I get really confused on the differences between compounding pharmacies and outsourcing facilities. I’ve never worked at either, but see a lot of 483s and warning letters. So today I spent some snow day time doing some reading. I then wrote this up as a reminder to myself.
The Drug Quality and Security Act (DQSA) of 2013 introduced significant changes by distinguishing between compounding pharmacies under Section 503A and outsourcing facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA). This distinction is crucial for ensuring the safety and quality of compounded drugs.
Compounding Pharmacies (503A)
Definition and Purpose: Compounding pharmacies are licensed by state boards of pharmacy and primarily focus on creating customized medications for individual patients when commercially available drugs do not meet their needs. These pharmacies must adhere to standards set by the United States Pharmacopeia (USP), such as USP 797 for sterile compounding and USP 800 for hazardous drugs.
Regulatory Framework: Compounding pharmacies operate under the supervision of a licensed pharmacist and require a prescription for each compounded product. They are generally limited to small batches and are not allowed to engage in office-use compounding without a prescription.
Outsourcing Facilities (503B)
Definition and Purpose: Outsourcing facilities, on the other hand, are registered with the FDA and specialize in producing large batches of sterile drugs, often without the need for individual prescriptions. These facilities are designed to address drug shortages and provide complex or rarely compounded preparations to healthcare organizations.
Regulatory Framework: Unlike 503A pharmacies, 503B facilities must comply with FDA’s Current Good Manufacturing Practices (CGMP) to ensure the quality and safety of their products. They are subject to regular FDA inspections and must report on their compounded products.
Recent Regulatory Actions: The Case of ProRx, LLC
This research came about because I was reading a recent warning letter issued to ProRx, LLC, which basically stated they were failing to comply with CGMP regulations for 503B outsourcing facilities. The FDA identified serious deficiencies in sterile drug production practices, posing significant patient safety risks.
Implications for 503B Facilities
The warning letter to ProRx, LLC, serves as a reminder of the high regulatory bar set for 503B outsourcing facilities. Key implications include:
- Enhanced Oversight: The FDA’s ability to inspect and enforce cGMP compliance means that 503B facilities must maintain meticulous quality control and production standards.
- Patient Safety: The primary concern is ensuring that compounded drugs are safe for use. Facilities must address any deficiencies promptly to avoid recalls and protect patient health.
- Partnerships and Supply Chain: The ability of 503B facilities to supply compounded drugs to healthcare organizations and pharmacies relies on their compliance with FDA regulations. Non-compliance can disrupt supply chains and impact patient access to necessary medications.
What I take away from my research is that 503B outsourcing facilities are GMP facilities, and are held to the same standard. Good to know as I evaluate their regulatory actions in the future. I think I’ve tended to dismiss them as not being in the same class of regulatory expectations.
Also, this is the second time this month where I really wonder what regulatory agencies fascination with pharmacists are in GMP facilities. Seems pretty clear to me that being a pharmacist is no indication of any capability around GMP activities.
Investigations of a Dog 
I have worked many years in 503B, and it is a very difficult and confused segment of the pharma industry. I came here after many years in pharma working in quality for some very large companies. It’s terribly challenging because most of the operational staff has no GMP experience ata lot of the outsourcing facilities. Typically, the resources are not there to fully comply with GMP expectations, and the FDA has been attempting to push outsourcing facilities to operate in better alignment with pharma manufacturers. A major difficulty, as you have noticed, is the role of pharmacists. You have to keep in mind that the 503b industry emerged out of the compounding world, which was run by pharmacists. So pharmacists had played a huge role in starting this industry and although clearly the GMP requirements and the expectations of the FDA are leaving them behind, many companies are having a hard time adjusting because they were founded and run by pharmacists. And you know people in power don’t tend to give up power. I work for a 503b that is going through warning letter issues right now and it’s finally gotten the message that we cannot be run by pharmacists. Another major issue in the industry is because it is an offshoot out of compounding, most of the production processes are simply larger scale compounding processes just like 503a prescription compounding pharmacies would be doing. You essentially have an IV tech with a peristaltic pharmacy pump in a laminate flow hood either feeling empty bags or syringes or adding solutions to diluent bag, one by one. Until the industry understands that getting people out of the process is the only thing that’s going to allow us to start to truly do quality by design, and we start to recognize the C in cgmp and move to automation, the industry will remain quagmired and unaligned with the industry’s expectations. And lengthy 483s and warning letters will continue unabated.
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Also, in reference to pharmacists… Each state requires that a 503B be licensed by the state board of pharmacy. And the BOPs require that a certain ratio of pharmacists to IV techs be adhered to in production. Additionally, California requires that any outsourcing facility that sells products in California be licensed by the California board of pharmacy and be inspected annually by them. California is a huge market, so most outsourcing companies to sell there. They also require the presence of pharmacists in the process. So, as you can see…. The regulatory bodies themselves can’t seem to decide if it’s pharmacy or GMP manufacturing.
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