Licensing Your Cord Blood

Transcription

1 Licensing Your Cord Blood A Guide to Getting FDA Approval for Marketing your Public Bank s Lifesaving Product as a Prescription Drug MEDIWARE Mediware.com

2 Contents Introduction 1 Profits for Today, Security for Tomorrow 1 Achieving Prescription Drug Status 2 Completing the Application 2 Ongoing Adherence to Standards 4 One Small Step for your Lab 5 References 5 CBUs stored prior to FDA licensure can be released as FDA-approved products only if you can document that these units were manufactured, stored, labeled, etc. using the exact process including equipment, procedures and personnel that was approved. Therefore, most prelicensure CBUs are released as INDs. An automated system that tracks and differentiates the two ensures that no mix-ups occur. Introduction Hematopoietic progenitor cell, cord blood is being utilized to treat a number of medical conditions, with tremendous hope for many more groundbreaking treatments to come. Most cord blood units (CBU) available for therapeutic use today are categorized as investigational new drugs (IND). However, a handful of public cord blood banks are pursuing or have received FDA licensure. This allows cord blood to be sold as a prescription drug known as HPC, Cord Blood on the consumer market. HPC, Cord Blood is sold the same way any prescription drug is sold. The license application process can be arduous and time consuming, especially if completed manually, but the expectation is that cord blood products subjected to this rigorous procedure will be of higher quality and will improve transplant outcomes. FDA licensure allows cord blood to be sold as a prescription drug known as HPC, Cord Blood on the consumer market. Profits for Today, Security for tomorrow Currently, only a small quantity of preserved cord blood products have received FDA approval, so, at this point, the best possible matches for transplant may be unlicensed. Therefore, the primary benefit to becoming FDA licensed now is financial. Cord blood products collected and stored prior to licensure are typically manufactured under an investigational new drug (IND) application with the FDA, resulting in cord banks operating under a cost recovery model. In this case, banks can charge only enough to recover the direct costs those specifically and exclusively attributed to the drug of making its investigational product available. 1 However, FDA-approved drugs can be sold at market price. In addition, licensed products can be marketed under a proprietary name such as Hemacord (the firstever FDA-approved HPC, Cord Blood product), which is manufactured by the New York Blood Center, Inc., and DUCORD, from Duke University s School of Medicine and the Carolinas Cord Blood Bank. A marketable brand name can increase exposure and, perhaps, cord blood donations to your organization. II

3 While licensing your cord blood products may not ensure a competitive advantage today, approved units should be perceived as higher quality for having passed FDA scrutiny. As therapeutic uses for cord blood increase, it s possible that, one day, only licensed products will be selected by transplant physicians and reimbursed by insurance companies. Getting licensed now may be a wise investment for your cord blood bank s future. Achieving Prescription Drug Status Meeting the requirements for FDA approval is a formidable task, and most public cord blood banks have multiple challenges to overcome in the process. Moreover, maintaining the license is an ongoing process that demands continual attention and effort. The primary challenge, and the one that demands the most resources, is ensuring and demonstrating that your facility operates in accordance with current regulations for both pharmaceuticals and biological products. 2 So, although cord blood banks must comply with current good manufacturing practices (CGMP) for biological products, the CGMP requirements for finished pharmaceuticals are significantly broader in scope. In addition, because HPC, Cord Blood falls into the category of human cells, tissues, and cellular and tissuebased products (HCT/Ps), regulations for current good tissue practices (CGTP) apply. However, the breadth of CGMP requirements for finished pharmaceuticals are generally considered to subsume relevant CGTP requirements. 2 Nevertheless, many cord blood banks seeking licensure have reported that meeting the broader regulations necessitated large-scale facility and equipment upgrades. Some banks have reported spending nearly $1 million while other banks have spent even more. Completing the application To apply for the biologics license, which you do using Form FDA 356h 3, you must provide significant documentation to demonstrate that you comply with all requirements related to the steps you perform. You can also request a pre-application meeting with staff from the Office of Cellular, Tissue and Gene Therapy, who can provide initial guidance to make the process go more smoothly. It s possible that, one day, only licensed products will be selected by transplant physicians and reimbursed by insurance companies. Getting licensed now may be a wise investment for your cord blood bank s future. Completing all requirements for the biologics license application (BLA) can take months but doing so manually could take years. Therefore, a software application that can manage your data, monitor your equipment and systems, track your supplies and reagents, label and trace your products and samples, and provide detailed reporting for all your lab activities would simplify the application process tremendously. The industry guidance, available here, is a useful tool for completing the application in a way that demonstrates how your facility operates in accordance with applicable CGMP requirements. In addition to assistance with the regulations, the guidance describes the steps necessary III

