Table top Container Closure Integrity Tester

The LF-S11 by Bonfiglioli is a countertop compact machine, designed for Non-Invasive, Non-Destructive Container Closure Integrity Testing of diverse types of Pharmaceutical Containers filled with liquid, lyo, powders, etc..

Suitable for In-Process Control and Laboratory use without altering container and/or content features.

The integrated software system allows full compliance to provisions stated in FDA 21 CFR part 11 as well as EMA Annex 11.

3 Configurations of the machine available to meet all specific requirements:

– BASIC, for most of the container formats 

– XL, designed specifically for large formats (more than 100ml)

– SY, designed for syringes, carpoules including automatic plunger stopping device

Equipment test method complies with:

– FDA Guidance for Industry “Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products”.

– United States Pharmacopoeia General Chapter «1207» “Packaging Integrity Evaluation”.

– EU Guidelines to GMP Medicinal Products for Human and Veterinary Use – Annex 1 “Manufacture of Sterile Medicinal Products”.

– PDA Technical Report No. 27 “Pharmaceutical Package Integrity”

All dedicated test chambers are designed according to the container characteristics for a maximum of leak detection sensitivity and are monitored by specially developed electronics during the testing process. The group has been recently redesigned to obtain improved functionality (quick

 single-handed opening and closing). It is directly installed onto the Testing Chamber supporting flange and it is composed by: – A fixed bottom part; – A removable top cap (upper part) that allows plugging up the testing group corresponding to Container loading and unloading operations.

HOW IT WORKS

The test chamber fixed bottom part is equipped with a mobile piston, plunger stopping device (PSD), having vertical motion between two limit positions, “upper” and “lower”, and having a section equal to that of the PFS plunger.

The initial vacuum, generated in the test chamber, produces an upward movement of the PSD.

The same “upper” position is kept until the second reading; at that time, the action of a dedicated pneumatic actuator provides for exhaust of vacuum in the test chamber bottom area and produces the PSD downward movement towards the “lower” position.

For more information, please call our office and we’ll be happy to assist.

Walk in Chambers – The future of storage

Bahnson Environmental specialties designs, manufactures, installs, and services custom chambers of all types and sizes, for a wide array of applications, including: GMP Shelf-Life Testing and Storage, Dry/Moist and Cold Storage for Seed and Agricultural Products, Nutritional Supplements, General Materials Testing, Mold and Fungal Incubation, Photography Storage, Concrete Curing, Roll-In Bottle Incubation Chambers and Cold storage solutions.

They are part of the EMCOR group a fortune 500 company with over 40 years of extensive experience in the field, providing the most resource-saving technologies in liquid-circuited cooling systems to ultrasonic humidification.

When custom solutions are required, the engineering team has the training and experience to ensure that optimal performance does not sacrifice energy efficiency. In their comprehensive experience they have encountered facilities that had lost multi-million dollar worth of research due to freezer or consolidated chamber failures.

In the recent years, Bahnson Environmental have become advocates for installing a consolidated walk in chamber over solving your storage problems by adding a new stand-alone freezer and ending up with the so called freezer farm.

The debate of Freezer farm vs Consolidated Storage has been showcased on our webinar series. Some of the more specific conclusions reached on that show were:

  • Freezer Farms are cheaper to be bought and are easier to be installed
  • Freezers are more prone to failures over Consolidated walk in chambers
  • Freezer farms have significantly higher maintenance fees
  • Freezers are less power efficient than consolidated walk in chambers
  • Freezers often have no to low fail safe assurance technology
  • There are no minimal or maximal space requirements in installing walk in chamber
  • Under some external third party studies 4 common ultra low freezers have the same power efficiency grade as a walk in chamber 20 times that size in volume

Bahnson’s standard and custom environmental chambers / rooms include:

  • Walk-in temperature and humidity chambers
  • Walk-in warm rooms
  • Walk-in cold rooms
  • Walk-in freezers
  • Walk-in incubators
  • ICH stability chambers
  • Shelf life study chambers
  • HEPA filtered clean cold rooms
  • HEPA filtered clean warm rooms
  • Test chambers
  • Plant growth chambers
  • Shelf lighted rooms
  • 1% and 2% dry rooms
  • Other low humidity dry rooms

These are just a sampling of room types included in the walk-in environmental chamber series.

