Container Closure Integrity Testing (CCIT) (2023)

FAQs

Container Closure Integrity Testing (CCIT)? ›

Container Closure Integrity Testing (CCIT) is an assay that evaluates the container closure and its ability of maintaining a seal to keep potential contaminants out. Potential contaminants include microorganisms, reactive gases, and other substances.

Container Closure Integrity Testing Method requires the creation of positive and negative controls, taking into consideration the design, material, expected package leak features and content. This is done to mimic defects and is inspected together with the intact samples.

Acceptance criteria for leak test method validation should include the following: All negative controls pass (no leaks are identified) (USP <1207.1>). All positive controls with leaks at or above the designated limit of detection fail (leaks are detected) (USP <1207.1>).

USP Chapter 1207 provides an overview of common CCIT tests and categorises them as being deterministic or probabilistic. The chapter states a preference for deterministic tests on the basis that they are non-invasive, produce repeatable and predictable results and are suited to 100% testing.

Unlike deterministic test methods which are based on measurable physicochemical technologies, a probabilistic test method only gives subjective and qualitative outcomes. Also, most probabilistic test results are visually assessed, hence subject to bias due to variation in a technician's experience and skills.

Typically, a zero-acceptance sampling plan may be used, where a total of 20 finished product samples are considered as a minimum sample size also for routine testing of CCIT.

Vacuum Decay is a non-destructive CCI testing method that focuses on package integrity and leak path detection. Unlike manual inspection and other non-deterministic testing techniques, Vacuum Decay provides quantitative, deterministic, and accurate test results to assure package integrity.

For the positive pressure method of this test, an operator injects helium into a sealed package or adds helium to the package headspace upon sealing. After this, a mass spectrophotometer is used to identify and quantify the presence of helium in the surrounding enclosed space.

The ideal container-closure will have low permeability to air and moisture and a high resistance to aging (2).

What are the Acceptance Criteria? In short, acceptance criteria are the conditions that a specific user story must satisfy to be considered as completed, you may think of them as a checklist that helps verify if a coding team built the right feature and whether it is completed correctly.

What is USP 671 method 5? ›

Method 5 is a required classification test for multiple unit solid oral dosage form (SODF) plastic packages; either those without an impervious (induction) seal, or those that will have an end-use and storage period with an open (broached) induction seal.

USP testing specifications include checking for sterility, bioburden, and endotoxin. These predetermined processes are used by a collection of industries in the country. Some USP testing methods consist of standards that make it universally beneficial to develop safe products.

USP <61> is often called a "Bioburden" or "Microbial Limits" test. This test determines how many microorganisms are present in non-sterile drug products. During a USP <61> test, a sample is prepared and plated on two types of growth media (Soybean-Casein Digest Agar and Sabouraud Dextrose Agar).

In deterministic models, the output of the model is fully determined by the parameter values and the initial values, whereas probabilistic (or stochastic) models incorporate randomness in their approach. Consequently, the same set of parameter values and initial conditions will lead to a group of different outputs.

While deterministic data is consistent, more accurate and always true, it can be hard to scale. Probabilistic data can solve the issue of scalability, but can be less precise. Therefore, most data management and marketing professionals combine both types of data to get the most valuable insights.

Deterministic: All individuals with Smoking = 1 have Cancer = 1. Probabilistic: Individuals with Smoking = 1 have higher likelihood of having Cancer = 1.

Acceptance sampling is used to assess the quality based on sample size, acceptance number, and desired quality level. C=0 sampling plans are based on the premise of accepting the lot if zero defects are found during the inspection, and rejecting the lot if one or more defects are found during the inspection.

These plans are designed to give (roughly) a 95-percent chance of acceptance at the acceptable quality level (AQL), which is one of the parameters for the plan's selection. The c = 0 plan, on the other hand, rejects the lot if any defects or nonconformances are found, but it requires a considerably smaller sample size.

A good maximum sample size is usually around 10% of the population, as long as this does not exceed 1000. For example, in a population of 5000, 10% would be 500. In a population of 200,000, 10% would be 20,000. This exceeds 1000, so in this case the maximum would be 1000.

