**2. Resource-based view (RBV) approach in health care organizations and tissue bank laboratory management**

#### **2.1 Resource-based view framework for health care organizations**

The resource-based view (RBV) is a theoretical framework used to study and explain the competitive behavior of organizations [6, 7] that emerged in 1980s and 1990s, after the major works published by Barney, J. *Firm Resources and Sustained Competitive Advantage*, Prahalad and Hamel *The Core Competence of the Corporation*, and Wernerfelt, B. *The Resource-Based View of the Firm*. Since then, RBV approach has been widely used and appreciated in the management of private organizations. However, it may also bring a promising framework to implement in the context of large-scale quality improvement within the public health care entities. Although these theories may be novel for the health management field, including models of strategic management originally developed for private sector firms, their application within publicly funded settings may be problematic or require customization, but nevertheless provide interesting insights [8]. It may provide a sustainable solution to manage quality driven, highly complex, and environmentally turbulenced settings such as tissue bank laboratories. RBV approach may be the answer to maximize growth, quality, and performance in a way to cope with modern, rapid technological changes and competitive medical environments.

The tissue banking sector quality improvement efforts take place in interorganizational networks rather than in a large, vertically integrated organization. Therefore, tissue bank managers encounter significant difficulties in understanding high organizational complexity that cannot be reduced to simple cause-effect relations or one variable [8]. The challenge is not only to be in compliance with applicable codes and quality regulations of good manufacturing practice (GMP), state regulatory agency, or pharmaceutical regulatory requirements, but also at the same time to optimize your business operations and standardize workflows in processing laboratories. Navigating through this complicated regulatory milieu and at the same ensuring efficient manufacturing process along with sensible business cost balance may require a RBV theoretical framework. Resource-based view and regulatory compliance are not mutually exclusive but should be combined to deliver excellent performance improvements and complex approach to stimulate organization's competitiveness, productivity, and innovation.

#### **2.2 RBV model**

The RBV resource approach assumes that the success of the organization lies within the organization itself, or to be exact, in its valuable, intangible, and not perfectly imitable resources (VRIO condition) allowing it to achieve a sustainable competitive advantage [9]. Resource-based view (RBV) analyzes and interprets resources of the organizations to understand how organizations achieve sustainable competitive advantage. The RBV focuses on the concept of difficult-to-imitate attributes of the firm as sources of superior performance and competitive advantage [10, 11]. It takes an 'inside-out' view of firm-specific perspective on why organizations succeed or fail in the market place [12]. According to this approach, resources are given the superior role in achieving higher organizational performance. The RBV model presents some critical assumptions regarding resources, which are about to be met, in order to obtain efficient manufacturing process in line with regulatory compliance. The first stage of the RBV model categorizes resources within the organization into two basic types: tangible and intangible resources. The literature categorizes

**139**

category (**Table 1**).

**Table 1.**

categories of physical and financial assets [14].

*Examples of tissue bank tangible and intangible resources and capabilities.*

tissue bank can be found in **Table 1**.

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

resources also into three main categories: tangible resources, intangible resources, and capabilities [13]. Capabilities refer to the skills organization possesses to coordinate the resources (i.a., teamwork, organizational culture, and trust); however, they are not clearly owned and difficult to measure. For the purpose of the RBV model in this paper, the author included capabilities into tangible and intangible resource

Tangible resources belong to the organization and can be divided into fixed assets (i.e., tissue bank facilities, land, laboratory machinery, clean room systems, and furniture) and current assets including, i.a., capital equipment, laboratory equipment, inventory, and financial means. Such assets are also referred to as property-based resources [6]. Other divisions of tangible resources include also

Intangible resources, also referred to as knowledge-based resources [15], consist of intellectual property and include, i.a., operational knowledge of the laboratory employees, process knowledge, procedures, accumulated experience, patents, tissue bank brand recognition, community relationship, trademark, and legal agreements. They can be further divided into infinite and finite intangible assets (**Figure 1**). Tangible and intangible resources can be further grouped into various subcategories. One of them was first presented by Barney [13] and included physical resources (physical, technological, plant, and equipment), human capital resources (training, experience, and insights), and organizational capital resources (formal structure). An example of broader classification of resources and capabilities of a

