503A Compounding Pharmacy vs. FDA 503B Outsourcing Facility

So, what is the difference?  CGMP!  Unlike a 503A compounding pharmacy, FDA 503B Outsourcing Facilities must validate every process according to CGMP.

“Pharmaceutical quality affects every American.  The Food and Drug Administration (FDA) regulates the quality of pharmaceuticals very carefully. The main regulatory standard for ensuring pharmaceutical quality is the Current Good Manufacturing Practice (CGMPs) regulation for human pharmaceuticals. Consumers expect that each batch of medicines they take will meet quality standards so that they will be safe and effective. Most people, however, are not aware of CGMPs, or how FDA assures that drug manufacturing processes meet these basic objectives.”[1]

CGMPs provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the CGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations. This includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories. This formal system of controls at a pharmaceutical company, if adequately put into practice, helps to prevent instances of contamination, mix-ups, deviations, failures, and errors. This assures that drug products meet their quality standards.

503A compounding pharmacies are primarily regulated by their State Board of Pharmacy, and although they are supposed to follow USP standards, it is understood that the process validation is lacking in comparison with that of CGMP. Furthermore, the manpower of the State BOP’s is severely limited in comparison to that of the FDA. So, inspections may not be as frequent, nor are they held to the same rigorous quality control standards as CGMP.

Now that you have this basic understanding, ask yourself- if you need a customized medication for yourself or a loved one, where would you feel more comfortable having it compounded?  One of the main reasons that Congress passed the Drug Quality and Security Act (DQSA) was to ensure that compounders who wanted to make larger batches were required to meet demanding and reliable quality standards.  There is a huge difference between 503A and 503B!

To further drive this point, it is important to reiterate why are CGMP’s so important.  A consumer usually cannot detect (through smell, touch, or sight) that a drug product is safe or if it will work. While CGMPs require testing, testing alone is not adequate to ensure quality. In most instances, testing is done on a small sample of a batch (for example, a drug manufacturer may test 100 tablets from a batch that contains 2 million tablets), so that most of the batch can be used for patients rather than destroyed by testing. Therefore, it is important that drugs are manufactured under conditions and practices required by the CGMP regulations to assure that quality is built into the design and manufacturing process at every step. Facilities that are in good condition, equipment that is properly maintained and calibrated, employees who are qualified and fully trained, and processes that are reliable and reproducible, are a few examples of how CGMP requirements help to assure the safety and efficacy of drug products.

At a recent FDA listening session that Sincerus Pharmaceuticals attended, Ian Deveau, Ph.D. Chief, Global compliance Branch of the Division of Drug Quality, Office of Compliance summed the above up succinctly by stating that you cannot simply test at the beginning and at the end.  It is critical that quality is baked into every process!  That encapsulated what CGMP does and why it is so important.  We are hopeful that you have a new-found appreciation for CGMP and this standard used in FDA 503b Outsourcing.

[1] https://www.fda.gov/drugs/developmentapprovalprocess/manufacturing/ucm169105.htm