One Q & a Lotta A’s about SOPs for Research Sites

By Laurie Meehan

Posted on LinkedIn in July:

“What are your thoughts about having SOPs for clinical research sites versus having working guidelines in lieu of SOPs?”

You know how it is with those LinkedIn discussion groups.  You think you’re posting an intriguing and brilliantly conceived question that will inspire your colleagues to clear their desks, seize their keyboards, and plunge headlong into enthusiastic electronic debate.  Instead, your post lands unceremoniously on the ground, with only the dullest of thuds, ignored and unloved.  So naturally, when I encountered the post above -- which had managed to attract 32 responses -- I was curious to see what had garnered such attention. (And yes, that was 3 months ago and I’m just getting around to writing about this now.  Don’t judge me.)


The people who offered their insights on this question hailed from the US, Canada, Europe, and the UK, and included study coordinators, Site Ops managers, ClinOps managers, site network managers, and QA auditors and consultants.  The breadth of interest and affiliation among these participants is not always seen in the echo chamber of social media, and so added to the discussion’s appeal and significance. Our blog post this month is a summary of this LinkedIn discussion, seasoned with a soupcon of commentary I couldn’t resist adding.  (Don’t even pretend to look surprised.)

SOP vs Work Instructions (WIs)

There was general consensus about many attributes and uses of SOPs and WIs.  First, SOPs are comparatively higher-level documents, while WIs contain more detailed information and procedures.  (One participant observed that SOPs “are the backbone” of a quality system, while WIs “are the meat.”  Most of the research sites that responded currently use SOPs and WIs in this sort of hierarchy.)  WIs should point to their “parent” SOP and should refine the SOP content, but never introduce anything the parent SOP did not contain.  While WIs can be written on a project-specific basis if needed, SOPs cannot.  Since WIs are more limited in scope and may only apply to a single department, they tend to be easier to modify; the review and approval processes can often be completed locally.

What Written Procedures Are Sites Required to Have?
Technically, there are no regulations requiring research sites to have SOPs, or even WIs.
[Polaris commentary:  ICH E6 Section 5.1.1 does require sponsors to maintain written SOPs as part of their Quality System.  Yes, ICH E6 is being changed, but not that part!]

But this may be a distinction without a difference.  The PI is responsible for ensuring the rights and safety of study volunteers and supervising the conduct of the trial.  So how do you do that without written procedures?  Well, FDA suggests you don’t try.  The agency’s 2009 guidance on Investigator Responsibilities recommends that sites have procedures for a number of study activities, including those in place to ensure high-quality source data, protocol compliance, and proper adverse event reporting.  But does the guidance say the procedures have to be in writing?  The discussion participants answered that question with another question.  Does it really matter?  Site staff can’t be expected to memorize procedures, let alone communicate them effectively, if nothing is written down.

How Do QA Auditors Approach Site SOPs and WIs?
Existence.  OK, so written site procedures are not required, but they’re necessary.  So when a QA auditor finds them inadequate, it can be a little thorny because there’s no specific regulation to point to.  This particular conundrum wasn’t raised in the LinkedIn discussion, but it’s pertinent, and I’d like to address it.

[Polaris commentary: It’s the job of the QA auditor to assess whether GCP procedures are being followed.  Even though written site procedures are not required per se, their absence would almost certainly contribute to other audit findings.  In these circumstances, Polaris auditors will include an observation in the audit report similar to this:

“ICH E6 2.13 states; 'Systems with procedures that assure the quality of every aspect of the trial should be implemented.' This is generally accomplished through the implementation of a SOP program.”]



Adherence and Control.  QA folks in the LinkedIn discussion said that when conducting an audit, they assess whether site personnel adhere to their SOPs and WIs, and how the site controls these documents.  They also noted that, in these respects, they treat SOPs and WIs the same.

[Polaris commentary: If there’s no regulatory requirement for sites to have written procedures, then there are certainly no requirements about what kind of control the site should maintain over them.  But SOPs and WIs that are not approved, regularly reviewed, easily accessible, nor replaced when obsolete – i.e., not controlled – will almost certainly contribute to GCP deviations.] 

One participant shared a helpful tip for getting good grades on procedure adherence.  She recommended that an instruction be designated as either a:
(1) “Requirement” to indicate a critical process from which staff cannot deviate, or
(2) “Best Practice” to provide guidance, but encourage the use of common sense for a process which can tolerate a degree of flexibility.

Compliance is a Means to an End
Of course, it’s important to keep in mind that the real goals here are protecting subjects’ rights, welfare, and safety, and producing reliable study data.  Whether or not having SOPs and WIs at a study site is a requirement or a strong suggestion isn’t the issue.  And while it’s true that the size and available resources at a site will influence the form and extent of its quality management system, here’s the take away:

You can’t run a safe, high-quality clinical trial without developing, maintaining, controlling, and training on written procedures. What form those procedures take -- SOPs or WIs -- is less important than effectively communicating their content and keeping them current.