According to RBV, not all resources of the firm will be strategic and, hence, sources of competitive advantage. Competitive advantage occurs only when there is a situation of resource heterogeneity and immobility [16]. The resource heterogeneity implies that organizations have varying capabilities and possess unique bunch of resources allowing them to design different strategies to obtain competitive advantage. Resource immobility may be understood as inability of competing firms

to obtain resources from other firms. If the resource is not perfectly mobile

*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*


#### **Table 1.**

*Biochemical Testing - Clinical correlation and Diagnosis*

**and tissue bank laboratory management**

tion's competitiveness, productivity, and innovation.

**2. Resource-based view (RBV) approach in health care organizations** 

The resource-based view (RBV) is a theoretical framework used to study and explain the competitive behavior of organizations [6, 7] that emerged in 1980s and 1990s, after the major works published by Barney, J. *Firm Resources and Sustained Competitive Advantage*, Prahalad and Hamel *The Core Competence of the Corporation*, and Wernerfelt, B. *The Resource-Based View of the Firm*. Since then, RBV approach has been widely used and appreciated in the management of private organizations. However, it may also bring a promising framework to implement in the context of large-scale quality improvement within the public health care entities. Although these theories may be novel for the health management field, including models of strategic management originally developed for private sector firms, their application within publicly funded settings may be problematic or require customization, but nevertheless provide interesting insights [8]. It may provide a sustainable solution to manage quality driven, highly complex, and environmentally turbulenced settings such as tissue bank laboratories. RBV approach may be the answer to maximize growth, quality, and performance in a way to cope with modern, rapid technological changes and competitive medical

The tissue banking sector quality improvement efforts take place in interorganizational networks rather than in a large, vertically integrated organization. Therefore, tissue bank managers encounter significant difficulties in understanding high organizational complexity that cannot be reduced to simple cause-effect relations or one variable [8]. The challenge is not only to be in compliance with applicable codes and quality regulations of good manufacturing practice (GMP), state regulatory agency, or pharmaceutical regulatory requirements, but also at the same time to optimize your business operations and standardize workflows in processing laboratories. Navigating through this complicated regulatory milieu and at the same ensuring efficient manufacturing process along with sensible business cost balance may require a RBV theoretical framework. Resource-based view and regulatory compliance are not mutually exclusive but should be combined to deliver excellent performance improvements and complex approach to stimulate organiza-

The RBV resource approach assumes that the success of the organization lies within the organization itself, or to be exact, in its valuable, intangible, and not perfectly imitable resources (VRIO condition) allowing it to achieve a sustainable competitive advantage [9]. Resource-based view (RBV) analyzes and interprets resources of the organizations to understand how organizations achieve sustainable competitive advantage. The RBV focuses on the concept of difficult-to-imitate attributes of the firm as sources of superior performance and competitive advantage [10, 11]. It takes an 'inside-out' view of firm-specific perspective on why organizations succeed or fail in the market place [12]. According to this approach, resources are given the superior role in achieving higher organizational performance. The RBV model presents some critical assumptions regarding resources, which are about to be met, in order to obtain efficient manufacturing process in line with regulatory compliance. The first stage of the RBV model categorizes resources within the organization into two basic types: tangible and intangible resources. The literature categorizes

**2.1 Resource-based view framework for health care organizations**

**138**

environments.

**2.2 RBV model**

*Examples of tissue bank tangible and intangible resources and capabilities.*

resources also into three main categories: tangible resources, intangible resources, and capabilities [13]. Capabilities refer to the skills organization possesses to coordinate the resources (i.a., teamwork, organizational culture, and trust); however, they are not clearly owned and difficult to measure. For the purpose of the RBV model in this paper, the author included capabilities into tangible and intangible resource category (**Table 1**).

