1. A Blueprint For ClinicalA Blueprint For Clinical
Research: StandardResearch: Standard
Operating ProceduresOperating Procedures
Karen Majchrzak, MS, CCRPKaren Majchrzak, MS, CCRP

2. What are SOPs?What are SOPs?
 International Conference onInternational Conference on
Harmonization (ICH) defines a SOP asHarmonization (ICH) defines a SOP as
“Detailed, written instructions to“Detailed, written instructions to
achieve uniformity of the performanceachieve uniformity of the performance
of a specific function.”of a specific function.” (ICH GCP 1.55)(ICH GCP 1.55)

3. What are SOPs?What are SOPs?
 In simple terms a SOP is…In simple terms a SOP is…
– A written processA written process
– A way for the clinical site to perform aA way for the clinical site to perform a
task the same way each time it istask the same way each time it is
completed.completed.

4. SOPs are used to:SOPs are used to:
 Identify the responsible person forIdentify the responsible person for
each task.each task.
 Describe actions (what is to beDescribe actions (what is to be
completed).completed).
 Train staff.Train staff.
 Monitor site performance.Monitor site performance.

5. Are SOPs Required byAre SOPs Required by
Law/Regulations?Law/Regulations?
 SOPs are not specifically mentionedSOPs are not specifically mentioned
in the FDA regulationsin the FDA regulations
– HOWEVERHOWEVER there is guidance and regulationsthere is guidance and regulations
that infer responsibility and SOPs formalizethat infer responsibility and SOPs formalize
investigator responsibilities.investigator responsibilities.
– 21 CFR312.53 the investigator will “ensure21 CFR312.53 the investigator will “ensure
that all associates, colleagues, and employeesthat all associates, colleagues, and employees
assisting in the conduct of the study (ies) areassisting in the conduct of the study (ies) are
informed of their obligations in meeting theinformed of their obligations in meeting the
above commitments.”above commitments.”

6. Are SOPs Required byAre SOPs Required by
Law/Regulations?Law/Regulations?
 Additionally, SOPs are mentionedAdditionally, SOPs are mentioned
repeatedly in the ICH GCP Guidelines.repeatedly in the ICH GCP Guidelines.
 ICH GCP 2.13 -“ICH GCP 2.13 -“Systems with
procedures that assure the quality of
every aspect of the trial should be
implemented.”

7. Benefits of a SOP?Benefits of a SOP?
 Ensures that all research conductedEnsures that all research conducted
within the clinical site follows federalwithin the clinical site follows federal
regulations, ICH GCP, and institutionalregulations, ICH GCP, and institutional
policies topolicies to protect the rights andprotect the rights and
welfare of human study participantswelfare of human study participants..

8. Benefits of a SOP?Benefits of a SOP?
 Provides autonomy within the clinicalProvides autonomy within the clinical
site.site.
 Improves the quality of the dataImproves the quality of the data
collected, thereby improving thecollected, thereby improving the
science of the study.science of the study.

9. Benefits of a SOP?Benefits of a SOP?
 Utilized as a reference and guidelineUtilized as a reference and guideline
as to how research will be conductedas to how research will be conducted
within the clinical sitewithin the clinical site
 Excellent training source for newExcellent training source for new
employees and/or fellowsemployees and/or fellows

10. SOP TopicsSOP Topics
 Preparing and Submitting Initial IRBPreparing and Submitting Initial IRB
DocumentsDocuments
 Preparing and Submitting ContinuingPreparing and Submitting Continuing
Review IRB DocumentsReview IRB Documents
 Preparing and Submitting Amendment IRBPreparing and Submitting Amendment IRB
DocumentsDocuments
 Establishing and Training the Clinical StudyEstablishing and Training the Clinical Study
Team, and Delegating ResponsibilitiesTeam, and Delegating Responsibilities
 Establishing Study FilesEstablishing Study Files
 Establishing Source DocumentsEstablishing Source Documents

