INVESTIGATIONS OPERATIONS MANUAL 2019

5.2.3.1.4 - OBSERVATIONS ................................................. 5-20 5.2.3.1.5 - MEDICAL DEVICE INSPECTIONS ...................... 5-21 5.2.3.1.6 - CORRECTION OF FDA 483 ERRORS ................ 5-21 5.2.3.1.6.1 - Errors Discovered Prior to Leaving the Establishment ........................................................................ 5-21 5.2.3.1.6.2 - Errors Discovered after Leaving the Establishment5- 21 5.2.3.2 - Reportable Observations......................................... 5-21 5.2.3.2.1 – ADULTERATION OBSERVATIONS .................... 5-22 5.2.3.2.2 - OTHER OBSERVATIONS ................................... 5-22 5.2.3.3 - Non-Reportable Observations ................................. 5-22 5.2.3.4 - Annotation of the FDA 483 ...................................... 5-23 5.2.3.5 - Government Wide Quality Assurance Program (GWQAP) .............................................................................. 5-24 5.2.3.6 - Distribution of the FDA 483 ..................................... 5-24 5.2.3.6.1 – non-eNSpect generated FDA 483 ....................... 5-24 5.2.3.6.2 – eNSpect generated FDA 483 .............................. 5-24 5.2.4 - RECEIPT - FACTORY SAMPLES.............................. 5-24 5.2.4.1 - Items Requiring Receipt .......................................... 5-24 5.2.4.2 - Items Not Requiring Receipt ................................... 5-24 5.2.5 - INSPECTION REFUSAL ............................................ 5-24 5.2.5.1 - Refusal to Permit Inspection ................................... 5-25 5.2.5.2 - Refusal to Permit Access to or Copying of Records 5-25 5.2.5.3 - Refusal after Serving Warrant ................................. 5-25 5.2.5.4 - Hostile and Uncooperative Interviewees ................. 5-25 5.2.5.4.1 - INDICATORS ....................................................... 5-26 5.2.5.4.2 - SAFETY PRECAUTIONS .................................... 5-26 5.2.5.4.3 - PROCEDURES WHEN THREATENED OR ASSAULTED ......................................................................... 5-26 5.2.5.4.4 - NOTIFICATION OF FBI AND US ATTORNEY..... 5-26 5.2.6 - INSPECTION WARRANT .......................................... 5-27 5.2.7 - DISCUSSIONS WITH MANAGEMENT ...................... 5-27 5.2.7.1 - Protection of Privileged Information......................... 5-27 5.2.7.2 - Refusals of Requested Information ......................... 5-28 5.2.8 - CONSUMER COMPLAINTS ...................................... 5-28 5.2.9 - INTERVIEWING CONFIDENTIAL INFORMANTS ..... 5-28 5.2.9.1 - How to handle the first contact ................................ 5-28 5.2.9.1.1 - INTERVIEWING METHODS/TECHNIQUES ........ 5-28 5.2.9.1.2 - ESTABLISH MOTIVATION .................................. 5-29 5.2.9.1.3 - ANONYMITY ........................................................ 5-29 5.2.9.2 - Protect the Identity of the Source ............................ 5-29 5.2.9.2.1 - ACCESS .............................................................. 5-29 5.2.9.2.2 - STORAGE REQUIREMENTS .............................. 5-29 5.2.9.2.3 - DISCLOSURE ...................................................... 5-29 5.2.9.2.4 - DESTRUCTION ................................................... 5-29 5.2.10 - ROUTINE BIOSECURITY PROCEDURES FOR VISITS TO FACILITIES HOUSING OR TRANSPORTING DOMESTIC OR WILD ANIMALS .............................................................. 5-30 5.2.10.1 - Pre-Inspection Activities ........................................ 5-30 5.2.10.2 - General Inspection Procedures ............................. 5-31 5.2.10.3 - Special Situation Precautions ................................ 5-32 CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2019 5-2 5.2.10.3 – Standard Operating Biosecurity Procedures for Egg Farm Inspections/ commercial Poultry Operations................. 5-32 SUBCHAPTER 5.3 - EVIDENCE DEVELOPMENT ............... 5-35 5.3.1 - TECHNIQUES ............................................................ 5-35 5.3.2 -SAMPLES .................................................................... 5-35 5.3.3 - EXHIBITS ................................................................... 5-35 5.3.4 - PHOTOGRAPHS ........................................................ 5-36 5.3.4.1 - In-Firm Photographs ................................................ 5-36 5.3.4.2 - Photo Identification and Submission ........................ 5-37 5.3.4.2.1 – FILM BASED PRINTS .......................................... 5-37 5.3.4.2.2 - COLOR SLIDE IDENTIFICATION ........................ 5-37 5.3.4.2.3 - NEGATIVE IDENTIFICATION .............................. 5-37 5.3.4.2.4 - VIDEO RECORDINGS ......................................... 5-37 5.3.4.2.5 – DIGITAL PHOTOGRAPHS OR VIDEO RECORDINGS ....................................................................... 5-38 5.3.4.2.6 – GLOSSARY OF DIGITAL TERMINOLOGY ......... 5-38 5.3.4.2.6.1 – Digital Data ....................................................... 5-38 5.3.4.2.6.2 – Analog Data ...................................................... 5-38 5.3.4.2.6.3 – Memory Card .................................................... 5-38 5.3.4.2.6.4 - Original .............................................................. 5-38 5.3.4.2.6.5 – Original Copy .................................................... 5-38 5.3.4.2.6.6 - Permanent Storage Media ................................. 5-38 5.3.4.2.6.7 - Time/Date Stamp ............................................... 5-38 5.3.4.2.6.8 - Working Copy .................................................... 5-38 5.3.4.3 - Preparing and Maintaining Digital Photographs as Regulatory Evidence .............................................................. 5-39 5.3.4.4 - Preparing Digital Photos for Insertion in a eNSpect Establishment Inspection Report (EIR) .................................. 5-39 5.3.4.5 - Photograph Requests .............................................. 5-40 5.3.5 - RECORDINGS ........................................................... 5-40 5.3.6 - RESPONSIBLE INDIVIDUALS ................................... 5-41 5.3.6.1 - Discussion on Duty, Power, Responsibility .............. 5-41 5.3.6.2 - Inspection Techniques How to Document Responsibility ............................................................................................... 5-41 5.3.7 - GUARANTEES AND LABELING AGREEMENTS ...... 5-42 5.3.7.1 - Guarantee ................................................................ 5-42 5.3.7.2 - Labeling Agreement ................................................. 5-42 5.3.7.3 - Exemption Requirements......................................... 5-42 5.3.8 - RECORDS OBTAINED............................................... 5-42 5.3.8.1 - Verification of Source Records ................................ 5-43 5.3.8.2 - Identification of Records Collected........................... 5-43 5.3.8.3.1 - ELECTRONIC RECORDS .................................... 5-43 5.3.8.3.1.1 ORIGINAL COPY ................................................. 5-44 5.3.8.3.1.2 WORKING COPY ................................................ 5-44 5.3.8.3.2 - ELECTRONIC DATABASES AND QUERIES ....... 5-44 5.3.8.3.2.1 - REQUESTING Electronic RECORDS from databases .............................................................................. 5-44 5.3.8.3.2.2 - ELECTRONIC RECORDS RECEIVED ON ELECTRONIC STORAGE MEDIA ......................................... 5-45 5.3.8.3.3.1 - IDENTIFYING AND SECURING ELECTRONIC STORAGE MEDIA ................................................................. 5-45 5.3.8.5 - Listing of Records .................................................... 5-46 5.3.8.6 - Patient and/or Consumer Identification on Records . 5-46 5.3.9 - REQUEST FOR SAMPLE COLLECTION................... 5-46 5.3.10 - POST-INSPECTION NOTIFICATION LETTERS ...... 5-47 SUBCHAPTER 5.4 - FOOD ................................................... 5-47 5.4.1 - FOOD and COSMETIC INSPECTIONS ..................... 5-47 5.4.1.1 - Preparation and References .................................... 5-47 5.4.1.2 - Inspectional Authority............................................... 5-47 5.4.1.2.1 - WRITTEN DEMAND FOR RECORDS .................. 5-47 5.4.1.2.2 - WRITTEN REQUEST FOR INFORMATION ......... 5-48 5.4.1.3 - Records Access Under Sections 414 and 704 of the FD&C Act ............................................................................... 5-48 5.4.1.4 - Food and Cosmetic Defense Inspectional Activities 5-49 5.4.1.4.1 - FOOD AND COSMETIC SECURITY .................... 5-49 5.4.1.4.2 - RECONCILIATION EXAMINATIONS ................... 5-49 5.4.1.4.3 - RECONCILIATION EXAMINATION GUIDANCE PART A .................................................................................. 5-50 5.4.1.4.4 - RECONCILIATION EXAMINATION GUIDANCE PART B ................................................................................. 5-50 5.4.1.4.5 - SPECIAL SAFETY PRECAUTIONS .................... 5-51 5.4.1.5 - Food Registration .................................................... 5-51 5.4.1.5.1 - FACILITIES EXEMPTED FROM REGISTRATION .. 5- 52 5.4.1.5.2 - FOOD FACILITY REGISTRATION RESOURCES 5-52 5.4.2 - PERSONNEL ............................................................. 5-53 5.4.2.1 - Management ........................................................... 5-53 5.4.2.2 - Employees .............................................................. 5-53 5.4.3 - PLANTS AND GROUNDS ......................................... 5-54 5.4.3.1 - Plant Construction, Design and Maintenance ......... 5-54 5.4.3.2 - Waste Disposal ....................................................... 5-54 5.4.3.3 - Plant Services ......................................................... 5-54 5.4.4 - RAW MATERIALS...................................................... 5-54 5.4.4.1 - Handling Procedure................................................. 5-55 5.4.4.2 - Condition ................................................................. 5-55 5.4.4.3 - Food Chemicals Codex ........................................... 5-55 5.4.5 - EQUIPMENT AND UTENSILS ................................... 5-55 5.4.5.1 - Filtering Systems ..................................................... 5-55 5.4.5.2 – Cleaning and Sanitization of Equipment and Utensils 5- 55 5.4.5.3 - Conveyor Belt Conditions ........................................ 5-55 5.4.5.4 - Utensils ................................................................... 5-56 5.4.5.5 - Mercury and Glass Contamination .......................... 5-56 5.4.5.6 - UV Lamps ............................................................... 5-56 5.4.5.7 - Chlorine Solution Pipes ........................................... 5-56 5.4.5.8 - Sanitation Practices................................................. 5-56 5.4.6 - PROCESS AND CONTROLS ................................... 5-56 5.4.6.1 - Ingredient Handling ................................................. 5-56 5.4.6.1.1 Cosmetics Ingredients .......................................... 5-57 5.4.6.2 - Formulas ................................................................. 5-57 5.4.6.3 - Food Additives......................................................... 5-57 5.4.6.4 - Color Additives ........................................................ 5-58 5.4.6.5 - Quality Control......................................................... 5-58 5.4.6.5.1 - INSPECTION SYSTEM ........................................ 5-58 5.4.6.5.2 - LABORATORY TESTS ........................................ 5-58 5.4.6.5.3 - MANUFACTURING CODE SYSTEM ................... 5-59 5.4.6.6 Packaging, Labeling, and Packing............................ 