SkillsPlus International Inc. The On-Site Series GMPs: Distribution Centers Learn to apply the GMP regulations as they relate to distribution center operations! FDA Past, Present, and Future and opener activity Definition Regulation timeline Predicate, omnibus, & industry rule Agency structure Drug development timeline Who regulates clinical research GMP objectives and elements 2. The growing influence of the FDA Historical dates US prohibition of adulterated drugs Pure Food and Drug Act Food, Drug, and Cosmetic Act KeFauver-Harris Amendment GMP update 1978 1980-1990 A year at a glance Into the new millennium 3. Regulatory inspections Traditional and new approaches QSIT - Quality Systems Inspection Sources of information for the FDA 4. Enforcement Legal consequences Actions without a warning letter The two most common mistakes 5. Responsibility and accountability Management responsibility Activity: What s It All About People and Procedures 1. Organization and personnel Organization chart and staffing Personnel training and training audit Consultants and contractors 2. Standard operating procedures What are SOP s Quality Assurance responsibility General format Writing guidelines Revisions, review, and approval Review frequency Activity: Writing Procedures Optional Activity: House Building 3. Investigations Investigation overview Types of investigation Investigation documentation Contamination Control and opener activity Regulatory issues What people are saying. I really liked Allan s energy and knowledge of the subject. The class was very interactive. It was a fun and lively environment. Accurate information. People really felt comfortable asking questions. 504-1
Skillsplus International Inc. 2. Sources of contamination Contamination sources Personal contamination rules Penicillin contamination 3. Personal hygiene Rest rooms and hand washing Clothing to be worn Documentation 1. Documentation rules and practices Regulatory issues Completing documentation Correcting documentation Error descriptions Unacceptable documentation practices Fraud and falsification policy Activity: You Can t Remember It All 2. Double checking Specific examples Options Activity: Documentation Adds Materials 1. Sourcing raw materials Regulatory issues Approving raw material suppliers Supplier qualification program 2. Quarantine system Definitions and purpose Quarantine, approved, and rejected Dedicated areas 3. Sampling Procedures and timing Container identification Activity: Bead Sort 4. Receipt of materials Receiving and storing Receiving inspection, and testing Examination Certificate of analysis 5. Identification of materials Lot numbers and expiration dates Containerization labeling Re-containerization 6. Contamination Types of adulterants Types of contaminants 7. Material controls Material storage space First In First Out Charge-in of active ingredients Amount of active ingredient On line testing Calculation of yield Double checking 8. Labels and labeling Packaging and labeling supplies Labels and labeling examination Activity: Product Labeling Strict control over labeling supplies Label accountability Returned labeling stock Destruction of labeling 9. Non-conforming materials Defined How to handle non-conforming materials Buildings and Facilities 1. Space and design Design and constructions features Sufficient space defined Defined and general areas Appropriate space Separate penicillin facilities 2. Logical flow Product, equipment, material flow 3. Designated spaces Receiving inspection space Storage environment Laboratory space Work in process (WIP) Reject and quarantine space Restricted or limited access 4. Environmental monitoring Rationale Methods and parameters Demonstrated control 504-2
5. Utilities Lighting Air systems, processes & differential Air classification and filters HEPA and laminar flow Computerized air systems Plumbing and classes of water Air breaks Facility alarms Refuse, trash, and hazardous waste Maintenance 6. Housekeeping Washing and toilet facilities Work space and levels of cleaning Pest control and suggestions Equipment and Calibration 1. Regulations Skillsplus International Inc. 8. Identification Requirements and exceptions 9. Calibration Purpose Key elements Measurement frequency Timing, standards, and procedure Logs for due dates Consultants and outside firms 10. Items to be calibrated Production and laboratory equipment Process instrumentation 11. Calibration actions Out of calibration Out of calibration investigation Out of service 2. Design Appropriate and suitable Equipment selection Blue prints of process Control devices 3. Construction Equipment materials of construction Lubricants 4. Filters Design and specifications Fiber releasing High Efficiency Particulate Air filters 5. Use Procedures Training requirements Training program structure 6. Cleaning Levels of cleaning Procedures Equipment cleaning logs 12. Documentation Calibration master log Stickers Certificate of calibration Retention times Activity: Equipment cleaning Quality Assurance Definitions and regulations Roles and direct reports 2. Suppliers and contractors Outsourcing and checklist Activity: Audit Team 3. Materials and products Responsibilities Approves or rejects Incoming materials Materials inspection and testing Labeling specifications Labeling control and use Non-conforming materials 7. Maintenance documentation Work orders and repair orders Logs 504-3
