Quality Assurance Journal - 2000 - Bohaychuk - Standard Operating Procedures For Clinical Research Personnel Part 1

The Quality Assurance Journal
Qual. Assur. J. 3: 137–150 (1998)
Standard Operating Procedures for

Clinical Research Personnel—Part 1
This is the first in a series of articles The systems for quality assurance (e.g. SOPs,
containing proposals for the wording planning, training), including those for quality
control (e.g. monitoring and data review) must
and content of Standard Operating be established in the clinical research department
Procedures (SOPs) for clinical before any clinical studies are undertaken. All
activities in clinical research must be described
research activities conducted by in SOPs.
sponsors and Contract Research
Clinical Development Plans (SOPs 103 and
Organizations (CROs). The 104):
procedures include those required A clinical study must be conducted within the
by the International Conference on context of a clinical development plan, which is
Harmonization (ICH), the Food a formal document describing the overall strat-
egy for the development of a medication/device.
and Drug Administration (FDA), The development plan will describe the extent
many other guidelines and and objectives of clinical studies that are neces-
sary in order to expose the minimum number of
regulations, and ‘best practice’ study subjects to the risks of clinical studies. The
observed by the authors. The model procedures for preparation, review, approval,
forms obviously require modification amendment and distribution of clinical develop-
ment plans must also be described in SOPs.
for actual use.1 (SOP 105, concerning distribution, is not repro-
duced in this article.)
Copyright © 1998 John Wiley & Sons, Ltd.
In this article, four Standard Operating Proce-

dures (SOPs) for general topics dealing in clinical SOP 101. GENERAL QUALITY
research management are addressed. The SOPs ASSURANCE AND QUALITY CONTROL
cover the following: PROCEDURES
General Quality Assurance and Quality Control

Procedures (SOPs 101 and 102): Policy
The systems for quality assurance (e.g. SOPs,
planning, training), including those for quality
control (e.g. monitoring and data review) must
Wendy Bohaychuk* and be established in the clinical research department
Graham Ball before any clinical studies are undertaken. (This
GCRP Consultants,
SOP includes procedures that require the in-
General Delivery, Lakehurst,
volvement of clinical research personnel; it must
Ont., Canada KOL 2JO
not supersede SOPs developed by personnel
* Correspondence to: GCRP Consultants, General Delivery,
more directly involved in quality assurance activ-
Lakehurst, Ont., Canada KOL 2JO. ities.)

