C h a p t e r 1

Quality Management Systems:

Theory and Practice

Tania L. Motschman, MS, MT(ASCP)SBB, CQA(ASQ);

Betsy W. Jett, MT(ASCP), CQA(ASQ)CQM/OE; and
Susan L. Wilkinson, EdD, MS, MT(ASCP)SBB

A PRIMARY GOAL of transfusion istration (FDA), especially in the current good

medicine, cellular therapies, and clinical manufacturing practice (cGMP) and current
diagnostics is to promote high standards of good tissue practice (cGTP) regulations.2-5 The
quality in all aspects of patient care and relat- FDA regulations in the Code of Federal Regula-
ed products and services. This commitment to tions (CFR) Title 21, Part 211.22 require an in-
quality is reflected in standards of practice set dependent quality control (QC) or quality as-
forth by the AABB. AABB standards use a quali- surance unit that has responsibility for the
ty management system as the framework for overall quality of the facility’s finished product
quality. A quality management system in- and authority to control the processes that
cludes the organizational structure, responsi- may affect this product.3 (See frequently used
bilities, policies, processes, procedures, and CFR quality-related citations in Appendix 1-2.)
resources established by executive manage- Professional and accrediting organizations
ment to achieve and maintain quality. (A glos- such as the AABB, 6,7 College of American Pa-
sary of quality terms used in this chapter is in- thologists (CAP), 8 The Joint Commission, 9,10
cluded in Appendix 1-1.) Clinical and Laboratory Standards Institute
The establishment of a formal quality as- (CLSI),11 and Foundation for the Accreditation
surance program is required under the Centers of Cellular Therapy (FACT),12 have also estab-
for Medicare and Medicaid Services (CMS) lished requirements and guidelines to address
Clinical Laboratory Improvement Amend- quality issues. The International Organization
ments (CLIA)1 and the Food and Drug Admin- for Standardization (ISO) quality manage-

Tania L. Motschman, MS, MT(ASCP)SBB, CQA(ASQ), Quality Director, Esoteric Business Unit, Laboratory
Corporation of America, Burlington, North Carolina; Betsy W. Jett, MT(ASCP), CQA(ASQ)CQM/OE, Vice Presi-
dent for Quality and Regulatory Affairs, New York Blood Center, New York, New York; and Susan L. Wilkinson,
EdD, MS, MT(ASCP)SBB, Interim Department Head, Analytical and Diagnostic Sciences, College of Allied
Health Sciences, and Associate Professor Emerita, University of Cincinnati, Cincinnati, Ohio
The authors have disclosed no conflicts of interest.

1
2 䡲 AABB TECHNICAL MANUAL

ment standards (ISO 9001) are generic to any mation to process managers regarding levels
industry and describe the important mini- of performance that can be used in setting pri-
mum elements of a quality management sys- orities for process improvement. Examples of
tem.13 The ISO 15189 standards are specific to quality assurance activities in transfusion
laboratory medicine.14 In addition, the Health medicine and cellular therapies include record
Care Criteria for Performance Excellence pub- reviews, monitoring of quality indicators, and
lished by the Baldrige Performance Excellence internal assessments.
Program15 provides an excellent framework for Quality management considers interrelat-
implementing quality on an organizational ed processes in the context of the organization
level. and its relations with customers and suppliers.
The AABB has defined the minimum ele- It addresses the leadership role of executive
ments that must be addressed in its quality management in creating a commitment to
system essentials (QSEs). 16 The AABB QSEs quality throughout the organization, the un-
were developed to be compatible with ISO derstanding of suppliers and customers as
9001 standards, the FDA Guideline for Quality partners in quality, the management of human
Assurance in Blood Establishments,5 and other and other resources, and quality planning.
FDA quality system approaches.17,18 The quality systems approach described
in this chapter encompasses all of these activi-
ties. It ensures application of quality principles
CO NCE P T S I N QUA LI T Y
throughout the organization and reflects the
Quality Control, Quality Assurance, changing focus of quality efforts from detec-
and Quality Management tion to prevention.
The purpose of QC is to provide feedback to Juran’s Quality Trilogy
operational staff about the state of a process
that is in progress. QC tells staff whether to Juran’s Quality Trilogy is one example of a
continue (everything is acceptable) or to stop quality management approach. This model
until a problem has been resolved (something centers around three fundamental processes
is found to be out of control). for managing quality in any organization:
Historically, transfusion services and do- planning, control, and improvement.19(p2.5)
nor centers have used many QC measures as The planning process for a new product
standard practices in their operations. Exam- or service includes activities to identify re-
ples include reagent QC; product QC; clerical quirements, develop product and process
checks; visual inspections; and measure- specifications that meet those requirements,
ments, such as temperature readings on refrig- and design the process. During the planning
erators and volume or cell counts on finished phase, the facility must perform the following
blood components. steps:
Quality assurance activities are not tied to
the actual performance of a process. Rather, 1. Establish quality goals for the project.
they include activities, such as the develop- 2. Identify the customers.
ment of documents like standard operating 3. Determine customer needs and expecta-
procedures (SOPs), to ensure consistent and tions.
correct performance of processes, training of 4. Develop product and service specifications
personnel, and qualification of materials and to meet customer, operational, regulatory,
equipment. Quality assurance activities also and accreditation requirements.
include retrospective reviews and analyses of 5. Develop operational processes for produc-
operational performance data to determine tion and delivery, including written proce-
whether the overall process is in a state of con- dures and resources requirements.
trol and to detect shifts or trends that require 6. Develop process controls and validate the
attention. Quality assurance provides infor- process in the operational setting.
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 3

The results of the planning process are re- Process Approach

ferred to as “design output.”13
In its most generic form, a process includes all
Once the plan is implemented, the con-
of the resources and activities that transform
trol process provides a feedback loop for oper-
an input into an output. An understanding of
ations that includes the following:
how to manage and control processes in trans-
fusion medicine, cellular therapies, and clini-
1. Evaluation of performance.
cal diagnostic activities is based on this simple
2. Comparison of performance to goals.
equation:
3. Action to correct any discrepancy between
the two. INPUT  PROCESS  OUTPUT

The control process addresses inputs, For example, a key process for donor cen-
production, and delivery of products and ser- ters is donor selection. The “input” includes
vices to meet specifications. Process controls the individual who presents for donation and
should allow staff to recognize when things are all of the resources required for that donor’s
going wrong and to either make appropriate health screening. Through a series of activities
adjustments to ensure a product’s quality or (a process), including the verification of the
stop the process. donor’s identity, a deferral status review, a
An important goal in quality manage- mini-physical exam, and a health history
ment is to establish a set of controls that en- questionnaire, an individual is deemed an “eli-
sure process and product quality but are not gible donor.” The “output” is either an eligible
excessive. Controls that do not add value donor who can continue to the next process
should be eliminated to conserve limited (blood collection) or an ineligible donor who is
resources and allow staff to focus attention on deferred. When the selection process results in
those controls that are critical to the opera- a deferred donor, the resources (inputs) asso-
tion. ciated with that process do not continue
Statistical tools, such as process capabili- through the process but contribute to the cost
ty measurement and control charts, allow a fa- of quality. One way that donor centers at-
cility to evaluate process performance during tempt to minimize this cost is to educate po-
tential donors before screening so that those
the planning stage and in operations. These
who are not eligible do not enter the selection
tools help determine if a process is stable
process.
(ie, in statistical control) and if it is capable of
Strategies for managing a process should
meeting product and ser vice specifica-
address all of its components, including its in-
tions.19(p22.19)
terrelated activities, inputs, outputs, and re-
Quality improvement is intended to en-
sources. Supplier qualification, formal agree-
able an organization to attain higher levels of ments, supply verification, and inventory
performance by creating new or better fea- control are strategies for ensuring that the
tures that add value or by removing deficien- inputs to a process meet specifications.
cies in the process, product, or service. Oppor- Personnel training and competence assess-
t u n i t i e s t o i m p r ove m a y b e re l a t e d t o ment, equipment maintenance and control,
deficiencies in the initial planning process; management of documents and records, and
unforeseen factors discovered on implementa- implementation of appropriate in-process
tion; shifts in customer needs; or changes in controls provide assurance that the process
starting materials, environmental factors, or will operate as intended. End-product testing
other variables that affect the process. Im- and inspection, customer feedback, and
provements must be based on data-driven outcome measurement provide data to evalu-
analysis; an ongoing measurement and assess- ate product quality and improve the process.
ment program is fundamental to that process. These output measurements and quality
4 䡲 AABB TECHNICAL MANUAL

indicators are used to evaluate the effective- In service, personnel need to be able to adapt
ness of the process and process controls. a service in a way that meets customer ex-
To manage a system of processes effec- pectations but does not compromise quality.
tively, the facility must understand how its To do this, personnel must have sufficient
processes interact and what cause-and-effect knowledge and understanding of interrelated
relationships exist between them. In the donor processes to use independent judgment ap-
selection scenario, the consequences of ac- propriately, or they must have ready access to
cepting a donor who is not eligible reach into higher-level decision makers.
almost every other process in the facility. For When one designs quality management
example, if a donor with a history of high-risk systems for production processes, it is useful
behavior is not identified as such during the to think of the process as the driver, with peo-
selection process, the donated unit(s) may re- ple providing the oversight and support need-
turn positive test results for one of the viral ed to keep it running smoothly and effectively.
marker assays, triggering follow-up testing, In service, people are the focus; the underlying
look-back investigations, and donor deferral process provides a foundation that enables
and notification procedures. Components staff to deliver safe and effective services that
must be quarantined and their discard docu- meet customers’ needs in almost any situa-
mented. Personnel involved in collecting and tion.
processing the unit(s) are at risk of exposure to
infectious agents. Part of quality planning is to Quality Management as an Evolving
identify these relationships so that quick and Science
appropriate corrective action can be taken
The principles and tools used in quality man-
when process controls fail.
agement today will change as research pro-
It is important to remember that opera-
vides new knowledge of organizational behav-
tional processes include not only product
ior, technology provides new solutions, and
manufacture or service creation, but also the
the transfusion medicine and cellular thera-
delivery of a product or service. Delivery gen-
pies fields present new challenges. Periodic as-
erally involves interaction with the customer.
sessments of the quality management system
The quality of that transaction is critical to
will help identify practices that are no longer
customer satisfaction and should not be over-
effective or that could be improved through
looked in the design and ongoing assessment
the use of new technology or new tools.
of the quality management system.