11. SOP TopicsSOP Topics
 Study Subject Recruitment PlanStudy Subject Recruitment Plan
 Contacting and Scheduling Potential StudyContacting and Scheduling Potential Study
Subjects for an Initial VisitSubjects for an Initial Visit
 Obtaining Informed Consent from aObtaining Informed Consent from a
Potential Study SubjectPotential Study Subject
 Enrolling a SubjectEnrolling a Subject
 Recording Subject DataRecording Subject Data
 Making Corrections on Study DocumentsMaking Corrections on Study Documents

12. SOP TopicsSOP Topics
 Monitoring Subject Compliance During aMonitoring Subject Compliance During a
StudyStudy
 Responding to a Clinical Hold OrderResponding to a Clinical Hold Order
 Receiving and Storing Investigational DrugsReceiving and Storing Investigational Drugs
 Drug and Study Supply Transfer BetweenDrug and Study Supply Transfer Between
SitesSites
 Dispensing Study Drugs to Study SubjectsDispensing Study Drugs to Study Subjects
 Identifying and Reporting Adverse EventsIdentifying and Reporting Adverse Events
 Packing, Labeling, and Shipping SamplesPacking, Labeling, and Shipping Samples
 Identifying and Reporting ProtocolIdentifying and Reporting Protocol
DeviationsDeviations

13. SOP TopicsSOP Topics
Additional TopicsAdditional Topics
 Contact with potential sponsorsContact with potential sponsors
 Budget review and determinationsBudget review and determinations
 Pre-study study site visitPre-study study site visit
 Initiation Site VisitInitiation Site Visit
 Monitor VisitsMonitor Visits
 AuditsAudits
 Data managementData management
 Study closureStudy closure
 Long term storageLong term storage

14. Writing SOPsWriting SOPs
 Develop a template for the SOP to be usedDevelop a template for the SOP to be used
throughout the document.throughout the document.
 Potential elements of the SOPPotential elements of the SOP
– Header – title, original version date, revisionHeader – title, original version date, revision
date, effective date, approved bydate, effective date, approved by
– Purpose – why one has the policyPurpose – why one has the policy
– Responsibilities – who the policy pertains toResponsibilities – who the policy pertains to
– Instruction/Procedures – how to accomplish theInstruction/Procedures – how to accomplish the
items of the policyitems of the policy
– References – what the policy is based onReferences – what the policy is based on
– Appendix – source documents/case report formsAppendix – source documents/case report forms

20. Process Mapping for WritingProcess Mapping for Writing
SOPsSOPs
 Determine which clinical site taskDetermine which clinical site task
needs mapping.needs mapping.
 Lay out all the steps currently used toLay out all the steps currently used to
complete that task.complete that task.
 ““Mapping” involves taking each step inMapping” involves taking each step in
the task and making it more efficientthe task and making it more efficient
and easier to follow.and easier to follow.

21. Process Mapping for Making aProcess Mapping for Making a
Cup of CoffeeCup of Coffee
Primary StepPrimary Step
Ensure
the coffee
maker is
ready
Add the
water
Turn on
the
machine
Serve the
coffee
Add the
coffee
Woodin, K. (2004) The CRC’s Guide to Coordinating Clinical Research p. 60-65. Centerwatch

22. Process Mapping for Making aProcess Mapping for Making a
Cup of CoffeeCup of Coffee
Ensure
the coffee
maker is
ready
Add the
coffee
Add the
water
Turn on
the
machine
Serve the
coffee
Secondary StepSecondary Step
Ensure
the
machine is
plugged in
Ensure
carafe is
empty and
clean
Place a
filter in the
basket
Measure
the coffee
Use the
carafe to
measure
the water
Place the
carafe on
the
heating
element
Wait until
the coffee
has
stopped
dripping

23. Process Mapping for WritingProcess Mapping for Writing
SOPsSOPs
 Once you have finished mapping,Once you have finished mapping,
convert your process map to anconvert your process map to an
outline for easy use.outline for easy use.
 Once a task has been mapped, itOnce a task has been mapped, it
should be tested.should be tested.

25. SOPs and GuidelinesSOPs and Guidelines
 Some SOPs have a two-tiered systemSome SOPs have a two-tiered system
that includes both SOPs andthat includes both SOPs and
guidelines.guidelines.
 SOPs provide a general view of all theSOPs provide a general view of all the
main steps whereas guidelines aremain steps whereas guidelines are
significantly more detailed.significantly more detailed.