138 W. Bohaychuk and G. Ball
10991786, 1998, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1099-1786(199809)3:3<137::AID-QAJ76>3.0.CO;2-E by Nigeria Hinari NPL, Wiley Online Library on [17/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Procedures
101.1 To assure that clinical studies will be conducted in accordance with the requirements of
GCP, appropriate SOPs must be prepared, implemented and enforced for all activities related
to the conduct of clinical research by the sponsor/Contract Research Organization (CRO).
Detailed requirements are described in SOP 102 and all other SOPs in this series.
101.2 All clinical studies must be undertaken in accordance with a clinical development plan to
ensure that subjects are not unnecessarily included in clinical studies. Clinical development
planning is described in SOP 103 and several other SOPs.
101.3 To assure compliance with the standards of GCP, adequate and documented proper training
of all personnel is essential. Detailed requirements are described in SOPs 110 and 318, and
other SOPs.
101.4 To control quality in clinical studies, regular and thorough monitoring is required. Detailed
requirements are described in SOPs 316, 328, 329, 401, and several other SOPs.
101.5 To further control quality in clinical studies, prompt and thorough data processing is re-
quired. Detailed requirements, related to clinical research personnel, are described in several
SOPs.
101.6 To independently assure and control quality in clinical studies, auditing is necessary. De-
tailed requirements, related to clinical research personnel, are described in SOP 115 as well
as other SOPs.
SOP 102. STANDARD OPERATING PROCEDURES
Policy
The purpose of this SOP is to describe the procedures for preparing and managing SOPs and SOP
revisions. A SOP is a formal document that describes the procedures that will be followed to accom-
plish various tasks. All activities in clinical research undertaken by [Company Name] and required by
current guidelines and regulations on GCP must be described in SOPs. All personnel involved will be
issued with copies of the most current SOPs and will be required to undertake clinical studies in
accordance with the SOPs. Changes in the structure of the organization of the company and outside
influences may require the preparation of new SOPs or revisions to current SOPs.
If work is contracted by a sponsor to a CRO, the CRO’s SOPs must be reviewed to ensure compliance
with the sponsor SOPs. The CRO is permitted to use standardized forms and documents to provide
evidence of compliance with the procedures; however, representatives of the sponsor will examine the
proposed documents, prior to commencement of the study, to assess and ensure appropriate compli-
ance.
Procedures
Preparation and Format of SOPs
102.1 The [Title] in the clinical research department will request preparation of new SOPs and
amendment of existing SOPs, as the need arises. The assignment of responsibility (to an
individual or a committee) for preparing a SOP will be documented.
102.2 Each SOP will provide the following information on the first (cover) page.
Copy number: each SOP will have a unique copy number.
Title: the title will comprise one or two lines indicating the topic of the SOP.
SOP number: each SOP will be numbered sequentially using five digits. The first set of
three digits identifies a SOP and the second set of two digits indicates the revision number.
Copyright © 1998 John Wiley & Sons, Ltd. Qual. Assur. J. 3: 137–150 (1998)
Standard Operating Procedures—Part 1 139
Issue date: this will be the date on which the SOP will take effect. This date will be on
or after the dates of approval. Dates will always be written in the format of two digits for
the day of the month, three letters for the month, and two digits for the year.
Supersedes: the SOP number, and the date of the SOP that has been preceded by the
current SOP, will be indicated.
Last review date: this will be the date on which the SOP was last reviewed.
Next review date: this will be the next scheduled date on which it is planned to review
the SOP.
Approved by: the SOPs will be approved by (as indicated by the dated signatures): the
head of the clinical research department [Title], the head of the relevant department [Title],
and the head of the quality assurance department [Title]. The dates of approval of the SOP
will also be written by each signatory. The approvals confirm that the SOPs describe the
procedures developed and used by [Company Name].
102.3 Each SOP will include the following sections in the text.
Table of contents: the table of contents will include a list of items included in the SOP,
with page numbers.
Policy statement: the statement should briefly describe the rationale for the SOP and the
relevant GCP principle. The scope of the SOP should also be indicated.
Procedures: the procedures section will follow the order noted in the table of contents
and, in general, will follow the order in which procedures occur. The style of the text of
the SOP should be clear, concise, brief and specific to the topic of the SOP. A SOP
should be written to provide instructions for the completion of certain procedures and,
therefore, must not be ambiguous or confusing. Statements concerning the procedures to
be followed should be made categorical by the use of such words as ‘must’ and ‘will’
(e.g. ‘the following procedure must/will be performed’). The word ‘may’ is to be used
only when the conditions are stated (e.g. ‘the investigator may enter a patient into the
study without patient consent only in an emergency, and when the patient is
unconscious’).
Appendices to the SOP will be numbered and listed in the order in which they are
addressed in the SOP. Appendices will be placed at the end of the SOP, with each page
numbered.
102.4 Page numbering in SOPs will always consist of x and y.
102.5 To protect confidentiality, the cover page of the SOP binder will state: ‘The STANDARD
OPERATING PROCEDURES described herein are the confidential property of [Company
Name]. They will not be shown or given to individuals outside the company without written
consent by [Company Name]’.
Review and Approval of SOPs
102.6 Approved SOPs will be reviewed at least annually (or more frequently, if necessary, because
of urgently needed changes) to determine whether new SOPs or revisions to existing SOPs
are needed.
102.7 The draft SOP or SOP revision will be circulated by the [Title] in the clinical research
department for review, in accordance with the procedures described below.
102.8 SOPs will be reviewed by the following: the clinical research department [Title]; the head of
the relevant department [Title]; and the head of the quality assurance department [Title]. The
reviewers must complete and sign Form 102-1.
102.9 All comments will be documented and filed in the sponsor/CRO project archives by the
[Title].
102.10 After review and consideration of comments during review, all proposed SOPs and SOP
amendments will be distributed for approval by the [Title].
102.11 The approval of proposed SOPs and SOP amendments will be documented on Form 102-2.
102.12 An approved SOP may be amended by preparing a new version of the entire SOP with a
new date of issue and with a covering letter indicating the amended sections of the SOP.
This task will be undertaken by the [Title].
Implementation of SOPs
102.13 SOPs will come into effect on the date of issue.

