Old V/s New Approach

Introduction to ISPE’s new Risk-based approach to Verification/Validation and ICH’s QbD (Quality by Design) guidelines – ICH Q 9 / ASTM E 2500.
Why change our work culture and regulatory framework to move from traditional Qualification approach to Value added model? According to Ms Janet Woodcock, MD, the answer is, “A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without excessive regulatory oversight.”
Were we working under the delusion of Quality by Accident before?
Quality Risk Management (QRM) is critical in development of the product Quality Control strategy.
An understanding of the product and process in terms of fundamental, mechanistic properties as opposed to empirical (based on observation and experience rather than theory or logic).
Utilization of prior knowledge in defining the product, process and facility.
Facility designed to accommodate the products’ life cycle.
Risk analysis, Risk assessment, Risk Management.
ICH – Q9 – Quality Risk Management (QRM) was published in 2005 and differentiates Commissioning and Qualification:
Traditional method – IQ, OQ, PQ (Installation Qualification, Operational Qualification, Performance Qualification), one followed by next step, mostly treated as quality/regulatory functions.
Current Risk based approach – ISPE Baseline Vol 5 – advocates Impact assessment, GEP (Good Engineering Practice), Commissioning concurrent with IQ/OQ and gives leverage to Commissioning.
  Latest – ASTM E 2500 – ISPE Baseline – Volume 12
  > Q b D
  > Verification Vs Qualification
Volume 5 guide (Original ISPE Base line) TO New Volume 12 guide (ASTM methodology)
Verification: The new approach
A systematic approach should be defined to verify that manufacturing requirements, acting singly or in combination, are fit for intended use, have been properly installed, and operating correctly.
The Verification approach should be documented
The extent of Verification and the level of detail of documentation should be based on risk to product quality and patient safety, complexity and novelty of the manufacturing system.
Qualification Vs Verification – Old Vs New
Old – Qualification consists of a series of IQ, OQ, PQ protocols
New – Subject Matter Experts (SMEs) should confirm that all acceptance criteria have been met and that the equipment systems are fit for use. This confirmation should be documented. Such documentation should include a review or overview of the results, and a review of any non-conformance to acceptance criteria. There should be a clear statement as to whether or not the manufacturing requirements are fit for intended use.
Risk Assessment – Old Vs New
Old – Impact Assessment, the process for evaluating the impact of the operating, controlling, alarming and failure conditions of a system on the quality of the product used to be conducted after design development. Instead of product/patient focused, it used to be system/component level focused and labor intensive.
New – An assessment of the chosen process design against a set of approved product and process user requirements. Assessment is performed throughout design development to assure the collection of systems and other facets of the design and operating philosophy are capable of monitoring and controlling risks to the manufacturing process, including control of process variability, control of contamination etc., and is linked to the identified CQA,s (Critical Quality Attributes) and CPPs(Critical Product Parameters).
Unacceptable risks are mitigated following the preferred hierarchy of:
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Elimination by Design
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Elimination by automated control
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Elimination by procedural controls