Understanding and Managing Bone Allografts A Guide for Perioperative Personnel. Practical guidance and tools

Transcription

1 iologics Understanding and Managing Bone Allografts A Guide for Perioperative Personnel Practical guidance and tools A supplement to March 2011 OR Manager newsletter Sponsored by:

2 CoNTACT your LoCAL MTF ALLogRAFT CoNsULTANT. LEARN THE TRUTH 125 May Street n Edison, NJ n n mtf.org

3 Table of contents PUBLISHER Elinor S. Schrader EDITOR Pat Patterson CLINICAL EDITOR Judith M. Mathias, MA, RN EDUCATION COORDINATOR Judy Dahle, MS, MSG, RN CONSULTING EDITOR Kathleen Miller, MSHA, RN, CNOR CONTRIBUTING WRITER Paula DeJohn Managing Biologics March 2011 A special supplement on managing biologics from OR Manager Sponsored by SENIOR VP/GROUP PUBLISHER DORLAND HEALTH/MEDIA/COMMUNICATIONS Diane Schwartz dschwartz@accessintel.com ASSOCIATE PUBLISHER Carol Brault cbrault@accessintel.com TRADE SHOW DIRECTOR Jenn Heinold ART DIRECTOR Tracey Lilly SENIOR PRODUCTION MANAGER Joann M Fato jfato@accessintel.com Advertising National Advertising Manager John R. Schmus Anthony J. Jannetti, Inc. East Holly Ave/Box 56, Pitman, NJ Tel: ; Fax: schmusj@ajj.com REPRINTS Wright s Media sales@wrightsmedia.com Vol. 27, No. 3, March 2011 Supplement OR Manager (ISSN ) is published monthly by Access Intelligence, LLC. Periodicals postage paid at Rockville, MD and additional post offices. POSTMASTER: Send address changes to OR Manager, 4 Choke Cherry Road, 2nd Floor, Rockville, MD Subscription rates: Print only: domestic $99 per year; Canadian $119 per year; foreign $139 per year. Super subscriptions (includes electronic issue and weekly electronic bulletins): domestic $149 per year; Canadian $169 per year; foreign $179 per year. Single issues $ For subscription inquiries or change of address, contact Client Services, clientservices@ accessintel.com. Tel: , Fax: Copyright 2011 by Access Intelligence, LLC. All rights reserved. No part of this publication may be reproduced without written permission. OR Manager is indexed in the Cumulative Index to Nursing and Allied Health Literature and MEDLINE/PubMed. SISTER Sites dorlandhealth.com patientadvocatetraining.com contexo.com Access Intelligence, LLC Chief Executive Officer Don Pazour Executive Vice President & Chief Financial Officer Ed Pinedo Exec. Vice President, Human Resources & Administration Macy L. Fecto Divisional President, Access Intelligence Heather Farley Senior Vice President, Chief Information Officer Robert Paciorek Senior VP, Corporate Audience Development Sylvia Sierra Vice President, Production and Manufacturing Michael Kraus Vice President, Financial Planning and Internal Audit Steve Barber 4 Choke Cherry Road, Second Floor Rockville, MD Welcome letter 4 Allografts: Overview of the process 5 Donor screening: First step in safety 7 Help for evaluating bone allografts 8 Bone allografts: Options for healing 11 Understanding tissue processing 13 Regulating allograft tissue 16 A sound process for acquiring tissue 17 A unified program to manage biologics 20 March 2011 Supplement to OR Manager Vol 27, No 3 3

4 Welcome Biologics To our readers, Chips, pastes, putties, gels, powders, wedges, DBM, BMP, and assorted kits the list of bone allografts and substitutes is long and confusing. These biologic materials have a big impact on the OR budget, but they are more than just another line of surgical supplies. Biologics originate with a family s decision to donate a loved one s tissue. From there, they may pass through many hands until they are brought to the operating room in a form that promises to help a patient heal a defect caused by injury or disease. In making decisions about which biologics to acquire, OR teams have to consider a variety of issues: Is the tissue safe from pathogens that could carry disease? Who is supplying the tissue? Tissue is handled by a complex network of suppliers. How is the tissue regulated? What are surgeons preferences for the grafts they use? What is the clinical efficacy? How is tissue tracked and monitored after it arrives in the facility? How much inventory should the OR maintain? And what is the cost? Managing bone biologics In this supplement, OR Manager is publishing information to help in managing this complex area. We believe we have found the right partner in the Musculoskeletal Transplant Foundation (MTF). The supplement is a collection of articles that appeared in OR Manager from October 2010 through February The articles are intended to help you and your team better understand and manage bone biologics. The articles begin with an overview of the tissue donation process and donor screening. Other articles feature: a guide to understanding the types of bone biologics and their role in healing a discussion of how tissue is regulated an explanation of tissue processing and sterilization tools to aid decisions about biologics, including questions to ask suppliers, regulatory issues, and other considerations. We hope these articles assist you and your team in making good decisions about the use of bone allografts, a gift of life. Pat Patterson Editor, OR Manager Kim Rounds Vice President, Marketing Musculoskeletal Transplant Foundation 4 Supplement to OR Manager Vol 27, No 3 March 2011

5 Allografts: Overview of the process Like organ donation, tissue donation is an end-of-life gift that can save or enhance the lives of 50 people, often many more. Donated human tissue, also called allografts, c a n b e used in a variety of replacement, reconstructive, or regenerative surgical procedures. Beginning with an individual s decision to donate, each step in the process of recovering, preparing, and distributing tissue is intended to ensure its safety for the recipient. Perioperative nurses are often involved with both sides of tissue donation first, as tissue donation occurs in the operating room and then as tissue is transplanted. Biologics What can be donated? Bone, corneas, hearts for valves, ligaments and tendons, skin, and veins and arteries can be donated after death. Many organ donors may also be cornea and tissue donors; in these circumstances, tissue and eye recovery is performed immediately following organ recovery. Unlike organs, which must be transplanted within hours of donation, most tissue is prepared and preserved for later use. Quality assurance is built in. Tissue donation fast facts The impact of tissue donation is great, and demand continues to grow. Thanks to the generosity of more than 30,000 donors and their families, over 2 million life-saving and life-improving tissue grafts were distributed in the US in In comparison, there were 14,631 organ donors, including 8,021 deceased donors and 6,610 living donors, resulting in 28,465 total organ transplants, an average of 2 transplants per donor. The tissue donation process Federal regulations require hospitals to report all deaths to their local Organ Procurement Organization (OPO) and to have an agreement with at least one eye and tissue bank. In most states, the OPO also serves as the tissue recovery agency, although tissue banks also provide these services. Once a referral is re- ceived, preliminary screening occurs, and a preliminary determination of donor eligibility is made. Factors such as age; cause of death; evidence of systemic infection; or evidence of risk factors for diseases such as HIV, hepatitis, syphilis and Creutzfeldt-Jakob disease (CJD) are considered (diagram). Each state has an Anatomic Gift Act that governs how donation may occur and who may make a gift of an organ or tissue. More than 86 million Americans have registered to be donors after their death ( In cases where the potential donor has not registered, the next of kin or other authorized person may give permission for donation. In either situation, a trained individual obtains information from a potential donor family about their loved one s medical and social history. The American Association of Tissue Banks (AATB) has standards for obtaining authorization for donation as well as for properly screening potential donors and for processing and distributing donated tissues. The standards emphasize the importance of compassionate care for family members as well as the need to eliminate any possibility of transmission of infectious diseases from donated tissue. Although the Food and Drug Administration and AATB have established donor screening guidelines, each tissue processor or tissue bank establishes its own donor criteria standards. It is important for perioperative nurses to be aware of the criteria used by the tissue bank that provides their facility with tissue. Tissue recovery Tissue recovery is performed using aseptic technique according to AORN recommended practices. The recovery takes place in an operating room or an OR-like environment such as a recovery suite at the local OPO or tissue bank. On occasion, recovery may take place in a medical examiner s or coroner s office or a funeral home. Quality assurance protocols are built into recovery procedures to avoid cross contamination of tissues. All tissue is cultured, labeled with a unique identifier, and packaged separately before being transported to the tissue processor. An essential part of the recovery process is the reconstruction of the donor. All donors are reconstructed March 2011 Supplement to OR Manager Vol 27, No 3 5

