Global Regulatory Perspectives

Transcription

1 Global Regulatory Perspectives ISCT 20 th Annual Meeting Pre-Conference Workshop- April 23, 2014 Anita Richardson, Associate Director for Policy Office of Compliance and Biologics Quality

2 Summary FDA Globalization Initiative PIC/S Engagement Recent Approvals & Guidance Compliance Update 2

3 FDA s Globalization Initiative FDA unveiled a new global strategy to help ensure safety and quality of imported products in June tionsandpolicy/globalproductpathway/default.htm

4 Primary Components to FDA s New Globalization Strategy Partner with foreign counterparts to create global coalitions of regulators focused on ensuring and improving global product safety. Work with these coalitions to build a global datainformation system and network and proactively share data with peers. Expand capabilities in intelligence gathering and use, with an increased focus on risk analytics and thoroughly modernized IT capabilities. Allocate agency resources effectively based on risk, leveraging the combined efforts of government, industry and public and private third parties. 4

5 FDA s Globalization Strategy The new strategy builds on changes FDA has already set in motion: Materially increased number of certain types of foreign inspections Opened a series of international offices in key locations. 5

6 FDA s Globalization Strategy (2) International standard setting of drug regulation through International Conference on Harmonisation. Joined Pharmaceutical Inspection Cooperation/Scheme (PIC/S) in January 2011, with manufacturing inspectorates from 39 countries. 6

7 FDA and PIC/S Benefits of PIC/S membership include: networking with our counterpart regulatory authorities sharing training opportunities promoting quality systems participating in Expert Circles and other committees and working groups. The Importance of PIC/S in Our Globalized World, Remarks of Margaret A. Hamburg, M.D., Commissioner, U.S. Food and Drug Administration, 40th Anniversary of PIC/S, May 31, 2011, Geneva, Switzerland

8 FDA and PIC/S (2) FDA s vision PIC/S Members must: Rely on each other to leverage resources to improve drug quality worldwide Work together to assure regulators around the globe have common knowledge, tools, and practices Think strategically about pooling resources and working together for the common good The Importance of PIC/S in Our Globalized World, Remarks of Margaret A. Hamburg, M.D., Commissioner, U.S. Food and Drug Administration, 40th Anniversary of PIC/S, May 31, 2011, Geneva, Switzerland

9 FDA and PIC/S (3) CBER has participated in the PIC/S Expert Circle for Blood and Tissue since its creation in 1993 Other Agency units are engaged in Committee Meetings, Seminars, and Expert Circles, for example: QRM Expert Circle GDP Expert Circle API Expert Circle

10 CBER s International Program Functional Areas: Regulatory harmonization, e.g. PIC/S, ICH, APEC Regulatory capacity building, e.g. Foreign Regulators Seminar Information sharing International standards setting Collaborative research

11 Recent Approvals and Guidance

12 FDA Approvals of Note: Cellular and Gene Therapy Products HPC, Cord (Hematopoietic Progenitor Cells) Hemacord, New York Blood Center November 2011 Clinimmune Labs May 2012 Ducord, Duke University October 2012 ALLLOCORD, SSM Cardinal Glennon May 2013 LifeSouth Community Blood Center June 2013 Allogeneic Cultured Keratinocytes and Fibroblasts in Bovine Collagen GINTUIT, Organogenesis Incorporated March 2012 For allogeneic cellularized scaffold product indicated for topical (non-submerged) application to a surgically created vascular wound bed in the treatment of mucogingival conditions in adults.

13 FDA Guidance For Industry Cellular and Gene Therapy Products Biologics License Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System March 2014 IND Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System March 2014 Preclinical Assessment of Investigational Cellular and Gene Therapy Products November 2013 (Draft) Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products July 2013

14 Compliance Update

15 HCT/P Inspections Inspections Performed in Fiscal Years 2005 to

16 Risk-based Inspections ~600 inspections/yr ~2700 active establishments Need to use resources smartly Use of open source intelligence, complaints, other information (e.g. HCT/P deviation reports), to guide yearly priorities 16

17 Risk-based Inspectional Approach to Prioritizing HCT/P Inspections (cont) Inspectional Focus FY-2013 HCT/P establishments that perform screening for non-living donors Newly registered establishments that recover and/or process musculoskeletal, skin, corneal tissues, or amniotic membrane Newly registered HCT/P establishments that handle reproductive tissues

18 FY13 HCT/P - Inspections Accomplished *Sum of individual inspections do not equal total due to some inspections that were conducted for products in multiple categories Type of HCT/P establishment # Inspections Accomplished Hours/ Inspection Reproductive tissues Cord blood stem cells Peripheral blood stem cells All other HCT/Ps (e.g. musculoskeletal, ocular, recovery, distributors) Total/Average 680*

19 HCT/P Inspection Results 40 Percentage of inspections resulting in issuance of Form FDA Fiscal Year 19

20 FDA Form 483 This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional observations, and do not represent a final agency determination regarding your compliance. If you have an objection regarding an observation, or have implemented, or plan to implement, corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA at the address above. 20

21 OAI/VAI/NAI? OAI Official Action Indicated objectionable conditions found that warrant action VAI Voluntary Action Indicated objectionable conditions found but do not meet the threshold for regulatory action NAI No Action Indicated no objectionable conditions found (generally no FDA-483) guidancecomplianceregulatoryinformation/u cm htm 21

