Regulatory,Quality & Emergency Preparedness MaryBeth Parache Director, Quality Affairs New York Blood Center 1
Regulatory 2
Who regulates us? Food and Drug Administration (FDA) Blood, tissue, HCT/P, medical devices Donor recruitment to crossmatch/issue Centers for Medicare and Medicaid Services (CMS) Clinical laboratories (CLIA) 3
Who else regulates us? DOT - hazmat transportation and shipping OSHA - blood borne pathogens, chemical safety, workplace safety NRC - irradiators EPA - biohazardous waste disposal State and local - building codes, waste management, other areas depending on state (NYS regulates labs under exemption from CLIA) AABB ** ( accreditation agency) 4
FDA Center for Biologics Evaluation & Review CBER regulates a variety of biological products, including blood and blood components blood grouping reagents human tissue and cellular products used in transplantation gene therapy products immune globulins, coagulation factors drugs and devices related to blood banking, HIV test kits 5
Why is CBER in the Drugs & Device Business? CBER has delegated authority to regulate: drugs closely related to biologics, such as anticoagulants used in blood collection bags medical devices used in blood banks to produce biologics such as automated cell separators, empty blood bags and transfer sets, blood storage refrigerators and freezers, and laboratory test systems and kits used in blood donor screening 6
How does CBER regulate? Reviews & monitors Investigational New Drug Applications Reviews & approves Biologics License Applications (BLAs) and supplements Also responsible for post marketing activities, surveillance, compliance and enforcement 7
How does CBER regulate? Pre-Marketing Drugs: IND NDA ANDA Biologics: IND BLA Devices: IDE 510(k) PMA (BLA) Drug Master Files Post-Marketing BLA updates: Annual Reports Supplements: CBE, CBE-30, PAS Required Reporting: BPDR Fatalities Compliance Inspections: 483s Warning Letters Consent Decrees Suspension Revocation Fines and Jail 8
FDA Registration All owners or operators of establishments that manufacture blood products, unless exempt under 21 CFR 607.65. List every blood product manufactured, prepared, or processed for commercial distribution. Register and list products within 5 days of beginning operation, and annually thereafter. Blood product listings must be updated every June and December. That includes most TRANSFUSION SERVICES! 9
regulated manufacturing activities versus the practice of medicine 10
FDA GxPs and Blood Regs What Where Title cgmps 21 CFR 211 Current Good Manufacturing Practice for Finished Pharmaceuticals cgmps 21 CFR 606 Current Good Manufacturing Practice for Blood and Blood Components cgtps 21 CFR 1271 Subpart D Current Good Tissue Practice GLPs 21 CFR 58 Good Laboratory Practice for Nonclinical Laboratory Studies GCP ICH-E6 Good Clinical Practice: Consolidated Guidance 11
FDA GxPs and Blood Regs What Where Title Establishment Standards Biologics Standards Blood Standards Blood Standards Tissue Standards HCT/P Standards HCT/P Standards HCT/P Standards 21 CFR 600 Biological Products: General 21 CFR 610 General Biological Products Standards 21 CFR 630 General Requirements for Blood, Blood Components, and Blood Derivatives 21 CFR 640 Additional Standards for Human Blood and Blood Components 21 CFR 1270 Human Tissue Intended for Transplantation 21 CFR 1271 Subpart A 21 CFR 1271 Subpart C 21 CFR 1271 Subpart E General Provisions Donor Eligibility Additional Requirements for Establishments Described in 1271.10 12
FDA Focus on Blood Safety 1. Donor selection (Donor history questionnaire, Mini-physical) 2. Donor deferral registries 3. Testing for infectious agents 4. Quarantine of blood pending lot release 5. Deviation management and corrective actions 6. Change Control 13
FDA Inspections Pre-license for BLAs; pre-approval for some supplements GMP inspections usually every 1 or 2 years for registered facilities depending on risk and inspection history Walk in with a Form 482 and walk out with a Form 483 No findings? No 483 14
FDA Inspection Tips Be cordial and cooperative, but not too friendly Don t offer information or records that weren t asked for Explain and clarify No arguments or stand-offs just take the hit (you ll do better in the 483 response) Redact any records (copies) they want to take and make a note of what they are 15
FDA 483 Response Tips Acknowledge the observation if correct Clarify the situation if incorrect don t say the inspector was wrong If the situation did not represent a risk to donor or patient safety, state this If the situation did not represent lack of control over operational or quality systems, state this Don t give excuses Provide corrective action plan and timeline Describe any corrective action taken so far and plans to monitor for effectiveness 16
CLIA 42 CFR 493 - Test categorization by complexity - Proficiency testing - Quality system - General laboratory systems (patient confidentiality, specimen identity and integrity, complaints, communications, personnel competency) - Personnel qualifications & responsibilities 17
CLIA 42 CFR 493 (continued) Pre-analytical Systems Analytic Systems Post-analytic Systems test request, specimen submission and suitability SOPs, test systems, equipment, reagents, supplies, calibration, validation controls, test records test report 18
Where to find it U.S. Code http://uscode.house.gov Code of Federal Regulations http://www.ecfr.gov/ Federal Register https://www.federalregister.gov/ http://www.archives.gov/federal-register/the-federal-register/ - back to 1994 Really OLD Federal Registers and CFRs back to 1930s http://home.heinonline.org/content/list-of-libraries/ CBER Guidance Documents http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatory Information/default.htm 19
Where to find it CLIA stuff CMS http://www.cms.gov/regulations-and- Guidance/Legislation/CLIA/index.html?redirect=/clia/ CDC http://wwwn.cdc.gov/clia/default.aspx FDA http://www.fda.gov/medicaldevices/deviceregulationandguidance/ivdregulato ryassistance/ucm124105.htm New York State Clinical Laboratory Evaluation Program http://www.wadsworth.org/labcert/clep/clep.html 20