In the pharmaceutical market, Bahnson is determined and focused on stability rooms, that strive on meeting and exceeding the ranges and uniformities of the ICH has allowed Bahnson to become the recognized leader in chamber design, construction, and stringent performance qualification in support of our clients’ validation.

Bahnson is also a well know brand that supplies universities, medical schools, and industrial customers with chambers requiring uniform dependable room conditions for storage and testing experiments.

Their comprehensive resume includes some of the largest installations of multiple environmental rooms in notable research buildings on campuses throughout the US.

 

Get in touch with our project engineer at 800-829-5741.

 

AirTech – BENEFITS OF VETROMECCANICA’S AIR CONVEYORS

Air conveyor belts are highly recommended to convey empty PET bottles/containers without damaging them.
Vetromeccanica’s air conveyor belt guarantees the hygienic, gentle and safe handling of empty PET bottles even at high speed, indeed.

The Air conveyor has been Vetro’s flagship model since their launch in 1992. It is a solution that they have delivered to hundreds of customers in more than 70 countries worldwide. The AirTech system it The model that is designed and built only by Vetromeccanica and listed below are some of the key features and benefits of running an Air conveyor over any other solution.

– FAST AND FLEXIBLE ARRANGEMENT 
AirTech can be easily installed on the wall, on the ceiling or on the floor according to the production plant needs, structure and resources

– EASY AND FAST FORMAT CHANGE-OVER  
Thanks to its special guides adjustment system this air conveyor belt can handle every bottle format, as it utilizes an approach of hanging the bottles down holding by the neck of the PET bottle.

– AIR FLOW ADJUSTMENT 

According to the bottle format to be conveyed. This feature can be used as a clinical buffer when you need to diverse or accumulate a minimal or maximal line accumulation.

– INTUITIVE AND TOUCH SCREEN HMI 
Facilitated monitoring operations and adjustments: intuitive and easy to use HMI.

– MINIMAL MAINTENANCE COSTS

Mainly because the whole guidance system is built from stainless steel and the deteriorating elements are reduced to the bare minimum.

– ENERGY SAVING LOGIC
Reduced energy consumption of just having a couple of fan blowers to convey your complete line over motors and drivers that run a belt operated standard conveyor

– AIRTECH CAN HANDLE CONTAINERS EVEN IN CASE OF HEAVY SLOPES

Vetromeccanica has built air conveyance solutions that housed elevators, lowerators, spirals and other stems used in multi level production plants. Their air conveyor is powerful enough to lift filled bottles up and down the heaviest slopes.

 

If conveyance is in your area of interest and you want to learn how this system can be connected to your manufacturing process, give us a call now and we’ll be happy to assist.

REVAMP YOUR OLD MACHINE FOR A NEW LIFE CYCLE

Did you know that your old machinery can be upgraded with the latest generation technology to increase machine life and achieve higher performance in terms of productivity, include remote access & increase autonomy of maintenance; all of this with no downtime?
Bonfiglioli Engineering, the worldwide leader in quality control solutions, continuously supports its clients to update their equipment with the most advanced solutions available in the field: JETS system.

JETS is a full-featured implementation of the Java SE platform, optimal for embedded systems. It offers many new features designed to improve functionality, accessibility, and reporting.
Here are the reasons why you should upgrade your machinery:

  • LONGER MACHINE LIFE 
  • REDUCED COSTS 
  • NO DOWNTIME 
  • AUTONOMY IN MAINTENANCE 
  • REMOTE ACCESS 
  • INDUSTRY 4.0 SYSTEM COMPLIANCY 

Only 5 working days for installation!
Customized maintenance contracts complete with worldwide dedicated technical services are also available to meet the specific customer’s requirements.
Discover the solution most suitable for you!

Contact us to receive your personal quotation by calling 800-829-5741

Cozzoli EXCLUSIVE OFFER!

Now until the end of 2018, take advantage of a 15% discount on parts and ensure your Cozzoli and MRM/Elgin machines are in peak condition!

A way to recondition an outdated machine, restoring it to optimum performance at a fraction of the cost and time of purchasing a new machine. We can perform small retrofits through whole overhauls either at your location or in our state of the art facility.