6 Overview of the donation process Hospital referral Preliminary screening Consent/ authorization Medical/ social history and review of donor suitability Recovery organization Tissue bank Tissue recovery Hospital Transplanting hospital Tissue distribution Tissue preparation Final donor suitability determination (medical director) Source: Musculoskeletal Transplant Foundation. with great care utilizing customized prosthetics and with great consideration of the family s wishes. Final review of suitability When tissue arrives at the tissue processing facility, it is held in quarantine until the final suitability review occurs. This final review consists of an evaluation of the pertinent medical information, records, serology tests, autopsy reports, and tissue and blood cultures as well as an examination of the medical and social history of the donor. All information is reviewed by the medical director of the tissue bank, and final suitability is determined. Once the review is completed, the preparation of the tissue occurs. Tissue distribution After tissue is prepared and packaged, it is distributed to hospitals and ambulatory surgical centers. In many cases, it is the practice of the tissue bank to return donated tissues to the community that provided the donation. It is always a good practice to know where the tissue recovered in your institution will be sent for processing and to learn as much as possible about the donor criteria, processing protocols, and whether the supplier provides priority access to tissues from your hospital or region. The gift of life Donation affects everyone. OR managers are directly aware that families often offer donation the gift of life at a painful time in their lives. The donor family remains at the heart and soul of the entire process of recovery, preparation, and distribution of tissue, and OR personnel need to be educated about all aspects of donation. v Martha Anderson Executive Vice President, Donor Services Musculoskeletal Transplant Foundation References American Association of Tissue Banks. About Us. Donate Life America. Understanding Donation. Youngner S J, Anderson M W, Schapiro R. Transplanting Human Tissue: Ethics, Policy, and Practice. New York: Oxford University Press, Supplement to OR Manager Vol 27, No 3 March 2011

7 Donor screening: First step in safety Screening of tissue donors is a critical step in ensuring tissue safety. Screening is a complex, multidisciplinary process that begins every time a family says yes to the option of donation and ends when tissue is released for transplant. Tissue banks vary in what is considered a suitable donor. Regulating tissue banks The Food and Drug Administration (FDA), the primary regulatory body for the tissue banking industry, sets mandatory standards related to donor suitability. The FDA s primary focus is to prevent the transmission of communicable diseases associated with use of donated tissues. The FDA s Good Tissue Practices, effective in 2005, include the Donor Eligibility Rule, which requires all tissue banks to screen for communicable diseases such as HIV, hepatitis, syphilis, and Creutzfeldt-Jakob disease. These regulations set the baseline for donor suitability that all tissue banks must follow. The American Association of Tissue Banks (AATB) is a voluntary association dedicated to ensuring that human tissues intended for transplant are safe and free of infectious disease, of uniform high quality, and available in quantities sufficient to meet national needs. The AATB not only requires donor screening and testing similar to the FDA but also focuses on the operational and organizational aspects of tissue providers. More information is at Biologics Reasons for musculoskeletal allograft recalls 1999-June 30, 2007 Additional donor criteria Tissue banks can also set their own donor criteria above those required by the FDA and AATB. Examples of criteria that may differ among tissue banks are donor age, evidence of osteoporosis, and malignancies, among others. In selecting a tissue bank, it is important to know and understand the differences in donor criteria and the effect these differences may have on the safety and quality of tissue. An example is donor characteristics that could affect the structural integrity of bone allografts, such as the donor s age, steroid exposure, and osteoporosis. A recent study published in Spine found that 50% (7 of 14) of tissue banks that process structural bone allografts accept donors with a diagnosis of osteoporosis, and 43% (6 of 14) have no upper age restriction for these types of grafts. Improper donor evaluation 67.15% Contamination 21.47% Recipient infection 9.79% Positive serology 0.98% Processing error 0.12% Other (ie, hemodilution, improper/invalid testing) 0.49% Total recalls: 49,133 Source: Mroz T E, Joyce M J, Steinmetz M P, et al. J Am Acad Orthop Surg. 2008;16: Tissue donation coordinators Also important to understand is who is involved in the donor screening process within a tissue bank and the experience of the medical director responsible for the final decisions. Some banks employ experienced critical care RNs as tissue donation coordinators to assist with the review of donor records and the initial suitability process. These coordinators are responsible for authorizing the recovery of tissue from potential donors who meet the criteria for donor suitability. The coordinators have 3 main functions: to support the preliminary screeners, to protect the recovery team, and to honor the gift of the tissue. Preliminary screening The preliminary screeners are employed by a recovery or screening organization and are trained to obtain complete medical and social histories and consents. Preliminary screening is challenging. It is not easy to speak with the family who has experienced a recent unexpected death of a loved one. Because the screeners are often individuals in entry level medical positions, such as EMTs or college students, the coordinator s role is March 2011 Supplement to OR Manager Vol 27, No 3 7

