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Container Closure Integrity Testing (CCIT)

From development to production, Pfeiffer Vacuum+Fab Solutions offers high-sensitivity, non-destructive, tailored CCI testing solutions to detect even the smallest leaks in the container closures – ensuring sterile barrier integrity, global compliance, and consistent drug product quality.

Why Container Closure Integrity Testing (CCIT) matters more than ever

As drug delivery systems become more complex, so does the need for precision in packaging. Whether you are working with pre-filled syringes, vials, auto-injectors, or IV (intravenous) bags, any micro-defect in the container and closure system can compromise sterility, patient safety, and regulatory compliance. Traditional leak tests like blue dye or microbial ingress have proven insufficient, often missing defects smaller than 10 µm. That is why regulators are pushing for deterministic, non-destructive test methods, and why leading pharma as well as biotech companies are making the shift today.

Pfeiffer offers expertise in three advanced technologies: helium mass spectrometry, mass extraction and optical emission spectroscopy, providing tailored solutions to meet stringent pharmaceutical and medical demands.

Key use cases

CCIT methods

Knowledge

Key use cases for Container Closure Integrity Testing

Modern pharmaceuticals and biologics require container closure systems that maintain integrity under diverse and demanding conditions. USP <1207.1> defines three distinct product life cycle phases where integrity testing plays a critical role:

Development and validation

Challenges:

  • New container formats or drug products with unknown leak tolerances
  • Complex interactions between sterile products and packaging
  • Process validation and transfer to manufacturing scale

Requirements:

  • Sub-micron sensitivity and deterministic testing methods
  • Verification of inherent package integrity under worst-case conditions
  • Full compliance with USP <1207> (including MALL definition and equipment qualification)

Recommended methods:

  • Helium mass spectrometry
  • Optical Emission Spectroscopy
  • Mass Extraction

Product manufacturing

Challenges:

  • Need for quick and reliable testing on high-speed lines
  • Avoiding operator bias or inconsistency
  • Traceability and compatibility with GMP and quality systems

Requirements:

  • Deterministic, automated methods with short test cycles
  • Scalable for at-line or 100% in-line integrity verification
  • Minimal impact on tested units (non-destructive)

Recommended methods:

  • Mass Extraction
  • Optical Emission Spectroscopy

Commercial product stability

Challenges:

  • Long-term storage under temperature, humidity, and transport stress
  • Risk of gas or moisture ingress, compromising drug product quality
  • Verification of headspace gas retention and sterility over shelf life

Requirements:

  • Repeatable, non-invasive testing at defined stability time points
  • Methods with detection limits close to the defined MALL
  • Consideration of potential interference from product contents (e.g., protein aggregation, crystallization)

Recommended methods:

  • Optical Emission Spectroscopy
  • Mass Extraction

CCIT technologies from Pfeiffer

Helium mass spectrometry / helium leak detection

  • Tracer gas detection with a mass spectrometer
  • Measures leakages down to ≤10-9 mbar·l/s (≤0.1 µm)
  • Requires precise tracer gas management
  • Testing is performed in a sealed vacuum test chamber
  • Conforms to USP <1207.2> for verifying inherent package integrity; ideal for establishing MALL
Matching products
helium_mass_spectrometry_helium_leak_detection_1

Optical Emission Spectroscopy (OES)

  • Patented tracer-gas-free method using natural headspace gases and the emission spectrum
  • Measures leakages down to ~10-6 mbar·l/s (≥0.2 µm)
  • Simultaneously detects N2, Ar, CO2, H2O and more
  • Easy to use, scalable for high-throughput lines
  • Detects both gross and fine leaks in one run
Matching products
optical_emission_spectroscopy_1

Mass Extraction

  • Vacuum-based leak detection down to defects ≥1.0 µm
  • Detects the air flow through a leak
  • Suitable for stability testing and 100% in-line inspection
  • Used by FDA labs, ASTM compliant
  • Recognized in USP <1207> for production-scale testing and compatible with off-line and in-line integration
Matching products
mass_extraction_1

Want to prove container closure integrity down to –80 °C?

cold_storage
Cryogenic storage increases leak risk due to moisture, gas ingress, and material stress – especially in biologics.

The Dry Chiller Module from Pfeiffer enables real time container closure integrity testing under deep-cold conditions (–80 °C or –112 °F) as described in USP <1207.1>, supporting biologic and temperature-sensitive product profiles.

Discover our Dry Chiller Module

Feasibility study: Find the suitable method

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Unsure which leak test method fits your packaging system? Aligned with USP <1207.1>, our feasibility studies include positive/negative control samples and method development guidance based on MALL and product–package profiles with three deterministic technologies (helium mass spectrometry, Optical Emission Spectroscopy, Mass Extraction).

  • Receive a summary report with regulatory-fit recommendations
  • Simulate real-world conditions using your container closures

Request your leak testing service

Knowledge and industry expertise

Access in-depth CCIT resources and tools to support your packaging validation journey.

These resources help you compare test methods, understand leak behavior, and select the optimal technology for your package integrity and regulatory context.

Bye, Bye Blue Dye: Moving on to Deterministic CCIT​​

Bye, Bye Blue Dye: Moving on to Deterministic CCIT​​

Understand challenges and limitations of the blue dye test. Compare the sensitivity of blue dye test to other deterministic and non-destructive methods based on a study.

Read more
​​Break the Ice: CCI Testing at Low Temperatures

​​Break the Ice: CCI Testing at Low Temperatures

​Discover the new cutting-edge solution for ensuring container closure integrity in deep cold storage, including comparison to commonly used technologies.

Read more
Defect Sizes Less than 0,2µm – Finally Reliable CCI Testing!