Skillsplus International Inc. GMP: Basics and Beyond 4. Investigations Investigations and reviews Structure of an investigation Investigation content Types of investigations 5. Documentation Standard operating procedures Process control records Document review Signature log Audit Deviation from standards Annual product review Review required content Recommended content Annual product review reminders Scale up and post approval changes Post approval changes 6. Recall procedure Purpose Product recall strategy Depth of recall Product recall classification Packaging & Labeling Control Regulations 2. Materials examination and usage Procedures and documentation Examination Acceptance or rejection Stored separately Restricted or limited access Destruction of obsolete labeling Gang printing and cut labeling Significant dates Imprinting devices 3. Sampling Statistical, random, representative Taking and labeling samples Labels and labeling 5. Packaging and labeling operations Lot numbers and expiration dates Physical or spatial separation Work in process Inspection 6. Expiration dating Regulatory requirements Expiration date exemptions 7. Specifications and supply source Where specifications come from Packaging and labeling suppliers 8. Tamper-evident packaging Regulatory requirements Exemptions Packaging requirements and labeling Tamper-resistant packaging Durability of packaging Validation Validation life cycle The business case for validation Re-validation triggers Assessing validation need Deciding what get validated 2. Qualification Qualification versus validation Flow chart Design qualification Installation qualification Operation qualification Performance qualification 3. Qualification documentation Design qualification protocol Installation qualification protocol Operation qualification protocol Performance qualification protocol Protocol supplement and deviations 4. Label issuance Label reconciliation Strict controls Destruction of unused labeling 504-4
4. Validation Definitions Process validation State of control Batch control Worst case Edge of failure Proven acceptable range Skillsplus International Inc. Breach practices Audit trails Time and date stamp Training Management role and responsibility Policy statements Agency certification Confidential records 5. Validation timing Prospective validation Concurrent validation Retrospective validation Re-validation 6. Cleaning validation Purpose Cleaning validation scope Objectives Acceptable levels of contamination Impurity accept limit Evaluation of cleaning validation Case example Activity: Validation 7. Validation documentation Master plan Validation protocol Final report Report format Protocol supplement Summary and evaluation Protocol certification Documentation retention Electronic Records & Signatures History of Part 11 regulation What the FDA looks for Program goals and definitions 2. Open & closed Systems Part 11 components Common requirements in perspective Records and documents Record protection and controls Archiving and retrieving records Accurate copies and file format Limited access and control Authority checks ID and password loss management 3. Open system requirements Goals Access control Period of access control 4. Computer validation Qualification Validation Performance Alarms Shutdown and recovery Worst case Change control Change Control Regulatory citations 2. What is a change Changes defined Planned versus unplanned 3. Change control procedures Identification of the change Effective date Responsibility Revision level Validation of changes and exceptions Communication Updating documentation Documentation distribution Remedial actions Submissions & exceptions Business factors and exhibits QA Review 504-5
FDA Inspections 2. QSIT Quality systems and rationale Benefits and structure Inspections abbreviated and full Compliance inspections Critical deficiencies 3. Checklist preparation First reception of FDA Official greeting plan Documentation control Inspection history Training 4. The inspection process Flow chart Receiving investigators Developing an agenda Company introductions Facility tour Interacting with the FDA Skillsplus International Inc. Unacceptable behaviors Data gathering Daily briefing 5. Behaviors Interacting with the FDA Unacceptable behaviors 6. Roles and responsibilities Escort qualifications and team Supervisors and plant personnel What the FDA is looking for 7. Legal consequences Warning letters Recalls Seizure: voluntary hold or embargo Injunction and consent decree Debarment Disgorgement and fines Prison Activity: Case studies Optional Activity: FDA Inspection Class Length: This class as published is a three-day class. The outline can be adjusted to fit your schedule and time availability. Disclaimer: This material is provided as an illustration of a class. It may not reflect your actual class. As the regulatory environment is constantly changing, we reserve the right to change, modify, or adjust the outline as we determine to meet the needs of the industry without constituting misrepresentation of facts, or breach of contract. Class Size: Class size is limited to 30 students. If your site needs exceed that please let us know. Fees: Our fee includes all student handouts, the quiz, and a certificate of completion for any employee who satisfactorily completes the class. Please call for a quote. Schedule: Although we can occasionally accommodate last minute schedules, it is best to schedule classes 60-90 days in advance to assure a schedule that meets your site needs. Advanced schedules can usually enjoy reduced travel expenses also! Customizing: We can customize our class to meet your site s specific needs. Please call us to discuss those learning needs in more detail. 504-6