Since many deficiencies identified in FDA’s 483s and Warning Letters can be traced back to SOP deficiencies—inadequately written, communicated, monitored, and/or enforced—this post discusses how to craft a well-written SOP to maintain regulatory compliance.

Well-written SOPs provide clear instructions, avoiding deviations. With a reduction in deviation, organizations can maintain compliance, deliver a quality product, and ensure patient safety.

Best practices for writing SOPs

Some basics to review: An SOP is a set of step-by-step instructions used to perform a specific routine operation. Its purpose is to ensure that people carry out the operations correctly and always in the same manner so there is efficiency, quality output, and uniformity of performance. It outlines who does what, when, and how to reduce miscommunication.

It is important that procedures are written from the perspective of end users. Here are guidelines to keep in mind:

• Write in a concise, step-by-step, easy-to-read format. Write what is done and in the order it is to be completed. Keep sentences brief and use simple common terms.
• Write the main point immediately, using the active voice and action verbs such as approve,  direct, assign, designate, evaluate, review, revise, or identify. Use the active voice with present tense verbs. One study shows that the passive voice can suggest “special connotations in addition to the basic message,” which blur overall meaning.
• Avoid ambiguous terms (e.g., periodically, generally, typically, may, and should). These terms indicate a preference and do not enforce consistent execution, a vital part of SOPs. Avoid terms such as “SOPs are reviewed periodically to verify the current process.” Say when they should be reviewed. “SOPs are reviewed annually to verify the current process.”
• Use terms may, must, and should appropriately.

1. May allows for flexibility. No deviation if it 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. (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 expiry date.”).
3. Should indicates 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.
  Bullet lists are effective because they quickly focus the reader’s attention on key elements they need to 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.

Here is a suggested format for an SOP:

• Header (Title, Document Number and Version) — It clearly identifies the activity, is unique, and contains keywords.
• 1.0  Purpose — This defines the intent of the document; it should be one or two sentences.
• 2.0  Scope — This defines to whom or what the document applies. And it can also outline to whom or what the document does not apply. The idea is to establish the range of activities the procedure applies to as well as its limitations.
• 3.0  References and Related Documents — Include documents and references necessary to understand and correctly execute the process. And ensure referenced documents are used within the procedure.
• 4.0  Definition of Terms — Here you can clarify terms not universally recognized by the audience to ensure consistency across functional areas.
• 5.0  Roles and Responsibilities — Identify roles that execute activities within the procedure and define the responsibilities associated with the role.
• 6.0  Procedure (Process Steps) — While the FDA wants to hold companies to standards set forth in written procedures, they do not want to bind them to standards and practices that are unnecessary or impossible to maintain. They want to ensure that standards are robust enough to meet compliance expectations without containing too much detail that may pose a compliance risk.Here you break down the procedure into:

1. Critical points or major steps (6.1, 6.2, 6.3, …). You want to include only the steps necessary for the end user to be successful in accomplishing the goal/objective of the procedure.
2. Critical points into individual action steps (6.1.1, 6.1.2, 6.1.3, 6.2.1, 6.2.2, 6.2.3, ….).
3. Call out notes separately. Notes provide information to enhance understanding of the process and responsibilities, as well as to call out warnings.

• 7.0  Appendices — Appendices can be a flow chart to help explain the procedures during audits or to include as a reference tool for visual learners. Appendices are used for supplemental information that provides greater detail than can be covered within the procedure.
• 8.0  Revision History — Here you capture the changes made to a procedure and justification or, if it is a new procedure, the reason why the procedure was created.

This development process yields clear, concise SOPs with well-defined roles and responsibilities. In this fashion, SOPs can be easily implemented and followed. This can result in greater compliance and reduction of time, effort and resources spent on investigation, deviations, and CAPA documentation.

What has been people’s experience in developing SOPs? What are some best practices you can share?