Control of Parenterals - Container/Closure Integrity Testing & Visual Inspection Systems

Name: Control of Parenterals - Container/Closure Integrity Testing & Visual Inspection Systems
Start: 2020-10-08
End: 2020-10-09
Location: Control of Parenterals - Container/Closure Integrity Testing & Visual Inspection Systems

6-8 October 2020

Barcelona, Spain

Course No 17272

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Tel.: +49 (0)6221 / 84 44 0 E-Mail: info@gmp-compliance.org

Speakers

Dr Martin Becker, IDT Biologika
Martin Dearden, ECA Visual Inspection Group
Dr Helmut Gaus, WinSol, previously Boehringer Ingelheim
Roland Koch, Gasporox
Felix Krumbein, Roche
Christof Langer, OSConsulting
Dr Daniel Müller, GMP-Inspector
Dr Tobias Posset, Roche
Dr Brian Turnquist, Boon Logic
Désirée Womser, Novartis

Objectives

CCI Testing

Different products and different container types require different testing methods: this event aims at giving an overview of the different CCI testing systems which are applied during production and as part of the quality control system. Apart from technical aspects the regulatory requirements on CCI testing will be highlighted as well as the applicability of inline and offline testing.

Visual Inspections Systems

Main topic of this course is the detection of defetcs like particles in injectables and their evaluation during batch release. Besides the current regulatory requirements with regards to particulate matter, routine 100% inspection of injectables will be addressed. Manual inspection as well as automated inspection systems will be covered, including validation, training, defect categories, AQL testing, trending and batch release considerations.

Background

CCI Testing

An intact container closure system, which is the sum of packaging components that protect the dosage form, is the pre-requisite for a safe and sterile drug product. The CC system protects the product from microbial contamination and also from exposure to gases or water vapour or the loss of solvent. Container Closure integrity testing is therefore a regulatory requirement and it is part of the whole life cycle of a sterile drug product.

Initially this testing was performed as part of the initial development of the packaging system and the system’s suitability verified in stability studies including on-going stability. Over the years, the expectation was raised to perform batch by batch verification with latest trends to 100% inline or offline testing wherever possible.

We will discuss and answer questions like:

What are the current and upcoming GMP- and compendial requirements in the US / EU / RoW?
Will container closure integrity testing change to 100% inline testing?
What does the Annex 1 require?
How do we have to define’ tight’?
Which testing technologies are available and suitable?
Is blue dye testing still a standard? And how does modern blue dye testing look like?
CCI testing of prefilled syringes
CCI testing of lyo & liquid vials
CCI testing of ampoules

Visual Inspections Systems

In most cases particles found in parenteral medicines will lead to a quarantined product or even to the recall of the product – as we have seen in the last years in the cases of several pharmaceutical companies. Responsible staff in charge will have to start root cause analysis to find the source of the particles and will have to do an evaluation of batches already shipped.

There is still confusion within the global pharmaceutical industry with regard to the requirements for testing for visible particles. After the USP chapters <790> and <1790> were published, things have become much clearer, at least for the US. But still, lots of questions arise, e.g. concerning re-testing, detection capabilities and revalidation of inspection Systems.

Furthermore there has been a recognisable trend towards automated inspection machines throughout the last years. The challenge for pharmaceutical companies is to find a suitable machine for their products and to determine reasonable inspection parameters during qualification and validation. But also during routine process there are questions arising like re-testing and the usage of test-sets, doing AQL-Testing as well as the adjustment of parameters of the vision systems.

We will address those topics during the conference and discuss and answer questions on

The latest compendial requirements concerning particulate matter
Compliance with the revised Annex 1
Training and qualification of operators in the manual inspection
Validation and operation of an automated inspection system
Trending and monitoring of visual inspection data
Correct AQL testing as part of the batch release
Re-inspection of defect fractions
Usage of artificial intelligence in visual inspection

Target Group

CCI Testing

This course is directed at specialists and executives from the areas engineering and production and QA dealing with the implementation and operation of systems for the container/closure-integrity testing of sterile medicinal products.

Visual Inspections Systems

This course is directed at staff from sterile operations, that is production, quality assurance and engineering. But also suppliers of primary packaging materials and inspections technology are target group of this Event.