8 to make sure all information to determine if the donor is suitable is collected. Another aspect of the coordinator s role is to reduce the risk of disease transmission to the recovery teams. Generally, serology testing is performed after tissue recovery. Recovery teams rely on the discussion between the screener and the tissue bank coordinators to uncover potential high-risk behavior in donors that could increase the odds of serologies being positive for pathogens. Honoring the gift A major component of donor screening is honoring the gift. When a family consents to donation, the intent is for the tissue from their loved one to provide life-changing grafts for recipients. The tissue bank coordinators want to accept as many donor referrals as possible. They work to maximize the chances that a donor for whom consent has been obtained will complete the screening process and provide transplantable grafts. Honoring the gift also means that sometimes coordinators need to explain to families the rationale for why the tissue bank is unable to accept the potential donation. v Judi Togerson, BSN, CTBS Associate Director, Donor Screening Musculoskeletal Transplant Foundation References Jurgensmeier D, Hart R. Variability in tissue bank practices regarding donor and tissue screening of structural allograft bone. Spine. 2010;35:E702-E707. US Food and Drug Administration. Current good tissue practice for human cell, tissue, and cellular and tissue-based product establishments; inspection and enforcement; final rule. Federal Register. 2004; 69(226): pdf Managing biologics Help in evaluating bone allografts Bone-graft substitutes in all of their many forms have one purpose to replicate the gold standard for bone repair and healing the patient s own bone. Though a patient s own tissue an autograft is the ideal replacement for injured or diseased bone, an autograft may not be feasible. The patient s bone may not be available or healthy. Retrieving an autograft also causes added pain and recovery time for the patient and consumes additional OR time. The host of graft materials that have arisen as a substitute for the patient s own bone are challenging to manage. They can be made from human tissue and cells (allografts), animal tissues (xenografts), synthetics, and combinations. These bone-graft substitutes come in an array of chips, putties, gels, and other materials with a variety of clinical applications from filling bone voids after a fracture to helping late unions to mend to aiding spinal fusions. Bone graft substitute market Bone allograft market Bone-graft substitutes are a large and growing industry, expected to generate $1.5 billion in revenue in 2010, according to the Millennium Research Group (chart). T h e m o s t common applicat i o n i s in spinal surgery, accounti n g f o r 83% of the use of these grafts in 2009, according to Orthopedic Network News (ONN). About 50% of spinal procedures use a bone graft or bone graft substitute. Other applications are in trauma surgery, joint replacements and revisions, and craniomaxillofacial surgery. Synthetic bone substitutes (such as Vitoss and Mastergraft) accounted for 54% of hospital spending for bone graft materials in 2008, ONN reports, with demineralized bone matrix (DBM) 2010 revenue in millions Growth factors including BMP $708 Synthetics $328 DBMs $276 Orthopedic stem cell products $102 Nonproprietary allograft $88 Total $1,502 BMP = bone morphogenic protein; DBM = demineralized bone matrix. Source: Millennium Research Group. Biologics 8 Supplement to OR Manager Vol 27, No 3 March 2011

9 Repairing bone Bone-graft substitutes seek to replicate the body s own healing process, which involves these 3 mechanisms. Cells Osteoprogenitor cells 1. Osteogenesis New bone is formed by living bone-forming cells from the patient s own bone marrow or allogeneic stem cells, which differentiate into osteoprogenitor cells and then into osteoblasts. 2. Osteoinduction Signals induce stem cells and osteoprogenitor cells to become bone-forming cells (osteoblasts). Growth factors can be supplied by the patient s surrounding bone or from exogenous growth factors from a product like bone morphogenic protein (BMP). Osteoblasts Bone formation occurs 3. Osteoconduction Bone is formed by osteoblasts that have infiltrated an environment conducive to bone formation. One function of bone grafts is to provide a structural support or scaffold for osteoconduction. at 24%, allograft bone at 15%, and other materials, 7%. Evaluating bone graft substitutes How can perioperative teams ensure that surgeons have the products they need yet avoid overlapping inventory and unnecessary costs? In evaluating bone allografts, it s helpful to know the categories they fall into and their roles in healing. (The color-coded chart on page 12 shows the categories of bone repair options.) Four components are essential for bone healing: 1. An adequate blood supply. 2. Mesenchymal stem cells (MSCs) and osteoprogenitor cells capable of forming bone (osteogenesis). 3. Biological signaling factors to stimulate MSCs and osteoprogenitor cells to differentiate into bone-forming cells, or osteoblasts (osteoinduction). 4. A scaffold to which bone-forming cells can attach and form new bone (osteoconduction). Bone biologic characteristics An abbreviated list of characteristics useful in evaluating and managing bone biologics includes: biocompatibility efficacy strength safety availability handling/storage cost. This article focuses on biocompatibility, efficacy, and strength. Ensuring safety in tissue donation and screening is addressed on pp 7-8. Tissue processing, product evaluation, and cost will be discussed later in this series. Biocompatibility The bone allograft must be biocompatible; that is, elicit a minimal immune response from the recipient. If the body recognizes the allograft as foreign, it can wall off the implant with fibrous tissue and prevent the graft from integrating with the patient s own bone. Allografts that provide a scaffold for bone growth, for example, are typically made of calcium phosphate material. These allografts are biocompatible because bone s normal structure is made up of inorganic materials and minerals like calcium phosphate. Efficacy The goal for a bone allograft is to form bone or enhance bone formation, in concert with the body s own healing response. Four common terms describe the efficacy of allografts: Osteoconductive Like the patient s own bone, a biologic that is osteoconductive March 2011 Supplement to OR Manager Vol 27, No 3 9

10 provides a biocompatible scaffold that allows for cellular migration and vascular in-growth and eventually can be replaced by the patient s own bone. Examples: Allografts (such as chips, struts, or shafts), synthetics (ceramics), collagen. Osteoinductive An osteoinductive allograft includes signaling factors that stimulate osteoprogenitor cells to differentiate into bone cells. A material is considered osteoinductive if in laboratory studies it forms bone when placed in a non-bony site, such as muscle. Examples: DBM (such as powders, putties, or pastes), active bone morphogenic protein (BMP). Osteogenic A biologic that is osteogenic has cells capable of forming bone. Examples: Autografts, fresh osteochondral grafts, the patient s own bone marrow, or stem cell technology. Osteopromotive Osteopromotive is a term used more recently to describe products and tissues that may not fall into one of the conventional categories of efficacy. The term may be applied to newer biologics that aren t necessarily osteoinductive but promote healing by certain factors that stimulate or enhance bone healing. Example: Platelet-rich plasma. Strength Biologics can be structural or nonstructural. A structural allograft, such as a strut or shaft, is used when the graft is needed to maintain a structure and provide support, as in joint reconstruction and spinal fusion. Nonstructural biologics don t necessarily maintain a structure The goal is to enhance healing. but fill a bony void or defect. An example is allograft chips. Applications for bone allografts Allograft materials are selected according to the surgeon s desired outcome for the patient. These are some examples of common applications. Materials are often used in combination. In cases where a scaffold is needed for structural support, as in spinal surgery, the surgeon may select a graft designed for the structural load that also allows for bony ingrowth. Examples are struts or shafts and allograft interbody spacers. Polyether-etherketone (PEEK) can be used as a spinal spacer and is filled with a synthetic or biologic material to enhance healing. PEEK does not remodel the host bone and remains in the body. If the graft is being used to fill a void or as a graft extender, as in trauma surgery, the surgeon may use graft material in a powdered or particulate form to provide a nonstructural scaffold that will allow bone to form. Examples are synthetic granules, foams, powders, and allograft cancellous chips. If the surgeon needs to enhance the patient s ability to form bone at the healing site, the graft material can provide a biological stimulant. Examples are putties or pastes containing DBM or BMP. If a patient has a complex fracture or multiple comorbidities that might inhibit healing, a surgeon might want to add cells to the fracture site, either by adding bone marrow aspirate from the patient or adding allogeneic mesenchymal stem cells, a new technology. Surgeons also consider factors that might hinder bone healing, such as the lack of blood supply to a fracture site, bacterial infection, or the complexity of the fracture. Understanding how bone allograft materials are categorized may help OR teams establish criteria for determining how a new graft material proposed for purchase will meet the needs of the surgeon and how it compares with graft materials already in inventory. v Heather Brannen, PhD Senior Product Manager Musculoskeletal Transplant Foundation Pat Patterson Editor, OR Manager Guide to bone-graft substitutes The American Academy of Orthopaedic Surgeons has a helpful publication, The Evolving Role of Bone-Graft Substitutes, posted at Included is a chart listing 50 commercial bone-graft substitute products, with claimed mechanisms of action, burdens of proof, and FDA status. Single copies are free for download. A chart with screening criteria for tissue donors is posted in the OR Manager Toolbox at 10 Supplement to OR Manager Vol 27, No 3 March 2011

