**4. Quality and risk management in compliance with GMP and with reference to RBV**

As described above, the cells were qualified by the European Medicines Agency as advanced therapy medicinal products (ATMPs), so their production is subject to good manufacturing practice (GMP) [17]. The ATMP implementation is therefore not only technologically complex but also strictly regulated by national and European laws. GMP, although it is the legal basis, is only a part of quality management at tissue banks [18]. By definition, resource-based view contains all the principles of good manufacturing practice. If the quality of the delivered product is defined by us as meeting the requirements and expectations of patients, simple observation of the GMP does not guarantee that these requirements will be met [18]. It seems that only the combination of GMP with the ISO 9001 standard, the RBV approach, and lean management enables a comprehensive approach to management, including quality and risk management. ATMP production is special and requires a rigorous and carefully monitored bioprocess to control the intrinsically complex and variable nature of the substance, especially since some ATMPs can be combined with medical devices, such as biodegradable matrices or scaffolds [19]. It should also be mentioned that material collection from a patient takes place in a hospital that is not a GMP-controlled environment, which additionally contributes to the increased variability of this stage [20] and leaves room for other management techniques, such as RBV and lean. A better understanding of graft production management requires risk analysis, including its identification, assessment, and control. The risk is determined by the likelihood of damage and the consequences of this damage. The risk associated with the quality of the advanced therapy medicinal product/tissue is one of the components of the total risk arising from the production and use of the graft. This indicates the need to extend quality management

**147**

*Resource-Based View of Laboratory Management: Tissue Bank ATMP Production as a Model*

with a resource approach. Product quality must be maintained throughout the entire production cycle and must allow identification and control of potential risks associated with development, production, and transplantation. The quality risk management principles include development, production, distribution, process reviews, and validations. An important element of the quality system resulting from GMP is the process of corrective and preventive actions (CAPA), which refers to deviations, i.e., events departing from the approved procedures or instructions. An example would be a change of the culture incubator during the process or allowing the tissue to be packaged without obtaining the results of quality control analyses. These types of activities are sometimes undertaken to rescue the medicinal product (graft) or to maintain the continuity of cell culture; however, the area of their application ends at the stage of production of the medicinal product. The initial stage in the CAPA process is to clearly define the problem, i.e., register the deviation and provide its short description containing the scope and area of the occurrence of the irregularity and to indicate the leader of the explanatory actions, who will be responsible for carrying out the entire explanatory procedure. At this stage, it must be added that the idea of corrective and preventive action implementation is not to blame anyone but to continuously improve the production process and the quality of grafts. In determining the actual or most probable cause of an adverse event, the following elements should be taken into account: the equipment and materials used, validity, feasibility and comprehensibility of procedures, the design of the entire process (including its bottlenecks), the level employee qualifications, software, and external factors. Any additional resources that may potentially have an impact on the adverse event that has occurred are also identified and documented. After preparing a list of probable causes, the information and data collection must ensue to be used to draw conclusions about the possible cause of the event. Then, the explanatory actions are implemented and the reasons for the deviation are identified. Repair/corrective actions and their implementation are also specified, and all these actions should be described in order to later verify the effectiveness of the steps taken. Then, there is risk communication, which is a process of sharing risk information and risk management methods between decision-makers and other parties. The parties exchange information at each stage of the risk management process. If the explanatory actions do not show the reason for the deviation, a quality risk assessment should be performed. A number of commonly accepted and well-defined methods and processes of risk analysis and quality risk management have been developed. Risk control in turn involves actions that introduce decisions in the area of risk management. The purpose of risk control is to make decisions, which lead to risk reduction to an acceptable level. The contribution of work devoted to risk management should be proportional to the risk weight. Preliminary hazard analysis (PHA) is an analytic tool based on the application of previous experience or knowledge about the threat or failure to identify future threats (Annex 20 GMP). One of the PHA variations is brainstorming, during which the expert group asks "what if" questions to identify the impact of individual elements on the production process and formulate recommendations for the actions to be taken. The quality of the results obtained using this method depends to a large extent on the experience and knowledge of the participants [20]. The hazard and operability studies (HAZOP) method of analysis was developed in the 1960s. Like the PHA, it is a systematic method; however, it requires more detailed information. The HAZOP method uses a predefined set of guiding words to

describe the parameters, which leads to the creation of a pair of words that is referenced to a point in the process that can potentially fail. As a result of using this method, a table is created that includes situations, which can cause a failure, together with its consequences and specific causes. However, this is a

