License Submission Checklist for Platelets, Leukocytes Reduced Collected by Pheresis

Transcription

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 Product Submission to CBER for Platelets Pheresis Leukocytes Reduced Sterile Connecting Device Miscellaneous Information Version 2, January

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) 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

3 Cover Letter FDA continues to encourage applicants to use a cover letter to introduce and summarize the application. 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. 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, e.g., 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 ). 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

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. 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 U.S.C. 282(j)(5)(B), with Requirements of ClinicalTrials.gov Data Bank (42 U.S.C. 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. Version 2, January

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 nonleukoreduced. 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). 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

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). 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. 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

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; )] Records of calculations [21 CFR (a)(5)] Version 2, January

8 Critical Control Points for Platelets Pheresis Leukocytes Reduced The table below lists some critical control points, by procedure, for Platelets Pheresis Leukocytes Reduced. SOP/Policy # Items Required for Licensure Attachment # SOP CCPs SOP that describes donor suitability needs to describe or include the following: Must meet FDA criteria for allogeneic whole blood donation (21 CFR and ). Persons who have recently ingested medication containing aspirin within 48 hours or Plavix and Ticlid within 14 days may not be suitable donors for Platelets Pheresis. Donation intervals: o If the donation is performed at the same frequency and interval allowed for whole blood, the donor should meet the whole blood suitability criteria. No additional laboratory testing is required for this frequency and interval. o Address the maximum number of procedures a donor can undergo per year and how it will be tracked. o A donor should not generally undergo a total of more than 24 platelet pheresis procedures during a rolling 12 month period. o With intervals of 48 hours between procedures, a donor should not undergo more than two procedures within a 7 day period. o Interval between collection of a double or triple Platelets, Pheresis and any subsequent collection of Platelets, Pheresis should be at least 7 days Platelet count: o If apheresis procedures are to be performed at a greater frequency or at shorter intervals than allowed for whole blood, and if the donor meets the whole blood donor suitability criteria, the following should occur: Blood sample should be drawn from the donor prior to the start of the initial platelet pheresis procedure Version 2, January

9 SOP/Policy # Items Required for Licensure Attachment # o A platelet count should be performed and the results reviewed prior to the donor undergoing each subsequent procedure. Counts obtained after the previous procedure may serve this purpose. The platelet count should be greater than 150,000/uL. Donors whose counts are less than those stated above should be deferred until the counts have returned to normal. Donor needs to meet all additional criteria outlined in the device operator s manual. o Total volume per donation limited to 500 ml or 600 ml if donor weighs >=175 lbs. o Donor who has donated a unit of whole blood, a single unit of Red Blood Cells by apheresis, or a single unit of Red Blood Cells by apheresis with Platelets, Pheresis in the previous 8 weeks is not allowed to donate Platelets, Pheresis, unless the extracorporeal red blood cell volume during the collection is expected to be less than 100 ml. SOP for the consent process should: Describe how and by whom the consent is obtained. Include and provide to the donor: o A description of the procedures to be followed, in language understandable to the donor. o A description of any reasonable foreseeable risks or discomforts that may occur, including side effects of the procedure and the hazards of solutions and/or drugs the donor will receive. o Donation frequency. o Presentation in such a manner that a clear opportunity to refuse is given. o A statement that participation is voluntary and the donor may withdraw his/her consent at any time. o A statement informing the donor of his/her right to ask questions of and discuss the procedure with a physician. o A statement that the donor has reviewed and understands the information provided to Version 2, January

10 SOP/Policy # Items Required for Licensure Attachment # him/her regarding the spread of the AIDS virus by donated blood and plasma. It should also state that if the donor considers him/herself to be at risk for spreading the virus known to cause AIDS, he/she will agree to not donate blood or plasma products for transfusion to another person or further manufacturing. o Long term effects of lymphocyte reduction are unclear. SOP that describes the collection of the product should include: Method of visually inspecting the plasma for hemolysis and the action to take if identified. Donor preparation (e.g., arm prep). Use of STCD (if appropriate). Name and manufacturer of the equipment used for platelet pheresis production. Instructions for management of equipment alarms. SOP that describes the donor deferral procedure on red cell loss should ensure that: Initial donor RBC loss less than 200 ml, no donation or total from initial and second loss less than 200 ml no deferral of donor. Initial donor RBC loss less than 200 ml, second donation more than 200 ml but less than 300 ml total RBC loss donor is eligible 8 weeks after second donation. Initial donor RBC loss more than 200 ml but less than 300 ml donor is eligible 8 weeks after donation. Initial donor RBC loss less than 200 ml, total RBC loss from initial and second donation more than 300 ml donor is eligible 16 weeks after second donation. Initial donor RBC loss more than 300 ml donor is eligible 16 weeks after donation. Version 2, January