26. SOPs and GuidelinesSOPs and Guidelines
 One advantage of a two-tiered systemOne advantage of a two-tiered system
is that SOPs will rarely need to beis that SOPs will rarely need to be
changed, whereas guidelines maychanged, whereas guidelines may
need to be changed or updated moreneed to be changed or updated more
frequently due to changes infrequently due to changes in
organizational structure or equipment.organizational structure or equipment.

29. Tips for Writing SOPsTips for Writing SOPs
 Use clear, concise language.Use clear, concise language.
 Use active voice.Use active voice.
 Avoid names; use titles instead.Avoid names; use titles instead.

30. Implementing and MonitoringImplementing and Monitoring
SOPsSOPs
 SOPs should be introduced gradually.SOPs should be introduced gradually.
 Prioritize most relevant SOPs andPrioritize most relevant SOPs and
present them first.present them first.
 Principle Investigator should approvePrinciple Investigator should approve
all SOPs and designate an effectiveall SOPs and designate an effective
date.date.

31. Implementing and MonitoringImplementing and Monitoring
SOPsSOPs
 SOPs should be reviewed on a regularSOPs should be reviewed on a regular
basis (usually annually) to ensurebasis (usually annually) to ensure
policy based regulations are up-to-policy based regulations are up-to-
date.date.
 Previous versions of SOPs should bePrevious versions of SOPs should be
retained.retained.

32. SOP TrainingSOP Training
 All staff should have SOP training.All staff should have SOP training.
 Training should be documented.Training should be documented.
 SOP should be accessible to staff.SOP should be accessible to staff.

33. What is the difference between aWhat is the difference between a
SOP and a Manual of ProceduresSOP and a Manual of Procedures
(MOP)?(MOP)?
 These terms have been usedThese terms have been used
interchangeably.interchangeably.
 Both provide a standardization of aBoth provide a standardization of a
process.process.

34. What is the difference between aWhat is the difference between a
SOP and a Manual of ProceduresSOP and a Manual of Procedures
(MOP)?(MOP)?
 SOP provides general information thatSOP provides general information that
is to be utilized throughoutis to be utilized throughout anyany
research study.research study.
– How as a clinical site we will assess delegationHow as a clinical site we will assess delegation
of duties.of duties.
 MOP is specifically written for aMOP is specifically written for a
particular research study which willparticular research study which will
incorporateincorporate elements of the SOP.elements of the SOP.

38. MOPMOP
 The MOP should be written so thatThe MOP should be written so that
anyone in your clinical site can followanyone in your clinical site can follow
the procedures for that study and findthe procedures for that study and find
all relevant materials.all relevant materials.
 The MOP should be extremelyThe MOP should be extremely
detailed.detailed.

39. SOP or MOPSOP or MOP
 Both documents are important!Both documents are important!
 Start with the SOP first. Once youStart with the SOP first. Once you
have written general procedures, thehave written general procedures, the
MOP will be easier.MOP will be easier.
 This process will take lots of time andThis process will take lots of time and
patience.patience.

40. SOP ResourcesSOP Resources
 Examples from National Cancer InstituteExamples from National Cancer Institute
https://cabig.nci.nih.gov/workspaces/CTMS/Meetings/SIGs/Best_Prahttps://cabig.nci.nih.gov/workspaces/CTMS/Meetings/SIGs/Best_Pra
 Standard Operating Procedures for Good Clinical Practice atStandard Operating Procedures for Good Clinical Practice at
the Investigative / Centerwatchthe Investigative / Centerwatch
http://www.ccrp.com/sop.shtmlhttp://www.ccrp.com/sop.shtml
Cost $995 for single site licenseCost $995 for single site license
 Standard Operating Procedures (SOPs) for Good ClinicalStandard Operating Procedures (SOPs) for Good Clinical
Practice / University of WashingtonPractice / University of Washington
http://www.crc.washington.edu/Resources/GCPSOPInvSites.aspxhttp://www.crc.washington.edu/Resources/GCPSOPInvSites.aspx
Cost $135Cost $135

41. Comments andComments and
Questions?Questions?