Service vs Production PRACTICAL APP L ICATION OF

QUAL I TY MAN AGE ME NT
Quality management principles apply equally
to a broad spectrum of activities, from those
PR IN CI PL E S
related to processing and production to those The remainder of this chapter addresses the
involving interactions between individuals in elements of a quality management system and
delivering a service. However, different strate- practical application of quality management
gies may be appropriate when there are differ- principles to the transfusion medicine, cellular
ing expectations related to customer satisfac- therapies, and clinical diagnostics environ-
tion. Although the emphasis in a production ments. These basic elements include the fol-
process is on minimizing variation to create a lowing:
product that consistently meets specifications,
service processes require a certain degree of 䡲 Organization and leadership.
flexibility to address customer needs and cir- 䡲 Customer focus.
cumstances at the time of the transaction. In 䡲 Facilities, work environment, and safety.
production, personnel need to know how to 䡲 Human resources.
maintain uniformity in day-to-day operations. 䡲 Suppliers and materials management.
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 5

䡲 Equipment management. 䡲 Identifying designees and defining their re-

䡲 Process management. sponsibilities when assisting executive
䡲 Documents and records. management in carrying out these duties.
䡲 Information management.
䡲 Management of nonconforming events. Executive management support for the
䡲 Monitoring and assessment. quality management system goals, objectives,
䡲 Process improvement. and policies is critical to the program’s success.
Executive management needs to clearly com-
Organization and Leadership municate its commitment to quality goals and
create an organizational culture that embraces
The facility should be organized in a manner
quality principles.
that promotes effective implementation and The individual designated to oversee the
management of its operational and quality facility’s quality functions should report di-
management system. The structure of the or- rectly to executive management. In addition to
ganization must be documented, and the roles having the responsibility to coordinate, moni-
and responsibilities for the provision of tests, tor, and facilitate quality system activities, this
products, and services must be clearly defined. person should have the authority to recom-
These provisions should include a description mend and initiate corrective action when ap-
of the relationships and avenues of communi- propriate.5 The designated individual need not
cation between organizational units and those perform all of the quality functions personally.
responsible for key quality functions. Each fa- Ideally, this person should be independent of
cility may define its structure in any format the facility’s operational functions. In small fa-
that suits its operations. Organizational trees cilities, this independence may not always be
or charts that show the structure and relation- possible and carrying out this function may re-
ships are helpful. quire some creativity. Depending on the orga-
The facility should define in writing the nization’s size and scope, the designated over-
authority and responsibilities of executive sight person may work in the transfusion
management to establish and maintain the service, have laboratory-wide responsibilities,
quality management system. These responsi- supervise other workers (eg, a quality unit), or
be part of an organization-wide quality unit
bilities include the following:
(eg, hospital quality or risk management). In-
dividuals with dual quality and operational
䡲 Establishing a quality policy and associated
responsibilities should not provide quality
quality goals and quality objectives.
oversight for operational work that they have
䡲 Providing adequate facilities as well as hu-
performed.
man, equipment, and material resources to
Quality oversight functions may include
carry out the operations of the facility and the following5:
the quality management system.
䡲 Ensuring appropriate design and effective 䡲 Review and approval of SOPs and training
implementation of new or modified pro- plans.
cesses and procedures. 䡲 Review and approval of validation plans
䡲 Participating in the review and approval of and results.
quality and technical policies, processes, 䡲 Review and approval of document control
and procedures. and record-keeping systems.
䡲 Enforcing adherence to operational and 䡲 Audit of operational functions.
quality policies, processes, and procedures. 䡲 Development of criteria for evaluating sys-
䡲 Overseeing operations and regulatory and tems.
accreditation compliance. 䡲 Review and approval of suppliers.
䡲 Periodically reviewing and assessing quality 䡲 Review and approval of product and service
management system effectiveness. specifications (eg, the requirements to be
6 䡲 AABB TECHNICAL MANUAL

met in the manufacture, distribution, or ad- Customer Focus

ministration of blood components, cellular
A primary focus for any organization interest-
therapy products, tissues, and derivatives).
䡲 Review of reports of adverse reactions, de- ed in quality is serving the needs of its custom-
viations in the manufacturing process, ers. Customers have a variety of needs and ex-
nonconforming products and services, and pectations. The most appropriate way to
customer complaints. ensure that these needs and expectations are
䡲 Participation in decisions to determine met is for the facility and its customers to de-
whether blood components, cellular thera- fine them in an agreement, a contract, or an-
py products, tissues, derivatives, and ser- other document. Additional information on
vices are suitable for use, distribution, or agreements can be found in the “Suppliers and
recall. Materials Management” section.
䡲 Review and approval of corrective action When planning for new or changed prod-
plans. ucts or services, the facility should take the
䡲 Surveillance of problems (eg, event or inci- customer’s needs and expectations into ac-
dent reports, Form FDA 483 observations, count. If these changes are determined to be
or customer complaints) and the effective- critical to the quality or effectiveness of the
ness of corrective actions implemented to products and services provided by the facility,
solve those problems. they should be incorporated into the product
䡲 Use of data resources to identify trends and or service specifications as customer require-
potential problems before a situation wors- ments. The facility must have a process to
ens and patients and/or products are af- manage needs and expectations that are not
fected. met. For example, for a facility that has agreed
䡲 Preparation of periodic (as specified by the to deliver leukocyte-reduced components dai-
organization) reports of quality issues, ly to one of its customers, processing compo-
trends, findings, and corrective and pre- nents in a manner that ensures adequate leu-
ventive actions. kocyte removal is critical to this product’s
quality. Such an expectation should be incor-
Quality oversight functions may be porated into the product specifications. Daily
shared among existing staff, departments, and delivery of products is a customer need and
facilities or, in some instances, may be per- expectation, but it is not critical to the quality
formed by an outside firm under a contract. of the manufactured product. The facility
The goal is to provide an independent evalua- should have a process to manage this agreed-
tion of the facility’s quality activities to the ex- on expectation and ensure that the product
tent possible. Policies, processes, and proce- delivery mechanism meets this customer
dures should exist to define the roles and need. If this need cannot be met, the facility
responsibilities of all individuals in the devel- should have a process to address this failure.
opment and maintenance of these quality Once agreements have been made be-
goals. Quality management system policies tween the facility and its customers, there
and processes should be applicable across the should be a means to obtain feedback from
entire facility. A blood bank, tissue bank, trans- the customer to ensure that the facility is
fusion service, or cellular therapy product ser- meeting the customer’s expectations. Mecha-
vice need not develop its own quality policies nisms for obtaining such feedback proactively
if it is part of a larger entity whose quality include satisfaction surveys and periodic re-
management system addresses all of the mini- views of agreements. Reactive feedback is ob-
mum requirements. The quality management tained through customer complaints. A review
system should address all matters related to of event data may also indicate failures to meet
compliance with federal, state, and local regu- customer needs and expectations. Data ob-
lations and accreditation standards that are tained through these mechanisms should be
applicable to the organization. evaluated, and appropriate follow-up actions
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 7

must be taken. One such action could be to Human Resources

change the agreement. Inadequately address-
This element of the quality management sys-
ing customer concerns or failing to meet ex-
tem is aimed at management of personnel, in-
pectations may result in loss of the customer.
cluding selection, orientation, training, com-
petence assessment, and staffing.

Facilities, Work Environment, and Selection

Safety
Each facility should have a process to provide
The facility should provide a safe workplace adequate numbers of qualified personnel to
with adequate environmental controls and perform, verify, and manage all activities in the
emergency procedures to ensure the safety of facility. Qualification requirements for person-
patients, donors, staff, and visitors. Space allo- nel are determined on the basis of job respon-
cation, building utilities, and the communica- sibilities. The selection process should consid-
tion infrastructure should adequately support er the applicant’s qualifications for a particular
the facility’s activities. The facility should be position as determined by his or her educa-
kept clean and well maintained so that the tion, training, experience, certifications, and
products and services provided are not com- licensure. For laboratory testing staff, the stan-
promised. Procedures should be in place to dards for personnel qualifications should be
address the following: compatible with the regulatory requirements
established under CLIA.1 Job descriptions are
䡲 General safety. required for all personnel involved in process-
䡲 Disaster preparedness, response, and re- es and procedures that affect the quality of
covery. tests, products, and services. Effective job de-
䡲 Biological safety (eg, protection from blood- scriptions clearly define the qualifications and
borne pathogens). responsibilities of the positions as well as their
䡲 Chemical safety. reporting relationships.
䡲 Fire safety.
䡲 Radiation safety, if applicable. Orientation, Training, and Competence
䡲 Discard of biologic and other hazardous Assessment
substances. Once hired, employees should be oriented to
their position and the organization’s policies
cGMP regulations require quality plan- and procedures and be trained in their new
ning and control of the physical work environ- duties. The orientation program should cover
ment, including the following: facility-specific requirements and policies that
address issues such as safety, quality, informa-
䡲 Adequate space and ventilation. tion systems, security, and confidentiality. The
䡲 Sanitation and trash disposal. job-related portion of the orientation program
䡲 Equipment for controlling air quality and should cover operational issues specific to the
pressure, humidity, and temperature. work area. Training should be provided for
䡲 Water systems. each procedure for which employees are re-
䡲 Toilet and hand-washing facilities. sponsible. The ultimate result of the orienta-
tion and training program is to deem new em-
An evaluation of the infrastructure and its ployees competent to independently perform
limitations before implementation of proce- the duties and responsibilities defined in their
dures or installation of equipment will help job descriptions. Time frames should be estab-
ensure maximum efficiency and safety. A more lished to accomplish this goal.
thorough discussion of facilities and safety can Before the introduction of a new test or
be found in Chapter 2. service, existing personnel should be trained
8 䡲 AABB TECHNICAL MANUAL

to perform their newly assigned duties and ble), specimen handling, processing, and
must be deemed competent in these duties. testing.
During orientation and training, employees – Performance of instrument maintenance
should be given the opportunity to ask ques- and function checks.
tions and seek additional help or clarification. 䡲 Monitoring of the recording and reporting
All aspects of the training should be docu- of test results.
mented, and the facility trainer or designated 䡲 Review of intermediate test results or work-
facility management representative and em- sheets, QC records, proficiency testing re-
ployees should mutually agree on how em- sults, and preventive maintenance records.
ployees’ competence will be determined. 䡲 Assessment of
FDA cGMP training is required for staff – Test performance by testing previously
involved in the manufacture of blood and analyzed specimens, internal blind test-
blood products, including staff involved in col- ing samples, or external proficiency test-
lection, testing, processing, preservation, stor- ing samples.
age, distribution, and transport. 3 Likewise, – Problem-solving skills.
cGTP training is required for personnel in-
volved in similar activities for human cells, tis- A formal competency plan that includes a
sues, and cellular and tissue-based products schedule of assessments, a defined minimum
(HCT/Ps).4 Such training should provide staff for acceptable performance, and remedial
with an understanding of the regulatory basis measures is one way to ensure appropriate
for the facility’s policies and procedures as well and consistent competence assessments. As-
as the specific application of the cGMP and sessments need not be targeted to each indi-
cGTP requirements as described in the facili- vidual test or procedure performed by the em-
ty’s own written operating procedures. This ployee; instead, they can be grouped together
training should be provided periodically to en- to assess similar techniques or methods. How-
sure that personnel remain familiar with regu- ever, any test with unique aspects, problems,
latory requirements. or procedures should be assessed separately to
To ensure that skills are maintained, the ensure that staff maintain their competency to
facility should have regularly scheduled com- report test results promptly, accurately, and
petence evaluations of all staff members proficiently.1 Written tests can be used effec-
whose activities affect the quality of laboratory tively to evaluate problem-solving skills and
testing, manufacture of products, or provision cover many topics by asking one or more ques-
of products or services.1,5-10 Competence as- tions for each area to be assessed. CMS re-
sessment of management personnel should quires that employees who perform testing
also be considered. be assessed semiannually during the first
Depending on the nature of the job du- year that patient specimens are tested and an-
ties, competence assessments may include nually thereafter.1 Initial training verification
written evaluations; direct observations of ac- activities may serve as the first of these com-
tivities; reviews of work records or reports, in- petence assessments.
formation system records, and QC records; The quality oversight personnel should
testing of unknown samples; and evaluations assist in the development, review, and approv-
of employees’ problem-solving skills.5 For all al of training programs, including the criteria
testing personnel, CMS requires that each of for retraining. 5 Quality oversight personnel
the following methods be used, when applica- also monitor the effectiveness of training pro-
ble, for each test system annually1: grams and competence evaluations, and they
recommend changes as needed. In addition,
䡲 Direct observations of The Joint Commission requires analyses of ag-
– Routine patient test performance (in- gregate competence assessment data to iden-
cluding patient preparation, if applica- tify staff learning needs.9
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 9