5-59 5.4.6.6.1 - QUANTITY OF CONTENTS................................. 5-59 5.4.6.6.2 - LABELING ............................................................ 5-59 5.4.6.6.3 – NUTRITIONAL AND ALLERGEN LABELING...... 5-59 5.4.6.6.4 – SANITARY OPERATIONS .................................. 5-59 5.4.6.6.6 Labeling violations ................................................ 5-59 5.4.6.6.7 Cosmetic product labeling making drug claims..... 5-59 5.4.7 - SANITATION .............................................................. 5-60 5.4.7.1 - Routes of Contamination ......................................... 5-60 5.4.7.1.1 - INSECTS .............................................................. 5-60 5.4.7.1.2 - RODENTS ............................................................ 5-60 5.4.7.1.3 - PESTICIDES ........................................................ 5-60 5.4.7.1.4 - OTHER ................................................................. 5-61 5.4.7.2 - Microbiological Concerns ........................................ 5-61 5.4.7.2.1 - PROCESSING EQUIPMENT ............................... 5-62 5.4.7.2.2 - EMPLOYEE PRACTICES .................................... 5-62 5.4.7.3 - Storage.................................................................... 5-62 5.4.7.3.1 - FOOD TRANSPORT VEHICLES ......................... 5-62 5.4.7.3.2 - VEHICLES AT RECEIVERS ................................ 5-63 5.4.7.3.3 - VEHICLES AT SHIPPERS ................................... 5-63 5.4.8 - DISTRIBUTION .......................................................... 5-63 5.4.8.1 - Promotion and Advertising ...................................... 5-63 5.4.8.2 - Recall Procedure ..................................................... 5-63 5.4.8.3 - Complaint Files........................................................ 5-63 5.4.9 - OTHER GOVERNMENT INSPECTION ..................... 5-63 5.4.9.1 - Federal .................................................................... 5-63 5.4.9.2 - State and Local ....................................................... 5-64 5.4.9.3 - Grade A Dairy Plant Inspections ............................. 5-64 5.4.10 - FOOD STANDARDS ................................................ 5-64 5.4.10.1 - Food STANDARDS Inspection .............................. 5-64 INVESTIGATIONS OPERATIONS MANUAL 2019 CHAPTER 5 5-3 5.4.10.2 - Food Inspection Report.......................................... 5-65 5.4.10.2.1 - ESTABLISHMENT INSPECTION RECORD (EI RECORD) .............................................................................. 5-65 5.4.10.2.2 - BODY OF REPORT ............................................ 5-65 5.4.10.2.3 - SPECIAL INFORMATION SECTION .................. 5-65 5.4.10.3 - Violative Inspections .............................................. 5-65 5.4.12 - PESTICIDES ............................................................ 5-65 5.4.12.1 - Pesticide Inspections ............................................. 5-65 5.4.12.2 - Current Practices ................................................... 5-66 5.4.12.3 - Growers ................................................................. 5-66 5.4.12.3.1 - PESTICIDE APPLICATION ................................ 5-67 5.4.12.3.2 - PESTICIDE MISUSE/DRIFT/SOIL CONTAMINATION ................................................................. 5-67 5.4.12.4 - Packers and Shippers ............................................ 5-67 5.4.12.5 - Pesticide Suppliers ................................................ 5-67 5.4.12.6 - Pesticide Applicators.............................................. 5-67 5.4.12.7 - Sample Collections ................................................ 5-67 5.4.13 – COSMETIC INSPECTIONS ..................................... 5-67 5.4.13.1 Preparation and References .................................... 5-68 5.4.13.2 – Documents and Records....................................... 5-68 5.4.13.3- Contaminated cosmetics........................................ 5-68 5.4.13.4 – Specific Types of Product Safety Concerns .......... 5-69 SUBCHAPTER 5.5 - DRUGS ................................................ 5-69 5.5.1 - DRUG INSPECTIONS ................................................ 5-69 5.5.1.1 - Preparation and References .................................... 5-69 5.5.1.2 - Inspectional Approach ............................................. 5-70 5.5.2 - DRUG REGISTRATION & LISTING ........................... 5-70 5.5.3 - PROMOTION AND ADVERTISING ............................ 5-71 5.5.4 - GUARANTEES AND LABELING AGREEMENTS ...... 5-71 5.5.5 - OTHER INSPECTIONAL ISSUES .............................. 5-71 5.5.5.1 - Intended Use ........................................................... 5-71 5.5.5.2 - Drug Approval Status ............................................... 5-71 5.5.5.3 – Drug Status Questions ............................................ 5-71 5.5.5.4 – Verification of Compliance with PDMA Requirements. 5- 71 5.5.5.5 - Drug/Dietary Supplement Status.............................. 5-71 5.5.5.6 - Approved Drugs ....................................................... 5-71 5.5.5.7 - Investigational Drugs ............................................... 5-72 5.5.5.8 - Clinical Investigators and/or Clinical Pharmacologists . 5- 72 5.5.5.9 – Delaying, Denying, Limiting or Refusing Drug Inspections ............................................................................. 5-72 5.5.8 - DRUG INSPECTION REPORT .................................. 5-72 SUBCHAPTER 5.6 - DEVICES.............................................. 5-72 5.6.1 - DEVICE INSPECTIONS ............................................. 5-72 5.6.1.1 - Technical Assistance ............................................... 5-72 5.6.1.2 - Sample Collection During Inspection ....................... 5-73 5.6.1.3 - Types of Inspections ................................................ 5-73 5.6.2 - MEDICAL DEVICE QUALITY SYSTEM/ GOOD MANUFACTURING PRACTICES .......................................... 5-73 5.6.2.1 - Pre-Inspectional Activities ........................................ 5-73 5.6.2.2 - Quality Audit ............................................................ 5-74 5.6.2.3 - Records ................................................................... 5-75 5.6.2.4 - Complaint Files ........................................................ 5-75 5.6.3 - STERILE DEVICES .................................................... 5-76 5.6.4 - LABELING .................................................................. 5-76 5.6.5 - GOVERNMENT-WIDE QUALITY ASSURANCE PROGRAM (GWQAP) ........................................................... 5-76 5.6.6 - CONTRACT FACILITIES ............................................ 5-76 5.6.7 - SMALL MANUFACTURERS ....................................... 5-76 5.6.8 - BANNED DEVICES .................................................... 5-77 5.6.9 – REPORTS OF CORRECTIONS AND REMOVALS ... 5-77 5.6.10 – TRACKED MEDICAL DEVICES .............................. 5-77 5.6.11 - DEVICE INSPECTION REPORTS ........................... 5-77 SUBCHAPTER 5.7 - BIOLOGICS.......................................... 5-77 5.7.1 - DEFINITION ............................................................... 5-77 5.7.2 - BIOLOGICS INSPECTIONS ....................................... 5-77 5.7.2.1.1 - BLOOD AND SOURCE PLASMA INSPECTIONS 5-77 5.7.2.1.2 – HUMAN TISSUE INSPECTIONS ........................ 5-78 5.7.2.2 – Donor Confidentiality .............................................. 5-78 5.7.2.3 – Inspectional Objectives........................................... 5-78 5.7.2.4 - Preparation .............................................................. 5-78 5.7.2.5 - Inspectional Approach ............................................. 5-79 5.7.2.6 - Regulations, Guidelines, Recommendations ........... 5-79 5.7.2.7 - Technical Assistance............................................... 5-79 5.7.2.8 Biologics Establishment Inspection Reports ............ 5-80 5.7.3 - REGISTRATION, LISTING AND LICENSING. ........... 5-80 5.7.3.1 - Registration and Listing ........................................... 5-80 5.7.3.1.1 – TRANSFUSION SERVICES ................................ 5-80 5.7.3.1.2 - HCT/PS ................................................................ 5-80 5.7.3.1.3 - LABORATORIES ................................................. 5-80 5.7.3.1.4 - MILITARY BLOOD BANKS .................................. 5-80 5.7.3.2 – MOUs ..................................................................... 5-80 5.7.3.3 - Biologic License ...................................................... 5-81 5.7.4 - RESPONSIBLE INDIVIDUALS .................................. 5-81 5.7.5 - TESTING LABORATORIES ....................................... 5-81 5.7.6 - BROKERS .................................................................. 5-81 SUBCHAPTER 5.8 - TOBACCO PRODUCTS ...................... 5-81 5.8.1 - DEFINITIONS ............................................................ 5-82 5.8.2 – TOBACCO INSPECTIONS ....................................... 5-82 5.8.3 - RETAIL COMPLIANCE CHECK INSPECTION CONTRACTS ........................................................................ 5-82 5.8.4 - GUIDANCE, COMPLIANCE & REGULATORY INFORMATION ..................................................................... 5-82 SUBCHAPTER 5.9 - VETERINARY MEDICINE ................... 5-82 5.9.1 - CVM WEBSITE .......................................................... 5-82 5.9.2 - VETERINARY DRUG ACTIVITIES ............................ 5-82 5.9.3 - MEDICATED FEEDS AND TYPE A ARTICLES ........ 5-83 5.9.4 - BSE ACTIVITIES........................................................ 5-83 5.9.4.1 – Biosecurity Procedures for BSE Inspections at Poultry Facilities and Farms .............................................................. 5-83 5.9.5 - DRUG RESIDUES ..................................................... 5-84 5.9.6 - VETERINARY DEVICES............................................ 5-84 5.9.7 - ANIMAL GROOMING AIDS ....................................... 5-85 SUBCHAPTER 5.10 – BIORESEARCH MONITORING (BIMO) 5- 85 5.10.1 – BIMO Establishment Type Definitions ..................... 5-85 5.10.2 – BIMO Assignments .................................................. 5-86 5.10.3 – BIMO Compliance Programs ................................... 5-86 5.10.4 – Postmarket Adverse Event Reporting...................... 5-86 5.10.5 - Risk Evaluation and Mitigation Strategies (REMS)... 5-87 SUBCHAPTER 5.11 – REPORTING ..................................... 5-88 5.11.1 - ESTABLISHMENT INSPECTION REPORT (EIR) ... 5-89 5.11.2 – ENDORSEMENT..................................................... 5-89 5.11.2.1 - Compliance Achievement Reporting System (CARS) 5- 89 5.11.2.1.1 - REPORTING CRITERIA .................................... 5-90 5.11.2.1.2 - DATA ELEMENTS ............................................. 5-90 5.11.3 – eNSpect ESTABLISHMENT INSPECTION REPORT COVERSHEET...................................................................... 5-90 5.11.3.1 – Inspection Basis ................................................... 5-90 5.11.4 - NARRATIVE REPORT ............................................. 5-91 5.11.4.1 – Summary of Findings report for NAI Inspections .. 5-91 5.11.4.2 – Summary of Findings for VAI Inspection .............. 5-92 5.11.4.3 - Individual Narrative Headings ............................... 5-92 5.11.4.3.1 - STANDARD NARRATIVE REPORT .................. 5-92 5.11.4.3.2 - SUMMARY ......................................................... 5-94 5.11.4.3.3 - ADMINISTRATIVE DATA ................................... 