Safa Karandish Office of Tissues and Advanced Therapies Division of Human Tissues. Pharma Conference February

Transcription

1 Safa Karandish Office of Tissues and Advanced Therapies Division of Human Tissues Pharma Conference February

2 Background HCT/P regulatory framework Definitions & exceptions Establishment registration- 21 CFR Part 1271, Subpart B Electronic registration system Registration & listing final rule (published August 2016) Frequently asked questions 2

3 Proposed Rule - May 14, Federal Register Finalized - Jan 19, Federal Register

4 Effective dates April 4, 2001 musculoskeletal, ocular, and skin January 21, 2004 hematopoietic stem cells and reproductive tissues May 25, 2005: heart valves and dura mater previously regulated as medical devices 4

5 Human cells, tissues, or cellular or tissue-based products (HCT/P) Articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient giftoflife.on.ca 21 CFR (d) 5

6 Musculoskeletal tissue Skin Ocular tissue Human heart valves Dura mater Reproductive tissue Hematopoietic stem/progenitor cells Other cellular therapies Tissue/device and other combination therapies 21 CFR (d) 6

7 Level of regulation is determined by the potential public health risk Two regulatory tiers: 361 HCT/Ps Regulated solely under the authority of section 361 of Public Health Service (PHS) Act Authorizes FDA to make and enforce regulations necessary to prevent the introduction, transmission, or spread of communicable diseases Subject to Tissue Regulations in 21 CFR Part 1271 if HCT/P meets all the criteria under 21 CFR (a) Premarket review and approval not required 21 CFR

8 Drugs, devices, and/or biological products* o Regulated under authority of section 361 of the PHS Act as well as section 351 of PHS Act and/or the Food, Drug & Cosmetic (FD&C) Act o Subject to Tissue Regulations (found in 21 CFR Part 1271) and premarket review requirements (21 CFR Parts 312, 601, 814, among others) * Includes 351 HCT/Ps 8

9 Establishments that manufacture HCT/Ps must register and list their HCT/Ps Provide information about the establishment and the products that they manufacture Applies to domestic and foreign establishments 21 CFR (b) 9

10 Establishment A place of business under one management, at one general physical location, that engages in the manufacture of HCT/Ps. Include: Individual, partnership, corporation, association, or other legal entity Facilities that engage in contract manufacturing services 21 CFR (b) 10

11 One general physical location could be reasonably construed to include separate buildings within close proximity provided that the activities in them are closely related to the same business enterprise, under the supervision of the same local management, and capable of being inspected at the same time. Guidance for Industry Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Small Entity Compliance Guide nformation/guidances/tissue/ucm htm 11

12 Manufacture Any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any human cell or tissue, and the screening or testing of the cell or tissue donor. 21 CFR (e) 12

13 a) Nonclinical scientific or educational purposes b) Autologous HCT/P removed and implanted during same surgical procedure c) Carriers (e.g. FedEx, UPS) d) Establishment that only receives or stores HCT/Ps solely for use within their own facility e) Establishment that only recovers reproductive cells or tissue for immediate transfer into the Sexually Intimate Partner (SIP) f) Individual who solely recovers HCT/Ps under contract, agreement or other arrangement with a registered facility (other requirements in 1271 subparts C & D may apply) 21 CFR

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15 Must Register & list HCT/Ps within 5 days after beginning operations Required information Establishment legal name Each physical location address, phone number, zip code Reporting official address, phone, , title, signature & date HCT/P types and proprietary names (if applicable) 21 CFR ,

16 Required information (cont.) Type of donor (if applicable) Reproductive cells or tissue (SIP, Directed, Anonymous) Cell therapy products (Autologous, Family related, Allogeneic) Manufacturing functions - Recover - Screen - Test (for relevant communicable disease agents or diseases) - Process (includes testing for microorganisms) - Store - Label - Package - Distribute 21 CFR

17 Foreign establishments sending HCT/Ps to the U.S. Must register and list HCT/Ps Must have a U.S. Agent Must reside or maintain a place of business in the U.S. Address, phone number, Foreign establishment is not required to notify their U.S. agent when shipping products CBER communicates with the U.S. agent concerning products and scheduling of inspections 21 CFR (b), (a)(6) 17

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19 Upon receipt of the registration information, FDA assigns each location an FDA Establishment Identifier number (FEI#) Registration information, including the assigned FEI #, is sent to the reporting official 21 CFR (a) 19

20 FDA acceptance of an establishment registration and HCT/P listing form does not constitute determination that an establishment is in compliance with applicable rules and regulations or that the HCT/P is licensed or approved by FDA. 21 CFR (b) 20

21 Must submit an amendment to registration: o Ownership, location change, or other material changes Annual Update Required even if there are no changes Annual update period: Nov 15 -Dec 31 Update manufactured HCT/Ps Other material changes 21 CFR ,

22 Updates must include: A list of each HCT/P you have begun manufacturing that had not been listed previously A list of each HCT/P listed previously that you have discontinued manufacturing, including date of discontinuance A list of each HCT/P you had discontinued previously, but have resumed manufacturing, including date of resumption 21 CFR (c) 22

23 If establishment has gone out of business or is no longer manufacturing HCT/Ps, inactivate registration 23

24 Electronic Human Cell and Tissue Establishment Registration Can be used for initial registration, submitting changes and the annual update, and inactivating registration Online instructions and link to help Can manage registration for multiple locations dex.cfm?cfid= &cftoken=3bf a55d0- A85D0D0F AE A9DF71D 24

