Equipment Life Cycle Program Development and Implementation
Developed and implemented Equipment Life Cycle Program for medical device manufacturer. The overall objective was to ensure that the Quality Systems Regulation and maintenance requirements were met as efficiently as possible throughout the equipment life cycle. Major components of the program included the following policies and procedures:
| Equipment Life Cycle Policy
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| Reliability Based Maintenance Policy
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Elements of a Reliability Based Maintenance Program
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Condition Based Monitoring Procedures
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Non-Destructive Testing Procedures
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Failure Analysis and Trending Procedure and Forms
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| Maintenance Program
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Maintenance Strategy Flow Chart
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Maintenance Activities and Records Flow Chart
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Maintenance Work Order Procedure and Forms
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Maintenance Work Permit Procedure and Forms
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Preventive Maintenance Procedures and Logs
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Lock-Out Tag-Out (LOTO) Procedure and Forms
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| Commissioning and Acceptance Testing
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Equipment Information Form
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Equipment Criticality Assessment Procedure and Forms
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| Drawing Control Procedure and Forms
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| Contractor Qualification and Training Procedures and Form
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Small Scale Fermentation Model Development
Provided guidance for the development of representative small scale fermentation model for vaccine manufacturing process. The fermentor model development included identifying the critical process parameters and demonstrating that the scaled critical process parameters would elicit responses that were equivalent to those at full scale. Mixing time comparisons of full and small scale fermentors were performed using computational fluid dynamics simulator software. Development of a robust model includes optimizing mass, heat and momentum performance characteristics to match those of the full scale.
Cleaning Validation Master Plans
Developed Cleaning Validation Master Plans for multiple biologics, drug and medical device manufacturing sites. Cleaning Strategies based on worst-case products, active pharmaceutical ingredient and equipment. Worst case product and active pharmaceutical ingredient evaluation based on toxicity, solubility, dosage and route of administration. Worst-case equipment based on equipment type, size, material of construction, configuration and cleanability. Sampling methods include visual, rinse water effluent, and swabs. Analytical test methods to suit client's needs and capabilities based on product, active pharmaceutical ingredient, and cleaning agent. Cleaning Strategies included procedure for evaluating the impact to current validation upon introduction of new products, active pharmaceutical ingredients, and equipment.
Process Validation Assessment
Performed assessment of formulation, filling, sterilization and cleaning validation protocols following 483 Observations. Purpose of assessments was to provide third party evaluation of validation protocols based on regulations, FDA guidance and accepted industry best practices. Deliverables included assessment of validation status and recommendations for remediation.
Small Scale Purification Model Development
Provided guidance for the development of representative small scale chromatography purification models for recombinant DNA protein manufacturing process. The purification model development included identifying the critical process parameters and demonstrating that the scaled critical process parameters would provide protein yields and purity comparable to those at full scale.
Policy and Procedure Development
Developed Policies, Procedures, Work Instructions and Forms for generating Records at multiple drug and device manufacturing and laboratory sites. All documents were written specifically for the Client and often required development of Work Flow Diagrams to assure that the documents fit the requirements and capabilities of the Client. Our documents are written with clarity, are technically correct, and do not allow for individual interpretation of instructions.
Sterile Process Validation
Provided project management for the installation of sterile drug manufacturing process. Performed vaporous hydrogen peroxide (VHP) sterilization cycle development and developed subsequent validation protocols. Process involved a glove box isolator, which was validated to ISO 14644 standards and included considerations presented by PDA on Part 7: Separative Enclosures.
