This article is the second in a series examining strategies that allow quality groups to collaborate with GCP and GMP groups to improve ICH E6(R2) compliance, increase clinical study robustness, and enhance data integrity.

The first article discussed how to provide training that GCP colleagues have never had before. This article focuses on how to write clear, concise, and action-driven SOPs.

SOPs are one of the basic building blocks that lead to better data integrity and successful clinical trials. Well-written, concise SOPs improve the clinical development process by providing clear direction that can be implemented consistently, which can result in reductions in churn, noncompliance, and questionable data. Consistent implementation of procedures allows clinical staff to better focus on study activities and keep patients safe.

Here are four pitfalls to watch for when creating GCP-oriented SOPs.

1. Creating SOPs In A Vacuum

Make SOP development a learning opportunity, as well as a team sport.

Collaboration and conversation at the beginning help. Everyone is involved, shares concerns, is transparent, and can address challenges early in the process. Quality can get the people involved in a procedure around a table to discuss the process and determine the necessary steps involved. This approach is educational, inclusive, and breaks down silos that are hurdles to efficient study start-up and management.

When I was tasked with developing or overhauling SOPs, I was instructed to just create or revise an SOP and route it for signature approval. Knowing this was not a recipe for success, I opted to first pull together a group of stakeholders to provide a forum for discussion and learning. It allowed everyone to think through and map the process, with myself acting as the student, asking a lot of questions to prompt discussion.

There was much return on the investment; in the end, it became a standard practice, with stakeholders feeling engaged and empowered to mold procedures and freely communicate with others outside their immediate sphere of influence. We had procedures that could be consistently, compliantly, and efficiently implemented, and we had empowered personnel who held each other accountable — resulting not only in a voluntary QA culture, but also more compliant studies.

2. Undefined/Vague Roles And Responsibilities

Be clear; focus on specifics.

Clinical SOPs usually have language that refers to a department rather than a specific role or title (e.g., “Clinical development is responsible for ensuring the study document is filed” rather than “The clinical trial manager ensures the study document is filed in the TMF”). People need to know what is expected of them, and it begins with clearly defined roles and responsibilities.

For clarity, it is important to point responsibility to a specific role rather than a department. Here is what happens when you have a department, rather than a specific role, responsible for something. I recently went on quite the “wild goose chase” just to track down a signed approval page for a study protocol. After three different people said they didn’t know who had the signed approval page, it became clear that either no one was following the procedure or we needed to revise the SOP.

After talking with the head of clinical operations, we created a new training process to ensure that people understood this specific SOP (and others) more clearly. As part of the training, we made it clear that if an SOP was not working or being followed correctly, people had the power to approach the head of ClinOps or myself to share what was wrong so we all could work to develop a more specific SOP. This created a dialog about processes where everyone becomes accountable — including the head of ClinOps, the clinical research associates, and quality. In this fashion, people understand how they are accountable and know they can raise a hand and point out an issue that we all can recognize and work to resolve.

One reason to link SOPs to specific roles or titles is that these responsibilities are connected to training requirements, files, and job descriptions. In other words, they link to the necessary training for executing that task. SOPs are noted in training files, which are the first items reviewed during an audit or inspection. Not only is this where you can demonstrate you have qualified people executing appropriate tasks, but also that people within specific roles are properly trained.

Clear roles and titles also ensure you are not overtraining people who are not involved in a procedure. For example, not everyone in clinical development must be trained on a procedure that is the specific responsibility of the data manager.

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3) SOPs With Many Pages

Length matters.

An inverse relationship exists between the length of your SOP and the ability of people to comply with the number of steps specified. Focus on a procedure’s basic elements so it can be followed consistently. Consistency breeds compliance, which in turn results in data with integrity.

4) SOPs That Don’t Commit

Language matters.

Vague language in SOPs leads to misinterpretation, inconsistency, and inefficiency. It does not provide clear direction and, as a result, creates confusion and misunderstanding, which can lead to noncompliance.

Write procedures from the perspective of end users. Here are best practices to keep in mind:

  • Write in a concise, step-by-step, and easy-to-read format. Write what action is done and the order in which the actions are to be completed. Keep sentences brief and use simple common terms.
  • Write the main point immediately, using the active voice, present tense, and action verbs such as approve, direct, assign, designate, evaluate, review, revise, or identify. One study shows that the passive voice can suggest “special connotations in addition to the basic message,” which can blur overall meaning.
  • Avoid ambiguous terms (e.g., periodically, generally, typically, may, and should). Should is one of the most overused words in clinical SOPs. Should, as well as the other terms identified above, indicate a preference and do not enforce consistent or required execution, which is a vital part of SOPs. Avoid these terms whenever possible.
  • Use the terms may, must, and should appropriately.
  1. May allows for flexibility, that is, there is no deviation if a step is not adhered to (“Based on the risk and criticality of the study, the auditor may conduct more than one critical phase audit.”).
  2. Must indicates a step that must be adhered to, and you must file a deviation if it is not adhered to (“The initiator must provide a justification for the extension as well as a new proposed expiration date.”).
  3. Should indicates that execution of the process is determined by a conditional clause. A deviation is required if appropriate conditional requirements are not adhered to (“If timelines are not met, the initiator should request an extension.”). Always describe the condition first and then the action to take, if that condition applies.
  • Use lists and bullets appropriately. Bulleted lists are effective because they quickly focus the reader’s attention on key elements they must remember. They give readers an opportunity to stop, slow down, and process critical information. The white space they create also provides a break between long, visually intimidating paragraphs.

You can find a simple SOP template here that serves as a starting point to guide you through this process.

Conclusion

Concise SOPs with well-defined roles and responsibilities allow for better understanding and, more importantly, result in greater compliance. In the long run, such SOPs also lead to less time, effort, and resources spent on investigations, deviations, and corrective and preventive actions (CAPAs). They are important starting points for building a voluntary QA culture within your organization, which can result in greater data integrity and robust studies.

In the next article, we will discuss developing systems for appropriately overseeing vendors and monitoring processes to ensure a high-quality study with data integrity — and minimize the risk to patients.

About the Author

Judy Carmody, Ph.D., is the Founder and Principal Consultant of Carmody Quality Solutions, LLC (CQS). She as 20+ years of expertise in applied technology, bench chemistry, analytical development, validation, quality management and senior leadership. She has built quality management systems for both start-up and Fortune 500 companies.

Dr. Carmody founded Avatar Pharmaceutical Services, an FDA-registered contract research organization that provided quality, submission-ready customized analytical services in compliance with cGMP. She grew Avatar to 25+ employees and more than 75 clients before it was purchased in 2010 by a Boston-based pharmaceutical company. She holds a Ph.D. in Analytical Chemistry from Clark University in Worcester, Massachusetts. You can connect with her on LinkedIn

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