SOPs & Other Procedural Documents

Sep 04, 2013

Pharmacovigilance, Drug Safety and Regulatory Affairs Author & Expert

Amongst other things as a pharmacovigilance consultant, I do a lot of audits and mock inspections in the FDA and EMA/EU styles.  A surprisingly consistent finding that I note is a frequent lack of understanding of what is expected from companies regarding standard operating procedures (SOPs), Work Instructions (WIs), Manuals, Guidelines, “Cheat Sheets” and other documents prepared for staff explaining precisely what their responsibilities are and how they are to do their tasks.

All of these documents can be lumped together and are called “procedural documents” and all should be versioned, controlled documents.  In this posting, I’m using “SOP” and “procedural documents” more or less synonymously.

The obvious first question is: do companies really need SOPs? The answer is a clear yes.  Written SOPs are mandatory in Quality Management Systems.

EMA: Good PV Guidelines Module 1 PV & Quality Systems page 10 ( :

“All elements, requirements and provisions adopted for the quality system shall be documented in a systematic and orderly manner in the form of written policies and procedures, such as quality plans, quality manuals and quality records [IR Art 8(4)].”

FDA: 21CFR314.80(b) and 310.305(c)(5):

“Any person subject to the reporting requirements under paragraph (c) of this section shall also develop written procedures for the surveillance, receipt, evaluation, and reporting of postmarketing adverse drug experiences to FDA.”

Several audit findings are so prevalent that they bear mentioning:

  • No SOPs: Some companies do not have any SOPs or procedural documents or the ones they do have are so non-specific that they are inadequate.  This will be a critical finding in an inspection.
  • Controlled Documents:Some companies do not understand that procedural documents must be controlled, versioned and tightly handled.For example, some companies have very high level, non-specific SOPs that are fully controlled, versioned, formally updated and follow the usual good documentation practices.  This is fine.  However, they do not have detailed Work Instructions, Guidelines, Manuals and other assorted procedural documents that are very detailed and actually explain how the job and tasks are to be done.  This presents a problem to the people who actually do the job and who need to know the intricate process details. One or two people in the department take it upon themselves to take the high level SOP and write up a more detailed step by step set of instructions on how to do a particular job or task. Sometimes these documents are well done and sometimes not.  They are not approved or signed off and often undated; and thus they are not controlled, versioned documents.  An inspector or auditor will cite this though it would probably not be a critical finding if the job is getting done well.  These “unofficial” documents should be harvested and made into formal procedural documents.
  • Cheat Sheets: These are very very unofficial documents prepared by workers in a department who find the SOPs or procedural documents (whether detailed or not) useless, incomplete, wrong or out-of-date.  Since they have to get their job done, they will take it upon themselves to write down how a task is done.  A frequent example of this is triage and data entry of a safety report into the safety database.  This is usually a complex task in which the case must be date stamped (or the email/fax date checked), the case read, coded and analyzed for seriousness and possibly expectedness and relatedness and then entered into the database or tracking log.  This usually must be done rapidly (e.g. same day or within 24 hours) and there may be different procedures for different types of cases (e.g. clinical trial vs spontaneous).Many safety specialists will then write up their own step-by-step version of the procedure and share it with their colleagues.  Sometimes they don’t share and each specialist writes up his or her own version of the procedure and puts it next to the PC in his or her cubbie!  I have seen as many as three or four different versions floating around in cubbies in the same company.  Sometimes they are the same and sometimes not.  Each cheat sheet is different and usually undated and uncontrolled.

    This presents major quality issues and would be cited during an inspection.

    This is a cri du coeur from the staff asking the company to create adequate SOPs or work instructions for them.

  • Out-of-Date SOPs: All procedural documents should be reviewed periodically and revised as needed.  For example, many companies often do a yearly review of all such documents.  Some documents are changed and updated; some are not.  But all have a notation either in the files or a new version issued tracking the changes if any and indicating that the document was reviewed and either updated or found not to need changes.  If changes are needed before the periodic review date, the SOP should be updated as needed.
  • Older Versions Still in Use: Another common problem seen most frequently in companies with paper SOPs rather than electronic ones is the use of out dated SOPs by some or all members of the staff.  This is a version control issue.  If paper procedural documents are used, they should be versioned and numbered such that every copy distributed to the staff is accounted for.  They are usually kept in a loose-leaf binder and when a new version is issued, someone physically brings the new version to each person and removes the older version and replaces it with the new one.  This should be done but this is not always the case.  This method is no longer the state of the art.The solution to this is electronic SOPs which are available to the staff on-line and contain only the latest version.  In this way, no one will use an out of date version.  If they are printed out, there should be a statement or watermark to the effect that any printed version is “unofficial” and the only official one is the version available on-line.

If an inspector finds an older, out-of-date version being used by the staff (or, worse, some of the staff but not all) there will be a citation.

  • Incomplete SOPs: Another common finding is that a company has fine SOPs but that either they are incomplete or some topics that need an SOP do not have one.  For example, a company may have an excellent SOP on triage of incoming safety reports but not indicate in the SOP that the four validity criteria (patient, reporter, drug, AE) should be looked for.  If that is not in the SOP it should be referenced in another document or regulation.Sometimes, entire topics are missing.  Common missing SOPs include: safety data exchange agreements, timing for task completion during the work flow for expedited reports, data retention, signaling and escalation of safety issues.
  •  Training Issues: Some companies have excellent well-handled procedural documents but do not do adequate training on them.  All procedural documents must have training done for the staff before the procedure goes into effect.  The auditor or inspector will compare the date the SOP goes into effect with training dates in the training folders of the employees in order to be sure that training was done and was done before the procedure went into effect.
  • Another interesting finding is often seen with new hires (“on-boarding”) in which the employee is trained on a dozen or more SOPs.  On examining the training records these dozen SOPs totaling perhaps hundreds of pages were all trained on the same day!  And sometimes the training is “read and understood”.  In other words, the training was simply having the new hire read the SOPs.  This will often (but not always) be cited during an inspection as inadequate training.
  • Language Issues: A couple of times I have seen documentation of training of an employee who doesn’t know English (usually in a subsidiary or external company) having been trained on an SOP in English that he/she obviously can’t understand!  Usually someone walked the person through the SOP and did indeed do training but this is rarely well documented.

If you think this is too bureaucratic and not that important, think about it the next time you get on an airplane.  I’m sure you want the pilot to be using the latest SOP and “how to fly the plane” manual!