Tangible resources belong to the organization and can be divided into fixed assets (i.e., tissue bank facilities, land, laboratory machinery, clean room systems, and furniture) and current assets including, i.a., capital equipment, laboratory equipment, inventory, and financial means. Such assets are also referred to as property-based resources [6]. Other divisions of tangible resources include also categories of physical and financial assets [14].

Intangible resources, also referred to as knowledge-based resources [15], consist of intellectual property and include, i.a., operational knowledge of the laboratory employees, process knowledge, procedures, accumulated experience, patents, tissue bank brand recognition, community relationship, trademark, and legal agreements. They can be further divided into infinite and finite intangible assets (**Figure 1**).

Tangible and intangible resources can be further grouped into various subcategories. One of them was first presented by Barney [13] and included physical resources (physical, technological, plant, and equipment), human capital resources (training, experience, and insights), and organizational capital resources (formal structure). An example of broader classification of resources and capabilities of a tissue bank can be found in **Table 1**.

According to RBV, not all resources of the firm will be strategic and, hence, sources of competitive advantage. Competitive advantage occurs only when there is a situation of resource heterogeneity and immobility [16]. The resource heterogeneity implies that organizations have varying capabilities and possess unique bunch of resources allowing them to design different strategies to obtain competitive advantage. Resource immobility may be understood as inability of competing firms to obtain resources from other firms. If the resource is not perfectly mobile

(i.e., the resource is not free to move between firms, or if a firm without a resource faces a considerable cost burden in developing, acquiring, or using it that a firm already using it does not), then the resource is likely to be a source of sustained competitive advantage [16].

In order for the resource to provide sustainable and desirable performance, VRIO framework criteria must be fulfilled. The original tool VRIN was described by Barney [10] in his work *Firm Resources and Sustained Competitive Advantage* and was later improved by Barney to VRIO in *Looking Inside for Competitive Advantage* (*1995*)*.*


**141**

**2.3 Summary**

**Table 2.**

*Examples of VRIO analysis: ADM patent.*

sustainable competitive advantage and growth.

**3. Activity and documentation of a tissue bank**

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

potential of its unique resources. Therefore, the resource itself does not confer any value to the company; it is crucial to organize the company allowing it to achieve not only temporary but also sustained competitive advantage.

The VRIO framework may therefore be a crucial strategic analysis tool uncovering resources and capabilities that give organizations a long-term competitive advantage. An example of VRIO analysis for tissue bank can be found in **Table 2**.

Internal resources and capabilities determine strategic choices made by firms while competing in their external business environment [15]. As resource requirements in health care organizations must be carefully managed due to cost constraints, RBV approach along with VRIO resource analysis adaptation to tissue bank not-for-profit settings seems intuitively sound. Resource-based view can ensure sensible balance between complying quality regulations that govern tissue banks and optimizing processing practices. Examining and identifying unique (valuable, rare, and costly to imitate) organizational resources through RBV and VRIO framework may deliver simple but excellent performance improvements. Finding out if the entity is organized to exploit the resources and protecting them may lead to better financial results as control of superior and unique resources is necessary to establish a cost advantage, which leads to profitability [14]. Finally, constant review of VRIO resources and capabilities enables organizations to establish clear-cut

The activity of a tissue bank may be limited to the preparation of biostatic (radiation sterilized) and biovital (living) grafts using documented and proven procedures. In this regard, a tissue bank operates under a Ministry of Health License and must demonstrate the implementation of a quality assurance system that meets the requirements of the Law of July 1, 2005, on the collection, storage, and transplantation of cells, tissues, and organs as amended (*Journal of Laws 2017 item 1000*). The regulation

*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*


#### **Table 2.**

*Biochemical Testing - Clinical correlation and Diagnosis*

competitive advantage [16].

**Figure 1.** *RBV model.*

disadvantage.

the market.

historical conditions.

