IDE Submissions for Devices Used to Manufacture Cell Therapy Products

Transcription

1 IDE Submissions for Devices Used to Manufacture Cell Therapy Products Janice Davis-Sproul, MAS Johns Hopkins Medicine 7 th Annual Somatic Cell Therapy Symposium 1

2 Overview Discuss an investigatorsponsored IDE submission to CBER Compare an IND submission to a CBER-IDE submission 2

3 Proposed Protocol Cell Therapy Product Lymphocytes, CD8 Depleted Collected from non-mobilized related donors via apheresis or whole blood donation 3

4 Background Cell Selection Devices are medical devices. Minimal Manipulation (21CFR (f)(2)) Definition: For cells, processing that does not alter the relevant biological characteristics of the cells. Therefore, unless post-selection manipulations are performed, selection is minimal manipulation. The CD8 Depleted Product meets the definition of minimally manipulated, but.. 4

5 Unapproved Devices A device or selection system may or may not be FDA approved or cleared for the desired selection process or for the clinical indication. Question: What regulatory pathway is suitable for the use of unapproved selection devices? 5

6 First Step Since the device proposed for use by the investigator was not FDA approved, the company was contacted for regulatory guidance and agreement preparation. 6

7 Regulatory Guidance The device is the investigational product, the cells (which do not contain any part of the device) are the therapeutic product. Submit an IDE to CBER since the investigational product is manufactured by the device manufacturer and not by the Cell Therapy Laboratory. 7

8 Agreements Non-disclosure Agreement signed, so Clinical Investigator s Brochure (CIB) can be provided. Also initiates a letter to the FDA, allowing permission to cross reference the Master File Clinical Research Agreement For IDE applications only For INDs the cell is the regulated product not the device. Hence, no Agreement with the manufacturer is required. 8

9 Laboratory Activities The device was already used in the lab for other applications, so Equipment Qualification (IQ, OQ) was complete. Plan and perform process validation Write process SOP/BPR, and a product specification Create a Product Label Train staff 9

10 Laboratory Preparation Define: Product release assay methods Sample test requirements Acceptance criteria Donor Eligibility ABO/Rh type CD4 + Cells/Kg CD8 + Cells/Kg CD8 + Cells Log Depletion Gram Stain/Sterility Cell Viability 10

11 IDE vs IND Similarities IDE content that was similar to an IND CMC Section: Donor eligibility determination (screening & testing) as per 21CFR 1271 Reagent List was included for items other than those listed in the Master File Vendor information & Certificates of Analysis or package inserts as appropriate. Sample test list Release criteria Action plan for culture-positive products 11

12 Submission Similarities IDE included: Reports of prior investigations including the validation data (IND sections 7, 8 and 9) Investigational Plan (IND section 3) Clinical protocol and consent forms (IND section 6) Monitoring Plan (IND section 6) Investigator Information CV, Research compliance training (IND section 6) IRB information (IND section 6) Cross reference permission letter 12

13 IDE vs IND Differences Document format/sequence was different. IDE: There is a section to describe the manufacturing, storage, and installation of the system (device and reagents) In our case, the cross reference letter. IDE did not contain a copy of the cell therapy lab s floor plan or an organizational chart. No 1571 or 1572 FDA forms. 13

14 Summary An investigator-sponsored CBER-IDE submission for a device-based product was similar to an IND submission for a cell-based product. Decision to use this regulatory pathway was based on the advice of the manufacturer. Contact the device manufacturer (or FDA) for submission information. 14