Validation of Musculoskeletal Tissue Capture from a Living Donor: Experience from a Multi-tissue Bank

ABSTRACT

Introduction:

The harvesting of musculoskeletal tissues is essential to ensure the supply of biological products of human origin with safety and clinical efficacy. The harvesting stage must undergo a validation process to guarantee the quality of the tissues.

Objectives:

This article describes the experience of a public human multi-tissue bank (HMTB) in validating the harvesting of musculoskeletal tissue (femoral head) from a living donor.

Methods:

This involves evaluating and adapting a harvesting protocol to promote excellence in the quality of tissues distributed for therapeutic and research purposes. To this end, a technical visit was carried out at another tissue bank, and meetings were held with the orthopedic service team to present and discuss the process flow. Donor screening was done by applying forms evaluating the selection and exclusion criteria. After acceptance, through the consent form, the donor’s serological tests were requested and collected. The harvesting kit, control of the temperature thermal transport box, and collecting microbiological material from the piece at the time of removal were validated. The validated harvested tissue underwent macroscopic, radiological, and microbiological evaluations to consider the process valid. The forms and other documents in the medical record were audited by the institution’s health quality and safety center. Process mapping was also carried out, targeting risks and opportunities for improvement.

Results:

The harvesting protocol was validated as foreseen in the action plan. The harvesting technique was performed sterilely in the operating room. Microbiological and serological analyses showed negative results, and the tissue was considered macroscopically viable. After the audit, the documentation was deemed adequate to comply with current legislation (Resolução da Diretoria Colegiada – RDC Nº 707, of July 1, 2022), and the mapping of processes guaranteed the security of harvesting and provided opportunities for improvement.

Conclusion:

A protocol for capturing musculoskeletal tissues in the reference service is presented, with the validation process being replicable through a fundamental tool to ensure harmlessness and safety in tissue harvesting.

Descriptors
Tissue donation; Tissue transplantation; Biological Quality Control; Harmless Products; Human Tissue Bank

RESUMO

Introdução:

A captação de tecidos musculoesqueléticos é fundamental para garantir o fornecimento de produtos biológicos de origem humana com segurança e eficácia clínica. Para assegurar a qualidade desses tecidos, é essencial que a etapa de captação passe por um processo de validação.

Objetivos:

Este artigo descreve a experiência de um banco de multitecidos humanos (BMTHs) público na validação da captação de tecido musculoesquelético (cabeça femoral) de doador vivo.

Métodos:

Trata-se da avaliação e adequação de um protocolo de captação visando promover a excelência na qualidade dos tecidos distribuídos para fins terapêuticos e de pesquisa. Para isso, foram realizadas uma visita técnica em outro banco de tecidos e reuniões com a equipe do serviço de ortopedia para apresentação e discussão sobre o fluxo do processo. A triagem do doador foi conduzida por meio da aplicação de formulários, avaliando os critérios de seleção e exclusão. Após a aceitação, mediante termo de consentimento, foram solicitados os exames sorológicos do doador e, por fim, a captação. Validaram-se o kit de captação, o controle de temperatura da caixa térmica de transporte e a coleta de material microbiológico da peça no momento da retirada. Para considerar válido o processo, o tecido captado passou por avaliações macroscópicas, radiológicas e microbiológicas. Os formulários e demais documentos do prontuário foram auditados pelo Núcleo de Qualidade e Segurança em Saúde (NQSS) da instituição. Também foi realizado o mapeamento dos processos, visando os riscos e oportunidades de melhoria.

Resultados:

O protocolo de captação foi realizado e validado conforme previsto no plano de ação. A técnica de captação foi realizada de forma estéril no centro cirúrgico. As análises microbiológicas e sorológicas apresentaram resultados negativos e o tecido foi considerado macroscopicamente viável. Após auditoria, a documentação foi considerada adequada ao atender a legislação vigente (Resolução da Diretoria Colegiada – RDC Nº 707, de 1 de julho de 2022). Além disso, o mapeamento dos processos garantiu a segurança da captação e proporcionou oportunidades de melhoria.