(i.e., the resource is not free to move between firms, or if a firm without a resource faces a considerable cost burden in developing, acquiring, or using it that a firm already using it does not), then the resource is likely to be a source of sustained

In order for the resource to provide sustainable and desirable performance, VRIO framework criteria must be fulfilled. The original tool VRIN was described by Barney [10] in his work *Firm Resources and Sustained Competitive Advantage* and was later improved by Barney to VRIO in *Looking Inside for Competitive Advantage* (*1995*)*.*

1.**Valuable (V):** a resource is considered valuable when it provides strategic value to organization, enabling it to exploit opportunities or defend against threats. The resource that is unable to meet this criterion leads to competitive

2.**Rare (R):** rare resources, hard to obtain by competitors, grant temporary competitive advantage. The resource must be rare enough to design and execute unique business strategy in comparison with other organizations on

3.**Imperfect imitability (I):** the resource leading to competitive advantage must be costly to imitate for other organizations that do not have it. The resource may also be hard to imitate not only because of financial reasons but also because of difficulties in acquiring it, its complexity, causal ambiguity, or even

4.**Non-Substitutability (N):** it is impossible for a competitor to substitute or replace a certain resource by other or alternative resource/**Organized to Capture Value (O):** it is the task of the organization to be able to organize its management systems, processes, and procedures in a way to fully realize the

**140**

*Examples of VRIO analysis: ADM patent.*

potential of its unique resources. Therefore, the resource itself does not confer any value to the company; it is crucial to organize the company allowing it to achieve not only temporary but also sustained competitive advantage.

The VRIO framework may therefore be a crucial strategic analysis tool uncovering resources and capabilities that give organizations a long-term competitive advantage. An example of VRIO analysis for tissue bank can be found in **Table 2**.

#### **2.3 Summary**

Internal resources and capabilities determine strategic choices made by firms while competing in their external business environment [15]. As resource requirements in health care organizations must be carefully managed due to cost constraints, RBV approach along with VRIO resource analysis adaptation to tissue bank not-for-profit settings seems intuitively sound. Resource-based view can ensure sensible balance between complying quality regulations that govern tissue banks and optimizing processing practices. Examining and identifying unique (valuable, rare, and costly to imitate) organizational resources through RBV and VRIO framework may deliver simple but excellent performance improvements. Finding out if the entity is organized to exploit the resources and protecting them may lead to better financial results as control of superior and unique resources is necessary to establish a cost advantage, which leads to profitability [14]. Finally, constant review of VRIO resources and capabilities enables organizations to establish clear-cut sustainable competitive advantage and growth.

#### **3. Activity and documentation of a tissue bank**

The activity of a tissue bank may be limited to the preparation of biostatic (radiation sterilized) and biovital (living) grafts using documented and proven procedures. In this regard, a tissue bank operates under a Ministry of Health License and must demonstrate the implementation of a quality assurance system that meets the requirements of the Law of July 1, 2005, on the collection, storage, and transplantation of cells, tissues, and organs as amended (*Journal of Laws 2017 item 1000*). The regulation contains the basic documents that a tissue bank quality system must include; however, some of the mentioned documents seem to be obsolete. The basic documents used in a tissue bank are standard operating procedures (SOPs). SOPs must describe the requirements regarding primarily the processes and activities related to the collection of cells or tissues, their acceptance, processing, storage, distribution, transport, as well as monitoring the condition of cells or tissues on their way from the donor to the recipient. Standard operating procedures should specify the medical devices and materials that have direct contact with cells or tissues. The criteria for the qualification and selection of the cell or tissue donor and the criteria for excluding the deceased donor, including the objection against the collection of tissues, must be clearly defined. Standard operating procedures should describe the method of cell or tissue collection, detailing the data necessary for the identification of the entity arranging the tissue collection and the data regarding the collection itself so as to ensure full traceability of the collected cells or tissues. The procedures must specify the means of transporting the collected cells or tissues and their acceptance into the tissue and cell bank. The quality system procedures in a tissue bank must specify how to identify and secure cells or tissues during transport, and describe the stage of acceptance of tissue and cellular material into the bank, specifying the information on:

