Five Things

Five things a Pharmacist should understand prior to writing that check for registration fees to the FDA for their brand new 503B outsourcing facility.

1. These facilities are inspected by USFDA following the applicable FDA Compliance Policy Guide 7356.002 Drug Manufacturing Inspections and 7356.002A Sterile Drug Process Inspections.  FDA follows a systems based inspection focusing on the quality, facilities and equipment, materials, production, packaging and labeling, and laboratory control system.  In an initial cGMP inspection such as the initial cGMP inspection following payment of the registration fee, 4 of the 6 systems must be inspected and the quality system must be included.  The good news is that this is not or rather should not be a surprise to the facility since the inspection methodology is included in the compliance policy guides and the FDA has issued a number of guidance documents to assist the compounding facility.  If desired please contact PV for a pocket guidebook that includes 21 CFR 210/211 and Drug Manufacturing inspection guide.
2. Most if not all 503B facilities fail their first inspection, some facilities have repeat failures – This should not be the case!  However, FDA publishes the redacted inspection report on the FDA website and this provides significant insight into what the FDA is finding during the inspection and provides an opportunity for new facilities to learn from the mistakes of those firms that have come before them.  Again preparation is the key.
3. Design of the facility and an understanding of the people and product workflows is an important consideration.  Poorly designed facilities will not fare well in the inspection process.  Proper design of the facility is a cGMP requirement and proper design can help minimize or mitigate risk.  Did you use contractors competent in the cGMPs when building out your facility or contractors who are more familiar with commercial construction?
4. Successful operation of the facility requires a top level commitment of all 503B employees to a quality mindset and commitment to operate the facility per the cGMPs.  From an FDA perspective 503B’s have the ability to compound products without a patient specific prescription, in bulk amounts, and ship across state lines which is an increased risk when compared to commercial manufacturing.  However, by following the cGMPs and with inspections by FDA this risk is mitigated.
5. How do we and what type of documentation is required?  The onus is on the facility to demonstrate to the FDA that the facility is operating in a “state of control” per the cGMPs.  As per the inspection guide (p. 4) “FDA expects that establishments that comply with CGMP are likely to operate in a state of control and consistently manufacture drug products of acceptable quality.”   The following links describes some of the activities that are used to provide a robust documentation schema for the facility:

Commissioning and Qualification Overview

Planning

Risk Management

User Requirements

Have a question on 503B’s feel free to contact Dr. Van Doel, or use our Contact Us page to send us your questions.