**6. Strategic potential of a tissue bank in terms of validation of processes and qualification of equipment and rooms**

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 using adequately verified equipment and rooms.

The expected effects are, therefore, the result of the tissue bank's implementation of adequately planned tasks. These tasks are directly related to the achievement of the intended objective. In this respect, the achieved production effects are the socalled determinants of a tissue bank success. We use this expression to appropriately define the ranges and criteria of acceptance that a given tissue bank product must meet before a batch is released to distribution. These criteria must be strictly defined in the production specification. Moreover, in addition to the so-called determinants of success, so-called success factors must also be defined. These factors result from adequately defined and purposefully adopted strategic potentials of the tissue bank. The strategic potentials include in particular the professional experience of human resources. Based on specific experience and "know-how," appropriate operational procedures should be created for all activities performed in the tissue bank. However, the final adoption of all the proposed solutions (e.g., methodological, analytical, and technological) requires evaluation that is very carefully planned and analyzed in terms of the correctness of the adopted assumptions. This means that each parameter that constitutes a specific stage or the whole of a given process must be subject to control in terms of meeting the expected assumptions. In case of changes in the specified parameter or parameters, a whole evaluation of the process must be repeated.

Procedures related to the evaluation of processes executed in the tissue bank are called validation procedures. In this respect, special consideration should be given to the validation of the manufacturing process of the hospital-exemption advanced therapy medicinal product (HE-ATMP), the process of manufacturing medical devices, tissue transplants, transport of these products, cleaning, and disinfection, including employee clothing. However, by contrast, the evaluation procedures related to the correct functioning of devices and rooms are called qualification procedures. In this respect, it should be clearly emphasized that the qualification of devices and rooms covers the entirety of undertakings related to the purchase, installation, and operation of a given device or room, starting from specifying the user's specific requirements to determining the conformity of the proposed preliminary design with the requirements, to subsequent processes confirming the compliance regarding the installation and proper functioning.

#### **6.1 Main validation plan**

The main validation plan (MVP) defines the approach to the qualification/validation of GMP areas for all validation activities carried out in the existing or newly designed premises of a tissue bank. It is aimed at ensuring that the expectations have been clearly communicated to all participants implementing the validation program. The MVP clearly and comprehensively defines the requirements and scope of responsibility in the validation process. The main objectives and tasks of the MVP are as follows:


**153**

devices.

protocols and test cards.

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

of particular systems, installations, and process equipment

6.Presentation of the approach to change control

and assessment of the deviation must be documented.

7.Drawing up a plan and scheduling validation activities

5.Outlining the validation strategy and indicating the documents defining the task and scope of responsibility for the tissue bank, contractors and suppliers

8.Ensuring consistent application of the terms in accordance with their established definitions (in documents such as the standard operating procedures

The MPV contains general guidelines for the preparation of other validation documents. Rational principles and a rational approach when using the MPV are recommended. In the event of circumstances unforeseen in the plan, the rationale

Validation/qualification activities will be carried out depending on the subject of validation/qualification and on the nature of the activities performed by the validation team appointed by the qualified/competent/responsible person to perform specific tasks. The validation team may consist of representatives of quality assurance, tissue bank user/manager, technical and technological experts, and quality control. This approach to validation and carrying out validation work fulfills the regulations and guidelines specified in the European Commission Directive 2003/94/ EC and the Regulation of the Minister of Health of October 1, 2008, on the requirements of good manufacturing practice (Journal of Laws 2008.184.1143) as amended. Validation is an action aimed at confirming, in a documented manner and in accordance with the principles of RBV and good manufacturing practice, those procedures, processes, devices, materials, activities, systems, and installations truly lead to planned results. This is achieved through the development of test plans, protocols, and procedures, as well as the implementation of the records made in the protocols and the documentation of the results obtained in the intermediate and final reports. The report is an approved written plan of the measurement, control, and methodology of testing and result documentation. The verification and validation of the qualification and validation documentation are performed in accordance with the internal procedure prior to the initiation of the qualification/validation activities. In any case, the validation activities performed by external companies must be supervised by an appropriate employee of the tissue bank and are subject to acceptance and approval by tissue bank employees. The same persons and the persons performing the tests (other than those included in the validation team) also check and approve the reports from a given qualification/validation phase following the tests, in order to confirm that the production environment, devices, and the process are indeed suitable for the production of HE-ATMP, medical devices, tissue grafts, etc., in the tissue bank and that they meet the requirements of good manufacturing practice. The full set of qualification and validation documents consists of

The installation qualification (IQ ) protocols pertaining to the equipment, installations, and clean rooms, similar to the operational qualification (OQ ) protocols of these systems, are developed for all critical modules of systems, installations, and

The process qualification (PQ ) protocols are developed only for those systems, installations, or devices for which their operation data are necessary to verify the correctness of the process and for which long-term monitoring of their performance is recommended (e.g., laminar chamber, CO2 incubator, bioreactor, and

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

(SOPs), validation protocols, etc.)