The way in which cells or tissues are accepted into a tissue and cell bank, taking the following into account:


The next step, which must be included in standard operating procedures, is the processing of cells or tissues. These procedures must take into account the requirements regarding the following elements of all cell or tissue type processing: labeling, processing conditions, and ongoing evaluation of the processing operations in order to ensure the safety and quality of the cells or tissues being processed. The SOPs must describe the manner of approval and documentation of the changes in the processing operations. A cell or tissue identification system must be developed and described at every stage of the processing to distinguish between authorized products and unauthorized products. The infected cell or tissue removal or withdrawal procedures must be developed and described to prevent infection of other processed cells or tissues, the processing products, environment, or personnel.

**143**

Inspectorate.

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

• The grace period conditions after the processing of cells or tissues

• The grace period conditions after the sterilization of cells or tissues

• The manner of storing the processed cells or tissues and releasing them for

Another stage that must be included in the quality system is the storage of cells or tissues after processing. Procedures in this regard must specify the requirements

• Separate storage conditions and maximum storage time for each cell or tissue type, taking into account the possibility of deterioration of the cell or tissue

• The development of a cell or tissue inventory and identification system at each

Standard operating procedures for the distribution of cells or tissues determine the requirements regarding labeling of materials intended for distribution as well as transport criteria and conditions. The scope of standard operating procedures must also include the monitoring of the quality of cells or tissues on their way from the

A very important aspect is to define the manner of recording significant adverse events and significant adverse reactions associated with the collection, testing, processing, storage, distribution and transplantation of cells or tissues, their reporting,

The documentation of the quality system must also contain the operating manuals specifying the applicable documentation, including types of documents, their keeping and circulation in the tissue and cell bank, and the manner of keeping records of specific activities performed in a tissue bank. The documentation must

The described quality system concerns procedures regarding tissue and cell banking. If a tissue bank additionally produces advanced therapy medicinal products (ATMPs) using the hospital-exemption advanced therapy medicinal product (HE-ATMP) production procedure, two complementary systems must be developed. Becoming a producer of hospital-exemption advanced therapy medicinal products, the tissue bank must additionally implement the good manufacturing practice (GMP) quality system certified by the Main Pharmaceutical

The system requires the development of documentation necessary to meet the requirements of the GMP quality system. The basic document containing the producer's characteristics is the site master file describing the activities of the production

authorization holder related to the good manufacturing practice.

• Separate storage conditions and maximum storage time for each type of product derived from the processed cells or tissues, taking into account the

possibility of deterioration of the product properties

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

The SOPs must include the following:

• The method of cell or tissue sterilization

distribution after the grace period

properties in the course of storage

and elimination of the reasons for their occurrence.

also contain reporting forms and donor cards.

for the following:

storage stage

donor to the recipient.

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

The SOPs must include the following:

*Biochemical Testing - Clinical correlation and Diagnosis*

contains the basic documents that a tissue bank quality system must include; however, some of the mentioned documents seem to be obsolete. The basic documents used in a tissue bank are standard operating procedures (SOPs). SOPs must describe the requirements regarding primarily the processes and activities related to the collection of cells or tissues, their acceptance, processing, storage, distribution, transport, as well as monitoring the condition of cells or tissues on their way from the donor to the recipient. Standard operating procedures should specify the medical devices and materials that have direct contact with cells or tissues. The criteria for the qualification and selection of the cell or tissue donor and the criteria for excluding the deceased donor, including the objection against the collection of tissues, must be clearly defined. Standard operating procedures should describe the method of cell or tissue collection, detailing the data necessary for the identification of the entity arranging the tissue collection and the data regarding the collection itself so as to ensure full traceability of the collected cells or tissues. The procedures must specify the means of transporting the collected cells or tissues and their acceptance into the tissue and cell bank. The quality system procedures in a tissue bank must specify how to identify and secure cells or tissues during transport, and describe the stage of acceptance of tissue