25 Electronic Human Cell and Tissue Establishment Registration CBER on-line Login Screen Create a New Account Log in with User Name & Password Same account for submitting: Tissue establishment registration Deviation reporting 25

26 Electronic Human Cell and Tissue Establishment Registration 26

27 Electronic Human Cell and Tissue Establishment Registration 27

28 Electronic Human Cell and Tissue Establishment Registration - Preview & Submit 28

29 Obtain HCT/P establishment registration and listing information and status of registration plianceregulatoryinformation/establishmentregistration/t issueestablishmentregistration/ucm htm 29

30 Registered: 2713 total (active & pre-registered) * Registered based on HCT/P types 395 international (mostly HPCs) HCT/P types listed: 1000 (conventional tissues) 1427 Cellular therapy (HPCs, therapeutic, somatic cells & pancreatic islet cells) 784 reproductive HCT/Ps 1031 Other HCT/P types * As of 1/23/ % 18% Conventional Tissues Reproductive 24% 34% Cellular therapy Other Note: Number of establishments by tissue type is not additive to the total because of overlaps 30

31 Conventional tissues Cell therapy** Reproductive International * As of Jan 23, 2017 ** PBSC, Cord blood & Somatic cells 31

32 Requirements for Foreign and Domestic Establishment Registration and Listing for Human Drugs, Including Drugs That Are Regulated Under a Biologics License Application, and Animal Drugs; Final Rule 21 CFR Parts 20, 201, 207, 314, 514, 515, 601, 607, and 1271 (Published August 31, 2016) 32

33 Amends regulations governing drug * establishment registration and listing: Aimed at modernizing regulations Requires electronic submission of registration information, unless waived in certain circumstances * Includes biological products 33

34 Registration and listing requirements in subpart B of Part 1271 applies to HCT/Ps that meet the criteria set out in (a)- 361 HCT/Ps HCT/Ps regulated as drugs, devices, and/or biological products under section 351 of the PHS Act or under the Food, Drug, and Cosmetic Act, are subject to registration and listing under part 207 or part 807 rather than part 1271 (refer to note on the next slide) Amended 21 CFR

35 Note: Establishments that only manufacture drugs and devices under an investigational new drug application (IND) (21 CFR Part 312) or an investigational device exemption (IDE) (21 CFR Part 812) are not required to register and list their HCT/Ps until the products are approved; or, cleared for premarket notifications Guidance for Industry Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Small Entity Compliance Guide ances/tissue/ucm htm 35

36 Each foreign establishment must submit the name, address, telephone number, and address of each importer that is known to the establishment, and the name of each person who imports or offers for import such HCT/P to the United States for purposes of importation Importer means a company or individual in the United States that is the owner, consignee, or recipient, at the time of entry, of the foreign establishment's HCT/P that is imported into the United States. New 21 CFR (a)(5), (mm) 36

37 If the ownership or location of your establishment changes, or if there is a change in the United States agent's name, address, telephone number, or address, you must submit an amendment to registration within 30 calendar days of the change. Note: Previously, changes in ownership or location had to be submitted within 5 days of the change. Amended 21 CFR

38 Must use electronic registration system for submission of registration information, unless waived in certain circumstances (no reference to FDA form 3356) May request a waiver (in writing) from the requirement for electronic submission o FDA will determine whether electronic submission of registration information is not reasonable for the registrant o If FDA grants the waiver request, FDA will specify the term and how to submit the registration information Amended 21 CFR (a), New

39 Effective Date: November 29, 2016 Compliance deadline for amended Part 1271 FDA will stop accepting paper submissions (Form FDA 3356), unless an individual waiver is granted, 1 year after the effective date of the final rule Greater than 98% of establishments currently register electronically Registration and listing updates in accordance with amended part 1271 is due after the first anniversary of the effective date of the final rule Final rule-august 31,

40 FDA will periodically issue guidance on recommended procedures for providing registration and listing information in electronic format (for example, method of transmission, media, file formats, preparation, and organization of files) Electronic HCT/P establishment registration system is undergoing revisions FDA will communicate changes through outreach to the stakeholders STAY TUNED New 21 CFR (b) 40

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42 if our hospital routinely shares the HCT/Ps that we receive for use at our own facility with other hospitals? Yes receiving HCT/Ps and making them available to other hospitals are storage and distribution, and therefore must register and list such HCT/Ps with CBER (21 CFR ; (e) and (bb)) 42

43 for distribution, if we receive and store HCT/Ps at our main hospital and subsequently send the HCT/Ps to our surgery center across the street? No as long as the hospital and the surgery center are under one management and can be considered to be at one general physical location (21 CFR (d)) 43

44 if we facilitate distribution of HCT/Ps (e.g. handling customer orders, arranging shipments, billing)? No as long as the facility doesn t take physical possession of an HCT/P (21 CFR (bb)) 44

45 Website: RegulatoryInformation/EstablishmentRegistration/TissueEstablish mentregistration/default.htm Questions: Tel:

46 CBER Contact Information Manufacturers Assistance Consumer Questions About Products Regulatory Questions 46

47 Website: tionandlisting/default.htm Contacts: edrls team at or CBER Website: rdevice/registrationandlisting/ Contact: 47

48 THANK YOU Safa Karandish