5-94 5.11.4.3.4 - HISTORY ........................................................... 5-94 5.11.4.3.5 - INTERSTATE (I.S.) COMMERCE ...................... 5-95 5.11.4.3.6 - JURISDICTION (PRODUCTS MANUFACTURED AND/OR DISTRIBUTED) ...................................................... 5-95 5.11.4.3.7 - INDIVIDUAL RESPONSIBILITY AND PERSONS INTERVIEWED ..................................................................... 5-95 5.11.4.3.8 - FIRM'S TRAINING PROGRAM .......................... 5-95 5.11.4.3.9 - MANUFACTURING/DESIGN OPERATIONS ..... 5-95 CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2019 5-4 5.11.4.3.10 - MANUFACTURING CODES ............................. 5-96 5.11.4.3.11 - COMPLAINTS................................................... 5-96 5.11.4.3.12 - RECALL PROCEDURES .................................. 5-96 5.11.4.3.13 - OBJECTIONABLE CONDITIONS AND MANAGEMENT'S RESPONSE ............................................. 5-96 5.11.4.3.13.1 - Supporting Evidence and Relevance ............. 5-96 5.11.4.3.13.2 - Discussion with Management ........................ 5-97 5.11.4.3.14 - REFUSALS ....................................................... 5-97 5.11.4.3.15 - GENERAL DISCUSSION WITH MANAGEMENT . 5- 97 5.11.4.3.16 - ADDITIONAL INFORMATION .......................... 5-97 5.11.4.3.17 - SAMPLES COLLECTED .................................. 5-97 5.11.4.3.18 - VOLUNTARY CORRECTIONS......................... 5-97 5.11.4.3.19 - EXHIBITS COLLECTED ................................... 5-97 5.11.4.3.20 – ATTACHMENTS .............................................. 5-98 5.11.4.3.21 - SIGNATURE ..................................................... 5-98 5.11.5 - EXHIBITS ................................................................. 5-98 5.11.5.1 - Electronic Records as Exhibits .............................. 5-98 5.11.6 - Corrections to Endorsed Establishment Inspection Reports .................................................................................. 5-98 5-1 FORM FDA 482 NOTICE OF INSPECTION .................. 5-100 5-2 - FORM FDA 482a ...................................................... 5-103 5-3 FORM FDA 482b ........................................................... 5-104 5-5 FORM FDA 483 ............................................................. 5-106 5-6 INSERTING DIGITAL PHOTOS INTO eNSpect (RESIZE PHOTO) ............................................................................... 5-108 5-65-7 INSERTING DIGITAL PHOTOS INTO eNSpect (INSERT PHOTO) ............................................................................... 5-109 5-8 INSERTING DIGITAL PHOTOS INTO eNSpect (RESIZING USING MS OFFICE PICTURE MANAGER) ........................ 5-110 5-9 FACTS CREATE SAMPLE ASSIGNMENT SCREEN.... 5-111 5-10 FORM FDA 482c NOTICE OF INSPECTION – REQUEST FOR RECORDS ..................................................................... 112 5-11 FOOD ADDITIVE NOMOGRAPH I ............................. 5-113 5-11 FOOD ADDITIVE NOMOGRAPH II ............................. 5-114 5-12 SUMMARY OF REGISTRATION AND LISTING HUMAN PHARMACEUTICALS ......................................................... 5-115 5-13 SUBSTANTIALLY EQUIVALENT MEDICAL DEVICES ..... 5- 116 5-14 eNSpect PROFLIE - COMSTAT ..................................... 117 5-15 COMPLIANCE ACHIEVEMENT REPORT ..................... 124 SUBCHAPTER 5.1 - INSPECTION INFORMATION 5.1.1 - AUTHORITY TO ENTER AND INSPECT See IOM 2.2 for discussion of statutory authority. It is your obligation to fulfill the following requirements be- cause failure to do so may prevent use of evidence and information obtained during the inspection. There may be occasions where you may be accompanied on your inspection or investigation by other officials. These officials may be state or local officials who have their own inspectional authority or other officials who do not have authority to enter the firm. You should obtain permission from the firm’s most responsible person if offi- cials without inspection authority wish to accompany you during your inspection/investigation. You should document in your EIR when other non-FDA officials accompany you during your inspection, and whether they entered under their own authority or the responsible individual at the firm gave permission (identify, by name and title, the responsi- ble individual giving permission). See IOM 5.2.2 and 5.11.4.3.3. 5.1.1.1 - FDA Investigator's Responsibility Your authority to enter and inspect establishments is predicated upon specific obligations to the firm as de- scribed below. It is your responsibility to conduct all in- spections at reasonable times and within reasonable limits and in a reasonable manner. Proceed with diplomacy, tact and persuasiveness. During inspections or investigations, when you have evidence of conditions whereby there is a reasonable probability the associated products will cause imminent and serious adverse health consequences or death, you should notify your supervisor immediately to consider a Risk Control Review (RCR) evaluation. 5.1.1.2 - Credentials Display your credentials to the top management official be it the owner, operator, or agent in charge. See IOM 5.2.2. NOTE: Although management may examine your creden- tials and record the number and your name, do not permit your credentials to be photocopied. Federal Law (Title 18, U.S.C. 701) prohibits photographing, counterfeiting, or misuse of official credentials. Do not permit a firm to take your fingerprints, contact your SCSO for more information. 5.1.1.3 - Written Notice After showing the firm's representative your credentials, issue the original, properly executed, and signed FDA 482, Notice of Inspection, to the top management official. Keep a copy for submission with your report. A notice of inspection is not required to be issued during foreign inspections; however credentials should be presented to the top management official. 5.1.1.4 - Written Observations Upon completing the inspection and before leaving the premises, provide the highest management official avail- able your inspectional findings on an FDA 483 - Inspec- tional Observations. See Section 704(b) of the FD&C Act [21 U.S.C. 374 (b)] and IOM 5.2.3 and 5.2.7. 5.1.1.5 - Receipts Upon completion of the inspection, furnish the top management official the original of the FDA-484 - Receipt for Samples describing any samples obtained during the inspection. See IOM 5.2.4. 5.1.1.6 - Written Demand for Records INVESTIGATIONS OPERATIONS MANUAL 2019 CHAPTER 5 5-5 In low-acid canned food and acidified food EI's, an FDA 482a - Demand for Records (exhibit 5-2) is required under 21 CFR 108.35(h) and 21 CFR 108.25(g) to obtain records required by 21 CFR 113 and 114. 5.1.1.7 - Written Requests for Information There are several methods of requesting records. These may include a request for information under LACF or AF inspections, 703 written requests, and requests for records under the BT Act (IOM 5.4.1.3). 5.1.1.7.1 – LACF / AF Food Inspections In low-acid canned foods and acidified foods EI's, an FDA 482b, Request for Information (exhibit 5-3), is required under 21 CFR 108.35(c)(3)(ii) and 21 CFR 108.25(c)(3)(ii) to obtain information concerning processes and procedures required under 21 CFR 113 and 114. 5.1.1.7.2 – Requests for Records under Section 703 of the FD&C Act Per CPG Sec. 160.300, Requests for Records under Section 703 [21 U.S.C. 373], evidence obtained in response to a specific written request under Section 703 cannot be used in a criminal prosecution of the person from whom obtained. With Supervisory approval, in certain circumstances, you may decide to issue a 703 written request when the importance of the evidence is crucial to protecting the public health. Procedure: All 703 written requests must comply with IOM 4.4.7.2.2. Consider obtaining the evidence from other sources before using the 703 written request. In the case of foods and feeds, if there is a risk or threat of serious adverse health consequences, the divisionprogram division should invoke the BT Act records access authority. All BT Act records requests must comply with IOM 5.4.1.3. 5.1.1.8 - Business Premises Authority to inspect firms operating at a business location is described in IOM 5.1.1 and requires issuing management an FDA 482, Notice of Inspection, and presenting your credentials. A warrant for inspection is not necessary unless a refusal or partial refusal is encountered or anticipated. 5.1.1.9 - Premises Used for Living Quarters All inspections where the premises are also used for living quarters must be conducted with a warrant for inspection unless: Owner Agreeable - The owner or operator is fully agree- able and offers no resistance or objection whatsoever. Cleary document in the EIR that you are inspecting a residence and the owner was agreeable. or; Physically Separated - The actual business operations to be inspected are physically separated from the living quarters by doors or other building construction. These would provide a distinct division of the premises into two physical areas, one for living quarters and the other for business operations, and you do not enter the living area. In both the latter cases, proceed as any other inspection with the appropriate presentation of credentials and issu- ance of a Notice of Inspection. For safety precautions, it is recommended that two credentialed FDA employees are present when conducting inspections in a residence. 5.1.1.10 - Facilities where Electronic Products are Used or Held Section 537(a) of the FD&C Act provides the FDA with the authority to inspect the facilities of manufacturers in cer- tain circumstances. The electronic product radiation con- trol provisions were originally enacted as the Radiation Control for Health and Safety Act of 1968 (P.L. 90-602) It is lawful for FDA personnel to enter the facilities of an electronic product distributor, dealer, assembler or user for the purpose of testing an electronic product for radiation safety when the entry is voluntarily permitted. Congress has not specifically prohibited FDA from conducting such voluntary examinations and such examinations would clearly agree with the congressional declaration of pur- pose expressed in section 532(a) of the RCH&S Act. Under the Medical Device Authority, electronic products utilized in human and/or veterinary medicine, e.g., x-ray, laser, ultra-sound, diathermy, etc. can be considered pre- scription devices. In these cases the authority of Section 704 of the FD&C Act [21 U.S.C. 374] can be used to obtain entry to inspect the user facility. If the Medical Device Authority is utilized, credentials must be displayed and a FDA 482, Notice of Inspection, must be issued. 