Quality 21
Quality Quality Control Process Control Quality Assurance Quality Management System 22
Elements of a Quality Management System AABB Stds. 29/30 Ed. Organization Resources- HR Equipment Supplier and Customer Issues Assessments : Internal /External Process Improvement through Corrective and Preventive Action Facilities and Safety Process Control Documents and Records Deviations,Nonconformances and Adverse Events 23
Elements of a Quality Management System Clinical Laboratory Standards of Practice- Part 1 -General Standards System Quality Management System Human Resources Facility Design /Resource Management Highlights : adequate training, qualifications, compliance program, investigation of non- conformance, quality manual etc. : Lab director/ assistant director time on site, involement roles and responsibilities, education and activities performed, Quality Systems Manager delegated by the Lab Director Adequate space, lighting, backup power for critical systems are controlled and can be recovered, temperature monitoring and environmental monitoring ( as appropriate) sharps, work surface decontamination, LIMS- validation 24
Elements of a Quality Management System cont d System SOP and Compliance Clinical Laboratory Standards of Practice- Part 1 -General Standards Pre- Examination Procedures Highlights Standardized format, available at all times to staff at bench. Archiving process for earlier editions, signed and dated prior to implementation by lab director Proper protocol for specimen identification, rejection and retention, disposal protocol, specimen packaging requirements, request form protocol Examination Procedures System in place to evaluate and define relationship between test results every six months ( if perform the same test in multiple sites ), Validation practice plan, summary available ( for after 2 years after method d cd) 25
Elements of a Quality Management System cont d System Post Examination Procedures Quality Assessment and Improvement Highlights Interpretation of results, process for errors and inaccuracies in patient reports On going monitors for performance, proficiency testing, referral notification, record retention 26
QA: Inputs Process Outputs Select and Qualify SOPs Facilities People Equipment Supplies Reagents Computer Systems 27
QA: Inputs Process Outputs Validate & Control QC CAPA SPC Automation Error Proofing CPI Feedback Loop 28
QA: Inputs Process Outputs Measure/Inspect Review Records Ask Customer Verify data, Information Inspect Product, Service Review Reports Monitor complaints, failures 29
How do we get to high quality products and services? Know what you want Know what your customers want Do it by design Don t skimp when you implement Monitor to make sure Approach improvement like a science experiment 30
Emergency Preparedness 31
Emergency Preparedness 1. Plan Hazard Identification Mitigation Preparedness Response Recovery Continuity of Operations 2. Coordinate, cooperate, communicate 3. Train, test, and practice 4. Incorporate lessons learned into plan 32
Emergency Preparedness Requirements Entity AABB OSHA Regulation /Standard Std 1.4 BB/TS shall have emergency operation policies, processes and procedures to respond to the effects of the internal and external disasters Std 1.4.1 the emergency management plan, including emergency communication systems, shall be tested at defined intervals Written plans must be in place for facilities with more than 10 people. 33
Emergency Preparedness Lessons Learned - Evacuation Learn how to transfer phones. Keep a doc on hand for patient care issues. Keep an admin support person close by too. 34
Emergency Preparedness Lessons Learned - Evacuation Blood irradiators don't have wheels. You may know where you are, but the hospital staff don t unless you tell them. If you ask nicely, not all patients need to be transfused right away. 35
Emergency Preparedness Lessons Learned - Evacuation Be clear about what areas need to evacuate large hospitals may be zoned. Find out who s in charge and how you will communicate with that person. 36
Emergency Preparedness Lessons Learned - Evacuation What s really useful? Defined emergency team critical players Defined areas of refuge, alternate work sites Reliable communication devices 2-way radios batteries charged know how to use them 37
What s really useful to have? Phone numbers key staff, key suppliers (office, cell, text or instant messaging) Land line that doesn t need electricity Shopping list what to take with you Things to consider checklist or decision tree diagram NOT too detailed! 38
Emergency Plan in Action What worked Had a plan Emergency response team Rapid notification to hospital staff Designated refuge area What didn t Too much detail Extra people in the way No evening and night shift notification No communications with refuge area 39
Emergency Plan in Action What worked Continuation of services plan Alternate work space identified Remote access to major computer systems Emergency contact list for hospital What didn t Ongoing hospital interactions Some critical supplies not available No access to local computer applications Contacts for suppliers 40
What about regional events? 9-11 The east coast earthquake Sandy Your plan has to address how to respond if you are in the middle of the disaster, or on the outside and trying to support another blood center or hospital. Transportation and communication will ALWAYS be a challenge. Effective messaging to the PUBLIC and your STAFF is really important. 41
Keep asking yourself: Do we still have control? Are we opening the door to errors? Are we taking too many risks? What s in the best interest of our patients? 42
Emergency Preparedness Useful websites CDC Emergency Preparedness and Response http://emergency.cdc.gov/ AABB Disaster Response https://www.aabb.org/programs/disasterresponse/pages/default.aspx FEMA http://www.ready.gov/ 43