License Submission Checklist for Platelets, …

1 Version 2, January 2008 1 License Submission Checklist for Platelets, Leukocytes Reduced Collected by Pheresis Purpose: To provide guidance when submitting documentation to FDA in support of a BLA or a License supplement. Definitions and Abbreviations .. 2 Cover Letter .. 3 Labeling Requirements .. 4 General Chemistry, Manufacturing and Controls .. 5 Critical Control Points for Platelets Pheresis Leukocytes Reduced .. 8 Reporting Changes to an Approved BLA .. 16 Product Submission to CBER for Platelets Pheresis Leukocytes Reduced .. 17 Sterile Connecting Device .. 18 Miscellaneous Information .. 19 Version 2, January 2008 2 Definitions and Abbreviations The table below lists the abbreviations that are used throughout this document. Abbreviation/Term Definition BLA Biologics License Application CBE Supplement Changes being effected (30 days waived)

2 CBE 30 Supplement Changes being effected in 30 days CBER Center for Biologics Evaluation and Research Collection Site Fixed or mobile location that collects the pheresis product CMC Chemistry, Manufacturing and Controls Form 2567 Transmittal of Labels and Circulars Form 356h Application to Market a New Drug, Biologic or an Antibiotic Drug for Human Use Infrequent Plasmapheresis Every four weeks or less frequently IQ Installation Qualification OQ Operational Qualification PAS Prior Approval Supplement PQ Performance Qualification STCD Sterile Connecting Device Version 2, January 2008 3 Cover Letter FDA continues to encourage applicants to use a cover letter to introduce and summarize the application.

3 It is recommended that the following topics be covered in the cover letter to the FDA for License Submission : Statement/purpose of Submission included in first paragraph Full facility name, FDA registration and License numbers Product(s) requested for licensure Manufacturing site(s) or area(s) affected and their CFN/FEI (includes off-site donor or QC testing) Collection device(s) in use at the blood center(s) (only those associated with the products included in the License Submission ) Anticoagulant used Description of operator s training List of all attachments included in the Submission Contact information for questions, concerns or requests for additional information Statement clarifying whether this is the facility s comparability protocol for use with future submissions Note: The Form FDA 356h should be included with each Submission to FDA relating to a BLA.

4 It is the cover sheet that allows proper identification, routing and filing of the attached information. Examples of how to complete Form FDA 356h are: Product Description indicate see cover letter for established and chemical name; refer to COI for indications; all else in this section is N/A. Application Description check the BLA and CMC boxes; we check PAS or CBE-30 boxes appropriately. Briefly describe the reason for the Submission , , Prior Approval Submission for Platelets, Pheresis using the Amicus cell separator. Establishment Information indicate see cover letter. Cross-references list any applicable previously approval STNs/approval dates or applicable Comparability Protocol STNs/approval dates. Page 2 of the 356h check boxes 4, 4A, and 20 ( see cover letter ).

5 To obtain the FDA form, go to Instructions for completing Form FDA 356h are found in Guidance for Industry for the Submission of Chemistry, Manufacturing and Controls and Establishment Description Information for Human Blood and Blood Components Intended for Transfusion or for Further Manufacture and for the Completion of the form FDA 356h Application to Market a New Drug, Biologic or an Antibiotic Drug for Human Use. The guidance can be obtained at Version 2, January 2008 4 Labeling Requirements Each label submitted for review should be submitted with the items listed below. SOP/ Policy # Reference to Prior Submission Items Required for Licensure Attachment # If a label has been previously approved and is to be used without change, do not submit for another review. Instead, reference the label review number to identify the previously approved label.

6 One copy of the current Circular of Information that includes the facility identification information. One original and one copy (labeling set) of each label. (Indicate if it is a printer s proof or final printed labeling for the product). A single Form FDA 2567, completed and signed by an authorized official, should accompany each label set and/or Circular of Information that is submitted for review. Completed Form FDA 3674, Certification of Compliance, under 42 282(j)(5)(B), with Requirements of Data Bank (42 282(j)) Note: Labels and Form FDA 2567 should be detached from the rest of the Submission . The FDA form can be obtained at Apheresis must be indicated on the label in the product name or attributes. Consult the FDA guidance document, Recognition and Use of a Standard for Uniform Blood and Blood Component Container Labels - Sep 2006, Guideline for the Uniform Labeling of Blood and Blood Components Aug 1985, and/or consult the FDA Consumer Safety Officer who will perform the review of your submitted labels.

7 Version 2, January 2008 5 General Chemistry, Manufacturing and Controls The table below lists the common CMC contents for blood products collected by apheresis that should be submitted, or referenced from prior FDA submissions , for all apheresis blood product License submissions . The products may be leukoreduced or non-leukoreduced. The table does not include requirements for additional products collected, including concurrent plasma. Note: Listing of applicable SOPs may be substituted if SOPs have been previously submitted and approved and there will be no significant changes. Ensure that data on submitted records are complete, acceptable and documented as reviewed. SOP/ Policy # Reference to prior Submission Items Required for Licensure Attachment # Standard Operating Procedures SOP that describes donor suitability requirement (donor selection) and donor educational material (pre-donation).

8 SOP that describes the donor consent process. SOP that describes the collection of the product for which License is being requested. SOP that describes donor deferral procedure on red cell and plasma loss. SOP that describes the management of donor and receipt complications and reactions (adverse events). SOP that addresses Medical Director review of charts. SOP that describes product acceptability (needs to be consistent with device operator s manual) and failure investigation. SOP that describes the handling of the products (components), to include processing, testing, storage and leukoreduction procedures when appropriate. SOP that describes the quarantine of potentially unsuitable products and subsequent evaluation and disposition. Version 2, January 2008 6 SOP/ Policy # Reference to Prior Submission Items Required for Licensure Attachment # SOP that describes the labeling process for the product to include the method to accurately track multiple units collected from each donation (as needed).

9 SOP that describes packing instructions for the shipment and distribution of the product. SOP that describes the quality control on the product and failure investigation. SOP that describes Equipment QC/ Preventive Maintenance (include cleaning) SOP that describes the use of STCD (if appropriate). Note: See the section on Sterile Connecting Device for procedural specifics. SOP/job description that describes the responsibilities of the collection device operator. SOP/ Checklist that describes training. SOP/ Checklist that describes competency. SOP for validation process. Records to Submit Submit two months of QC data for products collected after validation process. Include products from all collection protocols performed on all devices in use. Include data for each site for which licensure is being requested.

10 Identify facility where QC is performed. Submit relevant validation protocol and data. Complete Form FDA 356h for each product type, for each type of device, by collection site. Include name(s) of the anticoagulant(s) and device(s) that will be used to manufacture the product, and list the manufacturing site(s) that will be collecting the apheresis products. Version 2, January 2008 7 SOP/ Policy # Reference to Prior Submission Items Required for Licensure Attachment # Submit QC sheets that contain the following information: Facility [21 CFR (a)(1)] Device manufacturer and type [21 CFR (a)(2)] Blood Unit Number [21 CFR (c)] Date of collection [21 CFR (a)(1)] Date of testing [21 CFR (a)(7); (a); (a)(1)] Appropriate collection types (single, double, triple, autologous if applicable) Interpretation of results [21 CFR (a)(6); (a)(1); (a)(2)(i)] Interpretation of month Yield [21 CFR ; (b)(7)] Acceptable criteria [21 CFR (d)] Initials [21 CFR (a)(7); (a); (a)(1)] Evidence of review [21 CFR (a)(8.)]