 

Offer Includes

  • 15% discount on parts
  • Discounts on preventative maintenance
  • Consultation service call comped when recommended action is taken

 

Cozzoli currently offers multiple maintenance packages:

  • Preventative maintenance with one time evaluation or regular scheduled inspections
  • Restorative maintenance including improvements, upgrades, wear part replacement and

parts repair or re-conditioning

  • Operational & maintenance training for new employees and refresher courses for

experienced technicians

 

Preventative Maintenance can help limit downtime. Contact us today to set up a one time evaluation or arrange regularly scheduled inspections to check the condition of your machinery.

 

Restorative Maintenance keeps your machines running at maximum efficiency. Our Tech Service Department can advise replacement of wear parts and recommend improvements and/or upgrades. Parts may also be sent in for an estimate of repair/reconditioning.

 

Cozzoli and MRM/Elgin Machines, also offer Operational & Maintenance Training for new employees and refresher courses for experienced technicians. We will provide your team specialized training on your Cozzoli and MRM/Elgin machinery.

 

Our Customer Service Department can schedule performance evaluations and help get you the best deal on commonly used machine parts.

Call 800-829-5741 for more information.

Cozzoli Machine Company is your source for complete packaging and filling solutions

For nearly a century, Cozzoli has provided technologically advanced machinery for the packaging industry. Cozzoli is a global leader in the design, manufacture, distribution, and service of precision cleaning, sterilizing, filling, and closing systems. Quality craftsmanship has always been the cornerstone of our foundation and we are dedicated to continuing that tradition of excellence. The products we engineer today are designed to take you beyond tomorrow, because at Cozzoli research and development doesn’t end when a system is successful. We continually update our methods and equipment, integrating fast moving technologies that shape the products we provide worldwide.

Our expertise lies in the engineering and manufacturing of exceptional equipment custom designed to your specifications for a multi-faceted turnkey operation. As a single source provider of individual components through full lines, our projects are defined by your individual requirements. We utilize on-going technologies with design features that save time in product changeover and enhance productivity. Rugged construction and dedicated workmanship you can depend on contribute to an efficient smooth running operation.

Their most comprehensive capabilities include application analysis, product development, line integration, validation, parts and service, and installation. Whether you are a long time customer or a new client, Cozzoli will give you the same careful attention and unparalleled service.

Aseptic and non-aseptic pharmaceutical, cosmetic, health, beauty aids, personal care, food, beverage, chemical, paint, and industrial products are some of the industry segments Cozzoli serves.

 

Reach us now at 800 829 5741 and let us know how we can help you, with your next project.

Container Closure Integrity Testing Method Development and Validation for Prefilled Syringes

Utilization of prefilled syringes as a preferred container closure system for biologics has been increasing [1]. As a primary container closure system, prefilled syringes must provide an integral barrier that protects drug product stability and sterility throughout its entire shelf life. Drug manufacturers are required to check and demonstrate the system is capable of maintaining its microbial barrier integrity [2, 3]. In 2008, FDA further promoted container and closure system integrity (CCI) testing as a component of the stability protocol for sterile products

In response to the increasing regulatory expectations, the pharmaceutical industry has driven and witnessed significant technical advancements in CCI testing [5]. Instrumentation-based technologies, such as high voltage leak detection (HVLD) [6], vacuum/ pressure decay [7], mass extraction [8], and tracer gas detection (helium, oxygen etc.) [9, 10], have emerged and demonstrated improved detection capabilities compared to conventional dye and microbial ingress methods. Many of the technologies have been used for on-line 100% inspection and/or drug product stability CCI testing. In this article, we highlight our current thinking in an attempt to devise a systematic approach for CCI testing method selection, development, and validation.

General Considerations

In order to function both as a container closure system and as a drug delivery device, prefilled syringes feature many unique design elements. They usually include multiple containment compartments that are sealed by numerous interfaces. For example, the current stake needle glass syringes (Figure 1) provide a syringe barrel compartment for drug product containment and a separate needle shield compartment for needle protection. The syringe barrel compartment is sealed by the plunger on one end and by the needle on the other with the needle tip embedded in the needle shield. The needle shield compartment, sealed by the syringe barrel head,protects the needle exterior surfaces from potential contamination. The potential failure modes associated with each compartment and seal interface need to be identifi ed, assessed, and taken into account during CCI testing method development.