11 SOP/Policy # Items Required for Licensure Attachment # SOP that describes the management of donor complications and reactions (adverse events) should address: The documentation for recording these events. The results of investigation and follow-up. The management of a cardiopulmonary emergency including steps for contacting the physician, transport of donor, etc. Medical attendance in the event of donor adverse reactions or physician available within 15 mins. SOP that addresses the Medical Director review of charts should address the following: Time frames for review. Which adverse findings need to be reviewed prior to allowing the donor to return. SOP that describes product acceptability should be consistent with the device operator s manual and include Instructions for management of non-conforming units, to include: o Hematocrit should be performed on the final products containing visibly apparent red blood cells to determine total packed red blood cell volume; if more than 2mL, sample should be attached for compatibility testing. o Directions for management of units that exceed manufacturer s limitations for volume and/or platelet count. Determination of the actual platelet yield of product (volume x platelet count) on every unit. These data should be part of the issue records. SOP that describes handling of the products (components) including storage requirements should address: Specifications for each component to be prepared. Leukocyte reduction methods. Determination of weight/volume. Storage requirements during processing and storage: o Temperature o Agitation Version 2, January

12 SOP/Policy # Items Required for Licensure Attachment # SOP that describes the quarantine of products and disposition of unsuitable products should define: Responsibility for review and authority for disposition of unsuitable products. The process for identification, quarantine, retrieval and recall of unsuitable products. Segregation of unsuitable products. The process to prevent unintended distribution or use of unsuitable products. Release criteria for units later found to be suitable. Record keeping processes and review of such records at appropriate steps. Define documentation that will indicate final disposition of unsuitable units. SOP that describes the labeling process for the product should include the following additional requirements: Expiration date Volume of the product Estimated volume of anticoagulant Residual WBC count SOP that describes packing instructions for shipment and distribution of the product should include: Specification of shipping containers. Specification of the coolant material. Time allowed out of the storage environment. Verification record checks. Shipping records. Labeling of outer box to meet transportation rules. Version 2, January

13 SOP/Policy # Items Required for Licensure Attachment # SOP that describes the quality control on the product should list the method used for QC testing, sample handling requirements (including time limits for sample testing), and ensure: 75% of units tested must contain 3.0x10 11 actual platelet yield (AABB standard: 90% of units tested must meet this requirement). Testing of at least 4 units per month / per site / per product type / per instrument type. ph >6.2 A residual leukocyte count o Single collection -- <5x10 6 per collection or bag, depending on device manufacturer (AABB standard: 95% of units sampled). o Double collection collection < 8.0x10 6 ; components < 5x10 6 o Triple collection collection < 1.2x10 7 ; components < 5x10 6 Percent component retention should be 85% in 95% of the units tested. QC record includes: o Collection site o Name of device manufacturer o Date of collection o Test date o Unit number o Volume of product at time of QC o Actual platelet yield o Percent component retention o Residual WBC o ph o Test interpretation (i.e., acceptable ) o Date/initials of testing tech o Date/initials of reviewer QC review is overseen by qualified staff o Results are tracked. o Trends are identified and failures are investigated. o Corrective action implemented is reviewed for effectiveness. o Instructions are available for appropriate disposition of the unit(s) involved (i.e., failed QC). Version 2, January

14 SOP/Policy # Items Required for Licensure Attachment # SOP that describes the sterility method used during the validation phase should: Follow methodology described in 21 CFR Describe QC of media and storage requirements. Describe test samples, volumes. Describe temperatures and incubation period. Define necessity for repeat testing. Define interpretation of test results. SOP that describes equipment QC / preventive maintenance, including cleaning / calibration, should describe: The required process(es). Personnel assigned to perform the process. When the process is to be performed. Records should be concurrent, reviewed and readily available. What to do when equipment is not in compliance. Validation and Validation Data CCPs Facility instrument information should include: Manufacturer Model Software version Serial # Facility unique ID # (as appropriate) Date installed and placed into service Equipment qualification/validation plan should include: Scope Purpose Responsibility Summary of changes IQ/OQ/PQ requirements and acceptance criteria Validation test cases, if applicable Management discrepancies include a description of whether the discrepancy was included in the acceptance/failure decision or if it was excluded with rationale. Management of products that fail to meet validation release criteria and failure investigation Description of training to include trainer, program, requirements for passing, competency assessment. Version 2, January