Best Practice Paper

All participants receive the current version of ECA’s Best Practice Paper on “Visual Inspection” for free.

Programme

Container Closure Integrity Testing of Parenterals

Container Closure Integrity Testing of Sterile Drug Products – Requirements, Expectations and Exaggerations

Container Closure Integrity during development, qualification and stability testing
Regulatory, Pharmacopoeial and GMP requirements
System integrity versus container damages
Patient risks – do we need batch by batch testing?
Industrial best practices

Expectations of a GMP-Inspector regarding to Container/Closure Integrity Testing

Regulatory documents on container / closure integrity testing (an overview)
Testing methods for CCIT & validation strategies
Current situation on CCIT in pharmaceutical industry & challenges
Inspection findings & experience

Overview of Container/Closure Integrity Testing Technologies

The presentation gives a complete overview of the different aspects of leak testing to do CCIT in the pharmaceutical production. The systems presented can be used for the CCIT of vials, ampoules, syringes, BFS, IV bags, blisters etc.

Leak, leak rate and the relevant physical units
Leak test methods
- Pressure change methods (vacuum, pressure and LFC)
- Head Space Analysis using TDLAS
- Helium Leak Test and other Mass Spectroscopy Systems
- High Voltage Leak Detection (HVLD)
- Force Sensing Technology
Capabilities and examples of the different methods
How to select the right method
How to generate positive controls

Case Study: 100% Testing of Vials

System setup
Validation
Routine operation

100% inline CCI Testing of Ampoules

High Voltage inline testing: method description
Integration in the production process
Limits of the system
Qualification of the system
Validation
Routine Operation

Integrity Testing of Prefilled Syringes

Sampling plan
He-leak testing
Limitations of the He-leakage test
Cross validation with mCCI

Visual Inspection Systems

Regulatory Requirements for the Visual Inspection of Parenterals

Compendial Requirements
- 100% visual inspection & AQL testing
- PharmEur, USP, JP - similarities and differences
News from the Annex 1 revison
Risk Management Considerations

Expectations of a GMP Inspector regarding Visual Inspection

Regulatory documents on visual inspection of parenterals (an overview)
Manual inspection, semi-automated inspection (personnel, working place, equipment, training & qualification)
Automated inspection (incl. validation strategy)
Routine operations, AQL testing, handling of (r)ejects
Inspection findings & experience

Manual Visual Inspection – Theory and Practical Aspects

Probabalistic nature of visual inspection
Defect categorisation
Differentiation of test kits for training, qualification and routine
Qualification and training of personnel
Standardisation of working conditions in Manual inspection
Usage of the Knapp and the modified Knapp test

Automated Visual Inspection – from Setup to Routine Use

Limitations of automated inspection
Setting up a qualification strategy for automated systems
Cross validation during the PQ phase of an automated system
Importance of particle detection rates
System suitability, requalification and revalidation
Inspection of eject fractions
The Roche Inspection systems: manual, semi-automated and fully automated inspection

Requirements, Composition, and Handling of

Test Sets
Definition of defect categories
Set-up and composition of a test set
Test sets and their use for training, qualification and routine
Handling and release of test sets
Documentation

Handling Inherent Particulate Matter of Biologics

in Visual Inspection
Challenge of inherent particulate matter in drug product solution
Appearance and characteristics of inherent particulate matter
Impact on visual inspection
Handling inherent particulate matter in routine visual inspection
Establishment of a life-cycle management approach

Re-Inspection of Defect Fractions in

Visual Inspection
Different scenarios will be covered such as:
Re-inspection or additional inspection of “grey-channel” units from (semi-) automated inspection
Re-inspection in case of exceeding alert limits or
AQL failures
Focused re-inspection
Inspection approaches in case of investigations due to unexpected particles (e.g., to determine frequency of occurrence of visible particles when particles are found during release/stability testing

Automated Visual Inspection Based on Unsupervised Machine Learning

Vector segmentation using unsupervised machine learning
Characterizing variation using computer vision
Learning normal variation in defect-free bottles
Visual inspection via anomaly detection

Particle Testing and the Correlation with Trending and Batch Release

Why do we Monitor (What is it all about)
Data and measurement
The AQL trap
Improvement process map
Investigation and routine analysis,
Release Process. “To AQL or not to AQL that is the Question”
Product release: “Falling off a log”

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