4 An automated system that can manage your data, monitor your equipment, track your supplies and reagents, label and trace your products and samples, and provide detailed reporting for all your lab activities would simplify the application process. for completing the BLA. Two sections establishment and chemistry require significant supplemental information. Establishment The establishment section requires documentation of your physical locations and the systems and controls in place at your facilities to ensure that your product is safe. A floor diagram, which should indicate (or explain in narrative) the processing that occurs in each space, is required for each location. Here are a few of the additional facility details that need to be addressed: + Water source used in processing (if applicable) + The environmental quality of each room and each aseptic processing area as well as a validation summary + Facility controls, such as cleaning and sanitizing procedures, security, and any environmental monitoring program + Computer systems that control critical manufacturing processes + Contamination prevention procedures and validation Chemistry To complete the chemistry section, you must provide detailed information to show how you manufacture and identify your cord blood. Some of the required material includes: + Tests and results that demonstrate the safety, purity and potency + Documentation of all your manufacturing processes and procedures with SOPs, flow charts, test methods and more + Validation data for all processes + A sample label with a barcode (or request in writing an exemption from the barcode requirement) 4 FDA reviewers, who evaluate submitted BLAs, recommend that supplemental information included with Form 356h be clear and concise while also providing all the details needed to make your case. Ensure that your data is accurate, your information is presented in easy-to-read formats, and your documents are wellorganized and error-free. Creating and managing the many SOPs required for the biologics license application can be simplified with an automated system. The FDA will notify you if your application is incomplete or if additional information is needed. Once your documentation is complete, the FDA will contact you to schedule a pre-license inspection to verify your compliance. IV

5 Integrated lab management applications can generate and print CGMP-compliant labels that include barcodes for traceability at every step. Ongoing Adherence to Standards Once your facility is FDA-approved, maintaining licensure for newly manufactured products requires continual action a process that is significantly streamlined with a software application tailored specifically to the needs of cord blood banks. For example, even the slightest change in the procedures you reported in your BLA whether a change in processes, equipment, packaging, labels, etc., including responsible personnel must be approved by means of a supplemental application. The information in this application must clearly demonstrate that the new procedures result in outcomes that are comparable or better than your previous methods. 5 Additional guidance on change reporting can be found online. Likewise, reliable controls are critical for other aspects of the licensed HPC, Cord Blood manufacturing operation. For example, all collection kits, supplies and reagents must be current, so a system that alerts to upcoming expiration dates would prevent the usage of outdated products. Monitoring of environmental conditions, from sanitizing to storage temperatures and much more, must be documented, or, as the expression goes, it didn t happen. Failure to document these conditions on any given day would make products manufactured that day ineligible for licensure, but this problem is easily prevented with a software application designed to manage documentation in the cord blood bank. Finally, licensed manufacturers are required to report information about distributed products to the CBER. 7 Every six months, or as requested by the FDA, licensed HPC, Cord Blood manufacturers must report the quantity of licensed product distributed along with all the details about each lot. Another CBER requirement is the review and reporting of adverse experiences, so a method to track and report outcomes must be in place. Doing so manually would be burdensome and have tremendous potential for error. 8 In addition, licensed biological products must be tested prior to release to ensure conformity to applicable standards. The test results, as well as a wealth of other information such as lot identification, must be indicated on the product label, so the history of the batch can be determined. 6 Even the smallest error in noted test results or in the product label in general could prove disastrous. Reliable controls particularly in the form of automation are necessary. Proving that changes to a previously authorized procedure have comparable or better outcomes requires significant data gathering and analysis. Software applications that track your data in real time can easily provide clear evidence of outcomes. V

6 One Small Step for your Lab Clearly, seeking FDA approval is no small feat, but it could be a wise investment that will one day provide a valuable return. As you weigh the options, consider taking the first step in moving your lab forward by selecting an automated system to help manage your cord blood bank. This choice will pay dividends immediately and can help lay the foundation for completing the licensure process in the future. References 1. Code of Federal Regulations Title 21 Part cfcfr/cfrsearch.cfm?fr= March 2014 Guidance for Industry: Biologics License Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM pdf 3. Form FDA 356h - Application to Market a New Drug, Biologic, or an Antibiotic Drug for Human Use ManualsForms/Forms/UCM pdf and instructions ReportsManualsForms/Forms/UCM pdf 4. Code of Federal Regulations Title 21 Part cfcfr/cfrsearch.cfm?fr= Code of Federal Regulations Title 21 Part cfcfr/cfrsearch.cfm?fr= Code of Federal Regulations Title 21 Part CFRSearch.cfm?CFRPart= Code of Federal Regulations Title 21 Part cfcfr/cfrsearch.cfm?fr= Code of Federal Regulations Title 21 Part cfcfr/cfrsearch.cfm?cfrpart=600 Achieve and maintain FDA licensure requirements with Mediware s Transtem software. Learn more. About Mediware Mediware is the leading expert in software solutions for cellular therapy organizations. Our Transtem system was designed by industry professionals to provide a comprehensive solution for cell therapy labs, cord blood banks, transplant centers and academic medical centers. It provides complete chain of custody management, so your facility can easily meet licensure requirements. For more information about customized solutions for cellular therapy, go to Our thanks to Jonathan Wofford, product manager for Transtem, for his help in developing this white paper. Jonathan spent more than a decade as bioinformatics lead for a major cord blood bank and blood and marrow transplant program in St. Louis and has extensive experience in hematopoietic stem cell transplant and cellular therapy. Mediware Information Systems, Inc West 79th St., Lenexa, KS Mediware