15 SOP/Policy # Items Required for Licensure Attachment # During the validation of the procedure: The following determinations should be made for 20 consecutive units (20 singles, 20 doubles, etc.): o Hematocrit or red blood cell count o Platelet count o White blood cell count o ph determination o Total product volume The total number of platelets and the volume of red blood cells obtained from each platelet pheresis should be calculated. During this period, bacterial testing should be performed as described in 21 CFR on outdated units, or on a sample of the product separated at the time of preparation and stored at C for the duration of the dating period. The procedure may be considered established when all operators have been trained and 20 consecutive procedures yield consistently satisfactory products meeting all requirements. Version 2, January

16 Reporting Changes to an Approved BLA Licensed establishments must report changes to their approved application(s) in accordance with 21 CFR Refer to FDA s Guidance for Industry and FDA Review Staff: Collection of Platelets by Automated Methods, December 2007, for guidance. Additional guidance can be located in FDA s Guidance for Industry: Changes to an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or for Further Manufacture, July Version 2, January

17 Product Submission to CBER for Platelets Pheresis Leukocytes Reduced The table below lists the product submission requirements for platelet pheresis. Items Required for Licensure Prior to submitting products to CBER for testing, verify that the following have occurred: All validation has been completed and reviewed. Two consecutive months of QC records have been completed and reviewed within the last 6 months prior to product submission. There is verification that validation and QC were acceptable. Product Shipment to CBER Call or CBER to schedule shipment: Div. of Hematology Contact Name: CBER ship by: To arrive by: Number of products that will be submitted: Caution: Ensure that shipments will not be received over a weekend or during a holiday. Also, ensure the product will expire Sunday through Thursday after receipt at CBER. Submit: Products (2) from two procedures for single platelets pheresis. Products (4) from two procedures for double platelets pheresis. Products (6) from two procedures for triple platelets pheresis. Ensure that all product tie tags include the following: Identification of the machine (manufacturer) ph Platelet count WBC count Total volume of product Packed red blood cell volume Collection facility identification and address Ensure that the product submitted is labeled in accordance with the facility requirement for shipment of an unlicensed product (i.e., the license number on the product is crossed out). Version 2, January

18 Sterile Connecting Device Using a STCD to pool, mix or remove cellular components represents a change in the product that requires submission and approval of a license application or supplement. The table below lists the critical control points when using STCD. SOP/Policy # Items Required for Licensure Attachment # SOP CCPs A STCD may be used to: Add a new or smaller needle to a blood collection set. Prepare components (add an extra bag, filter, additive solution). Pool blood products. Make aliquots for pediatric use or divided units of WB, RBCs or FFP or Platelets Pheresis. Attach processing solutions (glycerol, saline). Remove samples from blood products for testing. SOP must reflect changes in the assembly of collection and storage containers and in processing steps that involve the STCD for every product made. Records must reflect the date of the sterile connections, the lot numbers of the original containers and needles (and of those being added), the lot numbers of the STCD wafers, the initials of the individual preparing the containers, and a record of each STCD weld inspection and any corrective action taken. Techniques for the detection of leakage or air bubbles and specific instructions for handling the products with faulty welds should be described in SOP. Final product labeling may need to be revised to reflect different product volumes and SOP should describe the minimum volume of split products as well as the expiration date of the final product(s). Procedures for labeling the aliquots or split products should be clearly stated in the SOP. Record keeping should be adequate to permit tracking and recall of all components. Version 2, January

19 Miscellaneous Information Pursuant to FDA regulations, all blood establishments must also maintain the following records. These records do not need to be submitted, but should be available for review during FDA inspections. Records related to instrument and disposable equipment failures and reporting of failures to device manufacturers. Establishments should follow the device operator s manual for corrective action for any adverse or unexpected event, e.g., evidence of product hemolysis. Documentation of observation, standardization and calibration of the automated equipment on a regularly scheduled basis, consistent with the device operator s manual. Documentation of installation, operation and performance qualification tests, as applicable, performed on the automated device prior to implementing routine collections, in accordance with the device operator s manual. Documentation of a thorough investigation, including the conclusions and followup, of any unexplained discrepancy or the failure of a lot or unit to meet any of its specifications. Records of any donor adverse reaction complaints and reports, including results of all investigations and follow-up. References: 21 CFR , , , and Version 2, January