Validation Master Planning
Developed multiple Validation Master Plans that conform to current regulations, regulatory guidance and accepted industry standards in both the US and Europe. The Validation Master Plans provide a comprehensive description of the Client's Validation Program and provide assurance that the:
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Processes described will be reliable and under control
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Responsibilities for validation activities have been assigned
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Client fully understands its regulatory obligations
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Each Validation Master Plan provides meaningful guidance on what validation activities are actually to be done by:
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Describing the validation philosophies and methodologies of the Client
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Providing guidance for the establishment of acceptance criteria
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Outlining the Client's understanding of the requirements for validation
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Defining areas of responsibility and accountability for the validation program
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Describing the validation programs that will be implemented
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Providing an overview of the facility, utilities, process equipment, and manufacturing processes
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Summarizing the programs required to maintain equipment, systems and processes in a validated state throughout their life cycles
Fermentor Process Validation
Developed and executed performance qualification protocol for process validation of therapeutic biologic fermentation. The Steam-In-Place (SIP) sterilization cycle that was developed employed biological indicators using the overkill approach, which saved the client considerable expense by avoiding the installation and validation of thermocouples and related equipment. The validation also included a media hold challenge duration that extended beyond the nominal fermentation time in Master Batch Record, and cleaning validation of the Clean-In-Place and Clean-Out of-Place (CIP and COP) procedures.
Process Validation
Developed and executed performance qualification protocols for the validation of generic solid dosage manufacturing processes, including computerized fluid bed coaters, high speed tablet presses, high speed encapsulation, aqueous and organic solvent tablet coaters, and high speed packaging lines.
Regulatory Oversight
Provided regulatory oversight after a merger that created one of the largest pharmaceutical companies in the world with over 80 billion euros in market capitalization. The project duration was over eight months and provided regulatory oversight in multiple therapeutic areas, including cardiovascular, thrombosis, central nervous system, oncology, metabolic disorders, internal medicine and vaccines.
Analytical Test Method Qualification and Validation Guidance
Provided regulatory guidance for the qualification and validation of analytical test methods for in-process and product release testing of recombinant DNA vaccine. Provided clarification on FDA and ICH guidance documents and helped the client navigate method characterization, qualification and validation from IND submission, Phase I and II clinical trials, and into Phase III and commercialization.
Protocol Execution
Provided low-cost staffing resources for execution of equipment qualification and cleaning validation protocols. Project scope included routing of Client generated protocols for review, final editing to incorporate review comments, routing of protocols for approval, field execution, and compilation of raw data for preparation of final reports.
Preventive and Predictive Maintenance Procedure Development
Developed Preventive Maintenance (PM) and Predictive Maintenance (PdM) procedures for facility and utility related equipment at an oligonucleotide manufacturing facility. Each procedure included special tools, frequency, spare parts list, equipment disassembly and reassembly instructions, equipment log books, and PM/PdM forms. Also developed facility walk-through inspection procedures to detect any deficiencies or nonconformities with the GMP facilities and cleanrooms and to monitor critical systems and equipment.
Process Capability Engineering Study
Developed and executed engineering study to assess process capability of high speed liquid fill equipment. Performed statistical analysis of raw data, including average, standard deviation, standard error, and Cpk capability index. Provided recommendations regarding process monitoring, interventions, and adjustments based on data analysis and batch record instructions.
Pre-Validation Process Characterization
Performed pre-validation process characterization, also known as design review, for multiple biologics manufacturing clients. Characterizations included process mapping, identification of analytical test methods, and risk analysis to prioritize process parameters. Subsequent to the risk analysis, process characterization experiments were statistically designed to determine critical and non-critical process parameters for each unit operation. The experiments included establishing edges of failure, proven acceptable ranges, and normal operating ranges that later serve as validation acceptance criteria, process alert limits, and process alarm limits.
Project Coordination & Management
Provided multi-site project coordination and management for major Pharmaceutical manufacturer. Responsible for managing tasks and updating timeline in MS Project.
Corrective Action Preventive Action (CAPA) Management
Manage CAPA investigations and closeouts. Review incident reports (IR's), followed up with key personnel to close out IR's or to obtain status updates on IR's. Worked with manufacturing regarding Notices of Rejection associated with Incident Reports. Worked with maintenance regarding Critical Systems Work Orders associated with Change Controls and Incident Reports.
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