*DOI: http://dx.doi.org/10.5772/intechopen.86561*

#### *Resource-Based View of Laboratory Management: Tissue Bank ATMP Production as a Model DOI: http://dx.doi.org/10.5772/intechopen.86561*

with a resource approach. Product quality must be maintained throughout the entire production cycle and must allow identification and control of potential risks associated with development, production, and transplantation. The quality risk management principles include development, production, distribution, process reviews, and validations. An important element of the quality system resulting from GMP is the process of corrective and preventive actions (CAPA), which refers to deviations, i.e., events departing from the approved procedures or instructions. An example would be a change of the culture incubator during the process or allowing the tissue to be packaged without obtaining the results of quality control analyses. These types of activities are sometimes undertaken to rescue the medicinal product (graft) or to maintain the continuity of cell culture; however, the area of their application ends at the stage of production of the medicinal product. The initial stage in the CAPA process is to clearly define the problem, i.e., register the deviation and provide its short description containing the scope and area of the occurrence of the irregularity and to indicate the leader of the explanatory actions, who will be responsible for carrying out the entire explanatory procedure. At this stage, it must be added that the idea of corrective and preventive action implementation is not to blame anyone but to continuously improve the production process and the quality of grafts. In determining the actual or most probable cause of an adverse event, the following elements should be taken into account: the equipment and materials used, validity, feasibility and comprehensibility of procedures, the design of the entire process (including its bottlenecks), the level employee qualifications, software, and external factors. Any additional resources that may potentially have an impact on the adverse event that has occurred are also identified and documented. After preparing a list of probable causes, the information and data collection must ensue to be used to draw conclusions about the possible cause of the event. Then, the explanatory actions are implemented and the reasons for the deviation are identified. Repair/corrective actions and their implementation are also specified, and all these actions should be described in order to later verify the effectiveness of the steps taken. Then, there is risk communication, which is a process of sharing risk information and risk management methods between decision-makers and other parties. The parties exchange information at each stage of the risk management process. If the explanatory actions do not show the reason for the deviation, a quality risk assessment should be performed. A number of commonly accepted and well-defined methods and processes of risk analysis and quality risk management have been developed. Risk control in turn involves actions that introduce decisions in the area of risk management. The purpose of risk control is to make decisions, which lead to risk reduction to an acceptable level. The contribution of work devoted to risk management should be proportional to the risk weight. Preliminary hazard analysis (PHA) is an analytic tool based on the application of previous experience or knowledge about the threat or failure to identify future threats (Annex 20 GMP). One of the PHA variations is brainstorming, during which the expert group asks "what if" questions to identify the impact of individual elements on the production process and formulate recommendations for the actions to be taken. The quality of the results obtained using this method depends to a large extent on the experience and knowledge of the participants [20]. The hazard and operability studies (HAZOP) method of analysis was developed in the 1960s. Like the PHA, it is a systematic method; however, it requires more detailed information. The HAZOP method uses a predefined set of guiding words to describe the parameters, which leads to the creation of a pair of words that is referenced to a point in the process that can potentially fail. As a result of using this method, a table is created that includes situations, which can cause a failure, together with its consequences and specific causes. However, this is a

*Biochemical Testing - Clinical correlation and Diagnosis*

• Explanatory proceedings regarding deviations and nonconformities

• Internal audits regarding the quality and observing the good manufacturing

The producers must provide clear and understandable operating instructions for the main production and control equipment. They must keep logs of the master and critical control equipment, production equipment, and areas in which production processes take place. There must be records regarding each area, device, method, calibration, maintenance, cleaning, or repair introduced in chronological order, dated and signed by the personnel performing these activities. A list of quality