11 Bone allografts: Options for healing These are examples of types of bone allograft products and purposes they serve. With the chart on page 12, this information can help OR teams determine where a new allograft product would fit into current inventory. Allograft cancellous chips Cancellous chips, a common nonstructural human allograft bone mat e r i a l, serve as a scaffold for new bone g r o w t h. A d d i n g o t h e r materials, such as bone marrow aspirate (BMA), provides a scaffold plus the patient s own cells to stimulate bone growth. Biologics Synthetics Synthetic bone graft materials, such as ceramics, are composed of nonbiologic biocompatible materials such as tricalcium phosphate and hydroxyapatite. They also provide a scaffold, though they are more expensive than biological bone grafts, according to idata Research. Synthetics can be combined with biologics such as BMA. Vitoss (Orthovita) has the most market share for synthetics at 35%. Vitoss granules are a ceramic material that provides a scaffold into which new bone can grow. Some surgeons add BMA to synthetics to enhance healing capacity. Combined products Examples of combined products are Vitoss foam and Mozaik (Integra), which include not only ceramics but also bovine collagen, a xenograft. These products provide a matrix for new bone growth and are approved for use with BMA. Demineralized bone matrix Demineralized bone matrix (DBM) comes in different forms: paste, putty, and strips, among others. This is a large and confusing product group, with dozens of options on the market. DBMs have both osteoinductive and osteoconductive properties and can be used as graft extenders or enhancers. Essentially, DBM is allograft bone that has had the minerals removed to expose the bone morphogenic proteins (BMPs) in the bone. The exposed BMPs, particularly BMP-2, are intended to make the allograft osteoinductive, providing signaling factors that induce stem cells to become osteoblasts. Because DBM is a powder, the material is combined with carriers such as sodium hyaluronate, gelatin, or glycerol, that allow it to be molded into a variety of shapes surgeons can more easily use. Bone morphogenic protein BMP products, highly concentrated forms of a single bone morphogenic protein produced by recombinant technology, act as osteoinductive agents. These BMPs provide a signal for bone growth that is much more concentrated than those in DBM. The BMPs commercially available today use a bovine collagen carrier, providing an osteoconductive scaffold. The addition of BMA yields a composite that comes close to mimicking autograft. Two BMP products are on the market: InFuse (Medtronic) and OP-1 (Stryker). InFuse is approved for limited indications, and OP-1 is used under a human device exemption for long-bone nonunions. A new study in Spine documents that between 2003 and 2007, 85% of InFuse used in principal spine procedures was used off-label. The authors note there are still safety concerns with BMP. The FDA issued an alert in 2008 about life-threatening complications when BMP is used off-label in the cervical spine. The Centers for Medicare and Medicaid Services held a meeting in September 2010 to discuss the on-label and off-label uses of BMP. Stem cell-based therapy A new frontier is allograft products with stem cells. This is the smallest but fastest growing segment of the market, according to Millennium Research Group. These biologics come the closest to replicating autografts because they include the 3 components necessary to form bone: mesenchymal stem cells (osteogenic cells) cancellous bone matrix (osteoconductive scaffold) demineralized bone (osteoinductive factors). Two stem-cell based products are currently available: Trinity Evolution (MTF/Orthofix) and Osteocel (AlloSource/NuVasive). (At deadline, a new stem-cell product for spine surgery, PureGen by Alphatec Spine, was announced.) The products are produced using a validated proprietary process in which the immunogenic components of donor bone marrow are removed and the mesenchymal stem cells preserved. What remains is the patient s cancellous matrix that was part of the bone marrow as well as the mesenchymal stem cells and os- March 2011 Supplement to OR Manager Vol 27, No 3 11

12 Bone repair options Provides scaffold for tissue ingrowth and/or support Provides signaling factors for cell differentiation or healing enhancement Provides cells Category Graft material Commercial options Autograft/ autologous materials (patient s own tissue) Allograft (human) Xenograft (animal) Autograft Bone marrow aspirate (BMA) Autologous plateletrich technologies Bone structure segments Nonstructural bone (eg chips, powders) Stem cells Demineralized bone matrix Bovine (bone, collagen) Allograft cancellous chips + BMA Scaffold + Cells Vitoss granules + BMA Vitoss foam + BMA Mozaik + BMA DBX + BMA Grafton + BMA Scaffold + Cells Scaffold + Cells Signal + Scaffold + Cells Infuse + BMA OP-1 + BMA Signal + Scaffold + Cells Synthetics Rh growth factors Ceramics, polymer Bone morphogenic proteins (BMPs) Trinity Evolution OsteoCel Signal + Scaffold + Cells Source: Musculoskeletal Transplant Foundation. teoprogenitor cells that were embedded in that matrix, explains Ray J. Linovitz, MD, FACS, medical director for Orthofix. He notes that as in normal marrow, there are 65-fold more mesenchymal stem cells attached to the cancellous matrix than can be obtained with a bone marrow aspirate. Demineralized cortical bone from the same donor is added in a consistent ratio to provide additional osteoinductive factors. Trinity Evolution is regulated by the FDA as an HCT/TP (human cellular tissue/tissuebased product). The main criterion for tissues under this regulation is minimal manipulation of cells; that is, the cells are not removed or expanded, and no carriers are added. In contrast, DBM products, which do have carriers, are regulated as medical devices, requiring 510(k) clearance. Trinity Evolution is labeled for all bone indications. It has been used for spinal fusion and in areas such as foot and ankle surgery for treatment of complex fractures. Stem cells: More to come Other stem cell products are in the pipeline. They are part of a movement toward tissue engineering, which promises to be exciting and challenging for surgical teams. 12 Supplement to OR Manager Vol 27, No 3 March 2011