*Biochemical Testing - Clinical correlation and Diagnosis*

The expected effects are, therefore, the result of the tissue bank's implementation of adequately planned tasks. These tasks are directly related to the achievement of the intended objective. In this respect, the achieved production effects are the socalled determinants of a tissue bank success. We use this expression to appropriately define the ranges and criteria of acceptance that a given tissue bank product must meet before a batch is released to distribution. These criteria must be strictly defined in the production specification. Moreover, in addition to the so-called determinants of success, so-called success factors must also be defined. These factors result from adequately defined and purposefully adopted strategic potentials of the tissue bank. The strategic potentials include in particular the professional experience of human resources. Based on specific experience and "know-how," appropriate operational procedures should be created for all activities performed in the tissue bank. However, the final adoption of all the proposed solutions (e.g., methodological, analytical, and technological) requires evaluation that is very carefully planned and analyzed in terms of the correctness of the adopted assumptions. This means that each parameter that constitutes a specific stage or the whole of a given process must be subject to control in terms of meeting the expected assumptions. In case of changes in the specified

parameter or parameters, a whole evaluation of the process must be repeated.

ance regarding the installation and proper functioning.

**6.1 Main validation plan**

protocols and reports

Procedures related to the evaluation of processes executed in the tissue bank are called validation procedures. In this respect, special consideration should be given to the validation of the manufacturing process of the hospital-exemption advanced therapy medicinal product (HE-ATMP), the process of manufacturing medical devices, tissue transplants, transport of these products, cleaning, and disinfection, including employee clothing. However, by contrast, the evaluation procedures related to the correct functioning of devices and rooms are called qualification procedures. In this respect, it should be clearly emphasized that the qualification of devices and rooms covers the entirety of undertakings related to the purchase, installation, and operation of a given device or room, starting from specifying the user's specific requirements to determining the conformity of the proposed preliminary design with the requirements, to subsequent processes confirming the compli-

The main validation plan (MVP) defines the approach to the qualification/valida-

1.Presentation of policy, requirements, and expectations regarding the validation activities in laboratory rooms where the tasks related to the production of advanced therapy medicinal products, HE-ATMP, analysis and quality control,

3.A brief description of the installations, systems, and devices that will be

4.Specification of the format of the validation documentation used in the

tion of GMP areas for all validation activities carried out in the existing or newly designed premises of a tissue bank. It is aimed at ensuring that the expectations have been clearly communicated to all participants implementing the validation program. The MVP clearly and comprehensively defines the requirements and scope of responsibility in the validation process. The main objectives and tasks of the MVP are as follows:

as well as research and development work are performed

2.Defining the organizational structure of validation activities

validated with reference to the existing documents

**152**


The MPV contains general guidelines for the preparation of other validation documents. Rational principles and a rational approach when using the MPV are recommended. In the event of circumstances unforeseen in the plan, the rationale and assessment of the deviation must be documented.

Validation/qualification activities will be carried out depending on the subject of validation/qualification and on the nature of the activities performed by the validation team appointed by the qualified/competent/responsible person to perform specific tasks. The validation team may consist of representatives of quality assurance, tissue bank user/manager, technical and technological experts, and quality control.

This approach to validation and carrying out validation work fulfills the regulations and guidelines specified in the European Commission Directive 2003/94/ EC and the Regulation of the Minister of Health of October 1, 2008, on the requirements of good manufacturing practice (Journal of Laws 2008.184.1143) as amended. Validation is an action aimed at confirming, in a documented manner and in accordance with the principles of RBV and good manufacturing practice, those procedures, processes, devices, materials, activities, systems, and installations truly lead to planned results. This is achieved through the development of test plans, protocols, and procedures, as well as the implementation of the records made in the protocols and the documentation of the results obtained in the intermediate and final reports. The report is an approved written plan of the measurement, control, and methodology of testing and result documentation. The verification and validation of the qualification and validation documentation are performed in accordance with the internal procedure prior to the initiation of the qualification/validation activities. In any case, the validation activities performed by external companies must be supervised by an appropriate employee of the tissue bank and are subject to acceptance and approval by tissue bank employees. The same persons and the persons performing the tests (other than those included in the validation team) also check and approve the reports from a given qualification/validation phase following the tests, in order to confirm that the production environment, devices, and the process are indeed suitable for the production of HE-ATMP, medical devices, tissue grafts, etc., in the tissue bank and that they meet the requirements of good manufacturing practice. The full set of qualification and validation documents consists of protocols and test cards.