Staffing that they are reliable sources of materials. The

facility should clearly define requirements or
Management should have a staffing plan that
expectations for its suppliers and share this in-
describes the number and qualifications of
formation with staff and suppliers. Suppliers’
personnel needed to perform the facility’s
ability to consistently meet specifications for a
functions safely and effectively. There should
supply or service should be evaluated along
be an adequate number of staff to perform the
with performance relative to availability, deliv-
operational activities and support quality
ery, and support. The following are examples
management system activities. Organizations
of factors that could be considered to qualify
should assess staffing effectiveness by evaluat-
suppliers:
ing human resource indicators (eg, overtime,
staff injuries, and staff satisfaction) in con-
䡲 Licensure, certification, or accreditation.
junction with operational performance indi-
䡲 Supply or product requirements.
cators (eg, adverse events and patient com-
䡲 Supplier-relevant quality documents.
plaints). The results of this evaluation should
䡲 Results of audits or inspections.
feed into the facility’s human resource plan-
䡲 Quality summary reports.
ning process along with projections based on
䡲 Customer complaints.
new or changing operational needs.
䡲 Experience with that supplier.
䡲 Cost of materials or services.
Suppliers and Materials Management 䡲 Delivery arrangements.
Materials, supplies, and services used as in- 䡲 Financial security, market position, and
puts to a process are considered critical if they customer satisfaction.
affect the quality of products and services be- 䡲 Support after sales.
ing produced. Examples of critical supplies are
blood components, blood bags, test kits, and A list of approved suppliers should be
reagents. Examples of critical services are maintained that includes both primary suppli-
infectious disease testing, blood component ers and suitable alternatives for contingency
irradiation, transportation, equipment cali- planning. Critical supplies and services should
bration, and preventive maintenance. The be purchased only from suppliers that have
suppliers of these materials and services may been qualified. Once suppliers are qualified,
be internal (eg, other departments within the periodic evaluations of supplier performance
same organization) or external (outside ven- help ensure suppliers’ continued ability to
dors). Supplies and services used in the collec- meet requirements. Tracking suppliers’ ability
tion, testing, processing, preservation, storage, to meet expectations gives the facility valuable
distribution, transport, and administration of information about the stability of each suppli-
blood components, cellular therapy products, er’s processes and commitment to quality.
tissues, and derivatives that have the potential Documented failures of supplies or suppliers
to affect quality should be qualified before use to meet defined requirements should result in
and obtained from suppliers who can meet the immediate action by the facility, including no-
facility’s requirements. Three important ele- tification of the supplier, quality oversight per-
ments of supplier and materials management sonnel, and management with contracting
are 1) supplier qualification; 2) agreements; authority, if applicable. Supplies may need to
and 3) receipt, inspection, and testing of in- be replaced or quarantined until all quality is-
coming supplies. sues are resolved.

Supplier Qualification Agreements

Critical supplies and services must be quali- Contracts and other agreements define expec-
fied on the basis of defined requirements. Sim- tations and reflect the concurrence of the par-
ilarly, suppliers should be qualified to ensure ties involved. Periodic reviews of agreements
10 䡲 AABB TECHNICAL MANUAL

ensure that the expectations of all parties con- tion, testing, storage, distribution, transport,
tinue to be met. Changes should be mutually and administration of blood, components, tis-
agreed upon and incorporated as needed. sues, and cellular therapy products also meet
Transfusion and cellular therapy services FDA requirements.
should maintain written contracts or agree- The facility must define acceptance crite-
ments with outside suppliers of critical mate- ria for critical supplies (see 21 CFR 210.3)3 and
rials and services, such as blood components, must develop procedures to control and pre-
cellular therapy products, irradiation, compat- vent the inadvertent use of materials that do
ibility testing, or infectious disease marker not meet specifications. Corrective action may
testing. An outside supplier may be another include returning the material to the vendor or
department within the same facility that is destroying it. Receipt and inspection records
managed independently, or it may be another enable the facility to trace materials that have
facility (eg, contract manufacturer). The con- been used in a particular process and provide
tracting facility assumes responsibility for the information for ongoing supplier qualifica-
manufacture of the product; ensuring the safe- tion.
ty, purity, and potency of the product; and en-
suring that the contract manufacturer com- Equipment Management
plies with all applicable product standards and
Equipment that must operate within defined
regulations. Both the contracting facility and
specifications to ensure the quality of blood
the contractor are legally responsible for the
components, cellular therapy products, tis-
work performed by the contractor.
sues, derivatives, and services is referred to as
It is important for the transfusion or cel-
“critical equipment” in the quality manage-
lular therapy service to participate in the eval-
uation and selection of suppliers. The service ment system. Critical equipment may include
should review contracts and agreements to en- instruments, measuring devices, and comput-
sure that all important aspects for their critical er systems (hardware and software).
Activities designed to ensure that equip-
materials and services are addressed. Exam-
ment performs as intended include qualifica-
ples of issues that could be addressed in an
tion, calibration, maintenance, and monitor-
agreement or contract include the responsibil-
ity for a product or blood sample during ship- ing. Calibration, functional and safety checks,
ment; the supplier’s responsibility to promptly and preventive maintenance should be sched-
notify the facility when changes have been uled and performed according to the manu-
made that could affect the safety of blood facturer’s recommendations and regulatory re-
components, cellular therapy products, tis- quirements of the FDA 2-4 and CMS.1 Written
sues, derivatives, or services for patients; and procedures for equipment use and control
the supplier’s responsibility to notify the facili- should comply with the manufacturer’s rec-
ty when information is discovered indicating ommendations unless an alternative method
that a product may not be considered safe, has been validated by the facility and, in some
such as during look-back procedures. instances, approved by the appropriate regula-
tory and accrediting agencies.
Receipt, Inspection, and Testing of When one selects new equipment, it is
important to consider not only the perfor-
Incoming Supplies
mance of the equipment as it will be used in
Before acceptance and use, critical materials the facility but also any issues regarding ongo-
such as reagents, blood components, cellular ing service and support by the supplier. There
therapy products, tissues, and derivatives should be a written plan for installation, oper-
should be inspected and tested (if necessary) ational, and performance qualifications.6 The
to ensure that they meet specifications for plan should provide for 1) installation accord-
their intended use. It is essential that supplies ing to the manufacturer’s specifications, 2)
used in the collection, processing, preserva- verification of the equipment’s functionality
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 11

before use by ensuring that the criteria estab- 䡲 Customer needs and expectations.
lished by the manufacturer for its intended use 䡲 Accreditation and regulatory requirements.
are met, and 3) assurance that the equipment 䡲 Specifications to be met.
performs as expected in the facility’s process- 䡲 Risk assessment.
es. After the equipment is installed, any prob- 䡲 Performance measures.
lems and follow-up actions taken should be 䡲 Nonconformance analyses.
documented. Recalibration and requalifica- 䡲 Current knowledge (eg, of other successful
tion may be necessary if repairs are made that practices).
affect the equipment’s critical operating func- 䡲 Resource needs (eg, financial, facility, hu-
tions. Recalibration and requalification should man, materials, and equipment).
also be considered when existing equipment is 䡲 Interrelationships of the new or changed
relocated. process(es) with other processes.
The facility must develop a mechanism to 䡲 Documents needed for the new or changed
uniquely identify and track all critical equip- process(es).
ment, including equipment software versions,
if applicable. The unique identifier assigned The documents developed should be re-
by the manufacturer may be used, or a unique viewed by management personnel with direct
identification code may be applied by the
authority over the process and by quality over-
transfusion or cellular therapy service or
sight personnel before implementation.
assigned through a laboratory-wide or organi-
zation-wide identification system. Maintain- Changes in policies, processes, and proce-
ing a list of all critical equipment helps in the dures should be documented, validated, re-
control function of scheduling and performing viewed, and approved. Additional information
functional and safety checks, calibrations, pre- on policies, processes, and procedures can be
ventive maintenance, and repair. The equip- found in the “Documents and Records” sec-
ment list can be used to ensure that all appro- tion later in this chapter.
priate actions have been performed and Once a process has been implemented,
recorded. Evaluating and trending equipment the facility should have a mechanism to
calibration, maintenance, and repair data help ensure that procedures are performed as de-
the facility assess equipment functionality, fined and that critical equipment, reagents,
manage defective equipment, and identify and supplies are used in conformance with
equipment needing replacement. When manufacturers’ written instructions and facili-
equipment is found to be operating outside
ty requirements. Table 1-1 lists elements that
acceptable parameters, the potential effects
constitute sound process control (among oth-
on the quality of products or test results must
er elements of a quality management system).
be evaluated and documented.
A facility using critical equipment, reagents, or
Process Management supplies in a manner that is different from the
manufacturer’s directions should validate such
Written and approved policies, processes, and use. If the activity is covered under regulations
procedures must exist for all critical functions for blood and blood components or HCT/Ps,
performed in the facility, and these functions
the facility may be required to request FDA ap-
must be carried out under controlled condi-
proval to operate at variance to requirements
tions. Each facility should have a systematic
approach for identifying, planning, and imple- (see 21 CFR 640.1202 or 21 CFR 1271.1554). If a
menting new (and making changes to existing) facility believes that changes to the manufac-
policies, processes, and procedures that affect turer’s directions would be appropriate, it
the quality of the facility’s tests, products, or should encourage the manufacturer to make
services. Such activities should include a re- such changes in the labeling (ie, the package
view of at least the following: insert or user manual).
12 䡲 AABB TECHNICAL MANUAL

TABLE 1-1. Components of a Quality Management System

Quality System Component Quality Functions and Responsibilities

Organization and leadership 䡲 Organization structure and function

䡲 Leadership roles and responsibilities, authority, and relationships
䡲 Establishment of a quality management system
䡲 Customer needs
䡲 Planned products and services
䡲 Documented, followed, and improved policies, processes, and
procedures
䡲 Quality representative
䡲 Management reviews
䡲 Provision of adequate resources
䡲 Adequate design and effective implementation
䡲 Conformance with requirements
䡲 Effective communication
䡲 Effective process improvement
Customer focus 䡲 Customer requirements
䡲 Agreements
䡲 Customer feedback
Facilities, work environment, and 䡲 Minimal health and safety risks
safety 䡲 Design and space allocations
䡲 Clean work environment
䡲 Controlled environment
䡲 Communication and information management systems
䡲 Storage facilities
䡲 Health and safety programs
䡲 Hazard discards
䡲 Emergency preparedness
Human resources 䡲 Adequate and qualified staff
䡲 Job descriptions and qualifications
䡲 Defined roles and responsibilities for all staff and their reporting
relationships
䡲 Staff selection
䡲 New hire orientation
䡲 Training on the quality system, job-related activities, computer use,
and safety
䡲 Staff competence
䡲 Continuing education
䡲 Staff identifying information
䡲 End-of-employment activities
Suppliers and materials 䡲 Supplier qualification
management 䡲 Qualifying materials
䡲 Agreement reviews
䡲 Inventory management
䡲 Adequate storage conditions
䡲 Receipt, inspection, and testing of incoming materials and products
䡲 Acceptance and rejection of materials and products
䡲 Tracing critical supplies and services
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 13

TABLE 1-1. Components of a Quality Management System (Continued)

