If you have any questions, please contact us:
Tel.: +49 (0)6221 / 84 44 0 E-Mail: firstname.lastname@example.org
Dr Gerhard Hauser
European Hygienic Engineering and Design Group (EHEDG)
Dr Jean Denis Mallet
ECA & Former Head of the French Pharmaceutical Inspection Dpt. AFSSAPS
Senior Consultant GMP-Engineering
Dr Ingrid Walther
Former Head of the Business Unit iv Drugs, Fresenius
This course explains how the requirements laid down in the GMP and FDA regulations can be put into technological and engineering practice. The whole lifecycle from the design, the qualification and the maintenance of equipment is covered. The new Annex 15 of the EU GMP Guide plays an important role here as well.
Technical compliance is a wide field, especially when taking into account the ICH framework which covers the whole lifecycle of pharmaceutical manufacturing.
It does not only mean to comply with regulatory guidelines but also with submissions and the technological state of the art, meaning ISO and other standards as well as accepted good practices in the pharmaceutical industry.
In this GMP course we want to focus on the main topics with regard to compliance in the technical environment:
Technical QA aspects:
There are a number of quality assurance systems which are crucial for the technical units. Most important are changes and deviations (as they also can occur in technical environment) which have or might have a direct impact on the pharmaceutical material produced. And even more important is the validation system, where the qualification of equipment, utilities and facilities has to be part of.
GMP Facility & Re-Construction
Designing an appropriate layout belongs to this part as well as understanding what the GMP requirements for the cleanrooms and for the HVAC systems are, depending on the type of manufacture. Re-Construction during on-going manufacture is supreme discipline in this field.
GMP-compliant design of equipment
A GMP-compliant design of equipment is the basis for fulfilling the technical requirements. In this respect, engineering assumes a prominent role in ensuring the safety of medicinal products. In this context, the need for material certificates is often subject to discussion.
Validation / Qualification
Validation / Qualification
Not only GMP regulations but also inspectors consider qualified equipment and validated processes as the prerequisites for producing pharmaceutical quality. The identification of the equipment that has to be qualified by means of a risk analysis is a crucial point. This field has now re-gained considerable attention as the regulations are changing: After FDA’s new guide on validation (and process verification) also Annex 15 of the EU GMP Guide has been revised.
Preventive maintenance in pharmaceutical production is an essential element of the Pharmaceutical Quality System. Systems for calibration & handling of repairs are of equal importance for maintaining the qualified state. That’s why maintenance and calibration are parts of an efficient requalification system, besides the change control and deviations systems of course. Finally, auditing the own technical suppliers is a recurring activity from the beginning of a project until the outsourcing of engineering activities later on.
This course is directed at staff in pharmaceutical engineering departments, at technicians, engineers, planners as well as plant constructors and equipment suppliers who are involved in tasks related to engineering work in a cGMP environment.
QA systems with technical relevance
Part 1: Change Control, Technical Changes and
Identification of „Changes“ - What has to be handled under Change Control?
CC-Workflow and pitfalls
Change Management in Routine Operations vs. Project work
Marketing Authorization - Regulatory Affairs for Engineers
Part 2: Deviations, CAPA & Malfunctions
Deviations in the technical environment
Documentation in logbook and higher-level systems
Evaluation of technical deviations
When does a deviation require CAPAs?
Handling of alarms
Correlation between changes, deviations, repairs and maintenance
Managing risks in the technical environment
Risk management tools
Qualification, Re-Qualification & Commissioning
What to write in a URS & what not
Using risk analysis from kick-off to routine operation
Handling impact and non-impact systems
From URS to PQ: step by step
How to ensure traceability?
System Verification / Validation
Re-Qualification: How to..? And how often?
Materials and Surfaces
Which materials can be used and for what purpose?
Stainless steel, plastics, polymers,…
How smooth have surfaces to be? Roughness and structures of cleanable surfaces
What are the requirements on welding?
Effects of corrosion, failures, and damage
GMP-compliant Equipment Design
Open and closed systems
Overview on important construction details for sterile and non-sterile applications
Design of gaskets and problems with gaskets
Examples of GMP-compliant equipment
GMP Zone Concepts (sterile/non-sterile/highlypotent)
Basic GMP requirements for materials & pharmaceuticals handling
Physical requirements (areas) vs Dynamic requirements (HVAC)
Finding the correct requirements depending on the manufacturing operation
Defining an appropriate layout and air lock concept
Defining personal & material flows
Product vs Personal Protection
Product Protection concepts, types of air flows
Avoiding Cross Contamination: the EMA idea
The future of barrier systems (isolator and RABS)
GMP Class Requirements (HVAC and Barrier Systems)
Some HVAC system concepts (e.g. fresh air / recirculated air)
Understanding the main parameters (volumes, pressure, cleanliness, etc.)
GMP Classification and ISO standards, and their interaction
The basics of air filtration and flushing air circulation
Particle testing depending on the cleanroom zone
Microbiological monitoring on a cleanroom
Requirements on construction of floors, ceilings and walls
Classification, Qualification, Requalification of Cleanrooms
Upgrading, Re-construction and Renovation of
Required as built documentation to start
What to consider in re-construction projects?
How to protect the ongoing manufacturing operations
Protection of products
Protection of equipment, rooms and HVAC
Flow concepts and control of external personal
Access control, pest control, cleaning
Documentation of protective measures
Examples from recent projects
Qualification and Management of Technical Suppliers
Contract management: Commercial- vs. Engineering- vs. GMP-issues
Selection and auditing of suppliers with a risk based approach
How much GMP must a supplier have?
Review of suppliers and their performance
How to audit a technical supplier?
Examples of managing suppliers for equipment, technical services, ...
Pharmaceutical Water Systems
Generation: Purified Water, WFI, Pure Steam
Components: working principles and hazards (Softener, EDI, RO,...)
Storage and Distribution concepts
Sanitisation principles, avoidance of biofilms
Automation, Instrumentation, Trending
How to handle OOS in a water system
Maintenance & Calibration
Life-cycle model of pharmaceutical equipment
How to set up and maintain a maintenance/calibration system
Definition and control: frequencies, activities, tolerances, acceptance criteria, etc.
Timing of activities
Documentation & labeling
Impact of the new GMP Thinking on Engineering
Impact of the new Annex 15
State of validation / qualification in the US
Impact of ASTM E 2500 on European projects
Changes coming from ICH Q 8-10
How to comply with EU and US requirements in technical projects