**4. Quality and risk management in compliance with GMP and with** 

As described above, the cells were qualified by the European Medicines Agency as advanced therapy medicinal products (ATMPs), so their production is subject to good manufacturing practice (GMP) [17]. The ATMP implementation is therefore not only technologically complex but also strictly regulated by national and European laws. GMP, although it is the legal basis, is only a part of quality management at tissue banks [18]. By definition, resource-based view contains all the principles of good manufacturing practice. If the quality of the delivered product is defined by us as meeting the requirements and expectations of patients, simple observation of the GMP does not guarantee that these requirements will be met [18]. It seems that only the combination of GMP with the ISO 9001 standard, the RBV approach, and lean management enables a comprehensive approach to management, including quality and risk management. ATMP production is special and requires a rigorous and carefully monitored bioprocess to control the intrinsically complex and variable nature of the substance, especially since some ATMPs can be combined with medical devices, such as biodegradable matrices or scaffolds [19]. It should also be mentioned that material collection from a patient takes place in a hospital that is not a GMP-controlled environment, which additionally contributes to the increased variability of this stage [20] and leaves room for other management techniques, such as RBV and lean. A better understanding of graft production management requires risk analysis, including its identification, assessment, and control. The risk is determined by the likelihood of damage and the consequences of this damage. The risk associated with the quality of the advanced therapy medicinal product/tissue is one of the components of the total risk arising from the production and use of the graft. This indicates the need to extend quality management

• Withdrawal from the market

• Complaints

• Returns

practice

• Record summaries

• Audits at suppliers

**reference to RBV**

management system documents should be kept.

• Change control

**146**

time-consuming and labor-intensive method and as such it generates considerable costs [20]. The process map is a technique based on a graphical representation of the functioning of a set of processes and their mutual relationships. The fault tree analysis (FTA) has been developed for the aviation industry and is a deductive method that assumes the occurrence of a defect in process functionality and can link multiple causes to identify the cause-and-effect chain. Failure mode and effects analysis (FMEA) is mainly focused on the optimization of the product and is particularly recommended in the situation of new product introduction because it allows for the recognition of the potential interfering factors. As a result of this quantitative method, we obtain the so-called risk priority number (RPN) and information about strong and weak points of production. The criticality of the defect is calculated, and the higher the calculated parameter, the greater the risk associated with the defect. After identifying the risks and weaknesses of the process and their characterization, decisions should be made on which risks should be reduced and which should be observed or eliminated. Controlling risks is a technological and economic challenge. Before making any changes, an assessment must be performed to ensure that the proposed change will not cause any new or unexpected risks. The fact that a change is inevitable makes it a critical factor, especially in GMP and ISO environments, where inappropriate or "uncontrolled" changes can affect patient safety and public health. For this reason, the concept of change control is closely related to compliance with GMP and ISO, where any changes in production and processes must be controlled. Change control procedures must be recorded in order to standardize the workflow, especially at key stages such as collecting material outside the production environment. The "uncontrolled" change refers to modifications made without verification and approval by the quality control manager and in special cases also the hospital management. In GMP and ISO environments, strict adherence to approved policies and procedures is a key factor in maintaining production efficiency in a controlled state, and change control is critical. Changes are subject to review and approval by the quality control unit. To summarize, GMP is a formalized procedure and imposes a heavy burden on the producer of transplants, and while compliance is a required minimum, it is not enough to ensure the right quality of using the manufactured products [18]. The specificity of risk management in the aspect of GMP consists in focusing on potential failures in the production of transplants and their safety for the patient. RBV refers to a broader management area including risk management at the time of collecting cellular material and its transplantation as well as the patient's fate. However, some authors point to limitations in the application of resource management in the public health service [8] due to the complex nature of such entities. Lean management possesses tools that are able to systematize it [21].

### **5. Production management**

The tissue bank is the place for graft preparation for the treatment of patients with severe burns and chronic wounds. As already mentioned, the preparations produced in our bank are biostatic grafts, which are subject to radiation sterilization and live cell transplants, produced under sterile conditions. Due to the specificity of the products manufactured in the laboratories, appropriate, supervised environmental conditions must be ensured. For this purpose, we use "clean rooms," in which, thanks to the use of special HEPA filters and laminar air vents, it is possible to obtain the appropriate class of air purity. The highest class achieved in our bank is air purity class A achieved under the laminar chamber, where the amount of particles and microorganisms generated during operation should be zero. In order

**149**

risk of culture loss.