22 FY13 HCT/P Inspection Classifications Type of HCT/P establishment NAI VAI OAI Reproductive tissues Cord blood stem cells Peripheral blood stem cells All other HCT/Ps (e.g. musculoskeletal, ocular, recovery, distributors) Total

23 FDA Compliance Programs (CPs) CPs provide instructions to FDA investigators for inspections of CBERregulated biological drug product and HCT/P Compliance Program Guidance Manual Inspection of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Compliance Program Guidance Manual Biological Drug Products Inspection of Biological Drug Products ulatoryinformation/complianceactivities/enforcement/compliancepro grams/default.htm

24 Regulatory Actions

25 HCT/P Regulatory Actions 25

26 Regulatory Actions FY-12 Warning Letters = 8 Musculoskeletal - New Life Generation, Inc. Ocular - Lone Star Lions Eye Bank, Inc. Repro - Reproductive Medicine Institute IVF, LLC Repro - Gramercy Fertility Services Repro - Family Beginnings, PC Cell therapy - IntelliCell Biosciences, Inc. Cell therapy - Thomas E. Young, LLC Cell therapy - CellTex Therapeutics Corporation Untitled Letters = 3 Musculoskeletal Alabama Organ Center Repro Gramercy Fertility Services Repro California Fertility Partners Order to Cease Manufacturing of HCT/P =1 -Repro Center for Reproductive Medicine 26

27 Regulatory Actions FY-13 Warning Letters = 7 Repro - Dr. Martin Balin; Repro - Olympia Women s Health Repro - Virginia Center for Reproductive Medicine Repro - The Center for Reproductive Medicine Musculoskeletal - RTI Biologics, Inc.; Musculoskeletal - Musculoskeletal Transplant Foundation Ocular - Tissue Bank International/The National Eye Bank Center Order to Cease Manufacturing of HCT/P = 2 Musculoskeletal - Pacific Coast Tissue Bank Repro - New York Fertility Institute 27

28 Regulatory Actions FY-13 (cont) Untitled Letters = Repro - Women s Health Consultants; Repro - Reproductive Institute of South Texas 351/361 - Surgical Biologics 351/361 - Accel Spine 351/361 - Tides Medical 351/361 - Castle Surgical 351/361 - Tri-State Biologics 351/361 - Osiris

29 Enforcement Update

30 United States v. Regenerative Sciences, LLC and Christopher Centeno, et al. The complaint for the injunction was filed August 6, 2010, by the Justice Department on behalf of the FDA in the U.S. District Court for the District of Columbia, against Regenerative Sciences and three of its employees, Christopher J. Centeno, M.D., John R. Schultz, M.D., and Michelle R. Cheever. The injunction the government requested would permanently prevent the company and cited individuals from adulterating and misbranding the cultured cell product (or any other drug) while the product, or one or more of its components, is held for sale after shipment in interstate commerce. Regenerative Sciences agreed to cease production of the cultured cell product while the case is pending. 30

31 US vs Regenerative Sciences LLC - 2 On July 23, 2012, United States District Judge Rosemary Collyer granted summary judgment for the government and issued a permanent injunction prohibiting the defendants, from distributing adulterated or misbranded drugs or causing them to become adulterated or misbranded after shipment of one or more of their components in interstate commerce. The product at issue is an autologous cultured cell product that was subject to more than minimal manipulation during manufacturing and that was promoted as a treatment for a variety of orthopedic conditions. The court held that this product is a drug under the Federal Food, Drug, and Cosmetic Act and rejected the defendants' argument that it falls within the "practice of medicine" and thus outside the scope of the Act.

32 US vs Regenerative Sciences LLC - 3 The court also held that the Act's interstate commerce requirement was satisfied because its components were shipped in interstate commerce. The court also dismissed the eight counterclaims filed by the defendants, which challenged, under various theories, FDA's authority to regulate the autologous cell products and FDA's regulations for human cellular and tissue based products. Regenerative appealed the decision and the DC Federal Circuit Court of Appeals ruled in the Agency s favor on February 4,

33 DOJ Announces Stem Cell Convictions September 7, 2012 Francisco (Frank) Morales & Lawrence Stowe Entered guilty pleas conspiracy to introduce misbranded & unapproved new drugs into interstate commerce supplements, vaccines, transfer factors, stem cells to treat ALS, MS, & other neurologic diseases Each falsely represented they were licensed to practice medicine & that they each operated medical clinics in Brownsville, TX Subject of 60 Minutes expose, 21 st Century Snake Oil, in ber/120907%20morales%20and%20stowe.html 33

34 DOJ Announces Stem Cell Sentence On January 16, 2014, U.S. District Judge Gray Miller handed Morales a sentence of 60 months in federal prison to be immediately followed by three years of supervised release. In handing down the sentence, Judge Miller noted his sentence was limited to 60 months by statute. Restitution was also ordered in the amount $479,862. Stowe is set for sentencing later in 2014.

35 Vision for CBER CBER uses sound science and regulatory expertise to: Protect and improve public and individual health in the US and, where feasible, globally Facilitate development, approval of and access to safe and effective products and promising new technologies Strengthen CBER as a preeminent regulatory organization for biologics INNOVATIVE TECHNOLOGY ADVANCING PUBLIC HEALTH

36 Public Access to CBER CBER website: Phone: or Consumer Affairs Branch (CAB) Phone: Manufacturers Assistance and Technical Training Branch (MATTB) Phone: Follow us on Twitter