The way in which cells or tissues are accepted into a tissue and cell bank, taking the

a.The common understanding of the purpose of the collected cells or tissues

b.Results of medical examinations, specialist examinations, and laboratory tests

c.Documented criteria of donor selection performed by an authorized person

e.The assessment of the quality of the cells or tissues accepted into the

f. The method of dealing with cell or tissue transplants that do not conform with the specification and have incomplete test results and unacceptable

g.The course of quarantine from the time of acceptance of cells or tissues into the tissue and cell bank until they are released for processing or withdrawn

The next step, which must be included in standard operating procedures, is the

processing of cells or tissues. These procedures must take into account the requirements regarding the following elements of all cell or tissue type processing: labeling, processing conditions, and ongoing evaluation of the processing operations in order to ensure the safety and quality of the cells or tissues being processed. The SOPs must describe the manner of approval and documentation of the changes in the processing operations. A cell or tissue identification system must be developed and described at every stage of the processing to distinguish between authorized products and unauthorized products. The infected cell or tissue removal or withdrawal procedures must be developed and described to prevent infection of other processed cells or tissues, the processing products,

d.Documented transport, packaging, and labeling conditions

and cellular material into the bank, specifying the information on:

following into account:

tissue and cell bank

quality or defects

environment, or personnel.

**142**


Another stage that must be included in the quality system is the storage of cells or tissues after processing. Procedures in this regard must specify the requirements for the following:


Standard operating procedures for the distribution of cells or tissues determine the requirements regarding labeling of materials intended for distribution as well as transport criteria and conditions. The scope of standard operating procedures must also include the monitoring of the quality of cells or tissues on their way from the donor to the recipient.

A very important aspect is to define the manner of recording significant adverse events and significant adverse reactions associated with the collection, testing, processing, storage, distribution and transplantation of cells or tissues, their reporting, and elimination of the reasons for their occurrence.

The documentation of the quality system must also contain the operating manuals specifying the applicable documentation, including types of documents, their keeping and circulation in the tissue and cell bank, and the manner of keeping records of specific activities performed in a tissue bank. The documentation must also contain reporting forms and donor cards.

The described quality system concerns procedures regarding tissue and cell banking. If a tissue bank additionally produces advanced therapy medicinal products (ATMPs) using the hospital-exemption advanced therapy medicinal product (HE-ATMP) production procedure, two complementary systems must be developed. Becoming a producer of hospital-exemption advanced therapy medicinal products, the tissue bank must additionally implement the good manufacturing practice (GMP) quality system certified by the Main Pharmaceutical Inspectorate.

The system requires the development of documentation necessary to meet the requirements of the GMP quality system. The basic document containing the producer's characteristics is the site master file describing the activities of the production authorization holder related to the good manufacturing practice.

The GMP documentation must also include the following manuals:


In-process control and process control in real time (PAT—process analytical technologies) that are used in the process must be specified along with the acceptance criteria:


The GMP system defines the types of records and reports:


In the GMP quality system, it is necessary to develop and supervise the documentation, which is defined in the good documentation practice. It includes the following recommendations:


**145**

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

read. The reason for the change must be provided in justified cases.