13 Understanding tissue processing Tissue cleaning and sterilization provide an additional level of safety beyond donor screening and procurement for preventing the transmission of infection from allografts. Tissue processors need to strike a fine balance between eliminating microorganisms and preserving the integrity and quality of the graft. This is an overview of tissue cleaning/disinfection and sterilization methods with suggestions for Biologics Sterilization is a controversial area. evaluating processing claims. Tissue processing is defined by the American Association of Tissue Banks (AATB) as any activity performed on tissue, other than tissue recovery or collection, including preparation, preservation for storage, and/or removal from storage, to ensure the quality and/or sterility of human tissue. Processing includes steps to inactivate and or remove adventitious agents. ( Adventitious refers to agents that occur sporadically and are not inherent or innate.) When sterilization is performed Sterilization methods can often be completed during tissue processing with cleaning and disinfection steps or in the allograft s final packaging with terminal sterilization. Sterilization is defined by the AATB as a validated process used to render tissue free from all viable microorganisms, including spores. If a sterilization step is employed by the tissue supplier, the process must be validated, a sterility assurance level must be set, and the process must reduce the allograft bioburden to the set level in its final packaged form. Tissue banks use proprietary methods to process and sterilize tissue and must independently validate the processes employed. The US Food and Drug Administration (FDA) does not require tissue to undergo sterilization. The FDA and AATB do not recommend specific tissue processing or sterilization methods but state that all tissue processors must validate all tissue processing methods used. Tissue processors must also ensure that cleaning/disinfection and sterilization methods maintain the tissue s mechanical and biological integrity. An allograft s strength is more important in some tissue forms than others. For example, soft tissue allografts must maintain strength to support the repair or replacement of the patient s own tissue. Strength is This is sort of a hot topic. Instead of doing fusions or artificial disks, we would like to be able to regrow the disc or at least regenerate cells so they can survive longer, Dr Linovitz says. Companies eager to get into the market are marketing cellular products derived from other sources, such as synovial fluid, fat, or amniotic fluid, and seeking to have them regulated as tissue products, he notes. Some are growing stem cells outside the body in quantity and combining them with carriers for indications such as bone growth and cartilage regeneration. These expanded stem cell products may also be combined with other materials and then are regulated as drugs or devices. Surgeons and OR personnel are going to start being inundated by companies saying they have stem cells but from various sources, he says. They are going to need to understand the differences in all of these cell sources. We are really at the tip of the iceberg. You are going to see a lot more of this. v References Food and Drug Administration. FDA public health notification of complications associated with recombinant human bone morphogenetic protein in cervical spinal fusion. July 1, www. fda.gov Ong K L, Villarraga M L, Lau E, et al. Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine. 2010;33: Rush S. Mesenchymal stem cell allografting in foot and ankle surgery. Foot Ankle Spec. 2010;3(3): , March 2011 Supplement to OR Manager Vol 27, No 3 13

14 Measuring tissue sterilization Sterilization is measured by a sterility assurance level (SAL), which the Association for the Advancement of Medical Instrumentation (AAMI) defines as the probability of a single viable microorganism remaining on an item after sterilization. AAMI states that an SAL of 10-6 is appropriate for medical devices, equating to a 1 in a million chance that a viable microbe remains on the device. AAMI also says that this level of sterility is appropriate if the medical device can withstand these sterilization methods without adversely affecting its essential safety and function. The FDA considers an SAL of 10-3 appropriate for biologic medical devices, which is an estimated 1 in 1,000 probability of the presence of a viable microbe (AAMI, 2007). The FDA does not require a specific SAL level for tissue banks; however, both the FDA and the AATB state that if a sterilization process is used, and an SAL is claimed, it must be validated. There are 2 methods to validate sterility of tissue: Sterilization for pharmaceutical-grade products The first method is per the US Pharmacopia (USP) guidance that governs sterilization for pharmaceutical-grade medical products that cannot undergo terminal sterilization (eg, injectable medications and sterile solutions). A tissue bank may choose to clean, disinfect, and aseptically process bone and soft tissue rather than use terminal sterilization because of the potential deleterious effect of terminal sterilization on tissue. The tissue bank uses a validated cleaning and disinfection method with strict adherence to aseptic technique. Sterility testing is then performed on the processed tissue in accord with the USP <71> Sterility Test. The test demonstrates that the tissue itself is not inhibitory to the growth of microbial contaminants. Tissue that is processed through aseptic means and passes all of the appropriate testing related to the USP guidance can be labeled as sterile per USP. Terminal sterilization In terminal sterilization, tissue is sterilized in its final package. Many tissue banks use a terminal sterilization step and claim to achieve a SAL of If this claim is validated, the FDA allows the bank to use the word sterile on its packaging. Allografts may be terminally sterilized by several methods, including ethylene oxide, gamma radiation, electron (E)-beam radiation, and hydrogen peroxide plasma. The most common sterilization technique used for tissue is gamma radiation. Many tissue banks use a low to moderate dose of gamma radiation to sterilize their tissues in their final packaging. High levels of gamma radiation have been shown to be detrimental to tissue integrity (Currey et al, 1997; Ijiri et al, 1994). Ethylene oxide has also been associated with negative effects on human tissue properties (Aspenberg et al, 1990). The tissue bank should provide the hospital with detailed data on the effects of its sterilization method on tissue integrity. also critical when cortical bone is used in load-bearing applications, such as in spine surgery and large joint reconstruction. Tissue cleaning/ disinfecting methods Common chemical methods for cleaning/disinfecting allograft tissue use aqueous solutions of detergents or surfactants, hydrogen peroxide or other peroxides, organic solvents, acids, and alcohol. Chemical methods are often combined with mechanical methods. These processes must: completely penetrate the tissue remove endogenous materials such as blood, lipids, cells (for acellular tissue forms), and bone marrow reduce the level of microbiological and viral contamination. Certain processing methods may have more deleterious effects on tissue properties than others. For example, extended exposure to hydrogen peroxide can significantly reduce the osteoinductivity of cortical bone; that is, the graft s ability to induce the growth of new bone cells (DePaula et al, 2005). Sterilization of tissue Sterilization of allograft tissues is a controversial area. It is difficult to sterilize many allograft tissues because of their sensitive structure and components. It is also challenging to remove all of the potential organisms within tissue without disrupting the allograft s biological and structural integrity. The issue becomes even more challenging as technology advances, and tissue banks introduce more fresh or cellular tissue forms. Because cells cannot withstand sterilization, some tissue banks rely on donor screening and mild processing techniques to maintain safety. 14 Supplement to OR Manager Vol 27, No 3 March 2011