For the vacuum to decay, it must be possible to build a bubble of total energy zero. In the absence of gravitation, this is no problem, no matter how small the energy-density difference; all one has to do is make the bubble big enough, and the volume/surface ratio will do the job.

Is vacuum decay inevitable? ›

As long as decay is possible, it's inevitable. At any instant in time there's a tiny but real probability that a patch of space will tunnel between the false and true vacuums. Wait long enough and it WILL happen.

To conduct a vacuum decay test, a container is placed in a tightly fitted chamber which is evacuated to a predetermined level of vacuum. After reaching the pre-set vacuum, a sensor measures the vacuum level over a predetermined time.

Typical covert integrity questions include: True or False: I don't like people telling me what to do. True or False: I consider myself a risk-taker. True or False: I find it hard to make connections with the people around me.

Seal Integrity . A continuous seal with no bubbles, blisters or other inconsistencies as per WB-10-02-06 and WB-10-02-02. If channels are observed during the dye penetration test, a minimum seal width of 7 mm must be maintained to accept the results.

ASTM F1886 is the standard test method for determining the integrity of seals for flexible packaging by visual inspection. Specifically, this ASTM package validation standard covers the determination of channels in the package seal down to a width of 0.003 inches.

IICL stands for "International Institute of Container Lessors". Essentially, the IICL has created a standard of inspection that insures that an ISO Storage Container is in adequate condition to be long-term leased for cargo transportation.

FDA�s guidance document requires the evaluation of four attributes to establish suitability: protection, compatibility, safety, and performance/ drug delivery2.

An o-ring or a closure liner is often used to maintain a seal. Linerless closures typically use a deformable plastic rim or structure. Secondary seals are commonly used with sensitive products that may deteriorate or where extra security is needed. Foil or plastic inner seals are used on some bottles.

There are two distinctive approaches to writing acceptance criteria: scenario-based and rule-based. Each one takes a slightly different focus and has its own set of appropriate use cases. However, both can play a key role in defining user requirements and design goals.

Definition of Done (DoD) is a list of requirements that a user story must adhere to for the team to call it complete. While the Acceptance Criteria of a User Story consist of set of Test Scenarios that are to be met to confirm that the software is working as expected.

Who should perform UAT testing? ›

Who performs UAT? End users normally perform user acceptance testing. They are the most effective group to test software in this form because they know exactly how the software will be used on a daily basis and what changes need to be made to be suitable for this day-to-day use.

USP 〈661.1〉 “Plastic Materials of Construction” introduces more rigorous standards and testing to demonstrate that polymer raw material is well-characterized and suitable for its intended use.

The United States Pharmacopeia – National Formulary (USP-NF) includes over 5000 quality standards for medicines, both chemical and biologic; active pharmaceutical ingredients (APIs); and excipients (inactive ingredients). It is the most comprehensive source for medicine quality standards in the world.

USP Official Reference Standards

USP offers over 7,000 USP Reference Standards, highly characterized physical specimens of drug substances, excipients, food ingredients, impurities, degradation products, dietary supplements, compendial reagents, and performance calibrators.

There are three different testing techniques available. They include white-box testing, black-box testing, and grey-box testing. Let's discuss each of these techniques.

The four fundamental methods of verification are Inspection, Demonstration, Test, and Analysis. The four methods are somewhat hierarchical in nature, as each verifies requirements of a product or system with increasing rigor.

Flow-Through Cell Dissolution Tester (USP Apparatus 4)

The USP apparatus 4 comprises of a media reservoir to hold the dissolution media, a pump that forces the media upwards through a vertically positioned flow-through cell that holds the dosage form and a water bath to maintain the cell temperature.

For instance, USP <51> is chapter 51, which covers preservative effectiveness testing. USP <61> is the chapter that describes microbial examination of nonsterile products. The method can be used to assess the microbiological quality of everything from face lotion to a diagnostic reagent.

USP <61> testing includes an enumeration plate count and suitability testing, which validates the plate count. USP 62 testing evaluates the presence or absence of specific organisms.

USP <1226>

The verification process for compendial test procedures is the assessment of whether the procedure can be used for its intended purpose, under the actual conditions of use for a specified drug substance and/or drug product matrix.