“In order to function both as a container closure system and as a drug delivery device, prefilled syringes feature many unique design elements.“

Furthermore, the plunger in a prefilled syringe is allowed to move within a range along the syringe barrel. When experiencing lower pressure environment during shipping and distribution, plunger movements in response to pressure variations may potentially aff ect seal integrity. Therefore, it is essential to evaluate plunger seal integrity following these special conditions.

In addition to the complex designs of prefilled syringes, the drug products packaged therein should also be considered. For example, prefilled syringes have been widely used for biologics, some of which could require extremely low temperature storage (e.g. -70°C). Since seal property of syringe components, especially elastomers (e.g. needle shields and plungers), is temperature dependent, CCI testing under extremely low temperatures could be required if theoretical justifications based on elastomer property are not adequate [11]. Moreover, drug-package interactions may impact method sensitivity and selection. For example, proteinaceous products could prevent mass transfer through CCI defects and reduce the sensitivity of a vacuum decay method [12].

Figure 1. Illustration of a stake needle glass syringe

CCI testing strategy for development

Many distinct CCI failure modes can occur throughout the life cycle of a syringe, ranging from component manufacturing, drug product filling and sealing, device assembling and packaging, to subsequent distribution and storage. It is essential to develop an overarching strategy to apply a series of CCI testing throughout the entire syringe life cycle.

CCI testing strategy development started with thorough understanding of syringe construction, design, and manufacturing processes. The CCI failure modes and eff ects associated with each aspect were first identifi ed. Using a risk-based approach, we further determined whether CCI testing is required, and if so, the intended uses and testing frequencies needed. For example, knowing the needle shield compartment seal integrity was tested by the component supplier, we elected to apply a non-routine CCI test to confirm its seal integrity upon drug product filling and sealing, and upon being assembled into devices. In contrast, for the product-containing syringe barrel compartment, we incorporated an extensive set of CCI tests into the entire product development cycle, including initial design confirmation, machinability studies, and product stability testing, to ensure CCI was achieved and well maintained.

Method selection

Table 1 lists the major CCI testing technologies available for prefilled syringes and their key characteristics. Note all the technologies have major limitations. When selecting appropriate methods, the following key aspects should be considered.

  • Suitable for its intended use. The selected method(s) must be suitable for the intended use and scope of a specific CCI test. For example, microbial ingress testing, although a good selection for media-filled syringes for fil lling process validation, cannot be used for stability testing because it does not apply to drug product filled samples. If a single method cannot meet all the testing needs, complementary methods may be applied in tandem to achieve definitive and comprehensive testing conclusions.
  • Applicable to the specific drug product-package. As previously mentioned, drug products can interact with CCI defects in various ways and may further aff ect the eff ectiveness of CCI testing methods. The method applicability to the specic product-package must be evaluated and adequately demonstrated.
  • Detection capability and eff ectiveness. Recent technologies utilizing mass extraction [8], HVLD [5], vacuum decay [7], have demonstrated reliable detection of CCI defects of 5-10 microns or smaller. These technologies are based on quantitative measurement of certain sample characteristics that can be further correlated to presence and/or sizes of CCI defects. The superior sensitivity and reliability made them preferred CCI testing methods over conventional dye or microbial ingress tests.
  • Non-destructive CCI testing. Non-destructive methods enable 100% CCI testing. In addition, they allow for further analysis of the failure modes and root causes, which in-turn provides valuable feedback for continuous improvement.

Method development

Upon establishing a preliminary method following vendor’s recommendations or literature search, we further focused on optimizing testing parameters and determining the appropriate pass/fail threshold.

Optimize Testing Parameters

First, various defect standards of known sizes (Table 2) were tested along with intact samples under different testing parameters. The correlations were thoroughly explored between key method parameters and instrument responses to intact and defect samples, aiming to identify a set of parameters that yield optimized separation between defect and intact samples (i.e. signal-to-noise ratio).

