Dr Martina Breuer, Haupt Pharma Münster GmbH
Walid El Azab, STERIS Corperation, Belgium
Peter Mungenast, Merck KGaA
Robert Schwarz, Shire, 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 of Cleaning Validation”, 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 new Guideline from EMA on Dedicated Facilities and Exposure Limits for Cleaning Validation and the revised Annex 15 now deal with a PDE (Permitted Daily Exposure) approach.
This course is directed at staff of R&D, production and quality assurance involved in cleaning validation. It also addresses engineering companies interested in learning more about the pharmaceutical industry‘s viewpoint and in exchanging experiences.
Note: The number of participants is limited.
Fundamental Concept of Cleaning Principle and Life Cyle
Cleaning Validation Concepts
- Clarifying the international regulatory evolution
- Cleaning design and processes
- Type and selection of cleaners
- Soil residue evaluations (Worst Case selection)
- Determination of the critical parameter (SMART objective)
- Sampling selection based on a risk-based assessment
- Cleaning documentation life cycle
Special Aspects of Cleaning Validation
- Introduction of relevant Guidelines
- CV Concepts
- CV Risk Management
- CV Plan
- CV Report
- CV Revalidation, CV Verification
- Typical inspection findings, warning letters
- Cleaning Validation in Biotech API Plants
- What is different between chemical and biotech APIs?
- Acceptance criteria for biotech APIs
- What is the adequate analytical method to detect biotech APIs in cleaning validation
Cleaning Evaluation and Validation in Chemical API Production
- Acceptance criteria
- Cleaning methods: CIP, WIP, manual cleaning
- Random Controls
- Hold time studies: DHT, CHT
- Validation of analytical methods used for CV
Technical and Organisational Aspects on Equipment Regarding Cleaning Procedures
- Differences regarding cleaning in API production to the production of medicinal products
- The challenges of API production
- Acceptance criteria
- Adequate sampling
- Is cleaning evaluation accepted by GMP?
How to write a Cleaning Validation Protocol
- Design and material aspects
- CIP aspects
- Riboflavin test
- Team and project validation creation (benchmarking best practice)
- GMP requirements and best practice for a protocol redaction and content
- Quality attribute to be tested for non- and sterile manufacturing
- Sampling and analysis methods overview
- Examples through a case study – validation and implementation in routine