*Resource-Based View of Laboratory Management: Tissue Bank ATMP Production as a Model*

to provide such sterile and dust-free conditions in air purity class A, the rooms located on the way to a class A clean room must meet a series of criteria. The main one is the maintenance of a pressure cascade, which means that in order to get to a class A clean room, you have to go through several airlocks separating neighboring rooms of the following purity class: gray (of the least air purity) D, C, and B. Positive pressure is maintained in each airlock in relation to the previous lock, employees wear dust-free and sterile clothes and gloves, and, finally, in the class B air purity room, they put on a sterile dust-free clean room suit covering their entire body. All these precautions are necessary because we want to protect the product we manufacture, i.e., the advanced therapy medicinal product in the form of cultured skin cells. The cultures that we prepare are supervised by the Main Pharmaceutical Inspector; therefore, as mentioned above, they must be prepared in accordance with good manufacturing practice (GMP). The requirements that we must meet in order to culture cells for a burn patient make all the preparations leading to the process initiation strategic. It should be noted that employees and resources (reagents and consumables) in the laboratory are in a constant state of readiness. At the same time, we are not able to estimate with 100% certainty whether, at a given time, we are going to culture cells at all and, if so, for how many patients. The unpredictability of the production process (cell culture) in the face of the risk of expiry of reagents necessary for maintaining production continuity means that a compromise must be found consisting in the continuous maintenance of small-scale stock of culture materials. The greater part of consumables used in the preparation of medicinal products is highly specialized and is not widely available, and the delivery of a larger quantity often takes a long time. Therefore, ensuring constant availability of materials seems to be one of the solutions enabling continuity of production. However, lean management requires keeping losses to a minimum, which is, in a way, contrary to the GMP assumptions making production halt risk minimization a priority. A common-sense approach should therefore be applied translating into ensuring the minimum amount of reagents that is sufficient to maintain the continuity of production, even in the case of mass events, such as an explosion in a coal mine, when mass production of cellular grafts must be available immediately. In the case of maintaining sterile environmental conditions, it is also important

to systematically and periodically perform cleaning and disinfection of rooms according to the adopted schedule. It is also necessary to permanently perform environmental monitoring: continuous monitoring of the amount of particles in class B rooms, as well as microbiological tests of air and clean room surfaces, carried out according to schedule. Control and supervision are also applied to devices used for cell culture and the conditions prevailing in them, e.g., the devices that are critical in the production process—incubators. A monitoring system is installed in the rooms. It monitors the environment and notifies employees supervising cell cultures about the occurrence of errors in the culture process. Such monitoring is necessary because it allows for quick response and taking action in the event of a

Highly specialized persons who have acquired appropriate skills in numerous training sessions are assigned to work in the clean rooms. Their professional experience and the ability to organize and manage their working time are also important. Due to the specifics of the work—a sterile, monitored and supervised environment in a clean room—each entrance to such rooms generates additional costs. That is why, employees working with cell cultures must carefully consider, plan, and organize all elements of their work in the laboratory before it begins. Employees involved in the preparation of cell cultures follow the applicable, written procedures and validated processes. Most processes should be validated based on reference reagents; however, the tissue material from which the cells are isolated

*DOI: http://dx.doi.org/10.5772/intechopen.86561*

#### *Resource-Based View of Laboratory Management: Tissue Bank ATMP Production as a Model DOI: http://dx.doi.org/10.5772/intechopen.86561*