Why is stochastic better than deterministic? ›

While both techniques allow a plan sponsor to get a sense of the risk—that is, the volatility of outputs—that is otherwise opaque in the traditional single deterministic model, stochastic modeling provides some advantage in that the individual economic scenarios are not manually selected.

The Monte Carlo simulation is one example of a stochastic model; it can simulate how a portfolio may perform based on the probability distributions of individual stock returns.

The primary disadvantage of stochastic methods is that their accuracy is not very good, though it's usually close enough. For this reason they are typically not used when another method is feasible. The other disadvantage of stochastic methods is without computer assistance, they are slow.

Conversational AI, on the other hand, is probabilistic. It relies on machine learning, natural language processing, deep learning, predictive analytics, and other language models to produce dynamic responses.

PERT is a probabilistic model i.e. It takes into account uncertainties involved in the estimation of time of a job or an activity.

In general, stochastic is a synonym for probabilistic. For example, a stochastic variable or process is probabilistic. It can be summarized and analyzed using the tools of probability. Most notably, the distribution of events or the next event in a sequence can be described in terms of a probability distribution.

For example, probabilities for stochastic models are largely subjective. One person might assign the odds of flipping a coin as a deterministic 50/50 chance of getting heads. Another person might say that that would happen only when the coin is perfectly balanced and fair, so a stochastic model might be appropriate.

Deterministic models assume that known average rates with no random deviations are applied to large populations. For example if 10,000 individuals each have a 95% chance of surviving 1 year, then we can be reasonably certain that 9500 of them will indeed survive.

For example, if you live in a cold climate you know that traffic tends to be more difficult when snow falls and covers the roads. We could go a step further and hypothesize that there will be a strong correlation between snowy weather and increased traffic incidents.

What is enclosure integrity test? ›

Enclosure integrity testing uses a blower door to measure the total leakage area of rooms protected by fire suppression systems. The measured leakage area from the blower door test can then be used to estimate retention times for various clean agent fire extinguishing systems installed in the protected room.

Self Sealability:- This test is applicable to closures intended to be used with water close the vials with the 'Prepared' closures. For each closure, use a new hypodermic needle with an external diameter of 0.8 mm & pierce the closure 10 times, each time at a different site.

For routine testing, the dye ingress method uses ten test samples and three positive controls. The samples are placed in a vacuum chamber with dye and either pressure or vacuum is applied to the samples. The positive controls are punctured with a microtube to allow dye into the vials.

So as I said, there are two main types of integrity tests: covert (personality-based) tests that measure traits linked to rule adherence; and overt tests which assess an applicant's attitudes towards various counterproductive work behaviors (CWBs) directly.

Structural Integrity Assessment is an approach to assess whether a structure is fit to withstand the service conditions safely and reliability throughout its predicted lifetime.

The Dye Ingress test is both a destructive and probabilistic method for measuring container closure integrity. For dye ingress, samples and positive controls are submerged into a dye bath. They are subjected to pressure cycles, and they are then visually evaluated or alternatively evaluated by spectrophotometry.

All of these defects can be picked up by Container Closure Integrity Testing (CCIT) – an assay that evaluates the adequacy of container closure systems to maintain a sterile barrier against potential contaminants.

QA, QC, and Testing are like a chain that works together to ensure a high-quality product. QA sets the standards for how it should be done, QC ensures those standards are followed, and Testing checks that everything is up to the quality standards.

Every time you open a new container of test strips or a new vial of QC solutions. If the meter is dropped. If there is a question about a patient's glucose results (i.e., if the glucose result is inconsistent with clinical presentation) to ensure the meter is working properly.

What is the methylene blue container closure integrity test? ›

During the test, the container closure test articles are put into an empty vacuum chamber to introduce negative pressure to the articles. This vacuum removes air inside the container/closure system. The vacuum is then released and methylene blue hydrate solution enters the chamber until it reaches atmospheric pressure.

It uses methylene blue dye or another colored chemical liquid to determine whether there is a leak or not. The test is done by placing the pack of blister into a container of vacuum leak detector which has been filled with methylene blue dye mixed with water.

The US Food and Drug Administration (US FDA) effectively expects confirmation that dye ingress methods can detect leaks ≤20 µm (6).