Quality System Component Quality Functions and Responsibilities

Equipment management 䡲 Selection and acquisition

䡲 Unique identification code
䡲 Verification of performance
䡲 Installation, operational, and performance qualification
䡲 Calibration
䡲 Preventive maintenance and repairs
䡲 Retirement
Process management 䡲 Process development
䡲 Change control
䡲 Process validation
䡲 Process implementation
䡲 Adherence to policies, processes, and procedures
䡲 Quality control program
䡲 Inspection of products and services
䡲 Concurrent creation of records
䡲 Requirements for critical activities
䡲 Traceability
Documents and records 䡲 Standardized formats
䡲 Document creation
䡲 Unique identification code
䡲 Review and approval process
䡲 Document use and maintenance
䡲 Change control
䡲 Record archiving and storage
䡲 Record retention and destruction
Information management 䡲 Confidentiality
䡲 Prevention of unauthorized access
䡲 Data integrity
䡲 Data backup
䡲 Alternative system
Management of nonconforming 䡲 Detection of deviations and nonconformances
events 䡲 Complaint file
䡲 Adverse event reporting
䡲 Investigations
䡲 Immediate actions
Monitoring and assessment 䡲 Monitoring and assessment of specified requirements
䡲 Quality indicators
䡲 Internal and external assessments
䡲 Laboratory proficiency testing
䡲 Data analyses
Process improvement 䡲 Identifying opportunities for improvement
䡲 Systems approach to continual improvement
䡲 Root cause evaluation
䡲 Corrective action plans
䡲 Preventive action plans
䡲 Monitoring for effectiveness
14 䡲 AABB TECHNICAL MANUAL

Process Validation specifications before reporting patient results.1

At a minimum, the following must be estab-
Validation is used to demonstrate that a pro-
lished for the test system:
cess is capable of consistently and reliably
achieving planned results.13 It is critical to vali-
䡲 Accuracy.
date processes in situations where it is not fea-
䡲 Precision.
sible to measure or inspect each finished prod-
䡲 Reportable range of test results for the test
uct or service to fully verify conformance with
system.
specifications. However, even when effective
䡲 Reference intervals (normal values).
end-product testing can be achieved, it is ad-
䡲 Analytical sensitivity.
visable to validate important processes to gen-
䡲 Analytical specificity, including interfering
erate information that can be used to optimize
substances.
performance. Prospective validation is used
䡲 Any other performance characteristic re-
for new or revised processes. Retrospective
quired for test performance (eg, specimen
validation may be used for processes that are
or reagent stability).
already in operation but were not adequately
validated before implementation. Concurrent
Based on performance specifications, the
validation is used when required data cannot
laboratory must also establish calibration and
be obtained without performance of a “live”
control procedures and document all activities
process. If concurrent validation is used, data
for test method validation. (See 42 CFR
are reviewed at predefined periodic intervals
before full implementation receives final ap- 493.1253.1)
proval. Modifications to a validated process
may warrant revalidation, depending on the
nature and extent of the change. It is up to the Validation Plan
facility to determine the need for revalidation Validation should be planned if it is to be effec-
on the basis of its understanding of how the tive. Development of a validation plan is best
proposed changes may affect the process. accomplished after one obtains an adequate
understanding of the system or framework
within which the process will occur. The plan
Test Method Validation should include conducting the process as de-
When the laboratory wishes to implement a signed. Additionally, a significant amount of
nonwaived test using an FDA-approved or effort should be targeted at attempts to
-cleared test system, CLIA requires that the “break” the process to identify weaknesses and
performance specifications established by the limitations. Many facilities develop a template
manufacturer be verified by the laboratory be- for the written validation plan to ensure that
fore it reports patient results.1 At a minimum, all aspects are adequately addressed. Although
the laboratory must demonstrate that it can no single format for a validation plan is re-
obtain performance specifications compara- quired, most plans include the following com-
ble to those of the manufacturer for accuracy, mon elements:
precision, reportable range, and reference in-
tervals (normal values). 䡲 System description.
If the laboratory develops its own meth- 䡲 Purpose or objectives.
od, introduces a test system not subject to FDA 䡲 Risk assessment.
approval or clearance, or makes modifications 䡲 Responsibilities.
to an FDA-approved or -cleared test system, or 䡲 Validation procedures.
if the manufacturer does not provide perfor- 䡲 Acceptance criteria.
mance specifications, then the laboratory 䡲 Approval signatures.
must establish the test system performance 䡲 Supporting documentation.
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 15

The validation plan should be reviewed its and specifications supplied by the
and approved by quality oversight personnel manufacturer.
before the validation activities are carried out. 䡲 Performance qualification demonstrates
Staff responsible for carrying out the vali- that the equipment performs as expected
dation activities should be trained in the pro- for its intended use in the processes estab-
cess before the plan is executed. The results lished by the facility and that the output
and conclusions of these activities may be ap- meets the facility’s specifications. It evalu-
pended to the approved validation plan or ates the adequacy of equipment for use in a
may be recorded in a separate document. This specific process that uses the facility’s own
documentation typically contains the follow- personnel, procedures, and supplies in a
ing elements: normal working environment.

䡲 Expected and observed results. Computer System Validation

䡲 Interpretation of results as acceptable or
The FDA considers computerized systems to
unacceptable. include “hardware, software, peripheral devic-
䡲 Corrective action for and resolution of un-
es, networks, personnel, and documenta-
expected results.
tion.”21 End-user validations of computer sys-
䡲 Explanation of and rationale for any devia-
tems and the interfaces between systems
tions from the validation plan.
should be conducted in the environment in
䡲 Conclusions and limitations.
which they will be used. Testing by the com-
䡲 Approval signatures.
puter software vendor or supplier is not a sub-
䡲 Supporting documentation.
stitute for computer validation at the facility.
䡲 Implementation timeline.
End-user acceptance testing may repeat some
When a validation process does not pro- of the validation performed by the developer,
duce the expected outcome, its data and cor- such as load or stress testing and verification
rective actions must be documented as well. of security, safety, and control features, to eval-
The responsible quality oversight personnel uate performance under actual operating con-
ditions. In addition, the end user should evalu-
should provide final review and approval of
ate the ability of personnel to use the
the validation plan, results, and corrective ac-
computer system as intended within the con-
tions and determine whether new or modified
text of actual work processes. The hardware
processes and equipment may be implement-
and software interface should be designed so
ed as planned or implemented with specified
that staff can navigate successfully and re-
limitations.
spond appropriately to messages, warnings,
and other functions. If changes to the comput-
Equipment Validation
er system result in changes to the way a pro-
Validation of new equipment used in a process cess is performed, process revalidation should
should include installation, operational, and also be performed. As with process validation,
performance qualifications, as follows20: quality oversight personnel should review
and approve validation plans, results, and
䡲 Installation qualification demonstrates that corrective actions and should determine wheth-
the instrument is properly installed in envi- er implementation may proceed with or with-
ronmental conditions that meet the manu- out limitations.
facturer’s specifications. For additional information, facilities
䡲 Operational qualification demonstrates should refer to FDA guidance on computer
that the installed equipment operates as in- system validation in the user’s facility.21 Those
tended. It focuses on the equipment’s capa- who develop their own software should con-
bility to operate within the established lim- sult Title 21 CFR Part 880 and FDA guidance
16 䡲 AABB TECHNICAL MANUAL

regarding general software validation princi- they must be controlled, what their require-
ples.22 ments are, and how to implement them. Rec-
ords provide evidence of what did happen
Quality Control (ie, that a process was performed as intend-
ed), and provide information needed to as-
QC testing is performed to ensure the proper
sess product and service quality. Together,
functioning of materials, equipment, and
documents and records are used by quality
methods during operations. QC performance
oversight personnel to evaluate the effective-
expectations and acceptable ranges should be
ness of a facility’s policies, processes, and
defined and be made readily available to staff
procedures. ISO 9001 provides an example of
so they will recognize, and respond appropri-
quality system documentation that includes
ately to, unacceptable results and trends. The
frequency for QC testing is determined by the the following items13:
facility in accordance with the applicable
䡲 The quality policy and objectives.
CMS, FDA, AABB, state, and manufacturer re-
䡲 A description of the interactions between
quirements. QC results should be documented
concurrently with performance.2 Records of processes.
䡲 Documented procedures for the control of
QC testing should include the following:
documents, records, and nonconforming
䡲 Identification of personnel performing the products and for corrective action, preven-
test. tive action, and internal quality audits.
䡲 Identification of reagents (including lot 䡲 Records related to the quality management
numbers and expiration dates). system, operational performance, and
䡲 Identification of equipment. product or service conformance.
䡲 Testing date and, when applicable, time. 䡲 All other “documents needed by the organi-
䡲 Results. zation to ensure the effective planning, op-
䡲 Interpretation (eg, meets or fails to meet es- eration, and control of its processes.”
tablished criteria).
䡲 Reviews. Written policies, process descriptions,
procedures, work instructions, job aids, labels,
Unacceptable QC results must be investi- forms, and records are all part of the facility’s
gated and corrective action must be imple- document management system. They may be
mented, if indicated, before the QC procedure paper based or electronic. A document man-
is repeated or the operational process is con- agement system provides assurance that doc-
tinued. If products or services have been pro- uments are comprehensive, current, and
vided since the last acceptable QC results were available and that records are accurate and
obtained, it may be necessary to evaluate the complete. A well-structured document man-
conformance of these products or services. agement system links policies, process de-
Examples of QC performance intervals for scriptions, procedures, forms, and records to-
equipment and reagents are included in Ap- gether in an organized and workable system.
pendix 1-3.
Documents
Documents and Records
Documents should be developed in a format
Documentation provides a framework for that conveys information clearly and provides
understanding and communicating about staff with the necessary instructions and
processes throughout the organization. Doc- templates for recording data. The CLSI offers
uments provide a description of or instruc- guidance regarding general levels of
tions regarding what is supposed to happen. documentation11 as well as detailed instruc-
Documents describe how processes are in- tions on how to write procedures.23 General
tended to work, how they interact, where types of documentation are described below.
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 17

