Nikolaus Ferstl, University Hospital of Regensburg
Dr Markus Keller, Fraunhofer Institute for Manufacturing Engineering and Automation (IPA)
Robert G. Schwarz, FH Campus, Vienna
Harald Stahl, GEA
This GMP training aims at unveiling possible risks of cross contamination during the production process of Pharmaceutical products and APIs. This is especially important for patients’ safety, product quality and to be in compliance with chapters 3 and 5 of the EU GMP regulation as well as the new EU GMP Annex 1. The prevention of cross contamination is part of the contamination control strategy and has to be documented accordingly taking into consideration QRM principles according ICH-Q9.
You will learn
- how to detect possible risks
- how to avoid cross contamination
- how to prove the avoidance of cross contamination
- how to document a regulatory compliant strategy
Cross Contamination is one of the highest risks for patients using pharmaceutical products. Not only the presence of small amounts of antibiotics or other highly potent compounds in medicinal products can cause severe damage, but also carryover of one product into another pharmaceutical product is of high risk to the patient. According to the Medicines & Healthcare Products Regulatory Agency in the United Kingdom for example, Product contamination is the second to third highest reason for recalls in the UK in recent years.
The EU commission already reacted on that in 2015 by updating the chapters 3 (premises & equipment) and 5 (production) with the focus on minimizing the risk of cross contamination. Already three years before a new EMA Guide on setting health-based exposure limits was published. This new guide has massive impact on the dedication of facilities and also on the calculation of limits for cleaning validation. Limits for the maximum carryover now have to be calculated by considering the toxicological/pharmacological properties of each single product, answering the question: how much cross contamination is allowed. The latest document addressing cross contamination is the new EU GMP Annex 1. It contains several paragraphs dealing with cross contamination and contamination in general which includes a risk-based Contamination Control Strategy (CCS) aligned with Quality Risk Management principles according ICH-Q9.
Reasons for cross contamination can be manifold and caused by technical as well as organisational deficiencies. Insufficient cleaning of equipment, poor facility design or inappropriate design of the HVAC system may be reasons as well as contamination via personnel or primary packing material. But also, the design of the production process itself can be the cause for cross contamination, for example due to open product handling during transfer or sampling operations in shared plants without adequate measures.
It is therefore extremely important to mitigate the risk of cross contamination, starting already at the design phase of processes and equipment. In addition, it is essential to understand howcontamination risks can be detected. Some measures include quality oversight walks in production areas or reviewing the documents (SOPs, technical drawings, etc.) already during process development, design qualification and additionally on a regular basis which has to be predefined. This mitigation of cross contamination risks should be included and regularly reviewed – and updated if required – as part of the contamination control strategy (CCS) which has to be documented accordingly.
This training is aimed at Production, QA and engineering Departments of pharmaceutical companies to maintain product Quality and patient safety in a regulatory compliant and agile production life cycle. Suppliers for the pharmaceutical industry are also addressed in order to better understand the requirements of their customers.
We use Webex for our live online training courses and webinars. At www.gmp-compliance.org/training/online-training-technical-information
you will find all the Information you need to participate in our events and you can check if your system meets the necessary requirements to participate. If the installation of browser extensions is not possible due to your rights in the IT system, please contact your IT department. Webex is a standard nowadays and the necessary installation is fast and easy.
Regulatory Requirements: Contamination Control Strategy & Cross Contamination
- The view of EMA
- The view of US-FDA
- Shared facilities regulations
- Contamination and sterile products
Sources of Contamination – Modes of Cross Contamination – Segregation
- Do different sources mean different impact?
- Where cross contamination could occur and different likelihoods
- Is segregation a no brainer?
- Cross contamination in Biotech
Containment Solutions – Avoiding Exposure – Minimizing Cross Contamination
- Exposure and how to calculate
- Equipment and containment concepts
- Closed product handling
- Material Transfer
- The PDE/ADE concept: how much contamination is allowed?
- Avoiding of cross contamination
- Air born contamination
- Contamination of surfaces
- Verification of the tightness of a containment system
Cross Contamination through poor Organisation
- Organisational points to consider
- The human factor
- The importance of training and motivation
Cross Contamination through poor HVAC Design
- Airborne particles
- Pressure / hygienic zones – maintaining over pressure
- The clean corridor Concept
- Simulation and visualisation of air flow
- Classification of ventilation Systems
- Concepts for HVAC Systems
- Components of AHUs (filters, Duct work, etc...)
- Classification and change of filters
- Control and monitoring strategies
Cross Contamination through poor Equipment Design
- Cleanability of equipment as the key to avoiding crosscontamination
- In-line cleanability? – Cleanability for parts that are disassembled?
- Importance of drainability (cross-contamination by product and detergent residues)
- Gap-free and dead-space-free design of system components
- Components (connections, valves, pumps, sensors)
- Mixing and preparation vessels, bioreactors
- Cross-contamination due to lack of technical support
- Deterioration of surface Quality
- Wear of static and dynamic seals
Cleaning & Cleaning Validation
- Poor Cleaning – main reason for cross contamination
- Dealing with multipurpose strategies in cross contamination Control
- Cross Contamination – main focus of cleaning validation
Documentation: CCS, HBEL assessment, QRM
- Cross contamination control and CCS
- HBEL – from the environmental risk to patient’s risk
- Cross contamination control – it is all about QRM