Refine Pass/Fail Threshold

To establish the preliminary pass/fail threshold, the optimized method was used to test multiple lots of filled intact syringes representing relevant product variations, including various packaging component sources/lots, drug products batches, as well as packaging sites and lines. The testing results were statistically evaluated to define the instrument baseline and variation (σ) for intact samples. Ideally, the pass/fail threshold should be at 10σ above baseline (i.e. above limit of quantitation LOQ). Defect standards of known sizes were then tested to further finalize and verify the pass/fail threshold. In cases where the 10σ threshold did not provide the desired sensitivity (as illustrated in Figure 2), the threshold setting was further adjusted between 3σ above baseline (i.e. limit of detection LOD) and the 10σ LOQ to achieve the desired detection sensitivity while keeping false positive detection probability (i.e. intact sampled detected as Fails) within the acceptable level.

Verify Method Effectiveness

Although defect standards are essential for initial method definition and optimization, they do not necessarily fully represent natural CCI defects. Natural CCI defects are of a large variety and most of them are not simple orifices or tubes. Therefore, the method performance was further evaluated using “real-world” CCI defects.

A good “real-world” defect sample set should represent all major probable CCI failure modes. Actual CCI defects could be obtained from various sources, such as reject samples from incoming or inprocess controls. When actual defect samples were not available for a specific failure mode and defect type, simulated defects were used.

A few iterations of the steps above may be needed to finalize the method. For methods used for stability testing, additional studies were performed to verify the methods are capable of detecting “aged” samples. Usually it was demonstrated by placing a set of productfilled samples with known defects on a stability study and testing the defect samples at various time points.

Method validation

Table 1. Characteristics of Major CCI Testing Methods

Table 2. Commonly-used CCI Defect Standards

In general, ICH analytical method validation guideline [14] was followed to validate instrument-based CCI testing methods. The key method characteristics, such as detection limit, range, accuracy, precision and robustness, were evaluated and demonstrated during the validation stage. In order to demonstrate detection capability in size, micro-pipettes, microtubes, and laser drilled standards of known sizes were usually used, which also allowed direct comparison of testing capability of various methods.

CCI testing methods were validated for the specific drug productpackage. Because the drug product formulation and package design may change during early development phases, a phase-appropriate approach was implemented to validate methods in concert with product development phases. For example, we utilized scientifically sound methods to support packaging system qualification and development stability studies. Once the product formulation and packaging design were finalized, the methods were then fully validated in support of primary stability and process validation CCI testing. Additional long-term method robustness may be further validated prior to implementing the method in QC laboratories for routine testing.

Figure 2. Approach to establishing Pass-Fail threshold

Summary

Appropriately selected and validated methods are essential for demonstrating container closure integrity during package and drug product development and manufacturing. However, it should be realized that current CCI testing technologies do not off er an ideal method that satisfy all prefilled syringe CCI testing needs. An integrated approach incorporating CCI testing and other engineering and administrative controls must be taken to ensure overall container closure integrity.

 

Fedegari Washing Solutions

Washer-Sterilisers (independent and combined use)

One of the most inovative solutions in the Fedegari washer range is also a unique and original. Combined Washer-Sterilisers have the ability to operate in three ways, they can be bought to be independent washing machines, operate as back up sterilisers when washing is not required or perform as a hybrid washer/sterilisers which allow you to wash, sterilise and dry machine parts, vessels and other materials in a single cycle.

 

Steam Washers

Fedegari high performance GMP Steam Washers capitalize on the experience acquired with the Combined Washer-Steriliser series within the pharmaceutical market. These machines represent a cost-effective solution for the highest performances. Fedegari steam washers use an integral steam generator to optimize performance and reduce operational costs. The state-of-the-art modular customizable rack can be adapted to every specific load configuration.

 

Free Standing Washers

The Fedegari laboratory glassware washer combines excellent washing and drying performances with first class materials, economical consumption, safety and operating ease. With its dedicated process controller and its integrated steam generator that allows steam injection directly in the chamber, this machine is suitable for use in many different applications.

 

Later this month we have prepared a special webinar broadcast with Fedegari that will focus on The Key Factors of an effective Pharmaceutical Cleaning Strategy.

For more information on the washing solutions by Fedegari, give us a call and we’ll be happy to assist you.