POLICIES. Policies communicate the organi- the requirements in a document management

zation’s highest-level goals, objectives, and in- system. Many facilities maintain a master set
tent. The rest of the organization’s documenta- of labels that can be used as a reference to veri-
tion interprets, and provides instructions fy that only currently approved stock is in use.
regarding implementation of, these policies. The accuracy of new stock labels should be
verified before this stock is put into inventory;
PROCESSE S. Process documents describe a
comparison against a master label provides a
sequence of actions and identify responsibili-
mechanism for this verification. Change con-
ties, decision points, requirements, and accep-
trol procedures should be established for the
tance criteria. Process diagrams or flowcharts
use of on-demand label printers to prevent
are often used for this level of documentation.
nonconforming modifications of label format
It is helpful to show process control points on
a diagram as well as the flow of information or content.
Each facility should have a defined pro-
and handoffs between departments or work
groups. cess for developing and maintaining docu-
ments. This process should identify basic ele-
PROCEDURES, WORK INSTRUCTIONS, AND ments required for documents; procedures for
JOB AIDS. These documents provide step-by- review and approval of new or revised docu-
step directions on performing job tasks and ments; a method for keeping documents cur-
procedures. Procedures and work instructions rent; a process for control of document distri-
should include enough detail to perform a task bution; and a process for archiving, protecting,
correctly but not so much as to be difficult to and retrieving obsolete documents. Training
read. The use of standardized formats helps should be provided to the staff responsible for
staff know where to find specific elements and the content of new or revised documents. Doc-
facilitates implementation and control. Job ument management systems include these es-
aids are excerpted from an approved docu- tablished processes:
ment and condense information into a short-
er, more readily viewable format. External doc- 䡲 Verifying the adequacy of the document be-
uments (eg, from a manufacturer’s manual or fore its approval and issuance.
package insert) may also be incorporated into 䡲 Periodically reviewing, modifying, and re-
the facility’s procedures manual by reference. approving documents as needed to keep
Relevant procedures should be available to the them current.
staff in each area in which the corresponding 䡲 Identifying changes and revision status.
job tasks are performed.2,5,8 䡲 Ensuring that documents are legible, iden-
tifiable, and readily available in the loca-
FORMS. Forms provide templates for captur-
ing data on paper or electronically. These doc- tions in which they will be used.
䡲 Retaining and retrieving previous versions
uments specify the data requirements called
for in SOPs and processes. Forms should be for the required retention period.
䡲 Preventing unintended use of outdated or
carefully designed to be easy to use, minimize
obsolete documents.
the likelihood of errors, facilitate data and in-
䡲 Protecting documents from alteration,
formation retrieval, effectively capture out-
damage, or unintended destruction.
comes, and support process traceability. When
it is not immediately evident what data should
External documents that are incorporated
be recorded or how to record them, forms
by reference become part of the document
should include instructions for their use.
management system and should be identified
Forms should indicate units of measure for
recording quantitative data. and controlled. The facility should have a
mechanism to detect changes to external doc-
LA BELS. Product labels, such as blood com- uments in its system, such as manufacturers’
ponent or HCT/P labels, are subject to many of package inserts or user manuals, so that corre-
18 䡲 AABB TECHNICAL MANUAL

sponding changes to procedures and forms 䡲 Creation of copies or backups.

can be made. 䡲 Retention periods.
When new or revised policies, process de- 䡲 Confidentiality.
scriptions, procedures, or forms are added to
or replaced in the facility’s manual, these doc- Records review is an important tool to
uments should be marked with the date on help evaluate the effectiveness of the quality
which they were first put into use (ie, effective management system. The facility should de-
date). fine a process and time frames for records re-
One copy of retired documents should be view to ensure accuracy, completeness, and
retained as defined by existing and applicable appropriate follow-up. It should determine
standards and regulations. how reports and records are to be archived and
A master list of all current policies, pro- how to define their retention period. Specific
cess descriptions, procedures, forms, and la- requirements for records to be maintained by
bels is useful for maintaining document con- AABB-accredited facilities are included in the
trol. It should include document titles, relevant AABB standards.
individuals or work groups responsible for Record-keeping systems should allow for
maintaining each document, revision dates, ready retrieval of records within time frames
unique document identifiers, and the areas in established by the facility and permit trace-
which each document is used. It should also ability of blood components, cellular therapy
identify the number and locations of con- products, tissues, and derivatives as required
trolled copies in circulation. Copies of docu- by federal regulations.2,4 When copies of rec-
ments that are used in the workplace should ords are retained, the facility should verify that
be identified and controlled to ensure that each copy contains the complete, legible, and
none are overlooked when changes are imple- accessible content of the original record before
mented. the original is destroyed.
If records are maintained electronically,
Records adequate backups should exist in case of sys-
tem failure. Electronic records should be read-
Records provide evidence that critical steps in able for the entire duration of their retention
a procedure have been performed appropri- period. Obsolete computer software that is
ately and that products and services conform necessary to reconstruct or trace records
to specified requirements. Records should be should also be archived appropriately. If the
created concurrently with the performance of equipment or software used to access archived
each significant step and should clearly indi- data cannot be maintained, the records should
cate the identity of the individuals who per- be converted to another format or copied to
formed each step and when each step was another medium to permit continued access.
completed.2,6,7 Data should be recorded in a Converted data should be verified against the
format that is clear and consistent. When original to ensure completeness and accuracy.
forms are used for capturing or recording data, Electronic media such as magnetic tapes, opti-
steps, or test results, the forms become rec- cal disks, or online remote servers are widely
ords. used for archiving documents. Records kept in
The process for managing records should this manner must meet FDA requirements for
address the following items: electronic record-keeping.24 Microfilm or mi-
crofiche may also be used to archive records.
䡲 Creation and identification of records. The medium selected should be appropriate
䡲 Protection from accidental or unauthorized to comply with the retention requirements.
modification or destruction. Each facility must have a policy for alter-
䡲 Verification of completeness, accuracy, and ing or correcting records. 6 The date of the
legibility. changes and the identity of the individual
䡲 Storage and retrieval. making each change must be documented. In
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 19

some instances, it may also be important to in- The facility should maintain a record of
dicate the reason for the change. The original names; inclusive dates of employment; and
wording must not be obliterated in written corresponding signatures, identifying initials,
records; the original may be crossed out with a or identification codes of personnel autho-
single line, but it should remain legible. Write- rized to create, sign, initial, or review reports
overs and scratch-outs should not be used. and records. Magnetically coded employee
Electronic records must permit tracking of badges and other computer-related identify-
both original and corrected data and must in- ing methods are generally accepted in lieu of
clude the date and identity of the person who written signatures, provided that the badges or
made the change. There should be a process other methods meet electronic record-keeping
for controlling changes. A method for refer- requirements.
encing changes to records that is linked to the
original record and a system for reviewing Information Management
changes for completeness and accuracy are es-
sential. Audit trails for changed data in com- The quality management system should en-
puterized systems are required by the FDA.24 sure the confidentiality and appropriate use of
The following issues might be considered data and information in both oral and written
when planning record storage: communications. Privacy of patient and donor
records should be addressed to maintain the
䡲 Storage of records in a manner that protects security and confidentiality of such records.
them from damage and accidental or unau- The system should prevent unauthorized
thorized destruction or modification. access, modification, or destruction of the
䡲 Degree of accessibility of records in propor- data and information. Individuals who are au-
tion to frequency of their use. thorized to make changes to data should be
䡲 Method and location of record storage re- defined by name, code, or job responsibility.
lated to the volume of records and the Information systems should be designed with
amount of available storage space. security features to prevent unauthorized ac-
䡲 Availability of properly functioning equip- cess and use. Systems may include levels of se-
ment, such as computer hardware, and curity defined by job responsibility and re-
software to view archived records. quire the use of security codes and passwords
䡲 Documentation that all records copied, or, for paper-based systems, locked cabinets
transferred to microfiche, or converted to and keys.
digital files legitimately replace originals The integrity of data should be main-
that are stored elsewhere or destroyed. tained so that data are retrievable and usable.
䡲 Retention of original color-coded records Periodic integrity checks should be conducted
when only black-and-white reproductions to ensure that critical data have not been inad-
are available. vertently modified, been lost, or become
inaccessible. When data are sent manually or
Considerations for electronic records in- electronically from one point to another, a
clude the following: process should be in place to ensure that the
data accurately and reliably reach their final
䡲 A method of verifying the accuracy of data destination in a timely manner.
entry. Backup versions (eg, disks, tapes, or du-
䡲 Prevention of unintended deletion of data plicate hard copies) of critical data should be
or access by unauthorized persons. maintained in the event of an unexpected loss
䡲 Adequate protection against inadvertent from the storage medium. It is advisable to
data loss (eg, when a storage device is full). store backup or archived computer records
䡲 Validated safeguards to ensure that a record and databases off-site at a sufficient distance
can be edited by only one person at a time. away to ensure that disasters will not affect
䡲 Security of and access to confidential data. both the originals and the backups. The
20 䡲 AABB TECHNICAL MANUAL

backup storage facility should be secure. Envi- basis of investigations and root cause anal-
ronmental conditions in the backup storage yses.
facility should be maintained in a way that 䡲 Implement preventive actions as appropri-
protects and preserves the equipment and ate on the basis of analyses of aggregate
media for the duration of their storage. Tem- data about events and their causes.
perature and humidity should be monitored 䡲 Report to external agencies when required.
and controlled. Archival copies of computer 䡲 Evaluate effectiveness of the corrective ac-
operating systems and applications software tions and preventive actions taken.
required to view original records should be
stored in the same manner. The CLSI has published a consensus stan-
The facility should develop and maintain dard on occurrence management that ex-
alternative systems to ensure access to critical plores event management in more detail.25
data and information in the event that com- Facility personnel should be trained to
puterized data or primary sources of informa- recognize and report such occurrences. De-
tion are not available. The backup and recov- pending on the severity of an event and risk to
er y procedures for computer downtime patients, donors, and products as well as the
should be defined, and validation documenta- likelihood of recurrence, investigation of con-
tion should show that the backup system tributing factors and underlying causes may
works properly. The associated processes be warranted. The cGMP regulations require
should be tested periodically to ensure that investigation and documentation of results if a
the backup system remains effective. Special specific event could adversely affect patient
consideration should be given to staff compe- safety or the safety, purity, or potency of blood
tence and readiness to use the backup system. or components. 2 , 3 The cGTP regulations
require similar activities for deviations and
Management of Nonconforming possible product contamination or communi-
Events cable disease transmission. 4 Tools and ap-
proaches for performing root cause analysis
The quality management system should in- and implementing corrective action are dis-
clude a process for detecting, investigating, cussed in the section on “Process Improve-
and responding to events that result in devia- ment.” A summary of each event, investiga-
tions from accepted policies, processes, and tion, and any follow-up activities must be
procedures or in failures to meet require- prepared. Table 1-2 outlines suggested com-
ments, as defined by the facility, AABB stan- ponents of an internal event report.
dards, or applicable regulations.2-4 This pro- Fatalities related to blood collection or
cess should be implemented after, for transfusion or to HCT/Ps must be reported as
example, the discovery of nonconforming soon as possible to the FDA Center for Biolog-
products and services or of adverse reactions ics Evaluation and Research (CBER). [See 21
to donation, blood components, cellular ther- CFR 606.170(b) and 1271.350(a)(i), respective-
apy products, tissues, or derivatives. The facili- ly.] Instructions for reporting to CBER are
ty should define how to perform the following available in published guidance27 and on the
for nonconforming events: FDA website.28 A written follow-up report must
be submitted within 7 days of the fatality and
䡲 Document and classify occurrences. should include a description of any new pro-
䡲 Determine the effect, if any, on the quality cedures implemented to avoid recurrence.
of products or services. AABB Association Bulletin #04-06 provides ad-
䡲 Evaluate the effect on interrelated activities. ditional information on these reporting re-
䡲 Analyze the event to understand root quirements, including a form for reporting do-
causes. nor fatalities.29
䡲 Implement corrective action as appropri- Regardless of their licensure and registra-
ate, including notification and recall, on the tion status with the FDA, all donor centers,
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 21

TABLE 1-2. Components of an Internal Event Report26

Component Examples

Who 䡲 Reporting individual(s)

䡲 Individual(s) involved (by job title) in committing, compounding, discovering, investi-
gating, and initiating any immediate action
䡲 Patient or donor identification code
䡲 Reviewer(s) of report
What 䡲 Brief description of event
䡲 Effects on and outcomes for patient, donor, blood component, or tissue
䡲 Name of component and unit identification number
䡲 Manufacturer, lot number, and expiration dates of applicable reagents and supplies
䡲 Immediate actions taken
When 䡲 Date of report
䡲 Date and time event occurred
䡲 Date and time of discovery
䡲 Date (and time, if applicable) that immediate action was taken

And as applicable, date and time of:

䡲 Blood component collection, processing steps, and shipping
䡲 Order for blood component
䡲 Order for patient testing
䡲 Patient sample collection, transport, and receipt
䡲 Test performance and reporting
Where 䡲 Physical location of event
䡲 Where in process event was detected
䡲 Where in process event was initiated
Why and How 䡲 How event occurred
䡲 Contributing factors to event
䡲 Root cause(s)
Follow-up 䡲 External reports or notifications (eg, regulatory* or accreditation agencies, manufac-
turer, or patient’s physician)
䡲 Corrective actions
䡲 Implementation dates
䡲 Effectiveness of actions taken
䡲 Linkage to preventive action if appropriate
*All blood establishments (including licensed, registered but unlicensed, and unregistered transfusion services)2 (21 CFR
606.121) are required to notify the FDA of deviations from cGMP, applicable standards, or established specifications that
may affect the safety, purity, or potency of biological products or otherwise cause the biological products to be in violation
of the Food, Drug, and Cosmetic Act or the Public Health Service Act (21 CFR 600.14).2 The FDA has identified the following
examples as reportable events if components or products are released for distribution:
䡲 Arm preparation not performed or performed incorrectly.
䡲 Units released from donors who are (or should have been) either temporarily or permanently deferred because of their
medical history or a history of repeatedly reactive viral marker tests.
䡲 Shipment of a unit with repeatedly reactive viral markers.
䡲 ABO/Rh or infectious disease testing not performed according to the manufacturer’s package insert.
䡲 Units released from donors for whom test results were improperly interpreted because of testing errors related to
improper use of equipment.
䡲 Units released before completion of all tests (except as an emergency release).
䡲 Sample used for compatibility testing that contains incorrect identification.
䡲 Testing error that results in the release of an incorrect unit.
䡲 Incorrectly labeled blood components (eg, ABO group or expiration date).
(Continued)
22 䡲 AABB TECHNICAL MANUAL

TABLE 1-2. Components of an Internal Event Report26 (Continued)

䡲 Incorrect crossmatch label or tag.

䡲 Storage of biological products at an incorrect temperature.
䡲 Microbial contamination of blood components when the contamination is attributed to an error in manufacturing.
Deviations involving distributed HCT/Ps and relating to core cGTP requirements must also be reported to the FDA if they
occurred in the facility or in a facility that performed a manufacturing step for the facility under contract, agreement, or other
arrangement.4 Each report must contain a description of the HCT/P deviation, information relevant to the event and the
manufacture of the HCT/Ps involved, and information on all follow-up actions that have been or will be taken in response to
the deviation.
CFR = Code of Federal Regulations, FDA = Food and Drug Administration; cGMP = current good manufacturing practice;
HCT/Ps = human cells, tissues, and cellular and tissue-based products; cGTP = current good tissue practice.

blood banks, and transfusion services must components having major blood group in-
promptly report biological product devia- compatibilities.9,10
tions—and information relevant to these Hemovigilance processes also provide the
events—to the FDA2,30 using Form FDA-3486 opportunity to detect, investigate, and re-
when the event 1) is associated with manufac- spond to adverse transfusion reactions and
turing (ie, collecting, testing, processing, pack- events that result in deviations from safe blood
ing, labeling, storing, holding, or distributing); transfusion and collection practices. Adverse
2) represents a deviation from cGMP, estab- transfusion reactions and events (or incidents)
lished specifications, or applicable regula- can be reported voluntarily to the Centers for
tions or standards or that is unexpected or un- Disease Control and Prevention (CDC) Nation-
foreseen; 3) may affect the product’s safety, al Healthcare Safety Network (NHSN) Hemo-
purity, or potency; 4) occurs while the facility vigilance Module. This system was developed
had control of, or was responsible for, the through a public-private collaboration that in-
product; and 5) involves a product that has left cluded the Department of Health and Human
Services and its agencies, and the private sec-
the facility’s control (ie, has been distributed).
tor, including AABB, America’s Blood Centers,
Using the same form, facilities must also
and the American Red Cross. The AABB Center
promptly report biological product deviations
for Patient Safety, a licensed Patient Safety Or-
associated with a distributed HCT/P if the
ganization, works with hospitals to provide ad-
event represents a deviation from applicable
ditional analysis and benchmarking of hospi-
regulations, standards, or established specifi-
tal transfusion event reports, while protecting
cations that relate to the prevention of com-
data confidentiality. AABB also administers
municable disease transmission or HCT/P the AABB United States Donor Hemovigilance
contamination. This requirement pertains to Program where blood collectors can report,
events that are unexpected or unforeseeable analyze, and benchmark adverse donor reac-
but may relate to the transmission or potential tions.
transmission of a communicable disease or Each facility should track reported events
may lead to HCT/P contamination.4 More in- and look for trends. The use of classification
formation concerning biological product devi- schemes may facilitate trend analysis and typi-
ation reporting can be found on the FDA web- cally involves one or more of the following cat-
site.31 egories: the nature of the event, the process (or
There must also be a mechanism to re- procedure) in which the event occurred, the
port medical device adverse events to the FDA outcome and severity of the event, and the
and the device manufacturer. 8,32 The Joint contributing factors and underlying causes. If
Commission encourages reporting of sentinel several events within a relatively short period
events, including hemolytic transfusion reac- involve a particular process or procedure, that
tions involving the administration of blood or process or procedure should be further inves-
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 23

tigated. The most useful schemes involve the Occasionally, there may be a need for a fa-
use of multiple categories for each event, cility to deviate from approved procedures to
which allows data to be sorted in a variety of meet the unique medical needs of a particular
ways so that patterns that were previously not patient. When this situation arises, a medically
obvious can emerge. (See example in Table 1- indicated exception should be planned and
3.) Such sorting or stratification can result in approved in advance by the facility’s medical
identification of situations that require closer director. The rationale and nature of the
monitoring or problems needing corrective or planned exception should be documented.
preventive action. For smaller facilities that Careful consideration should be given to
may not have sufficient data to identify trends, maintaining a controlled process and verifying
pooling data with a larger entity (eg, the labo- the safety and quality of the resulting product
ratory or all transfusion services in a health- or service. Any additional risk to the patient
care system) or following national trends from must be disclosed.
data provided by organizations such as the
AABB, CAP, or The Joint Commission, may also Monitoring and Assessment
prove helpful. The extent of monitoring and The quality management system should de-
the length of time to monitor processes de- scribe how the facility monitors and evaluates
pends on the frequency and critical aspects of its processes. Assessments are systematic ex-
the occurrences. Reporting and monitoring of aminations to determine whether actual activ-
events are essential problem identification ities comply with planned activities, are imple-
methods for process improvement activities in mented effectively, and achieve objectives.
a quality management system. Depending on the focus, assessments can

TABLE 1-3. Example of an Event Classification

Event: A unit of Red Blood Cells from a directed donor was issued to the wrong oncology patient. The unit
was not transfused.

Event Classification
䡲 Type of event: patient
䡲 Procedure involved: issuing products
䡲 Process involved: blood administration
䡲 Product involved: Red Blood Cells
䡲 Location: transfusion service
䡲 Other factors: directed donor
䡲 Other factors: oncology patient

Underlying Causes
䡲 Proximate cause: two patients with similar names had crossmatched blood available
䡲 Root cause: inadequate procedure for verification of patient identification during issue

Outcome
䡲 Severity: serious, FDA reportable
䡲 Patient: no harm, correct product was obtained and transfused
䡲 Product: no harm, product returned to inventory
䡲 Donor: not applicable

Successful Barriers
䡲 Problem detected during the patient identification verification step of blood administration

FDA = Food and Drug Administration.

24 䡲 AABB TECHNICAL MANUAL

include: 1) evaluation of process outputs (ie, with assessment results should be reviewed by
results); 2) the activities that make up a pro- executive management.
cess as well as its outputs; or 3) a group of re-
lated processes and outputs (ie, the system). Quality Indicators
Assessments can be internal or external
Quality indicators are performance measures
and can include quality assessments, peer re-
designed to monitor one or more processes
views, self-assessments, and proficiency test-
during a defined time and are useful for evalu-
ing. Evaluations typically include comparisons
ating service demands, production, personnel,
of actual to expected results.
inventory control, and process stability. These
indicators can be process based or outcome
Internal Assessments
based. Process-based indicators measure the
Internal assessments may include evaluations degree to which a process can be consistently
of quality indicator data, targeted audits of a performed. An example of a process-based in-
single process, or system audits that are dicator is turnaround time from blood product
broader in scope and may cover a set of inter- ordering until transfusion. Outcome-based in-
related processes. These assessments should dicators are often used to measure what does
be planned and scheduled. The details of who or does not happen after a process is or is not
performs the assessments and how they are performed. The number of incorrect test result
performed should be addressed. Assessments reports is an example of such an indicator. For
should cover the quality system and the major each indicator, thresholds are set that repre-
operating systems in the donor center and sent warning limits, action limits, or both.
transfusion or cellular therapy service. These thresholds can be determined from reg-
In addition, there should be a process for ulatory or accreditation requirements, bench-
responding to the issues raised as a result of marking, or internal facility data.
the assessment, including review processes Tools frequently used for displaying qual-
and time frames. The results should be docu- ity indicator data are run charts and control
mented and submitted to management per- charts. In a run chart, time is plotted on the
sonnel who have authority over the process as- x-axis and values on the y-axis. In control
sessed as well as to executive management. charts, the mean of the data and the upper and
Management should develop corrective ac- lower control limits, which have been calculat-
tion plans with input from operational staff ed from the data, are added to the chart. Single
and quality oversight personnel for any defi- points outside the upper and lower control
ciencies noted in the assessment. Quality limits result from special causes. Statistical
oversight personnel should track progress to- rules for interpreting consecutive points out-
ward implementation of corrective actions side 1 standard deviation (SD), 2 SDs, and 3
SDs should be used to recognize a process that
and monitor them for effectiveness.
is out of control. The root cause should be de-
To make the best use of these assess-
termined, and corrective action should be ini-
ments, there should be a process to track,
tiated, if indicated.
monitor trends in, and analyze the problems
identified so that opportunities for improve-
Blood Utilization Assessment
ment can be recognized. Early detection of
trends makes it possible to develop preventive The activities of blood usage review commit-
actions before patient safety, blood, compo- tees in the transfusion setting are an example
nents, tissues, or derivatives are adversely af- of internal assessment. Guidelines are avail-
fected. Evaluation summaries provide infor- able from the AABB for both adult and pediat-
mation that is useful for addressing individual ric utilization review.34-36 Peer review of trans-
or group performance problems and ensuring fusion practices, required by the AABB, is also
the adequacy of test methods and equipment. required by The Joint Commission9 for hospi-
Any corrective or preventive action associated tal accreditation, by CMS1 for hospitals to
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 25