The installation qualification (IQ ) protocols pertaining to the equipment, installations, and clean rooms, similar to the operational qualification (OQ ) protocols of these systems, are developed for all critical modules of systems, installations, and devices.

The process qualification (PQ ) protocols are developed only for those systems, installations, or devices for which their operation data are necessary to verify the correctness of the process and for which long-term monitoring of their performance is recommended (e.g., laminar chamber, CO2 incubator, bioreactor, and

refrigerator-freezer). Systems, installations, or devices for which PQ activities are necessary will be selected at the risk analysis (RA) stage. Any noncompliance with the conditions set out in the protocols encountered during the validation process will be recorded and evaluated. The registered nonconformities will be analyzed, and then the actions regarding the manner of further dealing with the nonconformities (e.g., the development of justification/explanation, making corrections, and then carrying out reclassification tests) will be defined. All such data will be documented and saved. The obtained results will be collected and presented in relevant reports after the completion of each qualification stage.

#### **6.2 Approach to validation**

Validation of rooms, devices, systems, and installations used in production carried out in the tissue bank constitutes a part of the quality assurance policy of the entire enterprise (tissue bank, hospital, and biotechnological or pharmaceutical company). Qualification/validation activities and the creation of appropriate documentation must be carried out in accordance with the qualification/validation schedule by tissue bank representatives, suppliers of installations, systems, process equipment, and/or contractors providing validation services. Supervision and coordination of qualification/validation activities should be carried out by a tissue bank representative. Validation teams and validation contractors are required to develop a series of protocols to check all critical parameters of rooms, systems, installations, and devices in the tissue bank. The protocols will be implemented in accordance with the test methods presented in the protocols. Each protocol will be used to obtain documentation that will confirm the compliance of the system, installation, or device with the GMP guidelines. To qualify equipment, rooms, and installations, the documents obtained after carrying out the service activities can be used. All protocols and reports will be archived after their final approval.

It should be emphasized that conducting validation cannot negatively affect the production process. In addition, special attention should be paid to the timely performance of validation work, and subsequent planned validation activities related to a given device, room, etc., should be carried out within the prescribed time limit. However, it is possible that the deadline of the next validation is not met. This disadvantageous situation may occur due to a number of possible occurrences that may affect the feasibility of performing validation work. The factors affecting the performed validation work time shift include, among others, production, sickness of the person performing the validation, mechanical failure, etc. The information about the validation time shift must be included in the validation protocol.

In order to summarize and approve the completion of individual stages of qualification/validation activities, appropriate reports are prepared, which are checked and approved by appropriate persons. The report must include a summary of the qualification/validation course, a description of test results, and documented, explained, and evaluated nonconformities. After the approval of the report, if no critical nonconformities were found or all critical nonconformities were resolved, you are allowed to proceed to the next qualification/validation phase.

#### **6.3 Summary**

The activities related to the performance of validation/qualification activities are aimed at ensuring the highest quality of the tissue bank products being developed. They take place in accordance with RBV and with the optimal use of the strategic potential of the laboratory. The approach to validation is part of the broadly understood RBV, which results from the conscious management of the unit using

**155**

**Author details**

Wojciech Smętek1

Małgorzata Kraut1

\*, Jacek Węgrzyk1

, Michał Szapski1

\*Address all correspondence to: fundusze@clo.com.pl

provided the original work is properly cited.

2 Silesian Higher Medical School in Katowice, Katowice, Poland

, Agnieszka Klama-Baryła1,2, Wojciech Łabuś1

and Diana Kitala1,2

, Mariusz Nowak1

1 Stanislaw Sakiel's Center for Burn Treatment, Siemianowice Śląskie, Poland

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

,

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

knowledge and science. The validation and qualification activities are necessary to verify the adopted methods and the continuous improvement of processes. This, in turn, fits into modern management systems using the PDCA or DMAIC approach, based on a thorough analysis of a given process and a thorough problem solution. It should also be emphasized that the validation activities require the involvement of appropriately qualified personnel, which will contribute to ensuring high quality

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

and safety of the obtained products.

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

knowledge and science. The validation and qualification activities are necessary to verify the adopted methods and the continuous improvement of processes. This, in turn, fits into modern management systems using the PDCA or DMAIC approach, based on a thorough analysis of a given process and a thorough problem solution. It should also be emphasized that the validation activities require the involvement of appropriately qualified personnel, which will contribute to ensuring high quality and safety of the obtained products.
