturing for biologic drugs, as well as a special forum presentation on Changing Contract Services sponsored by Pharmaceutical Technology and BioPharm International. Jim Miller, President of PharmSource spoke to a packed audience about the consolidation of the CMO universe and the evolution of new services combinations to fit the changing R&D requirements of bio/pharma companies. In addition, Miller offered an industry outlook for the next few years.

Featured presentations at the first ever PDA Education Sessions @INTERPHEX included Parenteral Packaging and Supply Chain for the 21st century.

On the show floor
It was nothing but positive news on the show floor as well. GE Healthcare Marketing Manager, Jiyoung Lee said, “We go to INTERPHEX every year and it’s always great; we are constantly generating leads.” The company took a unique approach to their booth this year, focusing on the four pillars of bioprocessing: upstream, downstream, single-use, and services.

A spokesperson from GEA Process Engineering also agreed that the show is a great way to network and get leads for potential customers for products like their MODUL Tablet Press, designed to process high-potency products.

Thermo Fisher Scientific – who has been exhibiting at the show for more than ten years in order to show the scale of their company’s capabilities – mentioned they have been getting tons of booth traffic. They also said they are pleased with the sponsorship opportunities that INTERPHEX offers them; they will be sponsoring the St. Patrick’s + 2 Industry Celebration tonight.

Get the most out of the show by connecting with us on Twitter, Facebook , LinkedIn and a Google+.

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What’s on tap for Thursday at INTERPHEX?


What’s on tap for Thursday?

As INTERPHEX 2014 winds down tomorrow, be sure to take advantage all of the free sessions at INTERPHEX Connects, such as The 7 Characteristics of a World Class Supply Chain sponsored by Contract Pharma, a roundtable discussion on new approaches to downstream processing, sponsored by BioProcess International, and a presentation on CMO selection and successful tech transfer for aseptic fill and finish services, brought to you by Pharmaceutical Processing.

Thursday will bring attendees two final PDA Education sessions on pharmaceutical water systems and closing plenary-aging facilities. President of PDA, Richard Johnson, will also give his closing remarks, reflecting on the program’s first year.

If you haven’t had a chance yet, check out the Life Science Connect Radio at – radio hosts will be streaming interviews with attendees, exhibitors, and subject matter experts live from the show floor.

Have a great last day at INTERPHEX tomorrow!



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