Contents: Issue 1
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[November 2007] A summary of ISPE Boston/NE joint chapter meeting on Standard ASTM E2500.
In June this year many representatives from pharmaceutical companies in North America joined to discuss the future of validation. The main subject of interest was ASTM E2500 which is titled “Standards for Specification, Design & Verification of Pharmaceutical & Biopharmaceutical Manufacturing Systems & Equipment”. This standard has been developed with input from industry and with the support of the FDA, EMEA and GAMP and was approved in May 2007 and published in July 2007.
So what is ASTM E2500? Basically it’s a consensus standard with legal relevance and global impact. Based on sound scientific, engineering and quality principles it is intended to separate business risk from patient safety risk. So basically it is a risk based approach to verify patient protection.
This standard proposes the almost complete destruction of the validation “V” model. Out goes the Design Qualification (DQ) with a Design Review (DR). Also for those that do them, Impact Assessments are out. Commissioning and Qualification are replaced by “Verification”, so the qualification phases (IQ, OQ, PQ) are obsolete.
So what does ASTM E2500 propose? Upfront things look similar to the process most Pharmaceutical engineers are used to. Product and process designs are to be well defined and detailed through URS, FRS and DDS type documents. The aim is to have the critical quality attributes satisfied by the design with the risk to product quality and patient safety appropriately considered. Any unacceptable risks are mitigated by the design (preferred) or defined by practice. This design is then reviewed and approved by the relevant subject matter expert. The big change comes in the verification stage of this approach. ASTM E2500 states that verification is “A systematic approach to prove that Critical Elements, acting singly or in combination, are fit for intended use, have been properly installed, and operating correctly”. This verification would normally be documented in IQ, OQ, and PQ documents however the new approach just states that the verification approach must be documented. The extent of verification and the level of detail of documentation should be based on risk to product quality and patient safety. This approach also allows more flexibility if the design changes before the final acceptance with GEP change managed by and approved by Subject Matter Experts (generally engineers). After acceptance GMP change is managed and approved by quality. So another key factor of this approach is that things change and as long as they are managed and documented correctly this is acceptable.
So when will this happen? The answer to this is not clear. This standard has the support of the FDA, EMEA and GAMP so technically many sites could implement this process. However, although many Pharmaceutical engineers and companies have been talking about a different approach to validation, it will take someone to take the first step in using this standard. This new process will also have a large impact on company practices which are defined by policies, plans and procedures which will need to be updated. So we will all have to what and see who and how this standard will be interpreted and implemented by. In the meantime the validation “V” model will continue to be the standard approach.
Current Standards Vs Proposed Standards
ISPE Baseline Guide 5
– Design Inputs
– Impact Assessment
– Design Qualification
– Commissioning
– Multiple Trial Runs to Get Things Right
– IQ, OQ, PQ and Acceptance Criteria
– GEP scope and QA scope overlapped
– Focused on Documentation Deliverables
– Rigid Change Management |
ASTM E2500
– Design Inputs
– Design Review
– Risk Mitigation
– Critical Control Parameters Define Acceptance Criteria
– Verification Testing
– Performance Testing
– GEP scope and QA scope have clear boundary
– Process, Product Quality and Patient Safety
– Quality by Design, Design Space and Continuous Improvement |
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