102.14 All individuals required to comply with the SOPs will complete and sign Form 102-3 stating
that they will conform to the requirements of the SOP and specifying the SOPs under
consideration (the recipient will retain one copy of the form).
Waiver and Violation of SOPs
102.15 Under exceptional circumstances, waivers from the SOPs may be allowed, when it is known
in advance that it will not be possible to comply with the SOP.
102.16 Waivers from SOPs must be requested in writing, with an explanation, and require the
approval of the [Title] in the clinical research department. Form 102-4 will be used for this
purpose.
102.17 Violation of SOPs (deliberately or through negligence) must be documented, with an expla-
nation, and reported to the [Title] in the clinical research department. Form 102-5 will be
used for this purpose.
102.18 Consistent and deliberate non-compliance with the SOPs without written authorization will
lead to disciplinary action.
Distribution and Archiving of SOPs
102.19 All individuals in the clinical research department, who are required to comply with rele-
vant SOPs, will receive copies of SOPs as they are issued.
102.20 A list of SOP recipients (Form 102-6) will be prepared and maintained by the [Title] in the
clinical research department. The unique number of the SOP copy and the name of the
person to whom the copy was distributed will be recorded on this form.
102.21 Reference copies of SOPs may be distributed to individuals in other departments within the
company, if required for the task being undertaken. To protect confidentiality, distribution
must be authorized by the [Title]. Further, the cover page of the SOP binder will state: ‘The
STANDARD OPERATING PROCEDURES described herein are the confidential property of
[Company Name]. They will not be shown or given to individuals outside the company
without written consent by [Company Name]’.
102.22 Reference copies of SOPs may be distributed to other external individuals (e.g. a CRO, if
required for the task being undertaken). Documented permission to distribute SOPs exter-
nally must be obtained from the [Title] to protect confidentiality.
102.23 To further control distribution of the SOPs, each SOP binder will have a copy number on
the front page. This number will be recorded on the list of SOP recipients.
102.24 All current SOPs and their most recent dates of issue will be listed in an index at the beginning
of the manual or binder containing all the SOPs. As each new SOP is generated, or as an existing
SOP is revised, the index will be revised by the [Title] in the clinical research department.
102.25 All current and superseded versions of SOPs must be available for audit and inspection.
102.26 Copies of superseded SOPs that have been distributed, both internally and externally, should be
collected and destroyed by the [Title] after issue of new and revised SOPs (master copies will be
retained).
102.27 Individual recipients of SOPs must not photocopy the SOPs or distribute them to personnel
outside [Company Name] without permission from the [Title].
102.28 Personnel who leave [Company Name] must immediately return the SOPs to the [Title].
102.29 All versions of SOPs and all forms noted in this SOP will be filed by the [Title] in the
sponsor/CRO project archives.
Note:
We have not included any guidance on the management of electronic SOPs, although there is a
growing trend in that direction. So far, the authors have not been favourably impressed with elec-
tronic SOPs because there seems to be many problems with access and control on distribution of
current versions. Also, more often then not, when we request specific SOPs during audits, they cannot
be found (this concerns us because perhaps the monitors cannot find them when they need them).
However, this will probably be the way of the future and we look forward to seeing improvements in
this area.
Form 102-1: SOP Review
Qual. Assur. J. 3: 137–150 (1998)

W. Bohaychuk and G. Ball

Form 102-2: SOP Approval
142
143
Qual. Assur. J. 3: 137–150 (1998)

Form 102-3: SOP Compliance Statement
Standard Operating Procedures—Part 1
Form 102-4: Request for SOP Waiver