15 Evaluating cleaning/ disinfection and sterilization methods Asking questions of your tissue bank can help in understanding the complex relationships between tissue banks, tissue processors, and distributors. Hospitals should set criteria for evaluating tissue suppliers. More information on evaluating processing and sterility claims and on developing criteria for tissue suppliers are in Hospital Tissue Management: The Practitioner s Handbook by the American Association of Blood Banks, AATB, and the Eye Bank Association of America. The handbook advises that criteria include whether the tissue supplier s facility and all related processors and intermediaries: are registered with the FDA hold state licenses (if applicable) are accredited. Among other attributes the handbook suggests considering: 1. The transparency of the supplier s organization and its willingness to provide information about its operations and tissues, including specific data on the efficacy of tissue processing or disinfecting methods. 2. The involvement and availability of the supplier s medical director. 3. The supplier s ability to provide the tissue needed and to meet any special requirements. The handbook also recommends asking for a tissue processor s inspection findings; FDA warning letters, if any; and any other related communications. This information can be requested from the FDA directly. Warning letters are posted at gov. Questions to ask about allograft processing Some questions to ask tissue suppliers: Registration and accreditation Is the supplier accredited by the American Association of Tissue Banks (AATB)? Is the tissue supplier registered with the Food and Drug Administration (FDA)? When was the last FDA inspection? What were the findings? Has the supplier received any warning letters from the FDA? If so, what action was taken in response? Thomas E. Mroz, MD, a spine surgeon, and his colleagues in a 2008 article suggested questions to ask of tissue banks. Among these are: Is the graft at risk of being structurally or biologically compromised because of the type of sterilization? Does the bank validate its technique? Is there a sterility assurance level? The safety and quality of the allograft are related not only to processing and sterilization but also to the initial donor screening and selection. The more stringent a tissue bank s donor criteria, the gentler it can be on cleaning and disinfection, and the more biological properties the tissue maintains. Ultimately, the techniques the tissue bank employs must yield Evaluation of incoming tissue What are the standard procedures for evaluating potential contaminants on incoming tissue? Does the serological evaluation of tissue include nucleic acid testing (NAT) for HIV and hepatitis C virus (HCV)? AATB requires NAT screening for HIV and HCV with FDA-licensed tests for human blood. Tissue processing How is the tissue processed and/or sterilized? How are processing methods validated? If terminal sterilization is performed, what method is used and at what level? Does the tissue carry a label claim for sterility? If so, how is the claim validated? What are the effects of the processing methods on the tissue s structural and biological integrity? How will this affect clinical outcomes? Source: Musculoskeletal Transplant Foundation. safe, effective allografts that are processed and validated to maintain the tissue s natural function to ensure the best possible outcome for recipients. v Joel Osborne Vice President, Quality Assurance and Regulatory Affairs Musculoskeletal Transplant Foundation References American Association of Blood Banks, American Association of Tissue Banks, Eye Bank Association of America. Hospital Tissue Management: A Practitioner s Handbook. Bethesda, MD: AABB, American Association of Tissue Banks. AATB Standards for Tissue Banking. McLean, VA: AATB, March 2011 Supplement to OR Manager Vol 27, No 3 15

16 Aspenberg P, Johnsson E, Thorngren K G. Dose-dependent reduction of bone inductive properties by ethylene oxide. J Bone Joint Surg Br. 1990;72: Association for the Advancement of Medical Instrumentation. Technical Information Report TIR37:2007: Sterilization of health care products Radiation Guidance on sterilization of human tissue-based products. Arlington, VA: AAMI, Currey J D, Foreman J, Laketic I, et al. Effects of ionizing radiation on the mechanical properties of human bone. J Orthop Res. 1997;15: DePaula C A, Truncale K G, Gertzman A A, et al. Effects of hydrogen peroxide cleaning procedures on bone graft osteoinductivity and mechanical properties. Cell Tissue Bank. 2005;6: Ijiri S, Yamamuro T, Nakamura T. Effect of sterilization on bone morphogenetic protein. J Orthop Res. 1994;12: ,1994. Mroz T E, Joyce M J, Steinmetz M P, et al. Musculoskeletal allograft risks and recalls in the United States. J Am Acad Orthop Surg. 2008;16: Managing biologics Regulating allograft tissue When your OR is selecting allograft tissue, how do you know which federal regulations govern their safety? The US Food and Drug Administration (FDA) uses a tiered approach to regulating these materials, explains Scott Brubaker, CTBS, chief policy officer for the American Association of Tissue Banks (AATB). Minimally processed tissue Conventional allografts, such as bone, tendons, ligaments, skin, and fascia lata, are regulated solely under Section 361 of the Public Health Service (PHS) Act (42 USC 264), which covers human tissues and cellular and tissuebased products (HCT/Ps), as long as they meet 4 criteria: are minimally manipulated are intended for homologous use are not combined with another article do not have a systemic effect or depend on the metabolic activity of living cells for their use. Tissue establishments that perform any manufacturing function for tissue regulated under Section 361 must meet requirements of 21 CFR 1271, which include the FDA s current Good Tissue Practice Rule, and Donor Eligibility Final Rule and Guidance. These focus on preventing disease transmission during each step from donor screening and tissue recovery to tissue distribution. There are donor eligibility and testing requirements; controls for tissue recovery; and expectations for tissue tracking, handling, labeling, and recordkeeping. Establishments must also have a quality program and comply with registration and reporting responsibilities. But unlike medical devices, conventional tissue allografts do not require FDA clearance (510k) or premarket approval (PMA). Tissue as a medical device Biologics that go beyond any of these criteria, such as gels, pastes, and putties with demineralized bone matrix (DBM) or implants combined with biologics, are regulated under a higher tier: Section 351 of the PHS Act and the Federal Food, Drug, and Cosmetic Act, which covers drugs, biological products, and medical devices. Manufacturers of these products must meet FDA s Good Tissue Practice rule as well as the Good Manufacturing Practice (GMP) regulation and, for products designated as medical devices, the Quality Systems Regulations (QSR). Basically, the manufacturer must demonstrate safety and effectiveness before the product can be widely marketed, either through the FDA s 510k process, in which the company demonstrates equivalence to a product already on the market, or a PMA. v References American Association of Blood Banks, American Association of Tissue Banks, Eye Bank Association of America. Hospital Tissue Management: A Practitioner s Handbook. Bethesda, MD: AABB, Wells M A, Hornatko-Munoz A. Human cell and tissue products. Chapter 28. Fundamentals of US Regulatory Affairs. 6th ed. Rockville, MD: Regulatory Affairs Professionals Society, Supplement to OR Manager Vol 27, No 3 March 2011

