Regulated Studies at UTMB

Transcription

1 Regulated Studies at UTMB 1 st Annual Summit of Academic Excellence in Quality Assurance & Regulatory Science May 2017 Melissa Eitzen, MT (ASCP), MS, RQAP GLP Director, Regulatory Operations 1 Schedule UTMB The Animal Rule Office of Regulated Nonclinical Studies (ORNcS) The Case for Quality Systems Gaps, Challenges, and Misconceptions 2 1

2 Schedule & Objectives UTMB The Animal Rule Describe the application of the FDA GLP regulations to Animal Rule studies Office of Regulated Nonclinical Studies (ORNcS) The Case for Quality Systems Examine sponsor requirements for Quality Systems Gaps, Challenges, and Misconceptions Identify at least one challenge when conducting regulated studies in an academic setting 3 The University of Texas Medical Branch (UTMB) 4 2

3 The University of Texas System 8 Academic Institutions 6 Health Institutions Galveston, TX 5 UTMB Opened in 1891 > 3200 students ~ 13,000 employees 6 3

4 UTMB Schools Medicine Nursing Health Professions Graduate Biomedical Sciences 7 UTMB Centers and Institutes 8 4

5 Galveston National Laboratory 47,826 ft 2 laboratory space (4,443 m 2 ) 12,222 ft 2 BSL 4 space (1,135 m 2 ) $174 million Move in date: October, 2008 Pathogens: Anthrax, avian influenza, bubonic plague, hemorrhagic fevers (such as Ebola), Zika virus, typhus, West Nile virus, drug resistant tuberculosis, etc. UTMB/NIAID GLP capability Why GLP? 9 Schedule UTMB The Animal Rule Office of Regulated Nonclinical Studies (ORNcS) The Case for Quality Systems Gaps, Challenges, and Misconceptions 10 5

6 Animal Rule May 31, 2002 FDA amended its new drug and biological product regulations (21 CFR Parts 314 & 601) to allow appropriate studies in animals in certain cases to provide substantial evidence of the effectiveness This rule will apply when adequate and wellcontrolled clinical studies in humans cannot be ethically conducted and field efficacy studies are not feasible. 11 Animal Rule Safety studies in humans Animal Rule studies (GLP to the extent Practicable) Research Non- Clinical Proof-of- Concept Non- Clinical Safety Clinical Phase 1 Clinical Phase 2 Clinical Phase 3 Approval Clinical Phase 4 Not regulated by FDA Well planned, documented studies. Studies conducted in compliance with Good Laboratory Practice regulations (GLP) 12 6

7 Animal Rule Demonstrating Efficacy Mechanism of toxicity is well understood Endpoints in the animal trials are clearly related to benefit in humans Efficacy is demonstrated in a species expected to react similarly to humans Data allow selection of an effective human dose [SAME] 13 Animal Rule SUPPLEMENTARY INFORMATION Introduction: All studies subject to this rule must be conducted in accordance with preexisting requirements under the good laboratory practices (21 CFR part 58) regulations and the Animal Welfare Act (7 U.S.C et. seq.). 14 7

8 Scope of GLP Regulations 21 CFR 58, Sec Scope. (a) This part prescribes good laboratory practices for conducting nonclinical laboratory studies that support or are intended to support applications for research or marketing permits for products regulated by the Food and Drug Administration Compliance with this part is intended to assure the quality and integrity of the safety data filed pursuant to sections 15 Definition Nonclinical laboratory study In vivo or in vitro experiments in which test articles are studied prospectively in test systems under laboratory conditions to determine their safety 16 8

9 Guidance FDA recommends the use of the GLP regulations, to the extent practicable, to ensure the quality and integrity of the data from these studies Guidance for Industry Applicability of the Animal Rule determined by FDA May be justifiable limitations to apply GLP Frequent Sponsor communication with FDA Sponsors seek concurrence from FDA for data quality and integrity plan 18 9

10 Guidance for Industry Quality includes, but is not limited to, whether the study was conducted in accordance with the protocol, standard operating procedures, and applicable standards of research. Integrity includes, but is not limited to, the assurance that the raw data and documentation are consistent with reported results. 19 Guidance for Industry Inspections FDA has the authority to inspect these studies prior to taking an action Inspectional observations will be shared with the inspected entity and evaluated by the review division determine the impact of the observations on the acceptability of the data to support drug approval FDA will verify that study personnel followed the agreed upon data Quality and Integrity Plan 20 10

11 Guidance for Industry Inspections Inspections verify the quality and integrity of the: Raw data Supporting documentation Facilities Equipment Results submitted to FDA in the final report 21 Guidance for Industry Study Conduct Animal Model Qualification FDA recommends the use of the GLP regulations, to the extent practicable, for the model defining natural history studies submitted to support the qualification of an animal model Qualification is a regulatory conclusion, and thus, these studies should be conducted in a manner that ensures data quality and integrity