Conclusão:

Apresenta-se um protocolo de captação de tecidos musculoesqueléticos no serviço de referência, sendo o processo de validação replicável, por meio de uma ferramenta fundamental para assegurar a inocuidade e segurança na captação de tecidos.

Descritores: Doação de Tecidos; Transplante de Tecidos; Controle de Qualidade Biológica; Produtos Inócuos; Banco de Tecidos Humanos.

Descritores
Doação de Tecidos; Transplante de Tecidos; Controle de Qualidade Biológica; Produtos Inócuos; Banco de Tecidos Humanos

INTRODUCTION

Human multi-tissue banks (HMTBs) are healthcare institutions that aim to ensure the safety of biological products provided during the tissue donation process¹. Different types of tissues, such as cornea, sclera, skin, vessels, heart valves and musculoskeletal tissues, can be obtained from donors with brain death (BD) and/or donors with cardiorespiratory arrest (CPA). Furthermore, some of these tissues can be obtained from living donors after an interview and authorization by the donor or family member^2,3. HMTBs are responsible for selecting potential donors, screening, collecting, processing, and distributing tissues for therapeutic and/or research/teaching purposes⁴.

Tissue harvesting, although considered an invasive technique with a high risk of contamination, is a fundamental step to ensure the supply of biological products of human origin with safety and clinical efficacy⁴. In Brazil, the technical-sanitary requirements for tissue donation are regulated by Decree No. 9,175 of October 18, 2017, which deals with the disposal of organs, tissues and parts of the human body for transplantation and treatment in the Consolidation Ordinance No. 4 of September 28, 2017, which deals with the systems and subsystems of the Unified Health System (Sistema Único de Saúde-SUS), and the Resolution of the Collegiate Board (Resolução da Diretoria Colegiada-RDC) No. 707, of July 1, 2022, which provides for good practices in human tissues for therapeutic use^5-7.

Harvesting is the removal of tissues carried out in a sterile environment, with all aseptic precautions once the selected donor meets all established criteria. Living donors of musculoskeletal tissues can donate to the femoral head when undergoing hip arthroplasty surgery, in which prostheses replace their joint components (acetabulum and femoral head). The femoral head, commonly overlooked, is collected by a team of tissue banks to be processed and used as a bone graft later⁸.

The search for operational excellence in harvesting based on regulatory instruments has led HMTBs to adopt rigorous process validation practices⁹. This validation integrates a set of programmed and ordered actions of the quality management system, which ensures that services, procedures and products comply with the evidence provided and current legislation¹⁰. Therefore, this article reports the experience of a public HMTB located in the interior of the state of São Paulo on the validation of the harvesting of musculoskeletal tissue (femoral head) from a living donor.

METHODS

This descriptive study of an experience report type addresses the actions developed in adapting and validating the harvesting of musculoskeletal tissue from a living donor at the HMTBs of the Hospital de Clínicas of the Universidade Estadual de Campinas. (HC-UNICAMP).

To develop a harvesting protocol that met the established regulatory requirements, detailed analyses of RDC 707/2022, which discusses good practices in human tissues for therapeutic use, were previously carried out. Furthermore, a technical visit was carried out to the Human Tissue Bank of the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP)/Universidade de São Paulo (USP) for technical/practical monitoring of the musculoskeletal tissue harvesting procedure from a living donor.

Additionally, the flowchart of the harvesting process (Fig. 1) was developed and presented to the orthopedics specialty team at HC-UNICAMP, responsible for performing hip arthroplasty surgeries for insertion of the tissue collection stage in surgery by the HMTBs team.

Figure 1
Flowchart of the process of harvesting musculoskeletal tissue from a living HMTBs donor.

In the days before the collection at HC-UNICAMP, the HMTBs team screened the potential donor to evaluate the selection and exclusion criteria for tissue collection, as established in RDC 707/2022. After the acceptance of the potential donor, an interview was conducted with the patient to authorize and sign the Free and Informed Consent Form (FICF). On the day of collection, laboratory tests were requested for serological screening and nucleic acid test (NAT), syphilis [venereal disease research laboratory (VDRL)], toxoplasmosis, cytomegalovirus (CMV), Chagas disease, hepatitis B (anti-HbsAg and anti-Hbc), hepatitis C (anti-HCV), human immunodeficiency virus (anti-HIV I and II) and human T-cell lymphotropic virus (anti-HTLV I and II)⁷.