to provide such sterile and dust-free conditions in air purity class A, the rooms located on the way to a class A clean room must meet a series of criteria. The main one is the maintenance of a pressure cascade, which means that in order to get to a class A clean room, you have to go through several airlocks separating neighboring rooms of the following purity class: gray (of the least air purity) D, C, and B. Positive pressure is maintained in each airlock in relation to the previous lock, employees wear dust-free and sterile clothes and gloves, and, finally, in the class B air purity room, they put on a sterile dust-free clean room suit covering their entire body. All these precautions are necessary because we want to protect the product we manufacture, i.e., the advanced therapy medicinal product in the form of cultured skin cells. The cultures that we prepare are supervised by the Main Pharmaceutical Inspector; therefore, as mentioned above, they must be prepared in accordance with good manufacturing practice (GMP). The requirements that we must meet in order to culture cells for a burn patient make all the preparations leading to the process initiation strategic. It should be noted that employees and resources (reagents and consumables) in the laboratory are in a constant state of readiness. At the same time, we are not able to estimate with 100% certainty whether, at a given time, we are going to culture cells at all and, if so, for how many patients. The unpredictability of the production process (cell culture) in the face of the risk of expiry of reagents necessary for maintaining production continuity means that a compromise must be found consisting in the continuous maintenance of small-scale stock of culture materials. The greater part of consumables used in the preparation of medicinal products is highly specialized and is not widely available, and the delivery of a larger quantity often takes a long time. Therefore, ensuring constant availability of materials seems to be one of the solutions enabling continuity of production. However, lean management requires keeping losses to a minimum, which is, in a way, contrary to the GMP assumptions making production halt risk minimization a priority. A common-sense approach should therefore be applied translating into ensuring the minimum amount of reagents that is sufficient to maintain the continuity of production, even in the case of mass events, such as an explosion in a coal mine, when mass production of cellular grafts must be available immediately.

In the case of maintaining sterile environmental conditions, it is also important to systematically and periodically perform cleaning and disinfection of rooms according to the adopted schedule. It is also necessary to permanently perform environmental monitoring: continuous monitoring of the amount of particles in class B rooms, as well as microbiological tests of air and clean room surfaces, carried out according to schedule. Control and supervision are also applied to devices used for cell culture and the conditions prevailing in them, e.g., the devices that are critical in the production process—incubators. A monitoring system is installed in the rooms. It monitors the environment and notifies employees supervising cell cultures about the occurrence of errors in the culture process. Such monitoring is necessary because it allows for quick response and taking action in the event of a risk of culture loss.

Highly specialized persons who have acquired appropriate skills in numerous training sessions are assigned to work in the clean rooms. Their professional experience and the ability to organize and manage their working time are also important. Due to the specifics of the work—a sterile, monitored and supervised environment in a clean room—each entrance to such rooms generates additional costs. That is why, employees working with cell cultures must carefully consider, plan, and organize all elements of their work in the laboratory before it begins. Employees involved in the preparation of cell cultures follow the applicable, written procedures and validated processes. Most processes should be validated based on reference reagents; however, the tissue material from which the cells are isolated

*Biochemical Testing - Clinical correlation and Diagnosis*

time-consuming and labor-intensive method and as such it generates considerable costs [20]. The process map is a technique based on a graphical representation of the functioning of a set of processes and their mutual relationships. The fault tree analysis (FTA) has been developed for the aviation industry and is a deductive method that assumes the occurrence of a defect in process functionality and can link multiple causes to identify the cause-and-effect chain. Failure mode and effects analysis (FMEA) is mainly focused on the optimization of the product and is particularly recommended in the situation of new product introduction because it allows for the recognition of the potential interfering factors. As a result of this quantitative method, we obtain the so-called risk priority number (RPN) and information about strong and weak points of production. The criticality of the defect is calculated, and the higher the calculated parameter, the greater the risk associated with the defect. After identifying the risks and weaknesses of the process and their characterization, decisions should be made on which risks should be reduced and which should be observed or eliminated. Controlling risks is a technological and economic challenge. Before making any changes, an assessment must be performed to ensure that the proposed change will not cause any new or unexpected risks. The fact that a change is inevitable makes it a critical factor, especially in GMP and ISO environments, where inappropriate or "uncontrolled" changes can affect patient safety and public health. For this reason, the concept of change control is closely related to compliance with GMP and ISO, where any changes in production and processes must be controlled. Change control procedures must be recorded in order to standardize the workflow, especially at key stages such as collecting material outside the production environment. The "uncontrolled" change refers to modifications made without verification and approval by the quality control manager and in special cases also the hospital management. In GMP and ISO environments, strict adherence to approved policies and procedures is a key factor in maintaining production efficiency in a controlled state, and change control is critical. Changes are subject to review and approval by the quality control unit. To summarize, GMP is a formalized procedure and imposes a heavy burden on the producer of transplants, and while compliance is a required minimum, it is not enough to ensure the right quality of using the manufactured products [18]. The specificity of risk management in the aspect of GMP consists in focusing on potential failures in the production of transplants and their safety for the patient. RBV refers to a broader management area including risk management at the time of collecting cellular material and its transplantation as well as the patient's fate. However, some authors point to limitations in the application of resource management in the public health service [8] due to the complex nature of such entities.

