27/28 September 2022
Emerich Grassinger, Takeda, Austria
Dr Gerald Kindermann, Capgemini Engineering, Switzerland
Dr Michael Möhlen, Valneva Austria, Austria
Prof Dr Martin Wesch, Wesch & Buchenroth, Law Office, Germany
The aim of this course is to demonstrate the process of the qualification of starting materials (APIs and excipients) and packaging materials (primary and secondary) and to define the prerequisites for implementing a system for reduced sampling and reduced testing for these products. This system has to be in compliance with the actual GMP requirements in Europe and in the US, though. Case Studies will show how to define and optimise sampling and testing procedures and you will discuss further details in a parallel session with 3 workshops.
Testing active pharmaceutical ingredients, excipients and packaging materials is one of the main tasks of the quality control units in the pharmaceutical industry. It must be ensured that the necessary tests are conducted on the incoming goods and that the materials are released only after their quality was judged as satisfactory.
According to the revised Chapter 5 – Production – of the EU GMP Guide in operation since March 2015, the selection, qualification, approval and maintenance of suppliers has to be documented and the level of control has to be proportionate to the potential risks posed by the individual materials. Manufacturers of medicinal products are responsible for testing the starting and packaging materials as described in the marketing authorisation dossier. However, it is explicitly accepted to outsource these testing activities, if the following requirements are fulfilled:
a. Distribution controls (transport, wholesaling, storage and delivery) to ensure the maintenance of the quality characteristics of the starting materials
b. Audits performed at appropriate intervals at the sites carrying out the testing
c. A certificate of analysis signed by a designated person with appropriate qualifications and experience
d. Significant experience in dealing with the starting material manufacturer (“history of compliance”)
e. Full analyses that are performed regularly by the medicinal product manufacturer or a contract laboratory acting on behalf of the manufacturer to compare the results with the supplier’s certificate of analysis.
It is the aim of this GMP Education Course to show how these requirements can be put into practice.
Other focus areas of this course are the regulatory requirements for sampling, the design and qualification of sampling areas and the handling of varying specifications in the different pharmacopoeias for identical APIs and excipients used for finished drug products dedicated for the markets in Europe, in the US, and in Japan. Must different tests be conducted according to EP, USP, and JP, respectively?
The course programme will be completed by a lawyer’s presentation about the legal and contractual liability of suppliers for defect products.
This GMP Education Course is directed at all those employees from quality control units in the pharmaceutical industry (including heads of quality control and laboratory managers) who are competent or responsible for sampling, testing and release of starting materials (APIs and excipients) and packaging materials (primary and secondary). This course is also of interest to personnel from quality assurance and to those employees from API, excipient or packaging material suppliers who want to inform themselves about the requirements of the pharmaceutical industry on the testing of these materials.
Regulatory Requirements for Sampling Procedures
- API and finished goods sampling
- Regulatory requirements
- EU GMP Part 1, Chapters 4, 5, 6
- EU GMP Part 2, Chapter 7
- EU GMP Chapter 4
- EU GMP Annex 8
- EU GMP Annex 19
- Other regulations
- US/FDA Requirements
- WHO - PIC/S - ISO 2859-1 (former Military Standard)
- Supplier qualification and audits
Design and Qualification of Sampling Areas for Incoming Goods Products
- Sampling area for raw materials, APIs and excipients
- Layout and design of premises and equipment
- “Cleanroom”-like classification?
- What are the appropriate environmental requirements for sampling areas?
- How to qualify and maintain sampling areas?
- Is a change of pallets/removal of cart boxes required?
- Are expectations increasing? - Lessons learned during inspections
Supplier Qualification and Supply Chain Traceability: an important Prerequisite for Reduced Sampling and Reduced Testing
- Qualification of packaging materials
- Qualification of APIs and excipients
- Supplier qualification/Supplier audits
- Quality Agreements
- Specifications/Pharmacopoeial monographs/Supplier CoA
- Complaint Handling
Sampling and Documentation to make the Supplier liable for Defect Products
- Legal and Contractual Liability
- Definition of a Product Defect
- Express Warranty
- Admissible Evidence
Case Study I: How to Define Inspection Procedures for Packaging Materials (Primary and Secondary) in the Incoming Goods Control
- Sampling Plans for printed packaging materials, glass containers, plastic containers, etc.
- AQL (Acceptable Quality Level)
- Tests required according to Ph.Eur. / USP
- Options for reduced sampling
- Options for reduced testing
- Skip lot testing
Case Study II: How to Define and Optimise Sampling and Testing Procedures for APIs and Excipients in the Incoming Goods Control
- Sampling of APIs and excipients
- Risk assessment and rational for different sampling plans and sampling procedures
- Options for reduced ID testing
- Options for reducing analytical costs (economic order size and accepting CoA from suppliers)
- Optimization of ID testing using NIR/RAMAN
Parallel Sessions: Working on specific Tasks
1. Strategies/Prerequisites for Reduced Testing/Reduced Sampling
The aim of this workshop is to evaluate in small discussion groups how the opportunities and requirements of EU GMP Chapter 5, Annex 8 and 21 CFR Parts 211 should be implemented in QA/QC.
2. Reduced Testing/Reduced Sampling for APIs/Excipients
Participants will discuss and calculate benefits of different measures in small groups. Scenarios of different materials/suppliers/qualification status, use of NIR/RAMAN for identity testing and optimization of the order size to reduce
testing effort will be evaluated including their Impact on the sampling and testing plans for APIs and excipients.
3. Reduced Testing/Reduced Sampling for Primary and Secondary Packaging Materials
Participants will discuss in small groups scenarios of different materials/suppliers/qualification status/etc. and their impact on the sampling and testing plans with regard to reduced sampling and reduced testing for packaging.
How to Deal with Divergent Compendial Method Requirements
- ICH QB4 and the Pharmacopoeial Discussion Group
- Divergent and conflicting pharmacopoeial requirements
- CDER’s MAPP 5310.7 “Acceptability of Standards from Alternative Compendia”
- How to proceed in case of missing harmonization?
- How to proof equivalence?