5.1.1.11 - Multiple Occupancy Inspections You are required per FD&C Act 704(a)(1) [21 U.S.C. 374(a)(1)] to issue a Notice of Inspection, FDA 482, to each firm inspected. When firms have operations located in different sites or buildings, you should use judgment to determine when multiple FDA 482 forms need to be is- sued. For sites located a distance apart, it is preferable to issue a FDA 482 to the most responsible person at each site. One rule of thumb which can be used is if the sites or buildings are within walking distance, your original Notice of Inspection can be considered sufficient to cover both. During your initial interview with management, after you issue the FDA 482, make sure you clearly indicate the facility and sites you intend to inspect. The Act requires the issuance of a Notice of Inspection, but does not prohi- bit issuing multiple notices if management so requests. As with all of our work, good judgment, and knowledge of the OEI and the FD&C Act are necessary in deciding what legally must be done. CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2019 5-6 5.1.1.12 - Authority for Examinations and Investigations Section 702(a) of the FD&C Act [21 U.S.C. 372 (a)] au- thorizes examinations and investigations for the purpose of enforcing the Act. 5.1.1.13 - Authority to Implement Section 702(e)(5) of the FD&C Act Section 702(e) of the FD&C Act [21 U.S.C. 372 (e)] con- tains certain authorities relating to counterfeit drugs in- cluding the authority to seize ("confiscate") counterfeit drugs and containers, counterfeiting equipment, and all other items used or designed for use in making counterfeit drugs prior to the initiation of libel proceedings. This au- thority has been delegated, with certain restrictions, to holders of official credentials consistent with their authority to conduct enforcement activities. Additional authority in 702(e) to make arrests, to execute and serve arrest war- rants, to carry firearms, or to execute seizure by process under Section 304 of the FD&C Act [21 U.S.C. 334] have not been delegated. The agency does intend to utilize the authority contained in Section 702(e) to execute and serve search warrants, but such use does not require delegation from the ACRA. Section 702(e)(5) contains authority for such delegated persons to confiscate all items which are, or which the investigator has reasonable grounds to believe are, sub- ject to seizure under Section 304(a)(2). Items subject to seizure, and thus to confiscation under Section 702(e)(5), includes most things associated with counterfeit drugs. Confiscation authority does not, however, extend to vehi- cles, records, or items (i.e., the profits) obtained as a re- sult of counterfeiting. 5.1.1.13.1 - SCOPE Under this delegation, with supervisory concurrence and prior to the initiation of libel proceedings, investigators and inspectors are authorized to confiscate: 1. Any counterfeit drug, 2. Any container used to hold a counterfeit drug, 3. Any raw material used in making a counterfeit drug, 4. Any labeling used for counterfeit drug, 5. Any equipment used to make a counterfeit drug includ- ing punches, dies, plates, stones, tableting machines, etc., 6. Any other thing which you have reasonable grounds to believe is designed or used in making a counterfeit drug. NOTE: You and your supervisor must be constantly aware of the potential dangers involved in confiscating property from individuals. Special care should be taken to ensure your safety. Arranging for teams of investigators to con- duct the investigation, or arranging for assistance by local police, or other agencies with police powers, should be considered in planning the confiscation of counterfeit ma- terials. 5.1.1.13.2 - INSPECTIONAL GUIDANCE Guidance provided for implementing the authority to con- fiscate drug counterfeits is as follows: 1. The authority is not to be utilized unless there has been an agency determination the drug to be confis- cated is a counterfeit and it is a drug which "without authorization, bears a trademark, *** or any likeness" of a legitimate product. The determination usually is based upon evidence supplied by the firm whose prod- uct is being counterfeited. A written agency deter- mination will issue to the Program Division Director from the Office of Enforcement and Import Operations (OEIO), in conjunction with the Center for Drug Evalua- tion and Research. 2. When engaged in counterfeit investigations, you should proceed as follows upon encountering items to be confiscated. a. Evaluate safety needs and check the location to en- sure it is safe to proceed. Do not attempt to remove an item by force. If it appears there will be resis- tance, contact the local police, or other agencies with police powers for backup, if not already done in advance. b. Inventory the items to be confiscated. c. Prepare a written receipt and offer it to the person in charge. d. Remove the items, if possible, from the premises (if they cannot be removed, secure them under seal). e. Place all items removed under lock at a secure location. In most cases, confiscated items will be stored at the program division or resident post office until they are seized. 5.1.1.13.3 - FOLLOW UP GUIDANCE After items are confiscated, certain actions must be taken to bring confiscated items under the control of the court. Proceed as follows: 1. After an item is confiscated, immediately notify your supervisor. 2. Supervisors must then notify the appropriate compli- ance units of the items confiscated. 3. Compliance units should initiate seizure proceedings against any items confiscated. 4. Office of Medical Products and Tobacco Program Operations (OMPTO) should be advised of any action utilizing this authority. 5.1.1.13.4 - SEARCH WARRANTS Section 702(e)(2) contains authority to execute and serve search warrants. Proceed as instructed by your program division after a search warrant has been obtained. 5.1.1.14 - Products Imported Under the Provisions of Section 801(d)(3) of the FD&C Act The FDA Export Reform and Enhancement Act of 1996 (PL 104-134 and 104-180) amended the FD&C Act by INVESTIGATIONS OPERATIONS MANUAL 2019 CHAPTER 5 5-7 adding Section 801(d)(3) ("Import for Export") which per- mits the importation of unapproved drug and medical de- vice components, food additives, color additives, and dietary supplements intended for further incorporation or processing into products destined for export from the United States. Section 801(d)(3) was subsequently amended by Section 322 of the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (Bioterrorism Act), Public Law 107-188, which specified certain requirements an importer has to satisfy in order to import a product under this Section. See IOM 6.2.3.4. 5.1.1.14.1 - REQUIREMENTS FOR BIOTERRORISM ACT These requirements include: 1. A statement confirming the intent to further process such article or incorporate such article into a product to be exported, 2. The identification of all entities in the chain of posses- sion of the imported article, 3. A certificate of analysis "as necessary to identify the article" (unless the article is a device), and 4. Executing a bond providing for liquidated damages in the event of default, in accordance with U.S. Customs. This bond remains in effect until the final product is ex- ported and destroyed. In addition, the initial owner or consignee must keep re- cords showing the use of the imported articles, and must be able to provide upon request a report showing the dis- position or export of the imported articles. An article im- ported under this section, and not incorporated or further processed, must be destroyed or exported by the owner or consignee. Failure to keep records or to make them avail- able to FDA, making false statements in such records, failure to export or destroy imported articles not further incorporated into finished products, and introduction of the imported article or final product into domestic commerce are Prohibited Acts under Section 301(w). Filers making entry under the Import for Export provisions must either identify entry submissions with the OASIS Af- firmation of Compliance "IFE" (Import for Export), or sup- ply FDA with written documentation stating the product is entered under the Import for Export provisions. A Certifi- cate of Analysis (as necessary) and identification of all involved entities must be submitted in writing to the import .program division. The import program division will forward all written documentation to the home program division of the initial owner or consignee for incorporation into the appropriate Establish-ment File. 5.1.1.14.2 - INSPECTIONAL PREPARATION Before conducting an Establishment Inspection, contact your program division’s designated individual with access to OASIS/ORADSS Reports to obtain a printout of any import entries made by the establishment under the Import for Export provisions through OASIS. In addition, check the program division factory file for copies of any Import for Export documents forwarded from the import program division where entry was filed. During the inspection examine the firm's records to determine the disposition of any items identified at time of entry as intended for incorporation into products for export. Document any instances in which such products were introduced into domestic commerce or cannot be accounted for (see IOM 6.2.3.4.3). 5.1.2 - INSPECTIONAL APPROACH An establishment inspection is a careful, critical, official examination of a facility to determine its compliance with the laws and regulations administered by FDA. Inspections may be used to collect evidence to document violations and to support regulatory action, when appropriate, or they may be directed to obtaining specific information on new technologies, good commercial practices, or data for establishing food standards or other regulations. In order to facilitate on-the-job training, multiple points of view, and perspectives of firms being inspected whenever practical, those with assignment authority, should consider assigning different Investigator/s or different Lead Investigators at different times. This is recommended particularly when there have been multiple sequential NAI inspections or when the firm's management has been uncooperative. The approach and scope (e.g. full scope, limited scope; Level I, II or III; and full or abbreviated) used to conduct an inspection is defined by the compliance program, assignment, and/or your supervisor. The inspectional approach used is according to the following definitions: Comprehensive Inspection -directs coverage to everything in the firm subject to FDA jurisdiction to determine the firm’s compliance status; or Directed Inspection -directs coverage to specific areas to the depth described in the program, assignment, or as instructed by your supervisor. See IOM Subchapter 1.5 and 1.5.5 for information on safety, use of protective gear, trash disposal, dealing with potential hazards and other safety issues. See special report requirements in IOM Subchapter 1.7.3 when objectionable conditions which may be of public health significance implicate establishments in other division(s). 5.1.2.1 - Depth of Inspection The degree and depth of attention given various opera- tions in a firm depends upon information desired, or upon the violations suspected or likely to be encountered. In determining the amount of attention to be given in specific cases, consider the: CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2019 5-8 1. Current Compliance Program, 2. Nature of the assignment, 3. General knowledge of the industry and its problems, 4. Firm history, and 5. Conditions found as the inspection progresses. 