In addition, a collection kit was organized according to the checklist form of material necessary for collection from a living donor (Fig. 2), assembly of the thermal box with controlled temperature and validated by HMTBs and contact with the orthopedics team, as per previously developed operational procedures.

Figure 2
Checklist form for living donor harvesting material.

At the time of harvesting, three fragments of the femoral head were removed, and a sample of the saline solution used to wash the tissue was collected and sent for microbiological analysis to verify the absence or presence of growth of aerobic, anaerobic bacteria and fungi in the harvested tissue. After harvesting, the harvester conducted macroscopic tissue analysis, and the HC-UNICAMP radiology service performed radiological analysis. For this, the tissue was placed in a thermal box maintained at a controlled temperature (2-8 °C). During the analysis of the requested tests, the tissue was stored in an ultra freezer at a temperature of -80 °C, where it remained until the results were released.

The technical team and technical director, together with the Health Quality and Safety Center (Núcleo de Qualidade e Segurança em Saúde -NQSS), analyzed the results achieved through an internal audit to evaluate the integrity of the actions developed to validate the harvesting of musculoskeletal tissue.

RESULTS

According to the action plan, three femoral heads were collected to validate the harvesting protocol. The harvesting technique was performed sterilely in a surgical center by the surgical team that performed the hip arthroplasty. After removing the femoral head, it was passed on to an HMTB employee, who was adequately dressed and present in the surgical field. Upon receiving the tissue, the professional removed three fragments of the femoral head with the help of a bone punch placed them in sterile vials, collected 5 mL of the saline solution used to wash the tissue and sent them for microbiological analysis. After macroscopic analysis of the pickup, the heads were considered suitable, placed in three triple-sealed packages, and identified using a sterile technique. All serological and microbiological analyses of the three tissues collected showed negative results.

During transport, the temperature was maintained between 2 and 8 °C (Fig. 3). The harvested tissue reception forms (Fig. 4a) and harvesting training forms (Fig. 4b) were filled out safely, with double check, following the requirements of the Quality Management System.

Figure 3
Temperature variation in the thermal box during the harvesting of musculoskeletal tissue from a living donor. 7:15 am = departure from HMTBs; 7:30 am = arrival at the collection site; 9:05 am = removal of the femoral head; 9:25 am = departure from the collection site; 9:35 am = arrival at HMTBs.

Figure 4
a) Reception form for harvested human musculoskeletal tissue (HMST); b) HMST harvesting training form.

The NQSS team mapped the processes and possible risks related to harvesting using the failure mode and effect analysis (FMEA) tool (Fig. 5). This tool is used to identify risks and prevent failures in recognizing causes and effects, based on three factors: severity (S), occurrence (O) and detection (D). Each factor describes different aspects of failures and is crucial in calculating the failure risk priority number (RPN), allowing teams to prioritize the most critical ones to implement corrective and preventive actions¹¹.

Figure 5
Mapping of processes and risks related to fundraising using the FMEA tool.

Finally, to evaluate the protocol’s compliance and the information inherent to the process, the NQSS audited, through a specific checklist, the forms and documents contained in the donor’s medical records (Fig. 6a), the stability of the temperature of the thermal box of tissue transport and the results obtained from serological and microbiological tests. The internal audit validated the actions developed based on the standards described in RDC 707/2022, according to the Organizational Development Register (Registro de Desenvolvimento Organizacional- RDO) (Fig. 6b).

Figure 6
a) HMST donation, collection, and distribution checklist form; b) RDO (Organizational Development Register) used for internal auditing.

DISCUSSION

This report describes a protocol for harvesting musculoskeletal tissues from living donors, the respective actions developed, and its validation to ensure the use of appropriate and reliable tools for harvesting human tissues. Furthermore, it was essential to promote the improvement of techniques relevant to the work and the improvement of the HMTBs team.