 

Dryer designed and built by VETROMECCANICA

EOLO DRY is a drying system designed and built by VETROMECCANICA S.R.L.

 

EOLO DRY is characterized by a manual adjustment system of the air blades that allows the ideal positioning for any format (bottle or can) and also for the neck. This drying system allows to obtain optimal results in the various phases and types of labeling, sealing and coding.

EOLO DRY is composed of blowers that feed the specifically designed manifolds to obtain the right balance between pressure, flow rate and temperature of the air that is warmed up by the compression.

The Eolo Dry System is AVAILABLE IN:

  • MODULAR SYSTEM
  • STAND-ALONE SYSTEM

 

MAIN CHARACTERISTICS of the EOLO DRY:

  • AISI304 STAINLESS STEEL STRUCTURE with polycarbonate opening doors
  • MODULAR SYSTEM: quick & easy installation on pre-existing lines
  • HIGH EFFICIENCY LATERAL CHANNEL MOTORS

§  4 ADJUSTMENTS TYPES OF THE AIR BLADES by: ·        DEPTH, ·        HEIGHT, ·        LONGITUDINAL INCLINATION, ·        BLADE INCLINATION

  • ANODIZED ALUMINUM AIR BLADES: aluminum treatment that assures lifelong guarantee of the blades
  • INVERTER ON EVERY BLOWER: allowing to optimization of the speed of the air leaving the blades according to needs of the product that’s supposed to be dried
  • ENERGY CONSUMPTION OPTIMIZATION
  • Waste water and drop collection
  • NOISE LEVEL COMPLIES WITH SAFETY RULES
  • COMPLIES WITH EC REGULATIONS, NEMA and CSA

 

Technical data:

 

Here is a video demonstration of the Dryer system

https://www.youtube.com/watch?v=xv–10AuUr0

 

For more information regarding the EOLO Dry systems please call our HQ at 800-829-5741

Setting up a pharmaceutical cleaning strategy

Cleaning is an essential practice for any pharmaceutical activity. Difficulties can arise from the fact that the concept of ‘clean’ is not easily defined or can be related to non-evident residues.

 

Defining differences between sterilization and cleaning treatments, for example, is important to understand in-depth the main problems and peculiarities when setting up a cleaning strategy.

 

The kinetics of ordinary sterilization processes are well understood: to sterilize means to destroy or inactivate microorganisms. In this perspective, we know the target and we can define it in terms of a number (CFU/unit) and resistance (D, z). Though the definition of sterile product/ item is probabilistic (PNSU – Probability of Non-Sterile Unit or SAL – Sterility Assurance Level), it is universally accepted.

 

On the other hand, for a cleaning process, the “enemy” is not defined and, in any case, can vary on a case-by-case basis: residue of previously processed product, diluents, solvents, lubricants, microorganisms, etc. There is no absolute definition of cleanliness. The kinetics of the cleaning procedure are unknown. Consequently, also the definition of “cleaning dose” to be provided is undetermined.

 

In these conditions, even regulatory bodies struggle. Essentially, they allow manufacturers considerable flexibility in establishing their own cleaning specifications. The FDA, for example, does not define methods describing how a cleaning process should be validated. FDA inspectors have to assess the rationale used to set the cleaning limits, making sure that their basis are scientifically justifiable and grounded on adequate knowledge of the materials involved.

This is the reason why Fedegari have published a new e-book: to discuss the main challenges on taking the right decisions while developing a cleaning strategy. New requirements have been faced by manufacturers, new targets have been fixed and the evidence that these are met is shown through successful case studies. Our aim was to highlight the best practices and existing solutions to support your decision-making.

This is certainly a multidisciplinary issue that involves various company areas: from “Regulations” to Engineering, from Quality Control lab to Production department. Fedegari have collected contributions of all these areas together in order develop a robust and repeatable cleaning process.

In their new E-book you will find:

  • Aspects Distinguishing a Cleaning Process
  • Steps for Setting Up a Cleaning Procedure
  • Case Study I: Removal of Bacterial Endotoxins
  • Case Study II: Application of a Washer Sterilizer
  • Case Study III: Soil Removal From Smart Plate

 

Download it here for free. If you want to discuss your cleaning strategy with us give us a call at 800-829-5741.

 

 

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