Lean management possesses tools that are able to systematize it [21].

The tissue bank is the place for graft preparation for the treatment of patients with severe burns and chronic wounds. As already mentioned, the preparations produced in our bank are biostatic grafts, which are subject to radiation sterilization and live cell transplants, produced under sterile conditions. Due to the specificity of the products manufactured in the laboratories, appropriate, supervised environmental conditions must be ensured. For this purpose, we use "clean rooms," in which, thanks to the use of special HEPA filters and laminar air vents, it is possible to obtain the appropriate class of air purity. The highest class achieved in our bank is air purity class A achieved under the laminar chamber, where the amount of particles and microorganisms generated during operation should be zero. In order

**5. Production management**

**148**

and the culture is established is so unique that it is not possible to replace it with the reference material. Therefore, all employees must comply with specific requirements. In standard work, it is important not only to maintain the purity and sterility of the cell culture and the rooms but also to ensure that all necessary reagents and materials are available in the laboratory. The duty of employees leaving the laboratory is to supplement, prepare, or provide information on missing items to all persons involved in the cell culture process. Each employee entering the laboratory studio must be sure that he or she will be able to perform all the tasks without any problems. Due to the need to monitor and maintain room sterility, any unnecessary entering and exiting the clean room creates a risk of pollution and generates costs of, among other things, used protective clothing and cleaning agents. All these activities are aimed at ensuring the sterility of the advanced therapy medicinal product manufactured in the tissue bank. **Figure 2** shows the increase in the number of cultures and autologous skin cell transplantations. This increase has been possible thanks to the standardization of production processes that has been achieved by minimizing material losses. The lean and TOC management methods contributed to the increase in the number of cultures, which made better management of laboratory resources possible.

As mentioned above, cell cultures can be established after the occurrence of a mass event, e.g., an explosion in a coal mine or a large fire, in which more people suffer burns. In such a situation, our only safeguard that makes it possible to take appropriate action is to keep reagents and consumables in the laboratory. In such cases, the experience of employees and cooperation with other hospital departments are very important. This allows for the planning of a strategic approach to the problem, which goes beyond the GMP management area, and still requires management and control. Establishing a cell culture is conditioned not only by securing the necessary reagents and materials but also by providing care for the most disadvantaged patients, which results from the efficient operation of the hospital, reinforced by the management system. In such cases, it is also important to adopt the right approach and plan the work of all personnel to avoid unwanted cross-infection or contamination, which could result in the loss of valuable cell culture. The resourcebased view (RBV) approach seems to be necessary to manage the aspects that are not covered by the GMP procedures.

The preparation of biostatic skin and human amnion grafts is much less restrictive. These are grafts, in which the final stage of preparation is radiation

**151**

added value.

**Figure 3.**

*Resource-Based View of Laboratory Management: Tissue Bank ATMP Production as a Model*

sterilization. This means that these transplants are not live and constitute only a temporary dressing. Due to the fact of sterilization, the grafts are also prepared in clean rooms, under the laminar chamber of class A air purity, but in the class C environment. When preparing tissue transplants, employees also use their experience in managing their working time, maintaining cleanliness and order in the laboratory and good manufacturing practice. These skills are very useful and promote continuous improvement of the produced grafts and production efficiency. The chart in **Figure 3** shows the increase in the surface area of biostatic amniotic and dermal grafts prepared in particular years. The use of a resource management approach, among others, has enabled the increase in productivity,

grafts. The increasing number of donors, and hence the amount of documentation to complete, makes it necessary to adopt a strategic approach to the work so that as much work as possible can be performed at the same time, thus generating