Similar experiences have already been described and published in Brazil by services located in São Paulo, such as the Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP) and Santa Casa de São Paulo^12,13. However, this report is the first to describe the validation and internal audit process carried out by the NQSS of HC-UNICAMP, which included mapping processes and risks to guarantee the harvesting protocol’s quality and safety.

The mapping and management of processes and risks presented here are practical tools for preventing process failures like those described in this study¹⁴.

Current legislation’s increased complexity and requirements make this practice even more important. Despite this, little literature in Brazil addresses the subject, resulting in a heterogeneity of practices adopted by the most diverse services^12,13. Teofili et al. (2022), in a study on the validation of bone marrow harvesting, developed a validation plan based on the FMEA methodology. Following this approach, the authors carefully reviewed the activities and procedures related to the collection, processing, and distribution of bone marrow at their institution, making it the first study to describe the use of this methodology in a bone marrow transplant program¹⁵. Shaping risk analysis based on local experience can be a reliable tool for identifying essential points, directing rigorous monitoring of critical steps, and/or even proposing improvements to related procedures. Thus, the authors describe that the FMEA approach allowed them to improve their processes, verifying their consistency over time¹⁵.

Brazilian legislation establishes essential criteria, but no standardized protocol exists in the literature on harvesting musculoskeletal tissues. All steps involving harvesting must be carried out sterilely, and breaking this barrier from removal to tissue packaging can lead to important risks⁹. Possible risks during the process include errors in donor identification and screening, use of expired materials and supplies and inadequate technique, which favor microbiological contamination and tissue disposal¹⁶.

Baseri et al. (2022) conducted a systematic review and meta-analysis of microbial contamination in human bone grafts from tissue banks from 2000 to 2021. In the studies analyzed, a global incidence of 7.5% bacterial contamination was observed in femoral heads harvested from living donors¹⁷. The study highlights the importance of implementing strategies such as process validation, which can identify possible risks inherent to the harvesting protocol.

The World Health Organization (WHO) proposed the development of a safe surgery checklist¹⁸. This initiative aimed to reduce the risk of complications, contribute to regulatory compliance and improve the traceability of information collected during surgical procedures¹⁸. Based on what was proposed by the WHO and by the normative instrument of good practices in human tissues for therapeutic use, the HMTB team created checklists to ensure that all necessary information is entered safely during tissue harvesting. The prior identification of process deviations through checklists allows corrective actions before they impact tissue quality and/or, consequently, patient safety¹⁹.

Internal audit acts as a line of defense against irregularities²⁰. By examining internal controls in HMTBs, the audit can prevent ethical deviations and inappropriate practices, ensure the safety and optimization of workflows, and ensure the quality of biological products of human origin provided²¹.

Finally, process validation is an essential component in managing human tissue banks. This involves confirming that the procedures adopted can produce consistent and safe results¹⁰. Detailed recording of each validation process step is critical to documenting compliance and providing a complete audit roadmap. This meets regulatory requirements and serves as a valuable tool in identifying and correcting potential flaws in procedures²².

CONCLUSION

The reported experience reinforces the importance of developing a rigorous protocol consistent with the methodology and validating the procedure for harvesting musculoskeletal tissue from a living donor. Validation proved to be an indispensable tool for identifying weaknesses, mitigating risks, and ensuring the use of appropriate and reliable instruments for tissue harvesting.

ACKNOWLEDGEMENT

Not applicable.

• FUNDING

  Not applicable.

DATA AVAILABILITY STATEMENT

All dataset were generated or analyzed in the current study.

