Robert G. Schwarz, FH Campus Vienna, Austria
Many questions relative to cleaning validation are still open and have to be answered within the companies:
- What does the cleaning validation concept have to look like to be GMP-compliant and cost-effective?
- Which risk analyses are applicable to cleaning validation?
- How helpful can a riboflavin test be?
- Which maximum value is scientifically acceptable, especially in the field of APIs?
- Which sampling procedure is appropriate for which process and facility?
- How can you cut costs by means of bracketing?
- How are critical areas defined?
- Is cleaning evaluation the solution for seldom manufactured products?
- Which microbiological maximum values are valid in the areas of non-sterile dosage forms and APIs?
- Special aspects of cleaning validation in biotech API plants
These questions will also be discussed with the help of practical examples.
In the manufacture of medicinal products and APIs, the cleaning of facilities and equipment is an important measure to avoid contamination and cross contamination. In compliance with the GMP regulations, cleaning is performed and documented according to the described procedures. In the past, cleaning effectiveness was often monitored only visually. However, residuals of APIs and excipients as well as of detergents are increasingly an issue in inspections and audits. The success of cleaning procedures has to be validated. In addition to the FDA “Guide to Inspection – Validation of Cleaning Validation Processes”, the PIC/S document PI 006 and Annex 15 address cleaning validation in a separate chapter. Moreover, the ICH Guideline Q7 “GMP for APIs” also requires cleaning validation – as well as two Guidelines by APIC, the association of European API manufacturers.
A Guideline from EMA on Dedicated Facilities and Exposure Limits for Cleaning Validation and the revised Annex 15 deal now with a PDE (Permitted Daily Exposure) approach.
The Annex 1 revision and it’s Contamination Control Strategy (CCS) also has an impact, especially on Cleaning Validation for sterile dosage forms.
The Pre-Course Workshop and the Main Course both are directed at staff of R&D, production and quality assurance involved in cleaning validation. They also address engineering companies and manufacturers of cleaning devices/equipment interested in learning more about the pharmaceutical industry’s viewpoint and in exchanging experiences.
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.
- EU GMP Guideline Part I, II and III
- EU GMP Guideline Annex 15
- EMA “Shared Facilities Guideline” (incl. PDE concept)
- PIC/S PI 006
- APIC Cleaning Validation Guidance for APIs
- PDA TR 29 – “Points to Consider for Cleaning Validation
- ISPE Cleaning Validation Life Cycel – Applications, Methods, and Controls
- FDA 21 CFR 211.67
- FDA Guide to Inspection – Validation of Cleaning Processes
Practical Pre-Requisites I – Hygienic Equipment Design
- What is hygienic design?
- Material aspects
- WIP/CIP aspects
- Riboflavin test
Practical Pre-Requisites II – Cleaning Process Development
- Developing a cleaning process – which steps are necessary?
- Which residues are common
- Type and selection of cleaners
- CIP vs WIP vs manual cleaning
- Cleaning Documentation
Sampling during Cleaning Validation
- How to define sampling points?
- Sampling techniques
- Analytical requirements
Cleaning Validation – incl. Practical Approaches
- Cleaning Validation Concepts
- Hold time studies (DHT, CHT)
- Cleaning Validation Risk Management
- Cleaning Validation Plan
- Cleaning Validation Report
- Cleaning Validation life cycle (Revalidation, Ongoing Cleaning Verification)
- Cleaning Evaluation
Workshop – Setting Sampling Points
- Setting sampling points on a risk-based Approach – what to consider
- Sampling point selection based on sampling technique and analytical method
- Different sampling points for different purposes
Handling Deviations and OOS during Cleaning Validation and Ongoing Cleaning Verification
- What is an OOS, what a deviation regarding Cleaning Validation?
- GMP-compliant documentation of OOS and deviations
Workshop – Case studies of Non-Conformities during Cleaning Validation and Ongoing Cleaning Verification
- Is always the cleaning process to blame?
- Which actions are adequate based on the Investigation and root cause?
- Actions depending on the time-point of detecting the Non-Conformity
- Does a Non-Conformity mean revalidation?
- Does a Non-Conformity always lead to Batch rejection?
Special Topics of Cleaning Validation
- Segregation & shared facility Guideline
- Cleaning Validation in Biologics & Biotech production
- Differences between chemical and biotech APIs
- Acceptance criteria for biotech APIs
- Analytical methods to detect biotech APIs in Cleaning Validation
Q & A sessions
Five Q &A sessions (one during the pre-course, two on day 1 and on day 2 of the main course) ensure interaction and that your questions are answered.