17 A sound process for acquiring tissue A surgeon has requested a new tissue graft not in the current inventory. From the company s literature, it s not easy to tell whether the tissue is similar to others already in stock. Decisions like these are challenging because tissue grafts come with a host of safety, clinical, and cost issues. We are dealing with donated tissue, the same as a unit of don a t e d b l o o d. T h i s i s not just a m e d i c a l supply, n o t e s Biologics Victoria Steelman, PhD, RN, CNOR, FAAN, of the School of Nursing, University of Iowa Hospitals and Clinics, Iowa City, an expert on tissue management. A systematic approach can help ensure that surgeons have the materials they need while also making sure newly acquired tissue is safe and avoids unnecessary duplication and cost. This article suggests steps and criteria for selecting bone allografts. Previous articles have covered the donor screening and recovery process, types of bone allografts and their roles in healing, and tissue processing and regulation. Critical elements in the selection process include: a multidisciplinary team physician participation criteria for selecting tissue suppliers and evaluating tissue. (Suggested criteria with questions to ask suppliers are in the sidebar, p 18.) This is not just a medical supply. Know your tissue supplier The first step is to select suppliers who adhere to strict standards for donor screening, tissue procurement, processing, and distribution. You want to make sure you are dealing with a supplier that is highly ethical, Steelman emphasizes. The reason became dramatically clear a few years ago when a ring operating in the Northeast procured tissue fraudulently, resulting in 25,000 grafts entering the market without proper donor consent or screening. A number of patients were harmed, including a Philadelphia woman who developed sepsis after receiving a graft in a hernia repair, a man who tested positive for HIV and hepatitis C after receiving bone implants, and a Colorado woman who needed repeated anterior cruciate ligament repairs after her tendon implant failed, according to Philadelphia magazine. A few years earlier, a 23-yearold Minnesota man died after receiving a contaminated knee graft. Investigators found 14 patients had received tainted grafts from the same tissue bank, the New England Journal of Medicine reported. When the tissue was recalled, hospitals and surgery centers had to scramble to identify whether grafts from these donors were in their inventory or had been implanted. The events led to more stringent requirements from the Food and Drug Administration (FDA) and the Joint Commission. Check registration, accreditation To know your supplier, at a minimum, make sure the supplier is registered with the FDA, says Steelman. Registration must be checked annually it s not a onetime check, she adds. Registered suppliers are posted in the FDA s online database. (See Resources, p 19.) Accreditation by the American Association of Tissue Banks (AATB) is also strongly recommended. It s important to check specifically what the supplier is accredited for, Steelman advises. Is the tissue bank accredited just for distribution or is it also accredited for processing and procurement? Expect the supplier to provide detailed information about its donor selection criteria, tissue testing, and tissue processing as well as evidence that these processes have been validated. Also find out if the FDA has taken any actions against the tissue supplier. Notices of recalls are posted on the FDA website. The FDA also issues several types of regulatory action letters against tissue banks, available on its website. Despite today s stricter standards, one area that still may be difficult to probe is where a supplier obtains its tissue. This information is difficult to get from some suppliers, Steelman notes. If the supplier obtains its tissue March 2011 Supplement to OR Manager Vol 27, No 3 17

18 Questions for tissue suppliers 1. How long have you been in the tissue banking industry? 2. What is the evidence attesting to the quality of your tissue bank? 3. What types of tissues do you process? Please include a brief description of tissues processed. 4. Are you accredited by the American Association of Tissue Banks (AATB)? If so, in what areas are you accredited? Please provide the current certificate. 5. If you do not perform tissue recovery, please list your recovery partners. 6. Where is the donor tissue recovered, domestically or outside the US? 7. How is donor tissue recovered? Under what types of controlled conditions? 8. From how many donors do you recover tissue annually? 9. Please supply your donor selection criteria with respect to criteria that may negatively affect tissue safety and quality. 10. Are consistent medical and social screening and selection criteria applied to all donors? 11. Who makes the final decision on donor tissue acceptance and release? What is this person s background? 12. Do you ever accept a deferred donor or donors previously rejected by one or more other tissue banks? 13. How is tissue processing performed? Is processing performed strictly aseptically, or are terminal sterilization methods used? 14. If terminal sterilization methods are used, what type is used, and what is the level of irradiation? 15. Please supply a description of your processing protocol. 16. What solutions are used in the processing of soft tissue grafts? 17. Do demineralized bone allografts that you provide possess any osteoinductive potential? Please substantiate such claims. 18. Please provide the percentage bone content and residual calcium levels in your demineralized bone products. 19. Do you have a validation process for package sterility? validation tests of the package s sterility use of identifying numbers by which the allograft can be traced to a specific donor as well as the time, place and manner in which the allograft was recovered. 20. Do you have the ability to trace all allograft tissue to the specific donor? Please provide specifics on your tracking methods. 21. What is the shelf life of the package, during which the sterility of its contents is guaranteed? Source: Musculoskeletal Transplant Foundation. from another source, it s important to ask how the supplier ensures the tissue is safe. Are tissues delivered appropriately? One weak point in tissue distribution continues to be hand delivery by vendor representatives. The hospital or ambulatory surgery center has no way of knowing how the tissue has been stored and if the requirements for storage have been met, Steelman points out, adding, This practice should be prohibited. Your facility is accountable for making sure tissue is transported properly. The Joint Commission tissue management standards require facilities to verify that the package integrity is met and transport temperature is controlled for tissues that require a controlled environment (TS ). FDA regulations require tissue suppliers to have conducted validation testing on their packaging methods. Small distributors of medical devices that provide tissue need to be registered with the FDA, just like any other tissue supplier. The selection process In acquiring new graft materials, a well-defined process is the best way to address surgeons requests, ensure tissue is acquired from a safe source, and assess whether the tissue is a clinically efficacious and cost-effective addition to the OR inventory, Steelman advises. This process is most likely to be successful if a strong medical director heads the tissue bank in your facility. The trend, she says, is to centralize tissue management in the blood bank. There are good reasons for that, she says. The blood bank is accustomed to 18 Supplement to OR Manager Vol 27, No 3 March 2011

19 the FDA tissue regulations, which were patterned after the regulations for blood. Process steps The process for considering new tissue materials might include: Criteria for tissue suppliers and tissue selection established in advance by a multidisciplinary team with input from surgeons. (Suggested questions to ask suppliers are in the sidebar, p 18.) A list, or formulary, of tissue materials that will be stocked in the facility, similar to a formulary for pharmaceuticals. A standardized process for considering surgeon requests for tissues not in the formulary. This might include a form for the surgeon to complete justifying the need for the tissue. A surgeon may have a valid reason for requesting a graft that is not on the facility s formulary. But having a defined process Tissue regulation resources American Association of Tissue Banks Food and Drug Administration Center for Biologics Evaluation and Research (CBER) with a formulary is a good way to manage the inventory and minimize the cost while still providing surgeons with what they need, she says. Then the onus is on the surgeons to support their requests. Registration of tissue establishments Information/EstablishmentRegistration/TissueEstablishment Registration/FindaTissueEstablishment/ucm htm Information on biologics for health care providers HealthcareProviders/default.htm Information on regulatory action RegulatoryInformation/ComplianceActivities/Enforcement/default.htm Warning letters Clinical efficacy Determining the efficacy of a tissue material is not always easy. Published evidence from the peer reviewed literature may be sparse or lacking. In evaluating a new tissue, it helps to know the graft s intended purpose and how is it classified. Is it osteoconductive, meaning it provides a scaffold for bone formation? Does the graft also need to provide signals to induce bone formation (osteoinductive) or have cells capable of forming bone (osteogenic)? (A chart for classifying grafts is on p 12.) The American Academy of Orthopaedic Surgeons (AAOS) outlines principles for assessing the clinical burden of proof in its publication, The Evolving Role of Bone- Graft Substitutes: Consider the healing environment where the graft is needed. Environments have different levels of difficulty for forming new bone. Examples are a metaphyseal defect, a longbone fracture, or an interbody spinal fusion. Seek the highest burden of proof from clinical and preclinical studies to justify the use of an osteoinductive graft material or the choice of one alternative over another. Recognize that there is no standardized burden of proof for materials such as demineralized cortical powder or platelet gels with autologous growth factors. These are regulated by the FDA as tissues rather than as medical devices because they involve minimal manipulation of tissue. As a result, says AAOS, there is no standardized level of proof of safety and effectiveness required before these products are marketed and are used in patients. There are no easy answers to managing the complex area of tissue grafts. But having a systematic process with strong multidisciplinary involvement and support is a step in the right direction. v Pat Patterson References American Academy of Orthopaedic Surgeons. The Evolving Role of Bone-Graft Substitutes. Rosemont, IL: AAOS, Single copies free for download at www. orl-inc.com/aaos_publications/ Kainer M A, Linden J V, Shaley D N, et al. Clostridium infections associated with musculoskeletaltissue allografts. N Engl J Med. 2004;350: March 2011 Supplement to OR Manager Vol 27, No 3 19

