Standard Operating Procedures (SOP):Content, Format, and Management

Carol De Sain and Charmaine V. Sutton

The Tamarack Group
HCR 3, Box 94
Tofte, MN 55615

Summary

The purpose of a standard operating procedure is to describe the performance of a controlled process. If it is written to fulfill only that purpose efficiently and effectively, it becomes a rugged, flexible, and valuable quality assurance tool.

INTRODUCTION

Once a chemical or pharmaceutical manufacturing process has been fully designed, developed, and demonstrated, the standard operating procedure (SOP) can be finalized and approved. Consider the following type of information, discovered during process design and development, that are required to accurately describe a processing event and its control.

• A list of materials and components required for processing, with minimum quality characteristics and/or vendors; specifically cite the part numbers that are approved for use.
• A full description of any reagent, component, or sample preparation/handling that must be performed before process initiation; describe compounding or formulation of reagents specifically or reference appropriate part numbers.
• A list of equipment required and the relevant characteristics of that equipment (capacities, precision, compatibilities, and limitations); indicate equipment specifically by name or equipment number when appropriate.
• Technician training requirements.
• A step-by-step description of the processing event to include the scale or capacity of the operations.
• Processing control parameters and the techniques or methods that ensure their control.
• Test methods or observations that ensure the effectiveness of process controls and documentation requirements associated with this testing.
• Process control effectiveness testing limits or acceptance criteria.
• Data-handling requirements with example calculations.
• Reporting and documentation requirements.

SOP FORMAT AND MANAGEMENT

Requirements for document identification and control, accountability and traceability, responsibilities, etc., must be included with every procedure. This can be accomplished by providing a consistent format and consistent document management requirements for every procedure.

There is no government regulatory agencies such as FDA-approved format for an SOP. There are, however, common expectations within the industry and from regulatory agencies that ensure the accountability, traceability, and consistency of these documents. When choosing a format for a procedure, consider the following.

• Company name and pagination - The company name and pagination (e.g., "page 3 of 7") must appear on every page of the document. These procedures can appear in submission documents; therefore, it should always be apparent which company is responsible for the document.
• Title - The title should be descriptive. Because a procedure describes how to do something, the title should use directive language to declare what is being done to what. An SOP titled "Water for Injection Still" is not descriptive of the procedure's content; a more appropriate title would be, "Operation of Water for Injection Still."
• Identification and control - Procedures must be uniquely identified. This identification supports accountability and traceability of the document throughout the facility and over time as it changes. the accountability and traceability of procedures are based on assigning them identification numbers or codes and control numbers or codes (e.g., revision or edition numbers).
• Purpose - the purpose or objective of a procedure should restate and expand a well-written title. Expand or qualify the directive language used in the title (e.g., operation, monitoring, and routine maintenance associated with ABC Corporation and XYZ Company WFI systems).
• Scope - The scope should provide limits to the use of the procedure. Are there certain samples that are appropriate to test by this method? Do these operations apply only to certain equipment or to certain departments? Is there a limit to the capacity, volume, or throughput of the procedure? State to what areas this procedure does and does not apply.
• Responsibility - Who is responsible for performing the work described? Who is responsible for reporting the work? Are there special training or certification requirements? As discussed below, this section defines the procedure's audience, i.e., who will be qualified to perform the work described. It will set the stage for the amount of detail in the document that follows.
• Procedure - Describe the procedure in a step-by-step, chronological manner. Use active verbs and direct statements, e.g., "Weight 5.00 g of sodium chloride, PN3244" or "Add 100.0 ml of Purified Water, PN 0128."
• Calculations / data handling / documentation requirements - Describe how the raw data are managed and reported. Provide examples of calculations, when appropriate.

SPECIALTY PROCEDURES

SOPs are often subdivided into types of procedures. There may be Manufacturing Procedures (MPs), Quality Test Methods (QTMs), or Test Methods (TMs), which are designed and formatted specifically for assays. Similarly, there may be Calibration Procedures or Preventive Maintenance procedures with specific format and design requirements. Categorization of procedures is useful, but it is best to categorize them based on the types of activity they describe. Focus on the directive language in the titles of procedures, and the list will begin to subdivide itself naturally (e.g., "Testing of...," "Operating of...." or "Maintenance of...").

The categorization affords a more specific format for each type of procedure. A reference section may be appropriate for testing procedures or a calibration standards section may be appropriate for calibration procedures. Categorization also facilitates a more appropriate review and approval process for the document. The maintenance department must review and approve calibration procedures, for example, but has no need to review and approve QC test methods. Rather than having all procedures reviewed and approved by all potentially interested parties, categorization could minimize the review and/or approval signatures and emphasize expert review.

WHAT DOESN'T REQUIRE A SOP?/HOW MANY SOPS ARE ENOUGH?

Are SOPs required for "Operation of a hand-held calculator," "Operation of a balance," "Operation of the coffee pot," "Operation of the copy machine," or "Measuring liquids in a graduated cylinder"? When can the writing stop? What needs to be established in writing and what can be left to training? These are important questions.

