How to Avoid the Number One Reason for Receiving FDA 483s

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An enterprise quality management software system can minimize human error and help pharmaceutical manufacturers maintain standard operating procedures to prevent deviations from GMP resulting from not having or following written procedures.

The most recent lists of Form 483 observations issued by FDA tell some interesting stories. Each item contains its own cautionary tale for all pharmaceutical manufacturers. However, the newest list, which spans the timeframe from Oct. 1, 2014, to Sept. 30, 2015, has a common theme. The number one reason for Form 483 observations is “Procedures not in writing or not fully followed.” This infraction was noted in 160 separate Form 483 instances (1).

In these instances, the 483s represented an FDA investigator’s observations regarding deviations from good manufacturing practice (GMP) regulations. These infractions should be taken seriously and require a thoughtful and thorough response because a Form 483 usually lists symptoms of underlying systemic problems that should be addressed with care, consideration, and detailed planning by everyone involved along the line.

For a pharmaceutical company to operate safely and within the bounds of compliance, FDA requires a pharmaceutical manufacturer’s standard operating procedures (SOPs) to be clearly written, modified, and maintained in a consistent and timely manner, and be centrally accessible. Problems and accidents are inevitable if the employees do not have current written instructions for their tasks or if they do not follow written instructions to the letter.

For example, in a June 2016 inspection, a pharmaceutical company received a Form 483 for this type of SOP deviation when FDA noted that its “responsibilities and procedures applicable to the quality control unit are not fully followed” (2). Pharmaceutical companies slip into these types of predicaments all too easily if their document control systems are paper-based or scattered between disparate locations or if they do not have adequate processes for tracking signatures, approvals, and audit trails. Crucial SOP documentation is more likely to get lost in such systems, and employees have greater likelihood of operating with out-of-date work instructions. Collaborating on, updating, or approving new or revised documents can be a time-consuming practice, particularly when manual and paper processes (which represent an open invitation to human error) or geographic barriers exist.

The best approach for minimizing human error and establishing a system where each step has to be followed is by implementing an enterprise quality management software (EQMS) system.  Best-practice features include prompting users with selected data to reduce data entry and avoid mistakes common in manual document management and data entry.

An EQMS system can automate a pharmaceutical company’s routing and delivery of SOPs, policies, work instructions, and other critical documentation to the appropriately designated personnel. It can automate notification, escalation, and approval of any form-based process for not only easy access, which can be crucial during an audit, but also faster turnaround. It can also be used to maintain SOPs and any other pertinent documentation in a secure, web-based repository.


Ideally, the EQMS should be format-agnostic-able to handle any type of file without regard to the software used to generate it. Maintaining, retrieving, and searching for audit-ready documents can be simplified with search functionality and configurable organizational functionality. Change control and audit trail functionality provide transparency and visibility into who has changed which document and when, ensuring that only the most current version of a document is in use.

Not fully following the procedures is often due to a lack of training, which can also be tracked in an EQMS system. Training should not be a one-time program-it should be a continuous and dynamic effort. Most 483 observations usually include an element of training that is either necessary or a result of inadequate training. Not only should the training itself be dynamic, but the documentation and certification for individuals should also be dynamic. After all, if an operator does something wrong, there are likely other people who have similar deficiencies in their training. Management can make adjustments more easily and with greater visibility with EQMS than is possible with a paper-based system. By employing these best practices and processes, pharmaceutical companies can markedly improve their chances of avoiding Form 483 observations.


  1. FDA, FY 2015 Inspectional Observation Summaries, - Drugs, accessed Jan.25, 2017.
  2. FDA, Form 483,, accessed Jan. 25, 2017.

About the Author
Oliver Wolf is a senior product manager at MasterControl.