As part of its federal authority, the FDA has oversight for the approval, manufacturing, and ongoing regulation of drug product in the US healthcare market. The FDA Form 483 relates to the manufacturing portion of FDA oversight. When the FDA visits a drug product manufacturing site for inspection, they record their observations on Form 483. The investigator(s) is usually from one of the FDA’s 20+ district offices and as part of the inspection will look at any and all areas of manufacturing to ensure companies in compliance with CFR 210 & CFR 211.
Historically, the FDA Form 483 has applied solely to food and drug manufacturers. However, under the new 503B regulatory compounding designation, FDA treats this type of compounding pharmacy almost exactly like a drug manufacturer (e.g. Pfizer, Amgen, Mylan, etc.). They perform unannounced inspections and hold the outsourcing pharmacy accountable for CFR 210 & CFR 211 along with other GMP standards.
Once an inspection is complete, the FDA will issue a Form 483 with observations to the inspected facility. The interesting point here is that only 483 inspection forms for 503B compounding pharmacies are available to the public. The 483s from manufacturers like Pfizer, Amgen, etc. are not available to the public, except through request using the Freedom of Information Act. I suppose the FDA wants to make an example of compounding industry and instill some public confidence given the NECC tradegy. I totally agree with this, but I also believe the 483s from the “big” drug manufacturers should also be available for public scrutiny. After all, they are supplying millions of doses of drug product per day.
How Many 483s does the FDA Issue?
The answer is a lot. As I mentioned previously, the 483s of compounding pharmacies, namely 503B, are available publicly on the FDA’s site. For regular pharmaceutical, food, and other GMP regulated industries, they are hidden behind the “firewall”. The number unavailable to the public is in the thousands. In fact, back in 2010, the FDA issued 9,910 Form 483s. That’s roughly 27 per day! Pretty staggering when you think about it.
What Happens When a 483 is Issued?
Once a company receives a 483 it is their choice whether or not to act. In any facility under good management, the choice is almost always on the side of action. The receiving party should respond to the FDA regarding the 483 observations within 15 days. After all, issues identified within a 483 may lead to a Warning Letter and possibly plant shutdown, so having a proactive dialogue with the FDA can go a long way. A manufacturing shutdown is something no facility of food or drug product wants, so most organizations tend to invest the time and resources in corrective and preventative actions (CAPAs) and other change processes needed to sufficiently address the FDA’s concerns. Premier Pharmacy Labs has invested significantly in addressing our 483 issues with robust organizational changes.
The 483 is just another tool that helps GMP regulated industries continually improve and trend towards the FDA’s latest regulatory desires. It is a constant natural evolution in the business of highly regulated industries. There is nothing wrong with receiving a 483 and my assumption is most manufacturers take them very seriously as I know we do. At the end of the day, I encourage all healthcare professionals involved in the patient supply chain of pharmaceutical to familiarize yourself with the FDA Form 483. It can be a useful tool in vendor selection and accountability. Particularly of note, you should be asking for those written responses and change processes that went into fixing the 483. These are the actions responsible for addressing the 483, aligning with the intentions of the FDA, and ultimately creating safer product for our patients.