12 Product Approval Under the Animal Rule BioThrax approved Rule Pyridostigmine bromide approved Cyanokit approved Draft Concept Paper Levofloxacin approved (for plague) Raxibacumab approved Draft Guidance FDA Education Grant Botulism Antitoxin approved Draft Guidance Neupogen approved Anthrasil approved Ciprofloxacin (for plague) approved Neulasta approved Avelox approved Final Guidance Anthim approved Product Approval Under the Animal Rule

13 Product Approval Under the Animal Rule 25 Product Labeling BAT

14 NPRM GLP 27 Schedule UTMB The Animal Rule Office of Regulated Nonclinical Studies (ORNcS) The Case for Quality Systems Gaps, Challenges, and Misconceptions 28 14

15 ORNcS Development Institutional Office of Regulates Nonclinical Studies 2004 = QA 2006 = GLP Program Office (Grants Management) 2011 = Recruited Director of Regulatory and Scientific Affairs 2012 = Established Institutional Office with Study Director(s) and Technical staff 29 ORNcS Organizational Chart Study Directors Technical / QC Equipment EDMS & IT Compliance Archivist QAU 30 15

16 ORNcS Pre & Post Award (Pre study) Pre Scope of Work (RFP, contracts, etc.) Regulatory Requirements Inspection requirements Proposal submissions Budget Education Post Quality Agreement / Plan Protocol review Data audits In life inspections (monitoring) QA inspection logs QA reports Education 31 UTMB Survey Results 2005 Survey distributed to attendees of (first) GLP training class: 68.1% Had never been taught QC/QA as part of a course or degree program (73.4% response rate) 32 16

17 Education Classes Laboratory Safety & Good Laboratory Practices CTPS 6108 Course Length: 8 hours Credit Hours: 1 Good Documentation Practices Course Length: 1 hour Writing Effective Standard Operating Procedures Course Length: 1 hour CTPS 6107: Animal Research Topics and IACUC Protocol Basics CTPS 6121: Effective Laboratory & Resource Management BBSC 6219: Vaccine Development Pathway GRAD 544: Ethical Conduct of Research Pilot Program / Rigor and Responsibility in Research 33 UTMB Partnership with FDA Data Quality and Integrity in BSL 4 laboratories Collaborative education grant day course Mock BSL 4 lab activity On line GLP course Continuing Education Units 17

18 Schedule UTMB The Animal Rule Office of Regulated Nonclinical Studies (ORNcS) The Case for Quality Systems Gaps, Challenges, and Misconceptions 35 The Case for Quality Systems Enhancing Reproducibility Documenting first discovery Transferring discovery protocol Developing regulatory protocol communication Research Non clinical Proof of Concept Non Clinical Safety Clinical Phases I III Approval Clinical Phase IV 36 18

19 The Case for Quality Systems SBIR, STTR 37 The Case for Quality Systems Track performance of animal studies and the performance of bacterial strains and controls as an ongoing QA/QC of reagents and strains. NIH RFP, 2010 The United States Government seeks laboratories that can provide microbiological support pathogen(s) including quality controlled master and working banks; SOPs for production & characterization of challenge material under standardized media and growth conditions, and master and working banks for cell lines where applicable BARDA RFI,

20 The Case for Quality Systems Documented experience/familiarity with performing validated ELISA assays NIH/NIAID RFP, 2011 (Technical Evalua on Factors) Some of the studies under this award will require GLP. Describe your present or planned GLP capabilities or any other standards of laboratory practices, meant to substitute for GLP for execution of animal model studies. BARDA RFP, 2011 (Scope of Work) 39 The Case for Quality Systems The study will be non GLP but must be performed in accordance with an approved quality plan The Offeror must have a validated or qualified quantitative virology assay to conduct sample analysis BARDA RTOR

21 Gaps, Challenges & Misconceptions Gaps Challenges Misconceptions Regulatory knowledge Shared equipment Quality is an add on Regulatory vernacular Regulated study timelines GLP Compliant Facility Training documentation System sustainability Short timeline to GLP Equipment records Appropriate budgeting (cost) Reproducibility = publication Good documentation practices Standardized procedures Academic Infrastructure (management) Culture Sponsor audits FOIA Audit reports do not require a response Melissa s List 41 Contact Information Melissa M. Eitzen, MT (ASCP), MS, RQAP GLP Director, Regulatory Operations University of Texas Medical Branch at Galveston Phone (409) mmeitzen@utmb.edu Web:

22 Reference Links The Animal Rule: /pdf/ pdf Guidance Document: Products Approved under the Animal Rule: ce/ucm htm Botulism Antitoxin Label: tsblas/fractionatedplasmaproducts/ucm pdf GLP Regulations: FDA Notice for Proposed Rule Making (NPRM) GLP /good laboratory practice for nonclinicallaboratory studies 44 22