…And the Top FDA Drug 483 Observation Is……
June 3rd, 2025 // 1:54 pm @ jmpickett
We reviewed FDA’s FY 2024 inspection list for drug companies last week. FDA performed 561 cGMP inspections of drug companies last year. California had the most cGMP inspections, followed by Texas. That got us wondering what the most common FDA 483 observation is. According to recent FDA data, the top cGMP citation on FDA 483s between 2009 and 2025 was…..
21 CFR 211.22(d) – Procedures not in writing or fully followed
Let’s look at the full FDA procedure:
PART 211 — CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS
Subpart B – Organization and Personnel
Sec. 211.22 Responsibilities of quality control unit.
(a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality control unit shall be responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company.
(b) Adequate laboratory facilities for the testing and approval (or rejection) of components, drug product containers, closures, packaging materials, in-process materials, and drug products shall be available to the quality control unit.
(c) The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product.
(d) The responsibilities and procedures applicable to the quality control unit shall be in writing; such written procedures shall be followed.
21 CFR 211.22(d) states that procedures and responsibilities related to the company’s quality control unit must be in writing and completely followed. FDA wants to stress the importance of drug companies having well-documented procedures for quality control to ensure it regularly follows cGMPs for quality. Of course, having well-documented quality control procedures that are fully followed sounds easy, but this requirement trips many of us up.
Common Issues with 211.22 – Lack of Communication
The first issue that leads to 483s with procedures is there is pressure from upper management or poor communication and visibility into critical quality metrics. This problem makes it more difficult for the quality unit to approve or reject drug products.
Keep in mind that the QU is liable for the quality of all drugs and materials coming in and out, as well as in process. They are on the hook for specifications, procedures, and everything for manufacturing the drug. The quality unit also must have the authority to reject or accept anything always.
This is where many FDA experts have seen drug companies have problems. Executives must grant and respect the quality unit’s ability to do its job, even if it means that a large number of products won’t go out the door tomorrow. Quality may be set up to be The Bad Guy, which means the company is usually guilty of poor communication between upper management and the QC people.
Of course, it’s easy for us to type ‘communicate better, guys!’ However, companies that never have 483s because of procedures not written or followed really do ensure good communication. Drug companies with outstanding communications between upper management and the QC rarely have significant 483 or warning letter observations.
If the company has several shifts per day, the morning shift convenes its quality status board. This can be a digital or physical board where they post issues noted during their work that day. The board is given to the QC team to get ready for the afternoon or evening shift.
The team will have a check-in before each shift starts where the issues on the board are discussed. Upper management may join in on the conversations and often do. This active commitment to communication is made part of the daily operations.
Observations can be made by management and the shift workers, and QC trends are made clear. FDA consultants say that every drug company should spend on reporting tools, processes, and effective routines. This ensures good communication and removes combativeness from the process.
Improper Use of Statistical Process Control (SPC)
Some drug company teams do not put enough diligence into the correct use of SPC and may not take advantage of its tremendous value. The value of SPC isn’t only the actual output of the process. It also gives you the critical intangible of looking at data and solving problems with it. Without the SPC data, the QC team could find a problem and begin blaming the other guy.
FDA consultants note that statistical process control can tell your company early on when a problem is brewing. If you utilize proper run rules, your team can probably determine how to solve the issue before it becomes a massive problem that puts you outside acceptance limits.
Keep in mind that SPC was developed to help us head off serious problems that lead to product failures. Sure, you need to gather the data and it’s time consuming. But taking that time is worth it. Your production team can come to QC and say that they reviewed SPC and two run rules are being missed. Also, quality should be able to go to production and say, we’re reviewing the SPC data and there could be a problem. What does it mean? The correct use of SPC data encourages communication, collaboration, and problem solving in the entire organization.
If you avoid these two issues with 211.22, you likely will never have the FDA hand you a 483 or warning letter for procedures not in writing or fully followed.