Qual. Assur. J. 3: 137–150 (1998)


Form 102-5: Report of SOP Violation
144
145
Qual. Assur. J. 3: 137–150 (1998)

Form 102-6: Recipients of SOPs

SOP 103. PREPARATION OF CLINICAL DEVELOPMENT PLANS
Policy
A clinical study must be conducted within the context of a clinical development plan to fulfil the
requirements of GCP. A clinical development plan is a formal document that describes the overall
strategy for the development of a medication/device. The development plan will describe the extent
and objectives of clinical studies that are necessary for development of medications/devices in order to
expose the minimum number of study subjects to the risks of clinical studies.
This SOP includes procedures that require the involvement of clinical research personnel. It must
not supersede SOPs developed by senior personnel responsible for final authorization of clinical
development plans or other personnel in other departments who contribute to the clinical develop-
ment plan.
Procedures
103.1 The design of a clinical development plan for a new medication/device will require the
assistance and co-ordinated activity of a number of departments or disciplines, such as the
following.
Exploratory research: this department will have been involved in the early screening
phases to find a new entity that fulfils particular effectiveness and safety characteristics.
Preliminary information concerning the possible mode of action and early pharmacology and
pharmacodynamics may also be available.
Pre-clinical research: further information concerning the mode of action, and pharmacol-
ogy and pharmacodynamics (especially details concerning absorption, distribution,
metabolism and excretion) should be included in the clinical development plan. The pre-clin-
ical safety profile of the medication/device must be established prior to starting a clinical
study. Additional toxicology studies may need to be conducted in parallel to the clinical
development.
Formulations/specifications: details concerning the current supply of the medication/
device and the future plans for the final formulation and/or specifications of the marketed
product are necessary to determine the type and timing of clinical studies.
Market research: the intended market must be defined and clinical studies must be
designed to fulfill the regulatory requirements for the market. The timing for launch of the
new medication/device onto the market will have an effect upon the clinical and non-clinical
development plans. Market surveys may be commissioned for inclusion in the clinical devel-
opment plan.
Regulatory affairs: this department will provide the details concerning the regulatory
requirements for the various countries in which clinical development will be conducted and
in which the new medication/device will be marketed.
Clinical research, including data processing and statistical applications: the required re-
sources (e.g. financial, personnel and external consultative needs) of the clinical research
department must be assessed and weighed against other priorities. This clinical research
department should also describe the various phases of development with summaries of each
proposed study/protocol as far as can be determined, and the time required for each study/
protocol. If any validation studies are required (e.g. validation of site or methods), these
must also be incorporated into the plan.
103.2 A summary of the interests and requirements of each department or discipline will be
considered and incorporated into the clinical development plan.
103.3 The format of the clinical development plan will be written in accordance with the decision
of the co-ordinator of the clinical development plan (details of the required format for the
clinical development should be described in the SOPs of the senior planning group; usually
a ‘product manager’ or ‘project manager’ will be assigned to this task).
103.4 The clinical development plan will also include the proposed timings for events, and the
times and criteria for development decisions.
103.5 In the clinical research department, the [Title] will be responsible for preparation of the
relevant sections in the clinical development plan. The timing will be at the discretion of the
co-ordinator of the clinical development plan for all departments and disciplines.
103.6 Advice and expertise may be sought from external specialists and/or a scientific advisory
board.
103.7 The [Title] in the clinical research department will also be responsible for attending clinical
development plan meetings and for documenting proceeding of the meetings.
103.8 Drafts of clinical development plans and documentation of the proceedings of clinical devel-
opment plan meetings must be treated as highly confidential documents and will have
restricted distribution. Any external distribution must be authorized and documented in
accordance with SOP 105.
103.9 The clinical development plan (original) and any reviewed drafts will be archived by the
[Title] in the sponsor/CRO project archives.
Related SOPs: SOP 104: Review, Approval and Amendment of Clinical Development Plans,
SOP 105: Distribution of Clinical Development Plans (and Amendment), SOP 106: Clinical
Study Plans.
Suggestions for SOPs: Study Site and/or Method Validation Studies.
Suggestions for Forms: Clinical Development Plan Outlines, Agenda for Clinical Develop-
ment Plan Meetings.
SOP 104. REVIEW, APPROVAL AND AMENDMENT OF CLINICAL DEVELOPMENT