5.1.2.2 - Inspection Walk Through A walk through inspection of the premises should be conducted as early as possible to become familiar with the operation and to plan the inspection strategy. A walk through visual inspection of the manufacturing site is helpful in establishing the depth of the inspection, learning about products and processes, identifying sources of manufacturing records and identifying potential areas of concern. The size of the facility, the number of employees, employee practices, environmental conditions inside and outside the plant, raw materials, manual and automated processes, sources of contamination, manufacturing flow, method of data collection including computer terminals, are some of the areas to be taken into consideration in establishing the depth of the inspection. A visual inspec- tion of a manufacturing site should also be used to check obvious potential problem areas such as: general house- keeping, state of operation for processes and processing equipment, and people dependent operations. Visual in- spections of areas used for failure investigation, product sampling and testing, product reworks, return goods, and product quarantine areas should be inspected for obvious potential product problems. Depending on the product being inspected, some of the general inspectional equipment an investigator should have available, may include, eye and ear protection, boots and protective clothing. Some specialized equipment may include radiation or ethylene oxide (EO) monitoring devices, magnifiers, and timing devices as needed. For some domestic and foreign plant sites, investigators may be required to be inoculated prior to the inspection for protection from potential environmental concerns such as hepatitis, yellow fever, malaria and live biological products which may be encountered in vaccine products. See subchapter IOM 1.5. 5.1.2.3 - Signing Non-FDA Documents Occasionally a firm will request you sign various docu- ments including: 1. A waiver which will exempt the firm from any responsibility or liability should an accident occur and you are injured on the firm's premises, 2. Form letters concerning access to confidential informa- tion the firm does not want released, 3. A training form acknowledging that you were briefed on the firm personnel gowning procedures, 4. Information/data you request during the inspection be put into writing, etc. If you receive such a request, inform the firm you are not authorized to sign such documents, letters, requests, waivers, etc., but will report the firm's request in your EIR. All FDA employees are authorized to sign-in and sign-out at a firm and to comply with security measures employed by the firm, including documenting the re- moval/replacement of seals to inspect vehicles and con- tainers. See IOM 4.3.4.3 and 4.5.4.6. Obviously, the key issue is you are not authorized to waive, without supervi- sory approval, any of FDA's rights to inspect, sample, photograph, copy, etc. or to sign any interstate shipping record document which could infer the firm could not be prosecuted under the Act. 5.1.2.4 - Technical Assistance If you determine specialized technical assistance is nec- essary in conducting inspections of new technologies, products or manufacturing procedures, it may be available through Produce Safety Network, Programmatic or National experts, other ORA components or Center scientists and engineers. If specialized skills are necessary and are not available locally or through your Division, contact the Division of Domestic Human and Animal Food Operations (DDHAFO) for CFSAN and CVM (food) products or Office of Medical Products and Tobacco Program Operations (OMPTO) for CBER, CDER, CDRH, CTP and CVM medical products. See FMD-142 and IOM 1.9.2.2.1 for additional information. 5.1.2.5 - Team Inspections The use of teams to conduct inspections may be benefi- cial. Very often individuals well versed in an analytical or inspectional technique or technology can provide assis- tance and advice. When inspection teams are involved in an inspection, one investigator will be designated as the team leader by the inspecting Division or by DDHAFO or OMPTO if a headquarters directed special inspection is involved. The team leader is in charge of the inspection and bears the overall responsibility for the inspection and the EIR. A team may consist of multiple investigators, laboratory personnel and other FDA employees, and your supervisor/coach, who may participate as part of the ORA Quality Assurance program. 5.1.2.5.1 - TEAM MEMBER RESPONSIBILITIES Each team member is responsible for preparing those portions of the report pertaining to his/her activities. Team members shall identify their portion of the report so they can later identify that portion as the part he/she performed and reported. Since reports should be written in the first person, one system might be to head each portion with a statement "The following operation(s) was/were observed and reported by Investigator ___________", who can then report in the first person. All team members must sign the EIR. Only those team members present at issuance sign the FDA-483. The issuance of the FDA-483 should not be delayed, in the absence of a team member's signature. See IOM 5.2.3 for instructions for signing a multi-page FDA 483. INVESTIGATIONS OPERATIONS MANUAL 2019 CHAPTER 5 5-9 5.1.2.5.2 - TEAM LEADER RESPONSIBILITIES The Team Leader shall be responsible for: 1. Issuing unused notebooks for taking regulatory notes during the EI or investigation to headquarters personnel on the team. He/she is also responsible for instructions on their use, if necessary, and when the report is finished, for obtaining the headquarters individual's signature on the original EIR and completed and properly identified regulatory notes and submitting them to the supervisor for filing. See IOM 2.1.3. 2. Directing the overall inspection to accomplish the objectives of the assignment including; a. Planning the inspection, b. Scheduling and coordinating team members' pre-in- spection preparations, c. Determining, to the extent possible, the firm will be open and operating, d. Planning for needs of visiting scientists if applicable. When the team leader is not familiar with all the processes or technology involved in the inspection, provide for primary coverage of selected areas by other team members, e. Determining an orderly, efficient, and effective ap- proach and sequence to be used and discussing the inspection plan with the team, f. Modifying the inspection plan as necessary during the EI, to permit following leads, documenting evi- dence, etc., g. Setting team policy on how communications with the firm are to be handled, h. Discussing personal conduct in dealing with head- quarters personnel as necessary, i. Assuring an early understanding by team members of their roles in note taking and reporting, j. Assuring communications are open among team members, especially if the team is allowed to sepa- rate and work independently, k. Reviewing inspection progress at least daily, dis- cussing remaining objectives with the team mem- bers, and setting objectives for the following day, l. Continually assessing the progress of the inspec- tion to evaluate how the inspectional approach is working and to keep the division supervisor advised of the inspection's progress, m. Providing guidance and direction to team members as necessary, n. Advising each team member of reporting responsibilities and dates when drafts are to be provided, o. Following up promptly on any delays or failures to report as required, and p. Assisting the supervisor with further follow up, as in- dicated. 3. Making sure any person who joins the team after the inspection has started presents credentials and issues a FDA 482, Notice of Inspection to the firm prior to actually taking part in the EI; 4. Completing and/or correcting the computer generated coversheet; 5. Preparing the Summary of Findings; 6. Completing all headings of an administrative nature in the narrative report; 7. Compiling and submitting the complete final report; and 8. Resolving any disputes or differences of opinion among the team members, including items, which may be listed on the FDA 483. 5.1.2.6 - Post-Inspectional Contacts If the firm contacts the Investigator after the inspection regarding the inspection or follow-up, the Investigator should refer the request to his or her supervisor or to Compliance Branch if a regulatory action is contemplated. The Investigator should not respond to the firm regarding the adequacy of the firm’s response to inspectional observations or any follow-up planned. After the inspection is concluded, if the Investigator finds that a document or other required information is missing, the Investigator should discuss the needed information and how to proceed with their supervisor. 5.1.3 - INSPECTION OF FOREIGN FIRMS Inspectional requirements apply to all inspections, includ- ing foreign inspections. However, there are some excep- tions. For instance the FDA 482 is not issued, unless the firm is a U.S. Military facility. Be guided by relevant Compliance Programs and the Guide to International Inspections and HHS Travel Manual for other differences. 5.1.4 - INSPECTIONAL PRECAUTIONS Our concern over microbiological contamination empha- sizes the need for you to be alert to criticism or allegations that you may have contributed to or caused contamination at a firm. This is especially important in drug firms and high-risk food firms, among others. You must adhere to good sanitation practices to refute any such criticisms. You could also unknowingly introduce or spread disease during inspections of or visits to animal production or sale facilities, conducting environmental investigations at poul- try layer facilities, conducting dairy farm inspections or audits of state activities, investigating drug residue reports or working in the veterinary bioresearch area. See IOM 5.2.10 for information outlining precautions for you to follow. Exercise caution in all activities in the firm. Follow the firm's sanitation program for employees and wash and sanitize hands, shoes, vehicles and equipment as indi- cated. Restrict unnecessary movement between various areas in plants and when possible, complete your activi- ties in one area before moving to the next. When inspecting areas where sterility is maintained or sterile rooms are located (especially in pharmaceutical or device firms), follow the sterile program required of the firm's employees. In general it is unnecessary to enter sterile rooms except in the most extraordinary circum- CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2019 5-10 stances. These areas are usually constructed to provide visual monitoring. Take no unsterile items with you (note- book, pencils, etc.). In this type of situation you can enter your observations in your regulatory notes immediately after leaving the sterile area. Always use aseptic techniques, including hand sanitizing, when collecting in-line and raw material samples, as well as finished product samples for microbiological examina- tion. See IOM 4.3.6. Do not use or consume a firm's products at any of a firm's facilities. This could be interpreted as accepting a product as being satisfactory and could possibly embarrass you and the Agency, both during the inspection and in the fu- ture. In general, consuming food products in a manufac- turing area is considered an objectionable practice. When conducting inspections of firm's using chemicals, pesticides, etc., ask to review the Material Safety Data Sheets (MSDS) for the products involved to determine what, if any, safety precautions you must take. This could include the use of respirators or other safety equipment. 