REFERÊNCIAS

• ¹
  Corsi CAC, Shoji M, Scarpelini KCG, Bento RL, Becari C, Assunção-Luiz AV, et al. Implementation and certification of ISO 9001:2015 seal in human tissue bank HCFMRP-USP. Cell Tissue Bank 2020;21(4):56371. https://doi.org/10.1007/s10561-020-09852-1
  » https://doi.org/10.1007/s10561-020-09852-1
• ²
  Johnston C, Callum J, Mohr J, Duong A, Garibaldi A, Simunovic N, et al. Disinfection of human skin allografts in tissue banking: a systematic review report. Cell Tissue Bank 2016;17(4):585-92. https://doi.org/10.1007/s10561-016-9569-2
  » https://doi.org/10.1007/s10561-016-9569-2
• ³
  Germain M, Strong DM, Dowling G, Mohr J, Duong A, Garibaldi A, et al. Disinfection of human cardiac valve allografts in tissue banking: systematic review report. Cell Tissue Bank 2016;17(4):593-601. https://doi.org/10.1007/s10561-016-9570-9
  » https://doi.org/10.1007/s10561-016-9570-9
• ⁴
  Bagaria V, Tiwari A, Kini A, Gajiwala AL, Bhagunde P, Dave A. It’s the biology orthopods! Heralding a reconstructive revolution through musculoskeletal tissue banks (MSTB) in India. India Journal of Orthopaedics 2022;56(9):1533-46. https://doi.org/10.1007/s43465-022-00661-0
  » https://doi.org/10.1007/s43465-022-00661-0
• ⁵
  BRASIL. Poder Executivo. Decreto Nº 9.175, de 18 de outubro de 2017. Regulamenta a Lei nº 9.434, de 4 de fevereiro de 1997, para tratar da disposição de órgãos, tecidos, células e partes do corpo humano para fins de transplante e tratamento. Brasília (DF): Poder Executivo; 1997.
• ⁶
  BRASIL. Ministério da Saúde. Portaria de Consolidação Nº 4, de 28 de setembro de 2017. Consolidação das normas sobre os sistemas e os subsistemas do Sistema Único de Saúde. Brasília (DF): Ministério da Saúde; 2017.
• ⁷
  BRASIL. Ministério da Saúde. Resolução da Diretoria Colegiada – RDC Nº 707, de 1 de julho de 2022. Dispõe sobre as boas práticas em tecidos humanos para uso terapêutico. Brasília (DF): Ministério da Saúde; 2022.
• ⁸
  Eagle MJ, Man J, Rooney P, McQuillan TA, Galea G, Kearney JN. Assessment of a closed wash system developed for processing living donor femoral heads. Cell Tissue Bank 2017;18(4):547-54. https://doi.org/10.1007/s10561-017-9664-z
  » https://doi.org/10.1007/s10561-017-9664-z
• ⁹
  Corsi CAC, Scarpelini KCG, Bento RL, Assunção-Luiz AV, Garcia FL, Martins LGG. O uso de técnicas para controle de qualidade microbiológico adotadas em um banco de tecidos humanos. Braz J Transplant 2024;27(1):e0924. https://doi.org/10.53855/bjt.v27i1.565_PORT
  » https://doi.org/10.53855/bjt.v27i1.565_PORT
• ¹⁰
  Corsi CAC, Assunção-Luiz AV, Cintra AS, Almeida EC. Models of quality management systems applied in specialized services for the donation and transplantation of human organs and tissues. Transplant Proc 2023;55(6):1337-45. https://doi.org/10.1016/j.transproceed.2023.01.026
  » https://doi.org/10.1016/j.transproceed.2023.01.026
• ¹¹
  Huang J, You JX, Liu HC, Song MS. Failure mode and effect analysis improvement: a systematic literature review and future research agenda. Reliab Eng Syst Saf 2020;199:106885. https://doi.org/10.1016/j.ress.2020.106885
  » https://doi.org/10.1016/j.ress.2020.106885
• ¹²
  Amatuzzi MM, Croci AT, Giovani AM, Santos LAU. Banco de tecidos: estruturação e normatização. Rev bras ortop [periódicos na Internet] 2000;35(5):165-72. [acesso em 01 Abr 2024]. Disponível em: https://www.rbo.org.br/detalhes/328/pt-BR/banco-de-tecidos--estruturacao-e-normatizacao
  » https://www.rbo.org.br/detalhes/328/pt-BR/banco-de-tecidos--estruturacao-e-normatizacao
