Footnotes in the new FDA Process Validation Guidance refer to ASTM documents (formerly American Society of Testing and Materials), a standardisation organisation in the USA. As a further development of a White Paper written by the International Society of Engineering (ISPE) on risk-based qualification, the ASTM Guide E2500-07 (Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment) especially tries to offer a modern approach to qualification (see GMP-News from 25 November 2009). It does not mention any more the classical qualification steps DQ, IQ, OQ, PQ but focuses instead on Subject Matter Experts (SMEs) in order to organise verification. Great importance is also attached to Good Engineering Practice, GEP.
But the document is relatively short and not very specific.
Here, an actual ISPE Guide helps. The document's name is "Science and Risk-Based Approach for the Delivery of Facilities, Systems, and Equipment" and it was written in 2011. The Guide provides direction to industry on the implementation of a science- and risk-based approach for demonstrating that facilities, systems, equipment and associated automation are fit for the intended use. So far, these activities fell under the concept of qualification.
The Guide is a comprehensive document, consisting of 116 pages but it can be read smoothly. It is divided into the following chapters:
2 Overview of the Life Cycle
4 Specification and Design
5 Verification, Acceptance, and Release
6 Continual Improvement
7 Quality Risk Management
8 Good Engineering Practice
9 Design Review
10 Change Management
11 - 17 Appendices
The following key concepts are listed in the introduction:
A table shows the expected benefits connected with the application of the key concepts mentioned above. In short, the following achievements should be possible by applying the concepts: a better definition of critical aspects, improvements in design, a lower cost of testing, a better application of resources and avoiding repeated specification and verification activities.
The chapter "Life Cylce" also contains a very interesting table describing the roles and relevant subject matter expertise of the persons concerned. This concerns the following roles: engineering, Quality Unit, process scientists, manufacturing personnel and automation. Especially interesting is the Quality Unit's role. It should be entrusted with reviewing activities and with the approval of (in most cases higher-level) documents.
The chapter "Requirements" contains an indicative list of requirements for equipment concerning product and process requirements. The tip to use a specific naming convention in order to avoid multiple sets of generic user requirements is very helpful.
Much attention is paid to specification and design. Quality by Design is part of this chapter as well as procurement.
The chapter "Verification, Acceptance, and Release" describes the risk-based verification process. Verification is based on a plan and includes testing of installation, operation, and performance. A consequent application of GEP is also very important. The contents of a verification plan are described. It is noticeable that tests for GEP-relevant, non-critical aspects may also be included. They may not require the same level of involvement of the Quality Unit as the other tests. This chapter also contains a table with roles, skills and responsibilities of SME and Quality Unit. Factory Acceptance Tests and Site Acceptance Tests will also be carried out as part of the verifications. Manufacturing systems with critical aspects should be reviewed in a summary document, with the Quality Unit's participation.
The chapter "Continual Improvement" is relatively short. It consists of 1.5 pages.
The chapter "Quality Risk Management" is significantly longer, consisting of 8.5 pages. Simple examples and exemplary lists according to ICH-Q9-risk management processes are given as practical aid. According to the Guide a good timing for reviewing risks may be in conjunction with the periodic review of equipment.
A chapter is dedicated to Good Engineering Practice. This chapter contains a very good exemplary list of project specific GEP procedures that might be applied.
The importance of the topic Quality by Design is also demonstrated in a second chapter on Design. But this second chapter is on Design Review. It describes the design review process aiming at a design review outcome. It is carried out in an iterative process opposing risk reduction to design decisions.
Chapter 10 describes change management in conjunction with the equipment's life cylce. It also lists some examples on introduction, implementation, acceptance and close out of a change.
The seven appendices are very interesting. Appendix 1 presents risk assessment methodologies in a very summarized way. Appendix 2 describes the impact assessment. Appendix 3 informs on commissioning. The field commissioning process is shown in a table (steps, activities, outputs, common terms for the stages and ISPE terms). Appendix 4 on qualification approaches is of particular interest. Until then the term "qualification" was omitted in the Guide. Here DQ, IQ, OQ and PQ are specifically addressed. It is explicitly mentioned that the Guide has been developed to meet the intent of international regulations with respect to ensuring facilities, equipment, systems, and associated automation are "fit for the intended use". This is also the aim of a classical qualification. But the Guide wants to eliminate non-value-added qualification activities. Nevertheless, the principles of this Guide still include the classical qualification steps. Parallels with them are also mentioned. The documentation on final risk assessment, critical aspects, and associated verification acceptance criteria, could be packaged as the design qualification with Quality Unit approval. The list of critical aspects and the installation and operational acceptance criteria documented in the final risk assessment/design review and approved by the Quality Unit could be labelled as the IQ/OQ acceptance criteria, according to the Guide. The work can be carried out under GEP by similar SMEs, continues the Guide. The process requirements relating to equipment or system performance can be listed under the cover of a PQ. Appendix 5 provides an overview of the regulatory basis and the background. This appendix contains once again a part on qualification. While the Guide no longer mandates explicit installation or operational qualification steps, companies that wish to retain the use of the term "qualification" are free to do so. Express reference is made to the fact that it is not necessary to conduct additional work in the form of separate DQ, IQ, and OQ protocols. The definition of DQ, IQ, and OQ is based on "documented verification". The Guide recommends a method for producing this verification evidence. Appendix 6 gives literature references and Appendix 7 is a glossary.
Conclusions: Until now, the ASTM Standard E 2500-07 has been relatively unimportant in Europe. The document is very short and lacks specificity. Now, the ISPE Guide describes how the principles mentioned in ASTM E2500 could be implemented science- and risk-based for facilities, systems, equipment and associated automation to make them fit for the intended use. It also solves the discrepancies concerning the missing qualification in ASTM E2500-07. This ISPE Guide will possibly encourage further use of ASTM E2500-07, especially in Europe. After all, it is already part of GAMP 5 with its verification model.
Unfortunately, the Guide is subject to payment. You can buy it here
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