5.1.4.1 - Clothing Wear clean coveralls or other protective clothing for each inspection and if circumstances dictate, use a clean pair when returning from lunch, or upon entering certain ma- chinery or critical areas. Remove all jewelry and secure pens, pencils, , etc., so they cannot fall into the product or machinery. Do not depend on clips on pens, etc., to hold these items in your outer pockets. Clean protective clothing should be either individually wrapped or placed in clean plastic bags and taped to pro- tect from contamination. If the package has been steril- ized, protect the package from possible contamination or puncture. The package should not be opened until you are ready to use the clothing. After use, clothing should be turned inside out as it is removed, and immediately placed in clean paper or plastic bags to prevent spread of con- tamination until washed and/or sterilized. Use disposable hair and head coverings throughout the inspection and disposable hand and foot coverings in ar- eas where floor tracking or cross contamination may be a factor. Use hard hats and other protective devices where the situation dictates. If reusable protective boots are used, wash and sanitize before each use. Always use sterile disposable boot cov- ers when entering machinery such as dryers or where un- avoidable contact with product is a factor. When discarding contaminated disposable head and boot coverings, it is suggested they be placed with used cloth- ing for proper disposal after leaving the plant area. See IOM 5.2.10.1 for protective clothing and equipment necessary when visiting livestock or poultry producing areas. 5.1.4.2 - PHS Recommendations - Basic Sanitary Practices FDA personnel are not required by law to have health cer- tificates, take physical exams or submit to requirements, which ensures their compliance with sanitary procedures in the performance of their official duties. However, it is critical you adhere to basic sanitation practices. See IOM 1.5.1.5. The Food Code 2017 is available electronically from the FDA CFSAN web page under Federal/State Programs- Retail Food Safety References. Printed copies may be ordered from the National Technical Information Service website. 5.1.4.3 - Representatives Invited by the Firm to View the Inspection While conducting an inspection, you may find the firm's management has invited individuals who are not directly employed by the firm to view the inspectional process (e.g., representatives from the press, trade associations, consumer groups, congressional staff, other company offi- cials). Regardless of whom the firm invites to observe the pro- gress of an inspection, the presence of outside represen- tatives should not disrupt the inspectional process. You should continue to conduct the inspection in a reasonable fashion. The presence of these individuals should have no impact on the manner in which the inspection progresses except you should take precautions to preserve the confi- dentially of any information you may have obtained as a result of the Agency's statutory authority. This is especially true when the inspection is recorded via videotaping, other photography, and/or audio recordings. Where applicable, refer to IOM 5.3.5 for procedures on how to prepare your own recording in parallel with the firm's recording. It is the Agency's position that while the investigator must protect privileged information provided to him/her during the inspection, it is the firm's responsibility to protect privileged/confidential information observed or recorded by those individuals invited by the firm. 5.1.5 - GENERAL PROCEDURES & TECHNIQUES The procedures and techniques applicable to specific in- spections and investigations for foods, drugs, devices, tobacco products, cosmetics, radiological health, or other FDA operations are found in part in the IOM (inspectional and investigational policy/procedure), and the Compliance Program Guidance Manual (program specific instructions). Some procedures and techniques which may be applica- ble to overlapping areas or operations are as follows: INVESTIGATIONS OPERATIONS MANUAL 2019 CHAPTER 5 5-11 5.1.5.1 - Candling Candling is defined as: "to examine by holding between the eye and a light, especially to test eggs in this way for staleness, blood clots, fertility and growth." Like most techniques learned through the food inspection programs, there are uses for this technique in other program areas such as looking for mold in bottled liquids which could be drugs, devices or biologics. Candling can also be useful in the examination of original documents to see below white- out or to look for over-writing. Many types of products lend themselves to inspection by some type of candling. For these products, firms generally have candling equipment which may be built into the pro- duction lines or may be a separate operation. Where checking products by candling, it may be possible to utilize the firm's candling equipment. Various other light sources for candling are also available including overhead projectors. Exercise care when using overhead projectors and protect the glass surface and the lens from scratches and damage. All candling is best accomplished when light outside the item being candled is masked so the light passes through the object rather than being diffused around it. A heavy paper or cardboard template can be quickly prepared at the time candling is done. 5.1.5.2 - Label Review Do not undertake a critical review of labels unless in- structed by the assignment, program, or your supervisor. Limit your comments to the mandatory label requirements required by the Acts. However, if after review of the for- mula, it is obvious an active ingredient or an otherwise mandatory ingredient statement does not appear on the label, such discrepancy may be called to management's attention. See also IOM 5.2.3.2 regarding labeling for blood and blood products. If asked for other label comments, refer the firm to the ap- propriate Center to obtain a label review. When the labeling is suspect or when you are requested to collect labels/labeling, collect three copies of all labels and accompanying literature for further review. For medi- cal devices, if there is a question regarding the need for a new 510(k) or PMA supplement, it is essential the label and labeling be collected. 5.1.5.3 - Field Exams A field examination is an on-site examination of a domes- tic product (or a foreign product in domestic channels of trade) sufficient in itself to determine if the product is in compliance with the Acts enforced by FDA. A field exam can be conducted of any commodity in any location. It is important to conduct field examinations during food inspections to detect violations, e.g., undeclared sulfiting agents, Certified color additives and allergens. If the examination does not reveal a violation or the appearance of a violation, a sample of the lot is usually not collected. If your exam reveals a violation or potential violation, you should collect an official sample. Instructions on how to conduct a field exam are contained in "Guides to Inspection of ***" and Compliance Programs. The Sample Schedules in Chapter 4 also provide guidance on lot examinations for special situations. SUBCHAPTER 5.2 - INSPECTION PROCEDURES 5.2.1 - PRE-INSPECTIONAL ACTIVITIES Prior to the start of any inspection or investigation, you should conduct a number of activities. These will differ based on whether this is an inspection or an investigation. Review establishments history, e.g. previous EIRs, complaints, registration listing, recalls. The purpose of this review is to determine the location of the establishment and obtain an overview of the establishment's operations and products as well as an understanding of their compliance history.Consumer complaint review will also determine if there are any complaints with open assignments, or with the status “Sureillance information for next EI” that need to be closed. You should also review the establishment factory jacket to determine if there were any prior safety issues noted, e.g. documented Investigator safety incidents or whether any specific per- sonal protective equipment is needed prior to the start of the inspection. If there has been a past personal safety incident, you should discuss with your supervisor and de- velop a Situational Plan prior to the start of the inspection. See IOM 5.2.1.4 – Personal Safety Plan. Prior to initiating any inspection you should become fa- miliar with the reporting requirements for the specific as- signment, as well as the requirements of IOM Subchapter 5.10. If the inspection or investigation is a directed assignment from a Center, ORA headquarters or another program division, read the assignment and attached materials to assure you understand the assignment. If the inspection or investigation is being conducted in part or solely as a recall follow-up or complaint, refer to Chapter 7 (Recalls) or Chapter 8 (Investigations) of the IOM for additional guidance. You should review the eNSpect assignment to determine if the Personal Safety Alert Indicator is set to yes for this specific firm. The reason for the Personal Safety Alert should be listed in the Endorsement for the previous inspection and should be accompanied by a memoto the Establishment File Jacket. See IOM 5.2.1.3 eNSpectPersonal Safety Alert. You should also review the applicable Compliance Pro- gram Guidance Manual(s) prior to the start of your inspec- tion or investigation. Division of Domestic Human and Animal Food Operations (DDHAFO)The Centers have issued numerous guidance documents for industry. These CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2019 5-12 documents are normally posted to the appropriate Center's Internet web site. Subchapters 5.4-5.9 of the IOM contain additional, pro- gram specific pre-inspectional activities, which you should follow. Imported products cross all program areas and our regu- lation of them does not stop at the border. Determine if there are any "import for export" follow-up assignments and be prepared to cover them during your inspection. See IOM 6.2.3.4 for guidance. Please be alert to imported products whenever you make an inspection. During in- spections of domestic firms, if you encounter imported products that appear adulterated, misbranded, counterfeit, tampered with or otherwise suspect, attempt to fully iden- tify the product and the source of the imported products. Contact your supervisor and Division of Import Operations (DIO) if necessary. 5.2.1.1 - Pre-Announcements Pre-announcements are mandatory for all medical device inspections in accordance with the criteria and instructions below and some BIMO inspections. In some other program areas, pre-announcements may be made at the discretion of the program division. If you are going to visit facilities where livestock (including poultry) or wild animals are housed or processed, review IOM 5.2.10. In general, it may be inappropriate to pre-announce inspections of food establishments, blood banks, source plasma establish- ments and some BIMO inspections, but this too is subject to program division discretion. If a program division believes pre-announcing an inspection of an establishment will facilitate the inspection process then the procedures below for doing pre-announcements for medical device inspections should be followed. ORA's primary purpose for pre-announcing is to assure the appropriate records and personnel will be available during the inspection. It is not to make an appointment for the inspection. It should not be referred to as an appointment to inspect. When doing a pre-announcement, it is important you communicate to the establishment the purpose of the inspection and a general idea of the records you may wish to review. If you find neither the appropriate personnel nor records available, note this in your Establishment Inspection Report (EIR). In the case of drug inspections, if efforts to schedule a pre-announced inspection are met with unreasonable delays by the establishment, including requesting a later start date without a reasonable explanation, it may constitute a delay of an inspection under section 501(j) of the FD&C Act [21 U.S.C. 351(j)]. FDA will make reasonable accommodations for local conditions such as weather, holidays, or, where