PLANS
Policy
Clinical development plans must be formally reviewed and approved to indicate authorization of the plan
by the sponsor/CRO. Any change to an approved clinical development plan must be implemented by a
formal amendment procedure.
This SOP includes procedures that require the involvement of clinical research personnel. It must not
supersede SOPs developed by senior personnel responsible for final authorization of clinical development
plans or other personnel in other departments who contribute to the clinical development plan.
Procedures
104.1 The draft clinical development plan will be submitted to the [Title] in the clinical research
department for review and comment.
104.2 All review comments should be recorded on Form 104-1 and retained by the [Title] for
possible further consideration if subsequent amendments of the clinical development plan are
necessary. The form must be completed for each draft circulated for review, thus more than
one copy of the form may be required.
104.3 After consideration of the review comments, the final clinical development plan must be
approved by the [Title] in the clinical research department, as well as authorized signatories
in other departments. The approval must be documented on Form 104-2.
104.4 The initial clinical development plan may be prepared at a time when there is little informa-
tion available. In addition, as development of a new medication/device progresses, new
information that becomes available may necessitate the amendment of the clinical develop-
ment plan. Therefore, at least annual review and amendment of the clinical development
plan should be undertaken, with more frequent review in the early stages of development.
104.5 Amendment of a final authorized clinical development plan, and the formal approval of the
amendment, must take place prior to a change in the development process.
104.6 All those departments involved in the design of the original clinical development plan must
be consulted prior to any amendments. Any review comments must be documented.
104.7 Following this consultative process, a draft amended clinical development plan should be
prepared and discussed for approval, by the same departments/individuals involved in ap-
proving the initial plan, prior to implementing a significant change. Approval of amend-
ments must be documented.
104.8 Form 104-1 and Form 104-2 will be archived by the [Title] in the sponsor/CRO project
archives.
Related SOPs: SOP 103: Preparation of Clinical Development Plans, SOP 105: Distribution of
Clinical Development Plans (and Amendments).
Suggestions for Forms: Review of Clinical Development Plan Amendments, Approval of
Clinical Development Plan Amendments.
Form 104-1: Clinical Development Plan Review
149
Qual. Assur. J. 3: 137–150 (1998)

Form 104-2: Clinical Development Plan Approval

Qual. Assur. J. 3: 137–150 (1998)

1. The full text of all 101 SOPs is available from the authors.

NOTES
150

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The Quality Assurance Journal

Qual. Assur. J. 3: 137–150 (1998)

Standard Operating Procedures for

In this article, four Standard Operating Proce-

General Quality Assurance and Quality Control

Copyright © 1998 John Wiley & Sons, Ltd.

SOP 102. STANDARD OPERATING PROCEDURES

Preparation and Format of SOPs

Review and Approval of SOPs

102.13 SOPs will come into effect on the date of issue.

Waiver and Violation of SOPs

Distribution and Archiving of SOPs

Form 102-1: SOP Review

Qual. Assur. J. 3: 137–150 (1998)

Copyright © 1998 John Wiley & Sons, Ltd.

Qual. Assur. J. 3: 137–150 (1998)

Form 102-4: Request for SOP Waiver

Qual. Assur. J. 3: 137–150 (1998)

Copyright © 1998 John Wiley & Sons, Ltd.

Qual. Assur. J. 3: 137–150 (1998)

Form 102-6: Recipients of SOPs

SOP 104. REVIEW, APPROVAL AND AMENDMENT OF CLINICAL DEVELOPMENT

Form 104-1: Clinical Development Plan Review

Qual. Assur. J. 3: 137–150 (1998)

Copyright © 1998 John Wiley & Sons, Ltd.

Qual. Assur. J. 3: 137–150 (1998)

Copyright © 1998 John Wiley & Sons, Ltd.

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