**6. Strategic potential of a tissue bank in terms of validation of processes** 

Tissue bank management requires well-established, thorough knowledge of the processes occurring in the area of clean room production. In this respect, the key issue for a tissue bank, as mentioned above, is to have adequately qualified personnel and therefore human resources possessing the required education, experience, competences, and abilities. The second important element in the process of managing a tissue bank is the possession of appropriate devices and rooms, i.e., the hardware and accommodation resources. User requirements for hardware and accommodation resources should be characterized and defined in detail. These elements, in the RBV approach, can be collectively referred to as strategic potential. In general terms, the strategic potential is a factor influencing the tissue bank's achievement of the expected results. The key effects include the ability to use resources to achieve the intended targets and, therefore, obtain the highest quality product according to the tested, repeatable, and effective production methodology

) of the prepared tissue and cellular

*DOI: http://dx.doi.org/10.5772/intechopen.86561*

which translates into the surface area (cm<sup>2</sup>

**and qualification of equipment and rooms**

*The surface area of prepared skin and amniotic grafts in years 2009–2018.*

using adequately verified equipment and rooms.

**Figure 2.** *Number of cultured and transplanted autologous skin cell cultures in years 2008–2018.*

*Resource-Based View of Laboratory Management: Tissue Bank ATMP Production as a Model DOI: http://dx.doi.org/10.5772/intechopen.86561*

#### **Figure 3.**

*Biochemical Testing - Clinical correlation and Diagnosis*

ment of laboratory resources possible.

not covered by the GMP procedures.

and the culture is established is so unique that it is not possible to replace it with the reference material. Therefore, all employees must comply with specific requirements. In standard work, it is important not only to maintain the purity and sterility of the cell culture and the rooms but also to ensure that all necessary reagents and materials are available in the laboratory. The duty of employees leaving the laboratory is to supplement, prepare, or provide information on missing items to all persons involved in the cell culture process. Each employee entering the laboratory studio must be sure that he or she will be able to perform all the tasks without any problems. Due to the need to monitor and maintain room sterility, any unnecessary entering and exiting the clean room creates a risk of pollution and generates costs of, among other things, used protective clothing and cleaning agents. All these activities are aimed at ensuring the sterility of the advanced therapy medicinal product manufactured in the tissue bank. **Figure 2** shows the increase in the number of cultures and autologous skin cell transplantations. This increase has been possible thanks to the standardization of production processes that has been achieved by minimizing material losses. The lean and TOC management methods contributed to the increase in the number of cultures, which made better manage-

As mentioned above, cell cultures can be established after the occurrence of a mass event, e.g., an explosion in a coal mine or a large fire, in which more people suffer burns. In such a situation, our only safeguard that makes it possible to take appropriate action is to keep reagents and consumables in the laboratory. In such cases, the experience of employees and cooperation with other hospital departments are very important. This allows for the planning of a strategic approach to the problem, which goes beyond the GMP management area, and still requires management and control. Establishing a cell culture is conditioned not only by securing the necessary reagents and materials but also by providing care for the most disadvantaged patients, which results from the efficient operation of the hospital, reinforced by the management system. In such cases, it is also important to adopt the right approach and plan the work of all personnel to avoid unwanted cross-infection or contamination, which could result in the loss of valuable cell culture. The resourcebased view (RBV) approach seems to be necessary to manage the aspects that are

The preparation of biostatic skin and human amnion grafts is much less restrictive. These are grafts, in which the final stage of preparation is radiation

*Number of cultured and transplanted autologous skin cell cultures in years 2008–2018.*

**150**

**Figure 2.**

*The surface area of prepared skin and amniotic grafts in years 2009–2018.*

sterilization. This means that these transplants are not live and constitute only a temporary dressing. Due to the fact of sterilization, the grafts are also prepared in clean rooms, under the laminar chamber of class A air purity, but in the class C environment. When preparing tissue transplants, employees also use their experience in managing their working time, maintaining cleanliness and order in the laboratory and good manufacturing practice. These skills are very useful and promote continuous improvement of the produced grafts and production efficiency. The chart in **Figure 3** shows the increase in the surface area of biostatic amniotic and dermal grafts prepared in particular years. The use of a resource management approach, among others, has enabled the increase in productivity, which translates into the surface area (cm<sup>2</sup> ) of the prepared tissue and cellular grafts. The increasing number of donors, and hence the amount of documentation to complete, makes it necessary to adopt a strategic approach to the work so that as much work as possible can be performed at the same time, thus generating added value.