appropriate, manufacturing campaign schedules. However, if faced with an unreasonable delay by the establishment, you may call the responsible person’s attention to 501(j) of the Act. Talk with your supervisor to determine whether the length of a particular delay may be considered unreasonable, even in cases in which the explanation given for the delay may be reasonable. The Program division may use this data in the future when considering whether this establishment should be eligible for pre-announced inspections. The following is the general outline for pre-announcement of medical device inspections. You are advising the establishment's management of the date and time you will be arriving at the establishment to conduct the inspection. The establishment has no authority to negotiate this. If you, as the investigator, feel the need to accommodate the establishment's request, be sure there are sound rea- sons for doing so and report them in your inspection re- port. 5.2.1.1.1 - BASIC PREMISES Pre-announcement of inspections is to be applied only to establishments that meet specific criteria. Pre-announce- ment may be considered for establishments that manu- facture both drugs and devices or biologics and devices. The eligibility of an individual establishment for pre-an- nounced inspection is at the discretion of the inspecting Division using clearly described criteria. (See Criteria for Consideration) The program division does not have the discretion to decide the types of medical device establishments eligible for pre-announcement, but may decide the specific establishments' eligibility because they meet the criteria. The pre-announcement should generally be no less than 5 calendar days in advance of the inspection. Should a post- ponement be necessary, the decision as to rescheduling rests with the investigator/team, but the new inspection date should not be later than 5 calendar days from the original date. Inspections may be conducted sooner than 5 calendar days if requested by or acceptable to the estab- lishment and if this date is acceptable to the investiga- tor/team. To participate in the pre-announcement portion of the pro- gram, establishments are expected to meet the commit- ment to have appropriate records and personnel available during the inspection. Pre-announced inspections will not limit an investigator's authority to conduct the inspection. Inspections will be as thorough as necessary. 5.2.1.1.2 - CRITERIA FOR CONSIDERATION When deciding whether an establishment qualifies for a pre-announced inspection, you must consider whether the type of inspection meets one of the following: 1. Pre-market inspections (PMA, 510(k)) 2. Foreign inspections 3. Quality System Surveillance Inspections: 5.2.1.1.3 - PROCEDURES INVESTIGATIONS OPERATIONS MANUAL 2019 CHAPTER 5 5-13 Procedures: 1. The investigator designated to conduct the inspection will contact the most responsible individual at the facil- ity. You should leave a message requesting a return call if the most responsible person at the facility is un- available at the time the call is made. The program division should use good judgment as to what is a reasonable time frame to await the return call. 2. Changes in dates should be kept to a minimum. If a change is made, a new date should be provided as soon as possible, which will facilitate the inspection and accommodate the investigator's schedule. The establishment should provide a valid reason for re- questing a change in the start date. A valid reason should be the same as you would accept if presented with the information during an unannounced inspec- tion. 3. Inform the establishment as to the purpose, estimated duration, and the number of agency personnel ex- pected to take part in the inspection. The products or processes to be covered should be described if this will facilitate and be consistent with the objectives of the inspection. 4. When known, specific records/personnel will be re- quested at the time the inspection is pre-announced. 5. The notification should be as specific as reasonably possible and specify the date for the start of the in- spection. Include in your EIR whether or not the inspection was pre- announced and include information on any difficulties ex- perienced in notification or accessing records or person- nel, which should have been available as a result of pre- announcing the inspection. For medical device establish- ment inspections, if not pre-announced, describe briefly in the EIR why not. If an establishment should become ineli- gible for pre-announcement, the endorsement of the EIR should include this statement. This information will be necessary for making a determination regarding future pre-announced inspections of the establishment. In addi- tion, it is advisable to inform the establishment during the current and subsequent inspections of the action(s), which may have caused them to be ineligible for pre-announce- ment. Subchapters 5.4-5.9 of the IOM contain additional, pro- gram specific pre-inspectional activities, which you should follow. 5.2.1.2 - Personal Safety ORA considers the safety of investigators, inspectors and all those who meet with regulated industry to be of the utmost importance. Personal safety concerns are defined as those factors FDA employees should maintain aware- ness of which potentially affect their safety during an in- spection, such a threatening situation; or where specific personal protective safety equipment is warranted; or where a particular inspection may be medically contraindi- cated for specific FDA personnel. When these conditions are noted during an inspection, the investigator should discuss the situation with their supervisor and ensure that the Personal Safety Alert is checked in FACTS/ eNSpect and a Memo to the File is generated – see IOM 5.2.1.3. For information concerning personal protective equipment, see IOM Subchapter 1.5. Physical resistance to FDA inspections and threats to, or assaults on, FDA employees engaged in their work are extremely rare. However, there will be times you are con- fronted by unfriendly or hostile persons. ORA has offered various conflict resolution training courses to assist and prepare you for how to diffuse a situation. In most in- stances, conducting your activities with tact, honesty, di- plomacy, and persuasiveness will be enough to diffuse the situation. While at times, you may have to adopt a firm posture, you should not resort to threats, intimidation, or strong-arm tactics. Refer to IOM 5.2.5.4 for Hostile and Uncooperative Interviewees. Safety is the responsibility of all FDA employees, including you, your supervisor and other Agency management. When you receive an assignment, it is important to evalu- ate the assignment not only in accordance with IOM Sec- tion 5.2.1, but also with respect to your personal safety. If you determine there is the possibility of a threat to your personal safety, consult with your supervisor. You and your supervisor should consider developing a Situational Plan in preparation for the inspection. 5.2.1.2.1 - PREPARATION Below are some suggested items the program division may consider when preparing for your next assignment to assess if there are potential personal safety issues. This list is not meant to be all inclusive. 1. Does the assignment involve working with other Fed- eral Agencies such as U.S. Marshals, Federal Bureau of Investigations, and U.S. Customs in executing search warrants, seizures, etc.? 2. Does the assignment involve working with or contacting FDA’s Office of Criminal Investigations (OCI)? 3. Does the assignment involve a firm where there is a suspicion and/or knowledge of questionable or illegal activities? 4. Does the assignment involve a suspected tampering and/or a visit to an individual’s residence? 5. What is the past history from a personal safety stand- point with the prior interactions with representatives of this firm? Have the FDA’s state counterparts or other Federal and/or local agencies indicated a concern for personal safety? What does the firm’s establishment file indicate about personal safety over the past in- spections? 6. What is the location of the firm or the operation? Is it in an area which may be unsafe? Have the inspected firm or any of its employees been uncooperative with gov- ernment officials? 7. Is the firm known to the Agency? Has the Agency any additional information which would assist in your evaluation? CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2019 5-14 If these questions and/or others result in a concern for your personal safety, then a Personal Safety Plan should be developed and approved by program division management before conducting the assignment. See IOM 5.2.1.4 – Personal Safety Plan. Due to the unlimited variability of potential safety situa- tions, it is not feasible to prescribe in the IOM what to do in every instance. The decision of what to do in each individ- ual circumstance rests with the investigator and their program division management. Your program division management is most familiar with the specific firm in question, the regulated industry, as well as other local Federal, State and Local officials who may be able to provide you additional information and assistance. In addition, the experience of your program division management combined with the various training courses on conflict resolution may also be consulted. Program division’s should notify OMPTO or OHAFO to inform headquarters of any potential safety concern, so that personal safety issues may be tracked. The headquarter component will also maintain a library of Personal Safety Plans which may also be of use to your Division. The headquarter component may be contacted at the following personal safety e-mail address: orahqcsosafety@fda.hhs.gov. 5.2.1.2.2 - PHYSICAL RESISTANCE/THREATS/ ASSAULTS If you receive physical resistance or threats, or if you sense the real possibility of an assault, disengage from the confrontation, get to safety, and call your supervisor immediately. Make careful and exact notes later of who said what to whom, who did what, and whether someone tried or succeeded in threatening, assaulting or taking information or equipment or samples from you. Be careful in any descriptions you give or write of such events, just as you are in recording other evidence that may result in a court case. Your safety is more important to the United States than the inspection or the sample collection. FDA will work with law enforcement government officials, e.g., the Federal Protective Service (FPS), FDA's Office of Criminal Investigations' (OCI) Special Agents, local police, or United States Marshals to assist an inspection team if there is a reasonable fear of danger to the investigator. If you are assaulted (either physically or put in fear by threats of physical violence), your supervisor can summon local police, the Federal Protective Service (1-877-437- 7411), United States Marshals, FBI or contact OCI headquarters for assistance (301-294-4030). While OCI does not normally provide physical security in these cases, they will assist in threat evaluation based on specific facts and available criminal databases. OCI can also make contacts with local police and federal agencies based on previous established liaisons. If you have been assaulted or threatened and you are unable to reach your supervisor or other division management, you should contact the local police in the area where the assault or threat occurred. Be careful in any descriptions you give or write of such events, just as you are in recording other evidence that may result