Defect Sizes Less than 0,2µm – Finally Reliable CCI Testing!

We provide valuable tips to create proper testing procedures to help you optimize your helium leak testing of pharmaceutical packaging - with best practice demonstration!

Read more

FAQ

What is container closure integrity testing (CCIT)?

Container Closure Integrity Testing (CCIT) ensures that the parenteral container maintains asterile barrier throughout its life cycle. Even microscopic leaks can allow ingress of potential contaminants like moisture, microbes, or reactive gases –compromising drug safety, shelf life, and consumer safety.

Modern CCIT methods are aligned with USP <1207>, EU GMP Annex 1, and FDA guidelines to detect even the smallest breaches.

Why are deterministic methods preferred over legacy tests like blue dye for CCIT?

CCIT has evolved from legacy probabilistic methods like blue dye or microbial ingress, which are subjective, destructive, and lack test method precision. These older techniques also show significant gaps in performance, with studies indicating that blue dye tests detect only around 70% of 10 µm defects.

Deterministic test methods are quantifiable, repeatable, and validated under standards like USP <1207>, which includes guidance on package integrity, test methodologies, and seal quality. They enable faster, non-destructive testing, are independent of operator interpretation, and meet full regulatory acceptance from authorities like the FDA and EMA.

What is the maximum allowable leakage limit (MALL)?

A container closure system must demonstrate that it can maintain integrity under all expected conditions. According to USP <1207>, the maximum allowable leakage limit (MALL) defines the largest leak that still preserves product sterility and quality. It varies by container closure system but is often ≤0.2 µm (approx. 6 × 10-6 mbar·l/s). Early development focuses on reaching MALL, while routine testing may cover larger ranges (2–20 µm).

What types of CCIT methods are available?

Probabilistic methods

  • Blue dye bath test: dye ingress detection; destructive and qualitative
  • Bubble emission test: visual bubble formation under vacuum
  • Microbial ingress testing: microbial immersion to assess sterility
  • Tracer gas detection, sniffer mode: leak localization via helium mass spectrometer

Deterministic methods (preferred for accuracy and compliance)

  • Helium mass spectrometry: highly sensitive; using helium as tracer gas
  • Mass Extraction: vacuum-based method; tracer gas free
  • Optical Emission Spectroscopy (OES): tracer gas free
  • Vacuum decay/pressure decay: detects pressure change from leaks
  • High voltage leak detection (HVLD): detects leakage current; used for certain container formats containing conductive liquid
  • Laser-based gas headspace (frequency modulation spectroscopy): measures O₂/CO₂ loss in headspace

How do CCIT methods from Pfeiffer compare to the blue dye test?

The table below compares different methods across key performance factors including sensitivity range, measurement outcome, and compatibility with automation. This helps identify the right technology for specific test samples.

Test method
Helium Masss Spectrometry
Mass Extraction
Optical Emission Spectroscopy
Blue Dye /Microbial Ingress
Deterministic
✓
✓
✓
X
Non-destructive
X
✓
✓
X
Objective
✓
✓
✓
X
Tracebeable
✓
✓
✓
X
Sensitivity (approx.)
≤0.1 µm
≥1.0 µm
≥0.2 µm
Visual only (>10 µm)
Easy to set up
X
✓✓
✓✓
✓✓
Fast testing
✓
✓
✓✓
X
Automated
✓
✓
✓✓
XX
Measurement outcome
Helium flow (mbar l/s)
Mass flow (µg/min)
Leakage (N2, Ar, CO2, H2O...) (mbar l/s)
Color change

Which Pfeiffer products fit my container closure system?

All CCIT solutions from Pfeiffer Vacuum+Fab Solutions are designed in accordance with USP <1207.1>, supporting compliant method selection, validation, and product life cycle integrity assurance.

  • ASM 2000 (helium mass spectrometry)
    Ideal for high-sensitivity testing (≤0.1 µm) of non-porous container closure systems during development and MALL studies – especially for sterile drug products.
  • AMI 1000 (Optical Emission Spectroscopy)
    Tracer-free solution for regular testing and stability studies across various formats. Suitable for high-throughput lines and cold chain drug products.
  • SpeedAir 3050 (Mass Extraction)
    Robust vacuum-based testing for flexible container closure systems like IV bags and blisters. Perfect for in-line QC and stability testing.

How to move away from traditional blue dye ingress tests?

Our white paper "Saying Goodbye to Blue Dye" provides a scientific comparison between the traditional blue dye immersion test and the modern quantifiable, reproducible test strategies helium mass spectrometry, Optical Emission Spectroscopy, and Mass Extraction. The study uses both positive control samples (with artificial defects) and negative controls (intact packaging) to simulate realistic leak scenarios.

The results highlight:

  • Clear differences in detection sensitivity
  • Risks of false negatives with traditional methods like blue dye
    Guidance for method selection based on packaging format, leak size, and regulatory needs


Download our white paper

How does CCIT differ across pharma, biotech, and medical devices?

  • Pharmaceuticals: Primary packaging such as glass vials, prefilled syringes, and ampoules require high-sensitivity leak testing to maintain product sterility.
  • Biotech: Complex and highly sensitive biologics demand low detection limits to preserve biological safety and product stability.
  • Medical devices: While medical devices like auto-injectors, catheters, or implantable components differ from traditional pharma packaging, CCIT still plays a vital role.

Can CCIT methods detect leaks and determine their location?

CCIT methods are designed to measure leaks and assess whether a container closure system is tight or not tight. However, they do not directly detect leak locations.

In vacuum mode methods like Mass Extraction or vacuum decay, for example, a predetermined vacuum level is applied to the container. These methods measure if the container maintains integrity and is sealed tightly, but they do not identify the exact position of a leak.