• ¹³
  Granjeiro RC, Souza BGSE, Antebi U, Honda EK, Guimarães RP, Ono NK, et al. Aspectos da distribuição de tecidos músculo-esqueléticos de um banco de tecidos. Acta ortop bras 2009;17(6):336-9. https://doi.org/10.1590/S1413-78522009000600004
  » https://doi.org/10.1590/S1413-78522009000600004
• ¹⁴
  De Freitas Filho LH, Silva NP, Neves CCS, Campos GC. O impacto da gestão por processos e pessoas na obtenção da licença sanitária de funcionamento [resumo]. Sínteses: Revista Eletrônica do SimTec [periódicos na Internet] 2023 [acesso em 09 Maio 2024];8:e02201008. Disponível em: https://econtents.bc.unicamp.br/inpec/index.php/simtec/article/view/18217
  » https://econtents.bc.unicamp.br/inpec/index.php/simtec/article/view/18217
• ¹⁵
  Teofili L, Bianchi M, Valentini CG, Bartolo M, Orlando N, Sica S. Validation plan of bone marrow collection, processing and distribution using the failure mode and effect analysis methodology: a technical report. Cytotherapy 2022;24(3):356-64. https://doi.org/10.1016/j.jcyt.2021.10.005
  » https://doi.org/10.1016/j.jcyt.2021.10.005
• ¹⁶
  Hovanyecz P, Lorenti A, Lucero JMJ, Gorla A, Castiglioni AE. Living donor bone banking: processing and discarding – From procurement to therapeutic use. Cell Tissue Bank 2015;16(4):593-603. https://doi.org/10.1007/s10561-015-9507-8
  » https://doi.org/10.1007/s10561-015-9507-8
• ¹⁷
  Baseri N, Meysamie A, Campanile F, Hamidieh AA, Jafarian A. Bacterial contamination of bone allografts in the tissue banks: a systematic review and meta-analysis. J Hosp Infect 2022;123:156-73. https://doi.org/10.1016/j.jhin.2021.10.020
  » https://doi.org/10.1016/j.jhin.2021.10.020
• ¹⁸
  Jain D, Sharma R, Reddy S. WHO safe surgery checklist: barriers to universal acceptance. J Anaesthesiol Clin Pharmacol 2018;34(1):7. https://doi.org/10.4103/joacp.JOACP_307_16
  » https://doi.org/10.4103/joacp.JOACP_307_16
• ¹⁹
  Diego LADS, Salman FC, Silva JH, Brandão JC, Filho GDO, Carneiro AF, et al. Construção de uma ferramenta para medida de percepções sobre o uso do checklist do Programa de Cirurgia Segura da Organização Mundial da Saúde. Braz J Anesthesiol 2016;66(4):351-5. https://doi.org/10.1016/j.bjan.2015.09.011
  » https://doi.org/10.1016/j.bjan.2015.09.011
• ²⁰
  Pinheiro MB, Campos RKGG, Maniva SJCF, Rolim KMC, Bonfim IM. Tecnologias disponíveis para o processo de auditoria interna em classificação de risco: revisão integrativa. Revista Brasileira De Pesquisa Em Saúde 2024;25(4):81-8. https://doi.org/10.47456/rbps.v25i4.41760
  » https://doi.org/10.47456/rbps.v25i4.41760
• ²¹
  De Freitas Filho LH, Neves CDCS, Silva NP, Corsi CAC, Cardoso EM, De Miranda JB, et al. Challenges of implementing a human multi-tissue bank in a public hospital in the interior of São Paulo: under the light of the quality management system. Transplant Proc 2024;S0041134524000113. https://doi.org/10.1016/j.transproceed.2024.01.007
  » https://doi.org/10.1016/j.transproceed.2024.01.007
• ²²
  Dos Santos RHA, De Oliveira EPDS, Dinelly KMDO, Cunha ICDO, Dinelly JADS, Oliveira DMDM, et al. Gerenciamento de ferramentas utilizadas em auditorias internas e o aperfeiçoamento dos processos de saúde. Braz J Hea Rev 2023;6(6):30721-32. https://doi.org/10.34119/bjhrv6n6-315
  » https://doi.org/10.34119/bjhrv6n6-315

Edited by

Seccion editor: Ilka de Fátima Santana F. Boin https://orcid.org/0000-0002-1165-2149

Publication Dates

• Publication in this collection
  15 July 2024
• Date of issue
  2024

History

• Received
  05 Apr 2024
• Accepted
  09 May 2024