in a court case. Make sure that any inspected facility where weapons are observed, or where threats or assaults occur, is identified on that facility's Endorsement page of the inspection report for that facility and to your supervisor, so that Investigators or Agents who follow you into that facility will be alert to those possibilities. Your supervisor would also be responsible for checking the Personal Safety Alert box in FACTS and for beginning the notification process to alert other Federal or State agencies that also inspect the facility of the possible danger. For more information see IOM 5.2.1.3 Personal Safety Alert. For specific safety guidance related to inspections and interviews, see IOM 5.2.5.4.2 Hostile and Uncooperative Interviewees. In addition, in any instance where you have perceived a threat to your personal safety during an inspection, investigation or sample collection, you should exit the situation immediately and report it to your supervisor. Potential threats may include geographic locations, concern about entering into a residence to conduct official business, or animals that are not caged or contained. You should then write a memorandum of the event in a factual manner including information pertaining to the who, what, when, where, and how of the event. Be careful in any descriptions you give or write of such events, just as you are in recording other evidence that may result in a court case. This memo will be filed in the official establishment file jacket and copies be sent to any and all resident posts and import program division offices who may interact with this firm. The memo will be filed on the opposite side of the folder from all other documents and will be a printed on eye-catching color paper in order for the document to be visible to the next Investigator. The memo should be retained and maintained within the division. A copy of the Memo documenting the personal safety situation should also be sent to the headquarter component via orahqcsosafety@fda.hhs.gov. 5.2.1.3 – eNSpect Personal Safety Alert In eNSpect, the person creating an assignment may add a "Active Personal Safety Alert" (PSA) on the "Firm" page. This field is editable any time after the assignment is created. The "Personal Safety Alert" tab on the "Firm Details" page in Management Services (FMS) should be checked for the existence of a PSA when assignments are created and before inspections are conducted. Only the FACTS Supervisor Role will allow for updating the Maintain Firms screen. This personal safety alert may be selected when there is a potential hazard identified: 1. Where a previous threat/assault or physical resistance occurred 2. Where specific personal protective equipment is needed (respirators, etc.) 3. Where there are specific medical considerations for a population of investigators (e.g. the firm manufactures a drug hazardous to women of child-bearing years or those with allergies to peanuts, penicillin, or other products.) INVESTIGATIONS OPERATIONS MANUAL 2019 CHAPTER 5 5-15 In any example listed where there is a Personal Safety Alert, the specific safety alert should be documented both in the Endorsement and in a Memo to the File. The memo should be flagged “MEMO TO FILE - PERSONAL SAFE- TY ALERT” and should provide the factual information to support why the investigator should be alerted to the safety issue. Be careful in any descriptions you give or write of such events, just as you are in recording other factual evidence that may result in a court case. The memo should be filed in the official establishment file jacket and copies sent to any and all Resident Posts and import program divisions who may interact with the firm. The memo will be filed on the opposite side of the folder from all other documents and will be a printed on eye- catching color paper in order for the document to be visible to the next Investigator. The memo should be retained and maintained at the Program division office. A copy of the Memo documenting the personal safety situation should also be sent to orahqcsosafety@fda.hhs.gov . The supervisor and/or other program division management will be responsible for evaluating any corrective actions taken by the firm or individual to remove or stop the potentially dangerous situation or condition. Follow-up inspections at the facility should continue to document whether or not the safety situation continues exists. If the situation has been resolved (new management, dismissal of an employee, cessation of penicillin in a facility, etc.) the Personal Safety Alert should be removed from FACTS by the supervisor. 5.2.1.4 – Personal Safety Plan A Personal Safety Plan is an investigative tool developed to assist in managing and preparing for a potentially dangerous situation. Program division’s should develop a Personal Safety Plan when the conditions surrounding the specific inspection, investigation or sample collection indicate a plan is needed. The plan allows all those involved to carefully evaluate the specific inspection in order to prepare for a successful conclusion. Utilizing Personal Safety concepts prior to a potentially dangerous situation is part of the training programs of many other Federal Agencies. The plan should document what specific roles and responsibilities are needed to conduct the inspection/investigation or sample collection. The plan should also answer the questions: Who, What, Why, When and Where concerning the potential danger. There are seven principles to a Personal Safety Plan. These are: 1. Summary of Potential Hazards: This section of the personal safety plan includes all of the potential hazards, in a detailed description, that prompted the need for a personal safety plan. Be sure to answer the questions: Who, What, Where, When, and Why. Also include any specific hazards that require personal protective equipment or situations at the facility that may cause allergic reactions for investigators or analysts. Include in the section information from past inspection reports, discussions with previous FDA, State or local investigators, as well as any environmental or plant/facility specific information that would negatively impact a successful personal safety plan when initiated. 2. Sources of Information: This section of the personal safety plan includes all the sources from which your potential hazards were collected. For instance, document which FDA investigator or State inspector supplied factual statements; state the documents or databases from which you obtained information to assist in your hazard summary. This section is important, as it documents factual evidence, similar to all of your other FDA factual inspection gathering information. 3. Response Alternatives: This section will be the most important part of your plan because it includes all of the details of what will be done to mitigate the hazards. In this section, provide a list of factual, practical responses or options to consider. This will also allow your supervisor to see all the possible ways to handle the situation. The response plan should also outline all of the tools that you possess to assist you in handling the situation carefully, including training, experience, and other procedures you have at your disposal. Roles and responsibilities of all involved in the plan should be identified including those intended to be on-site, and those who will be off-site, and participating in the plan. 4. Communication: provide all information about how communication will occur between on-site and off-site participants; between those present on-site, and any emergency, law enforcement or medical responders. Also consider types of communication, e.g. code words for emergencies. 5. Transportation: Provide information in the plan as to how travel to the facility will happen. Is there a coordination point? Do you intend to use Government marked or unmarked cars? Who will ride in each car? What route will be taken going to and leaving the facility? Consider where you will park the car when you arrive at the facility. Consider what modes of communication will be used to communicate if multiple vehicles are used. 6. Equipment: Include in this section all equipment needed to initiate this plan. Is personal protective equipment needed? Is there any special sampling equipment or other equipment needed? Include in this section, equipment such as communication tools, FDA forms, etc. Assure that the equipment needed is in full functioning mode. 7. Emergency Exit Strategy: Describe in this section what the exit strategy will be in the event of an emergency. Consider emergency strategies for safety (issues), as well as any medical emergency. How will the emergency be communicated on-site and off-site? How do you exit the facility and return to your vehicle? Is there a scheduled meeting point to assure all are safe? The goal is to have no one left behind. Remember to contact your supervisor when you return to safety. CHAPTER 5 INVESTIGATIONS OPERATIONS MANUAL 2019 5-16 Once the plan has been completed, a debriefing of the situation should occur with all who were involved in the plan development. Evaluate what went well, what needed improvement, what would be done differently the next time. Evaluate whether the plan was successful and document lessons learned for the next time. The Personal Safety Plan should be developed by the investigator, supervisor, other investigators who may be familiar with the facility, compliance officer, if needed, and any other individuals (Program Division or HQ experts, etc.) who may be able to assist in the depth, scope, and specifics of the firm in question. The decision of who should be involved in the development and approval of the plan is left to the program division’s discretion. Program division management and all involved in writing the personal safety plan should meet when necessary in order to assure a well-developed, and understood personal safety plan. You and your supervisor should maintain contact during the execution of the personal safety plan. The supervisor should contact the employee during these personal safety situations at a predetermined frequency outlined in your plan. A debriefing session should be held following the execution of the plan. Discussions should include what actions worked well and where there are areas of improvement. For foreign inspections where a Personal Safety Plan is warranted, headquarters POC will assist the inspection team. The inspection team’s management may also wish to participate so that there is clear understanding of what actions will be taken for the foreign inspection. The Personal Safety Plan should be placed in the official establishment file jacket separate from any EIRs in the same location as any Personal Safety Alert memos. A copy of completed and executed Personal Safety Plans must be sent to orahqcsosafety@fda.hhs.gov in order to maintain a reference library of all Personal Safety Plans. 5.2.2 - NOTICE OF INSPECTION Upon arrival at the firm locate the owner, operator or agent in charge of the establishment. This should be the top Management Official on site. Be certain of this individual's status. Introduce yourself by name, title and organization. Show your credentials to this person and present a properly signed, completed original of the FDA 482, Notice of Inspection. The FDA-482 should have the address of the home district of the firm. * If additional Agency personnel accompany you during the inspection, they must show their credentials to the top Management Official upon arrival at the site. A new FDA 482, Notice of Inspection must be issued. Submit a cop