20 A unified program to manage biologics Biologics A unified program for managing biologics, including tissues and blood, has helped a Massachusetts hospital to meet regulatory requirements, track adverse events, and have a consistent process for bringing new tissues into the organization. The year-old Biovigilance Program at Baystate Medical Center in Springfield was created to help meet the expanding requirements of the Joint Commission, the Food and D r u g Administration ( F D A ), and other accrediting and regulatory bodies. Previously, responsibilities for tracking, compliance, and infection control for biologics were split among several departments. The Biovigilance Program integrates these functions with oversight from the medical directors of transfusion medicine services and of the operating rooms. The program is managed by Theresa Stec, BA, MT (ASCP), who was previously the quality improvement coordinator for transfusion services. She reports clinically to both medical directors and administratively to the director of surgery and anesthesia. Baystate has 18 inpatient ORs, 12 outpatient ORs, and 4 ORs in an offcampus orthopedic facility. Qualifying tissue suppliers Baystate s process for acquiring new tissue includes credentialing for suppliers. Tissue suppliers are asked to complete a form. The New biologics are subject to value analysis. credentialing information is then entered into the hospital s tissuetracking software. I definitely want to make sure [suppliers] are FDA registered and have a way for tracking tissue, says Stec. Under federal regulations, all establishments that provide human cells, tissue, and cellular- and tissue-based products must register with the FDA. An annual update is required in December. If the tissue is classified as a medical device, she verifies that it has received FDA 510(k) clearance. As part of credentialing, the supplier is also asked to provide the package insert and manufacturers instructions. Stec checks for the supplier s accreditation and for a written quality plan and a recall process. Suppliers are expected to indicate if they have issued customer notifications or recalls. They are asked to supply tissue delivery information, including the shipping method, storage requirements, and standard and emergency delivery times. Documents are kept in individual supplier files, which also include any supplier issues, complaints, and pricing information. Value analysis New biological materials that surgeons want to use, such as a new demineralized bone matrix (DBM), are subject to the hospital s value analysis process. Surgeons who want to use a new material inform the RN service coordinator for their specialty, who submits a request form and related information to the value analysis team (VAT). The request is placed on the VAT s agenda, and the surgeon is asked to attend the meeting and make a presentation. The VAT then conducts a review, including a cost analysis that considers both direct and indirect costs. For example, a new tissue may cost more than a current material but save OR time because it doesn t have to be mixed. Or the new tissue may be able to be stored at room temperature, while the current one requires refrigeration. A trial of the proposed tissue is then conducted, results are reviewed by the VAT, and the request is granted or denied. When a request for a new biologic comes in to the purchasing department, the purchasing agent communicates with Stec so the supplier s qualification can be completed before the item is placed on the VAT agenda. Though some biological materials still find their way into the OR without value analysis, she says the process has helped to better manage the tissue acquisition process. Tissue tracking Baystate recently introduced its tissue-tracking software, Tissue TrackCore (TTC) from LPIT Solutions, as part of the Biovigilance Program. Stec has guided the implementation, including training for the clinical staff. Tis- 20 Supplement to OR Manager Vol 27, No 3 March 2011

21 sue-tracking software is a major boon in meeting FDA and Joint Commission requirements, which stipulate that tissue must be traceable from the donor to the patient and vice versa. When a new biological material is received, the staff enters prereceiving information, which verifies that the shipping container is intact and conditions were acceptable as well as the date and time of receipt. When tissues are received in the clinical area, each item in the shipment is inspected for package integrity, expiration date, and temperature range. If these are acceptable, additional tracking information is entered. Each item is assigned a unique identifier in TTC. An item-specific barcode label with that TTC number, item description, and information is printed and applied to each item. Lot numbers aren t sufficient to identify biological materials, Stec notes, because multiple items can have the same lot number and/or serial number. Which materials are included? Stec works with the OR staff to determine which materials need to be included in tissue tracking. She interprets the FDA rules as requiring that all tissues need to be tracked, including human tissue as well as tissue from bovine, Don t live in silos. porcine, or other biologic sources. The FDA is concerned about any biological product that goes into a human patient and the ability to trace it in case of an adverse event, Stec says. The Joint Commission s Transplant Safety chapter covers human and nonhuman cellular- and tissuebased transplantable or implantable products, whether classified by the FDA as a tissue or a medical device. The standards also apply to products classified by the state as a tissue even if that falls outside the scope of the Joint Commission definition. Collagen and tissue products derived from plastics and polymers are not considered cellular-based products and thus are not covered by the standards, the standards state. I ve instructed the nurses that if it s a synthetic, we don t need to enter it into Tissue TrackCore. But if it s a collagen from a bovine source or a matrix, we do include it. We are tracking more than other places are tracking, she notes. Scanning tissue in the OR Barcode scanners are available in the ORs. When tissue is used for a patient, the circulating nurse scans the barcode label to associate the unique TTC ID with the product in the tracking system. The scanners capture the data easily and help avoid data entry errors. Having a coordinated process has brought the best of both the blood bank and the ORs together for tissue safety. Stec s most important advice Don t live in silos. There are other experts in the hospital who can help you with this. v Pat Patterson Registered tissue establishments are posted on the FDA website at www. fda.gov/biologicsblood Vaccines/GuidanceCompliance RegulatoryInformation/ EstablishmentRegistration/ TissueEstablishmentRegistration/ FindaTissueEstablishment/ucm htm Reference Stec T C, Fuller D A, Albert M, et al. Development of a hospital biovigilance program integrating surgical services and transfusion medicine services. Abstract AP167. Transfusion. 2009;49 (Suppl):305A. March 2011 Supplement to OR Manager Vol 27, No 3 21

22 Notes 22 Supplement to OR Manager Vol 27, No 3 March 2011

23 DBM PRP ALLOGRAFTS STEM CELLS Is your biologics Inventory getting out of control? get It under WrAPs your local Mtf representative can show you how. 125 May Street n Edison, NJ n n mtf.org