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Differences from Commercial Manufacturing: Night and Day (Never say "Never" in R&D)Characteristic | Development | Commercial |
Operating | Transitioning from non GMP to GMP | Operating in full GMP Mode |
Traceability Lifecycle | Need to be able to go back in time many years – find/search for data easily over time period | Processes run for long time but generally no need to have long term traceability |
Traceability Direction | Go back in Development and feed forward to Commercial Ops | Feedback to Development Ops |
Process Flexibility | Highly iterative business process, changes w/rev control. High degree of flexibility | Fixed/Controlled operation |
Role of Batch Records | Planning/analysis focus | Execution |
Operating “Discontinuities" | High – stop/go nature of campaigns is typical | Low – Operations are continuous, no stopping |
Data Capture Definition | Capture all data, don’t know what will be important until after the fact. | Data to be captured during execution is well defined |
Analytical Methods Focus | Develop and Execute Analytical Methods | Execute Analytical Methods |
Process Understanding | Create underlying foundation for Science “Process Understanding”, (prove “process understanding”) | Improve Operations, Quality and demonstrate Compliance (execute against established SOPs, specification mgmt) |
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FDA GUIDELINES CHANGING DRUG DEVELOPMENT
ICH (INTERNATIONAL CONFERENCE ON HARMONIZATION) Q8 Pharmaceutical Development Q9 Risk Management Q10 Quality System Quality by Design (QbD) Pharmaceutical cGMP for 21st Century
Q8 PHARMACEUTICAL DEVELOPMENT
Guideline for development of drug products Quality cannot be tested into products Manufacturing process understanding within an approved design space without further regulatory review “Real time” quality control leading to a reduction of end-product release testing
Q9 QUALITY RISK MANAGEMENT
The evaluation of the risk to quality should ultimately link back to the protection of the patient The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk and be based on scientific knowledge
Q10 PHARMACEUTICAL QUALITY SYSTEM
Outlines Management responsibility for Quality Improvements for process performance and product quality Guidelines for overall pharmaceutical quality system
PHARMACEUTICAL QUALITY ASSESSMENT SYSTEM (PQAS) IN THE 21ST CENTURY
Promotes science and risk-based approach to regulation Initiative applies to new drugs, including biotech products Established to facilitate the implementation of Quality-by-Design
The FDA says that they want the current system migrated to the new desired state:
Empirical development -->Submission (Lack of PD and MS)-->Traditional CMC Review
needs to migrate to:
Development (QbD)-->Submission (Knowledge Rich in PD and MS)-->PQAS
The S88 Concepts for Development:
Flexibility Mapping S88 Objects to Laboratory Procedures Batch Tickets Unit Operations S88 Commands SKIP COMPLETED REDO Conditionals (If, Then)
CONCEPTS: EXECUTION MODIFICATIONS
Drug Substance | Drug Product | ||||||
Lab | Early Dev | Late | GMP CT | Pre-Form | Formulation | GMP CT | |
Operator | Exec | Exec | Exec | ||||
Engineer | Exec/ Edit | Exec/ Edit | Edit | Exec/Edit | Edit | ||
Scientist | Exec/Edit | Exec/ Edit | Exec/ Edit | Edit | Analysis | Exec/Edit | Edit |
QbD IS AN ACCELERANT FOR S88 ACCEPTANCE!