In order to properly archive documents, the relationship between the record and the production activity should be clearly defined as well as the place where the

It is also necessary to have the properly approved and dated specifications of

The acceptance of each delivery of any starting material (including bulk products, intermediate products, and finished products) of any direct, external, and printed packaging material requires written procedures and records. It is necessary to develop written procedures for material and product testing at various stages of production, describing the methods and equipment used. The executed tests should

As part of the GMP system, written procedures for releasing or rejecting materials and products, including the certification of the finished products by the qualified person, must be developed. All entries must be available to the qualified person. The developed system must immediately identify deviations and any

be kept and stored in order to withdraw a series from the market if necessary. The system also requires the development of written procedures, programs, protocols, reports, and related records regarding undertaken actions or final

• Personnel issues, including a list of specimen signatures, and training in

• Technical issues, protective clothing and hygiene, as well as the verification of

conclusions. These procedures should include the following:

the effectiveness of the training sessions conducted

• Process, equipment, and system validation and qualification

The distribution records of each manufactured batch of medicinal product must

starting and packaging materials as well as the finished products. The following documents should also be developed:

• Production recipes and production manuals

• Every change of a record in a document should be signed and dated, and the means of introducing the change must enable the original information to be

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

record has been entered.

• Packaging instructions

• Batch production records

• Batch packaging records

changes implemented in the critical data.

• Device assembly and calibration

respect to the requirements

• Environmental monitoring

• Maintenance, cleaning, and disinfection

be documented.

• Technology

• Pest control

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

• Every change of a record in a document should be signed and dated, and the means of introducing the change must enable the original information to be read. The reason for the change must be provided in justified cases.

In order to properly archive documents, the relationship between the record and the production activity should be clearly defined as well as the place where the record has been entered.

It is also necessary to have the properly approved and dated specifications of starting and packaging materials as well as the finished products.

The following documents should also be developed:


*Biochemical Testing - Clinical correlation and Diagnosis*

for quality assessment.

operation execution

contractor for commissioned activities

The GMP system defines the types of records and reports:

in detail.

execution

tance criteria:

The GMP documentation must also include the following manuals:

• Specifications describing in detail the requirements for a medicinal product or material used or obtained in the production process. They constitute the basis

• Production recipes, processing and packaging instructions, and testing manuals. This documentation must provide details of all the output materials, devices, and computer systems used. All instructions regarding the processing, packaging, sampling, and sample testing must also be specified

In-process control and process control in real time (PAT—process analytical technologies) that are used in the process must be specified along with the accep-

• Protocols presenting the manuals and records of the concerned operation

• The records provide evidence of actions taken to demonstrate compliance with the manual, e.g., activities, events, tests, and, in the case of batch production, the history of each batch of a medicinal product, including its distribution. Records contain raw data that are used to create other entries. All data used as the basis for quality activities should be defined as raw data.

• The analytical certificates provide a summary of the medicinal product sample or material test results including the assessment of compliance with a given specification. Alternatively, the certification can be based entirely or in part on real-time process control (summaries and deviation reports) for a batch associated with real-time batch control (PAT—process analytical technologies), with parameters and measurements that must comply with the

approved documentation attached to the marketing authorization.

well as results, conclusions, and recommendations.

mentation, which is defined in the good documentation practice.

It includes the following recommendations:

medicinal products are reproducible.

• The reports document the execution of individual tests, projects, or studies as

In the GMP quality system, it is necessary to develop and supervise the docu-

• The manually entered data must be clear, legible, and impossible to delete.

• The records must be made or supplemented in the course of execution of each activity in such a way that all important activities related to the production of

• Procedures: standard operating procedures (SOP) determining the manner of

• Contractual agreements referring to arrangements between the client and the

**144**


The acceptance of each delivery of any starting material (including bulk products, intermediate products, and finished products) of any direct, external, and printed packaging material requires written procedures and records. It is necessary to develop written procedures for material and product testing at various stages of production, describing the methods and equipment used. The executed tests should be documented.

As part of the GMP system, written procedures for releasing or rejecting materials and products, including the certification of the finished products by the qualified person, must be developed. All entries must be available to the qualified person. The developed system must immediately identify deviations and any changes implemented in the critical data.

The distribution records of each manufactured batch of medicinal product must be kept and stored in order to withdraw a series from the market if necessary.

The system also requires the development of written procedures, programs, protocols, reports, and related records regarding undertaken actions or final conclusions. These procedures should include the following:


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 management system documents should be kept.