qualify for Medicare reimbursement, and by evolving technologies and products, such as
some states for Medicaid reimbursement. growth factors and cytokines.
Transfusion audits provide reviews of pol-
icies and practices to ensure safe and appro- External Assessments
priate transfusions and are based on measur-
External assessments include inspections, sur-
able, predetermined performance criteria.
veys, audits, and assessments performed by
(See Chapter 28.) Transfusion services should
those not affiliated with the organization, such
investigate an adequate sample of cases (eg,
as the AABB, CAP, CMS, COLA, FACT, the FDA,
5% of cases within a defined time frame or 30
The Joint Commission, or state and regional
cases, whichever is larger). Audits assess a fa-
health departments. Participation in an exter-
cility’s performance and effectiveness in the
nal assessment program provides an indepen-
following6:
dent objective view of the facility’s performance.
External assessors often bring broad-based ex-
䡲 Ordering practices.
perience and knowledge of best practices that
䡲 Patient identification.
can be shared. Such assessments are increas-
䡲 Sample collection and labeling.
ingly being performed unannounced or with
䡲 Infectious and noninfectious adverse events.
minimal notification.
䡲 Near-miss events.
In the preparation phase, there is typically
䡲 Usage and discard.
some data gathering and information to sub-
䡲 Appropriateness of use.
mit to the organization performing the assess-
䡲 Blood administration policies.
ment. To prepare, facilities can perform inter-
䡲 Ability of services to meet patient needs.
nal audits and conduct drills to ensure that
䡲 Compliance with peer-review recommen-
staff can answer questions. For most external
dations.
assessments, there is an increased emphasis
䡲 Critical laboratory results before and after
on observations of the processes and dialogue
transfusion.
with nonmanagement staff, so preparation is
key. During the assessment phase, it is impor-
One method of assessing the blood ad-
tant to know who is responsible for the asses-
ministration process is to observe a predeter-
sors or inspectors while they are in the facility.
mined number of transfusions by following a
Clear descriptions of what information can be
unit of blood as it is issued for transfusion and
given to these individuals—and in what form—
is then transfused.34
help the facility through the assessment or
Assessments of transfusion safety policy
inspection process. After the assessment,
and practice may include reviews of transfu-
identified issues should be addressed. Usually,
sion reactions and transfusion-transmitted
a written response is submitted.
diseases. The review committee may monitor
policies and practices for notifying recipients
Proficiency Testing for Laboratories
or recipients’ physicians of recalled products
and notifying donors of abnormal test results. Proficiency testing (PT) is one means for deter-
Other assessments important in transfusion mining that test systems (including methods,
practice include reviews of policies for in- supplies, and equipment) are performing as
formed consent, indications for transfusion, expected. As a condition for certification, CMS
releases of directed donor units, and outpa- requires laboratories to participate successful-
tient or home transfusions. Additional assess- ly in an approved PT program for CLIA-
ments should include, where appropriate, 1) regulated testing. When no approved PT
therapeutic apheresis; 2) use of blood recov- program exists for a particular analyte, the lab-
ery devices; 3) procurement and storage of he- oratory must have another means to verify the
matopoietic progenitor cells; 4) perioperative accuracy of the test procedure at least twice
autologous blood collection; 5) procurement annually.1 Some accrediting agencies may re-
and storage of tissue; and 6) evaluation of quire more frequent verification of accuracy.
26 䡲 AABB TECHNICAL MANUAL

PT must be performed using routine work American Society for Quality.37-39 The Joint
processes and conditions if it is to provide Commission standards for performance im-
meaningful information. PT samples should provement are outlined in Table 1-4.9,10
generally be handled and tested in the same Corrective action is defined as action tak-
way as patient or donor specimens. However, a en to address the root causes of an existing
CLIA-certified laboratory is prohibited from nonconformance or other undesirable situa-
discussing the PT or sending the samples to a tion to reduce or eliminate the risk of recur-
laboratory with a different CLIA number dur- rence. Preventive action is defined as action
ing the active survey period, even if the two taken to reduce or eliminate the potential for a
laboratories are within the same organization nonconformance or other undesirable situa-
and that would be the routine manner for han- tion to prevent occurrence. Corrective action
dling patient or donor specimens. Supervisory can be thought of as a reactive approach to ad-
review of the summary evaluation report dress the root causes of actual nonconfor-
should be documented along with investiga- mances, deviations, complaints, and process
tion and corrective action for unacceptable re- failures, whereas preventive action can be
sults. Quality oversight personnel should thought of as a proactive approach to address
monitor the PT program and verify that test the underlying causes of anticipated prob-
systems are maintained in a state of control lems identified through the analysis of data
and appropriate corrective action is taken and information.40 In contrast, remedial action
when indicated. is defined as action taken to alleviate the
symptoms of existing nonconformances or any
Process Improvement other undesirable situation.41 Remedial action,
sometimes called correction, addresses only a
Continual improvement is a fundamental goal
problem’s visible indicator and not the actual
in any quality management system. In transfu-
cause. (See comparisons in Table 1-5.) Effec-
sion and cellular therapies and clinical diag-
tive corrective and preventive action cannot
nostics, this goal is tied to patient safety goals
be implemented until the underlying cause is
and expectations for the highest quality health
determined and the process is evaluated in re-
care. The importance of identifying, investi-
lationship to other processes. Pending such
gating, correcting, and preventing problems
evaluation, it may be desirable to implement
cannot be overstated. The process of develop-
interim remedial action.
ing corrective and preventive action plans in-
volves identification of problems and their
Identification of Problems and Their
causes as well as identification and evaluation
Causes
of solutions to prevent future problems. This
process should also include evaluation of Sources of information for process improve-
near-miss events and a mechanism for data ment activities include process deviations,
collection and analysis as well as follow-up to nonconforming products and services, cus-
evaluate the effectiveness of the actions taken. tomer complaints, QC records, PT, internal au-
Statistical tools and their applications may be dits, quality indicators, and external assess-
found in publications from the AABB and the ments. Active monitoring programs may be set

TABLE 1-4. Applicable Joint Commission Performance Improvement Standards9,10

䡲 The organization collects data to monitor its performance, including the following:
– Blood and blood component use.
– All confirmed transfusion reactions.
䡲 The organization compiles and analyzes data.
䡲 The organization improves performance on an ongoing basis.
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 27

TABLE 1-5. Comparison of Remedial, Corrective, and Preventive Actions40

Action Problem Approach Outcome

Remedial Existent Reactive Alleviates symptoms

Corrective Existent Reactive Prevents recurrence
Preventive Nonexistent Proactive Prevents occurrence

up to help identify problem areas. These pro- tion is impractical, impossible, or outside the
grams should be representative of the facility boundaries of the organization. Use of the “re-
processes and consistent with organizational petitive why” prevents the mistake of inter-
goals, and they should reflect customer needs. preting an effect as a cause.
Preparation of a facility quality report at least
CAUSE-A ND-E FFECT DIAGRA M. The cause-
annually in which data from all these sources
are aggregated and analyzed can be valuable and-effect diagram, also known as the Ishika-
to identify issues for performance improve- wa or fish-bone diagram, uses a specialized
ment. form of brainstorming that breaks down prob-
Once identified, problems should be ana- lems into “bite-sized” pieces. (An example of a
lyzed to determine their scope, potential ef- cause-and-effect diagram is shown in Fig 1-1.)
fects on quality management and operational The method used in the diagram is designed to
systems, relative frequency, and extent of their focus ideas around the component parts of a
variation. Such an analysis is important to process as well as to give a pictorial represen-
avoid tampering with processes that are mere- tation of the ideas that are generated and their
ly showing normal variations or problems with interactions. When using the cause-and-effect
little effect. diagram, one looks at equipment, materials,
The underlying causes of an undesirable methods, environment, and human factors.
condition or problem can be identified by an These three tools identify both active and
individual or group. The more complex the latent failures. Active failures are those that
problem and the more involved the process, have an immediate adverse effect. Latent fail-
the greater the need to enlist a team and to for- ures are more global actions and decisions
malize the analysis. Three commonly used with potential for damage that may lie dor-
tools for identifying underlying causes in an mant and become evident only when triggered
objective manner are process flowcharting, by the presence of localized factors. The key to
use of the “repetitive why,” and the cause-and- successfully determining root causes is to
effect diagram. avoid stopping too soon or getting caught in
the trap of placing blame on an individual.
PROCESS FLOWCHART . A process flowchart
Most problems, particularly those that are
gives a detailed picture of the multiple activi-
complex, have several root causes. A method
ties and important decision points within that
that can be of use when such problems occur
process. By examining this picture, one may
is the Pareto analysis. A chart of causes, laid
identify problem-prone areas.
out in order of decreasing frequency, is pre-
REPETITIVE WHY. The “repetitive why” is pared. Those that occur most frequently are
used to work backward through the process. considered the “vital few”; the rest are consid-
One repeatedly asks “Why did this happen?” ered the “trivial many.” This method offers di-
until 1) no new information can be gleaned; 2) rection on where to dedicate resources for
the causal path cannot be followed because of maximal effect. An example of a Pareto chart is
missing information; or 3) further investiga- shown in Fig 1-2.
28 䡲 AABB TECHNICAL MANUAL

Root Cause Analysis of Failed Test Runs

FIGURE 1-1. Example of a cause-and-effect diagram.

SOP = standard operating procedure.

Identification and Evaluation of scale solutions can be tried on a limited basis

Solutions and can be expanded if successful; small-scale
solutions can be implemented pending an ef-
Potential solutions to problems are identified
fectiveness evaluation. Data should be collect-
during the creative phase of process improve-
ed to evaluate the effectiveness of the pro-
ment. Brainstorming and process flowcharting
posed change. Data can be collected using the
can be particularly helpful in this phase.
methods employed initially to identify the
Benchmarking with other organizations can
problems or methods specially designed for
also be helpful. Possible solutions should be
the trial. Once solutions have been successful-
evaluated relative to organizational con-
ly tested, full implementation can occur. After
straints and should be narrowed down to
implementation, data should be collected at
those that are most reasonable. Individuals
least periodically to ensure the continuing ef-
who implement the process are usually the
fectiveness and control of the changed pro-
most knowledgeable about what will work.
cess.
They should be consulted when possible solu-
tions are being considered. Individuals with
Other Process Improvement Methods
knowledge of the interrelationships of pro-
cesses who have a more “global” view of the Failure modes and effects analysis is a system-
organization should also be involved in this atic stepwise approach for identifying all pos-
step. Solutions may fail if representatives with sible failures within a process, product, or
those perspectives are not involved. service; studying and prioritizing the conse-
Potential solutions should be tested be- quences, or effects, of those failures; and elim-
fore full implementation and a clear plan inating or reducing the failures, starting with
should be created regarding methods, objec- those of highest priority. Despite their relative
tives, timelines, decision points, and algo- complexity, LEAN and Six Sigma process im-
rithms for all possible results of a trial. Large- provement methods from the manufacturing
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 29

FIGURE 1-2. Example of a Pareto chart.

industry are finding increasing use in the tion of these principles and techniques can
health-care setting. LEAN emphasizes speed improve performance, reduce costs and waste,
and efficiency. Six Sigma emphasizes precision cut time, and eliminate non-value-added ac-
and accuracy. Six Sigma uses the data-driven tions. Additional information about both
approach to problem solving of define, mea- methods can be found on the website of the
sure, analyze, improve, and control. Applica- American Society for Quality.42

KEY POINTS

1. Organization and Leadership. A defined organizational structure in addition to top man-

agement’s support and commitment to the quality policy, goals, and objectives are key to
ensuring the success of the quality management system.
30 䡲 AABB TECHNICAL MANUAL