The consistency of operations must be ensured for all activities that directly affect the product or the decisions about product quality. What types of activity, if performed inconsistently, could affect product safety, performance, and quality? The answer is different for every manufacturer.

The operation of the coffee pot or the copy machine should not directly affect product quality. Once could argue that if a batch record is copied with pages missing, then the product could be affected, but controls should be in place to ensure that this event is unlikely to occur, i.e., official issue of batch records with signatures. Consider that the tasks (the consistent use of a balance, measurement of liquids in graduated cylinders, and use of a hand-held calculator) can be directed, confirmed, and documented during employee training sessions rather than with event-based procedures and data collection documents.

HOW MUCH DETAIL IS ENOUGH?

The level of detail required in a procedure is affected directly by the level of expertise of the individuals performing the work and the rigor of training associated with the task. There are no rules about the level of detail in SOPs that apply to all companies. Procedures must be written to communicate effectively with the individuals who perform the work routinely. Every procedure should describe this audience and its required level of expertise and training in the responsibility section of the SOP.

Deciphering "what matters" from "what doesn't matter" in a process is also important when writing a procedure describing the process. When processing is poorly developed or is undeveloped, the author must guess at the significance of many process steps and controls. When this occurs, procedures inevitably contain a lot of unnecessary detail. One way to begin to edit this detail is to ask, If this weren't done exactly as directed, would it deserve to be written up as a procedural deviation? SOPs must be followed; if they are not followed, then the event should be considered a reportable deviation.

How does one write an SOP that has enough detail to be useful to the technician without having so much detail that it triggers meaningless deviation reports? One way is to focus on the purpose of the procedure. It has already been stated that the procedure defines a process, process controls, and process control effectiveness testing criteria. These are fundamental requirements that cannot be eliminated. How these requirements are met, however, can vary, and the procedures can be written to facilitate this flexibility.

For example, if a processing step requires centrifugation of a sample, then the process design and controls associated with this step are: "Spin at 10,000 X g; 20-25 min; 2-8 ûC". This directive is fundamental to consistent processing, but it is useless to the technician who routinely stands in front of a centrifuge and simply needs to know what settings to choose. "Setting #5 on refrigerated centrifuge Beckman BJ-15; 22 min" might routinely achieve the directive by providing the information the technician needs to know, but it does not adequately establish the process design or control parameters (10,000 X g, etc.) and it unnecessarily limits the processing event to a particular brand of centrifuge.

Instead, consider the following: "Spin at 10,000 X g; 20-25 min; 1-8 ûC; for example, setting #5 on refrigerated centrifuge Beckman BJ-15; 22 min." This statement established the process design and control and offers, by example, equipment-specific directives for the technician.

KEEPING REGULATORY PROMISES

A SOP also ensures that promises made to government agencies in regulatory submissions, letters, memos, and meetings are fulfilled. It is important, as a result, to review these submission documents to identify the commitments and then to ensure that procedures are in place to routinely generate evidence that the promises are kept.

NO SPECIFICATIONS IN SOPS

An SOP should be standard -- that is, it should be useful for many different types of products and situations. Standard test methods, for example, should be applicable to many types of samples and products. the procedure does not change, although the specifications for the results of testing will change form product to product. To ensure that a procedure is standard, therefore, do not put specifications for the results of the procedure in the SOP.

Procedures, however, must contain specifications, limits, requirements, or acceptance criteria for the process or test method controls. These controls include the results of positive and negative samples, blanks, standard preparations, calibrations, equipment monitoring values -- that is, any controls that help to ensure that the procedure was performed as directed and that the information coming out of the procedure is reliable.

WHO SHOULD WRITE THE SOP

When a test method or process has been developed in-house, the individual who has designed the process and its controls, as described above, should write the procedure. The more knowledgeable the author, the more accurate the procedure will be. In addition, if the author is directly familiar with the work, the procedure will communicate effectively and the requirements of the work will be user-friendly.

Many procedures, however, are not designed or developed. Some test methods, for example, are standard methods from the U.S. Pharmacopoeia or the Association of Official Analytical Chemists; some equipment operation procedures are copied from vendor manuals; some processes are developed by the workers who simply have identified and agreed upon a convenient and successful way to do the work. Again, the procedures should be written by an individual who performs the task routinely or someone who is directly responsible for the performance of the task.

ACKNOWLEDGMENT

This article is adapted from the authors' book, Documentation Practices: A Complete Guide to Document Development and Management for GMP and ISO 9000 Compliant Industries.

RECOMMENDED READING

C. V. De Sain and C.V. Sutton, Documentation practices: A Complete Guide to Document Development and Management for GMP and ISO 9000 Compliant Industries (Advanstar Communications, Cleveland, OH, 1996).

C. V. De Sain, Documentation Basics That support Good Manufacturing Practices (Advanstar Communications, Cleveland, OH, 1993).

C. V. Sutton and C.V. De Sain, Meeting GMP and ISO 9001 Expectations for Product Development (Parexel International, Waltham, MA, 1996).

D. Warburton, "Problem Procedures: Five Common Mistakes Engineers Make in Writing Manufacturing Procedures," Medical Device and Diagnostic Industry, 224-228 (May 1995).