2. Customer Focus. Quality organizations should understand and meet or exceed customer
needs and expectations. These needs and expectations should be defined in a contract,
agreement, or other document developed with feedback from the customer.
3. Facilities, Work Environment, and Safety. Procedures related to general safety; biological,
chemical, and radiation safety; fire safety; and disaster preparedness are required. Space al-
location, building utilities, ventilation, sanitation, trash, and hazardous substance disposal
must support the organization’s operations.
4. Human Resources. Quality management of all personnel addresses adequate staffing levels
and staff selection, orientation, training, and competence assessment as well as specific
regulatory requirements.
5. Suppliers and Materials Management. Suppliers of critical materials and services (ie, those
affecting quality) should be qualified, and these requirements should be defined in con-
tracts or agreements. All critical materials should be qualified and then inspected and test-
ed upon receipt to ensure that specifications are met.
6. Equipment Management. Critical equipment may include instruments, measuring devices,
and computer hardware and software. This equipment must be uniquely identified and op-
erate within defined specifications, as ensured by qualification, calibration, maintenance,
and monitoring.
7. Process Management. A systematic approach to develop new, and control changes to, poli-
cies, processes, and procedures includes process validation, test method validation, com-
puter system validation, equipment validation, and QC. Validation must be planned and re-
sults reviewed and accepted.
8. Documents and Records. Documents include policies, process descriptions, procedures,
work instructions, job aids, forms, and labels. Records provide evidence that the process
was performed as intended and allow assessment of product and service quality.
9. Information Management. Unauthorized access, modification, or destruction of data and
information must be prevented and confidentiality of patient and donor records main-
tained. Data integrity should be assessed periodically and backup devices, alternative sys-
tems, and archived documents maintained.
10. Management of Nonconforming Events. Deviations from facility-defined requirements,
standards, and regulations must be addressed by documenting and classifying occurrences,
assessing effects on quality, implementing remedial actions, and reporting to external agen-
cies as required.
11. Monitoring and Assessment. Evaluation of facility processes includes internal and external
assessments, monitoring of quality indicators, blood utilization assessment, proficiency
testing, and analysis of data.
12. Process Improvement. Opportunities for improvement may be identified from deviation
reports, nonconforming products and services, customer complaints, QC records, profi-
ciency testing results, internal audits, quality indicator monitoring, and external assess-
ments. Process improvement includes determination of root causes, implementation of
corrective and preventive actions, and evaluation of the effectiveness of these actions.

REFER ENCES

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 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 33

䡲 APPENDIX 1-1
Glossary of Commonly Used Quality Terms
Biovigilance Collection and analysis of adverse event data for the purpose of improving out-
comes in the use of blood products, organs, tissues, and cellular therapies.
Calibration Comparison of measurements performed with an instrument to those made
with a more accurate instrument or standard for the purpose of detecting,
reporting, and eliminating errors in measurement.
Change control Established procedures for planning, documenting, communicating, and exe-
cuting changes to infrastructure, processes, products, or services. Such proce-
dures include the submission, analysis, approval, implementation, and
postimplementation review of the change and decisions made about the change.
Formal change control provides a measure of stability and safety and avoids
arbitrary changes that might affect quality.
Control chart A graphic tool used to determine whether the distribution of data values gener-
ated by a process is stable over time. A control chart plots a statistic vs time and
helps to determine whether a process is in control or out of control according to
defined criteria (eg, a shift from a central line or a trend toward upper or lower
acceptance limits).
Design output Documents, records, and evidence in any other format used to verify that design
goals have been met. Design output should identify characteristics of a product
or service that are crucial to safety and function and to meeting regulatory
requirements. It should contain or make reference to acceptance criteria. Exam-
ples of design output include standard operating procedures; specifications for
supplies, reagents, and equipment; identification of quality control require-
ments; and results of verification and validation activities.
End-product test and Verification through observation, examination, or testing (or a combination) that
inspection the finished product or service conforms to specified requirements.
Near-miss event An unexpected occurrence that did not adversely affect the outcome but could
have resulted in a serious adverse event.
Process capability Ability of a controlled process to produce a service or product that fulfills
requirements or a statistical measure of the inherent process variability for a
given characteristic relative to design specifications. The most widely accepted
formula for process capability is Six Sigma.
Process control Activities intended to minimize variation within a process to produce a predict-
able output that meets specifications.
Qualification Demonstration that an entity is capable of fulfilling specified requirements and
verification of attributes that must be met or complied with for a person or thing
to be considered fit to perform a particular function. For example, equipment
may be qualified for an intended use by verifying performance characteristics,
such as linearity, sensitivity, or ease of use. An employee may be qualified on
the basis of technical, academic, and practical knowledge and skills developed
through training, education, and on-the-job performance.

(Continued)
34 䡲 AABB TECHNICAL MANUAL

䡲 APPENDIX 1-1
Glossary of Commonly Used Quality Terms (Continued)
Quality assurance Activities involving quality planning, control, assessment, reporting, and
improvement necessary to ensure that a product or service meets defined qual-
ity standards and requirements.
Quality control Operational techniques and activities used to monitor and eliminate causes of
unsatisfactory performance at any stage of a process.
Quality indicators Measurable aspects of processes or outcomes that provide an indication of the
condition or direction of performance over time. Quality indicators are used to
monitor progress toward stated quality goals and objectives.
Quality management The organizational structure, processes, and procedures necessary to ensure
that the overall intentions and direction of an organization’s quality program are
met and that the quality of the product or service is ensured. Quality manage-
ment includes strategic planning, allocation of resources, and other systematic
activities, such as quality planning, implementation, and evaluation.
Requirement A stated or obligatory need or expectation that can be measured or observed
and that is necessary to ensure quality, safety, effectiveness, or customer satis-
faction. Requirements can include things that the system or product must do,
characteristics that it must have, and levels of performance that it must attain.
Specification Description of a set of requirements to be satisfied by a product, material, or
process indicating, if appropriate, the procedures to be used to determine
whether the requirements are satisfied. Specifications are often in the form of
written descriptions, drawings, professional standards, and other descriptive
references.
Validation Demonstration through objective evidence that the requirements for a particular
application or intended use have been met. Validation provides assurance that
new or changed processes and procedures are capable of consistently meeting
specified requirements before implementation.
Verification Confirmation, by examination of objective evidence, that specified requirements
have been met.
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 35

䡲 APPENDIX 1-2
Code of Federal Regulations Quality-Related References
Code of Federal Regulations, Title 21

Topic Biologics, Blood Drugs Tissues, HCT/Ps

Personnel 600.10, 606.20 211.25, 211.28 1271.170

Facilities 600.11, 606.40 211.42-58 1271.190
Environmental control 211.42 1271.195
and monitoring
Equipment 606.60 211.63-72, 211.105, 1271.200
211.182
Supplies and reagents 606.65 211.80 1271.210
Standard operating 606.100 211.100-101 1270.31, 1271.180
procedures
Process changes and 211.100-101 1271.225, 1271.230
validation
Quality assurance/quality 211.22
control unit
Label controls 610.60-64, 211.122-130 1271.250, 1271.370
606.120-122
Laboratory controls 606.140 211.160
Records and record 600.12, 606.160 211.192, 211.194, 1270.33, 1271.55
reviews 211.196 1271.270
Receipt, predistribution, 606.165 211.142, 211.150 1271.265
and distribution
Adverse reactions 606.170 211.198 1271.350
Tracking 211.188 1271.290
Complaints 606.170-171 211.198 1271.320
Reporting deviations 600.14, 606.171 1271.350
Storage 640.2, 640.11, 211.142 1271.260
640.25, 640.34,
640.54, 640.69
HCT/Ps = human cells, tissues, and cellular and tissue-based products.
36 䡲 AABB TECHNICAL MANUAL

䡲 APPENDIX 1-3
Suggested Quality Control Performance Intervals for Equipment and Reagents*

Equipment and Reagent Frequency of Quality Control

Refrigerators/freezers/platelet storage

Refrigerators

䡲 Recorder Daily
䡲 Manual temperature Daily
䡲 Alarm system board (if applicable) Daily
䡲 Temperature charts (review daily) Weekly
䡲 Alarm activation Quarterly
Freezers
䡲 Recorder Daily
䡲 Manual temperature Daily
䡲 Alarm system board (if applicable) Daily
䡲 Temperature charts (review daily) Weekly
䡲 Alarm activation Quarterly
Platelet incubators
䡲 Recorder Daily
䡲 Manual temperature Daily
䡲 Temperature charts (review daily) Weekly
䡲 Alarm activation Quarterly
䡲 Ambient platelet storage Every 4 hours

Laboratory equipment

Centrifuges/cell washers
䡲 Speed Quarterly
䡲 Timer Quarterly
䡲 Function Yearly
䡲 Tube fill level (serologic) Day of use
䡲 Saline fill volume (serologic) Weekly
䡲 Volume of antihuman globulin dispensed (if applicable) Monthly
䡲 Temperature check (refrigerated centrifuge) Day of use
䡲 Temperature verification (refrigerated centrifuge) Monthly
 CHAPTER 1 Quality Management Systems: Theory and Practice 䡲 37

䡲 APPENDIX 1-3
Suggested Quality Control Performance Intervals for Equipment and Reagents*
(Continued)
Equipment and Reagent Frequency of Quality Control

Heating blocks/waterbaths/view boxes

䡲 Temperature Day of use
䡲 Quadrant/area checks Periodically
Component thawing devices Day of use
pH meters Day of use
Blood irradiators
䡲 Calibration Yearly
䡲 Turntable (visual check each time of use) Yearly
䡲 Timer Monthly/quarterly
䡲 Source decay Dependent on source type
䡲 Leak test Twice yearly
䡲 Dose delivery check (with indicator) Each irradiator use
䡲 Dose delivery verification
– Cesium-137 Yearly
– Cobalt-60 Twice yearly
– Other source As specified by manufacturer
Thermometers (vs NIST-certified or traceable thermometer)
䡲 Liquid-in-glass Yearly
䡲 Electronic As specified by manufacturer
Timers/clocks Twice yearly
Pipette recalibration Quarterly
Sterile connecting device
䡲 Weld check Each use
䡲 Function Yearly
Blood warmers
䡲 Effluent temperature Quarterly
䡲 Heater temperature Quarterly
䡲 Alarm activation Quarterly

(Continued)
38 䡲 AABB TECHNICAL MANUAL

䡲 APPENDIX 1-3
Suggested Quality Control Performance Intervals for Equipment and Reagents*
(Continued)
Equipment and Reagent Frequency of Quality Control

Blood collection equipment

Whole blood equipment

䡲 Agitators Day of use
䡲 Balances/scales Day of use
䡲 Gram weight (vs NIST-certified) Yearly
Microhematocrit centrifuge
䡲 Timer check Quarterly
䡲 Calibration Quarterly
䡲 Packed cell volume Yearly
Cell counters/hemoglobinometers Day of use
Blood pressure cuffs Twice yearly
Apheresis equipment
䡲 Checklist requirements As specified by manufacturer

Reagents

Red cells Day of use

Antisera Day of use
Antiglobulin serum Day of use
Transfusion-transmissible disease marker testing Each test run

Miscellaneous

Copper sulfate Day of use

Shipping containers for blood and component transport Twice yearly
(usually at temperature extremes)
*The frequencies listed above are suggested intervals, not requirements. For any new piece of equipment, installation, oper-
ational, and performance qualifications must be performed. After the equipment has been suitably qualified for use, ongoing
QC testing should be performed. Depending on the operational and performance qualification methodology, the ongoing QC
may initially be performed more often than the ultimately desired frequency. Once a record of appropriate in-range QC
results has been established (during either equipment qualification or the ongoing QC), the frequency of testing can be
reduced. At a minimum, the frequency must comply with the manufacturer’s suggested intervals; if no such guidance is pro-
vided by the manufacturer, the intervals given in this table are appropriate to use.
NIST = National Institute of Standards and Technology, QC = quality control.