Before 503
In 2012, New England Compounding Center’s caused a tragedy where 64 patients died and 751 injured with fungal infection due to contaminated steroid injectable vials. As a result, the Food and Drug Administration (FDA) has stepped in as the primary regulatory body for regulating the compounding pharmacies and have divided the pharmacies into two sectors: 503A and 503B facilities.
503A
This is your traditional compounding pharmacy. They provide medications to fill individual patient-specific prescriptions. These medications are dispensed in limited amounts and cannot be produced in large batches. 503A compounding pharmacies are required to comply with USP <795> and <797>, as well as the state boards of pharmacy.
503b
The Drug Quality and Security Act (DQSA) was signed into law in 2013 creating Section 503B, allowing this new type of compounding pharmacy to exist. Because these entities produce a much wider range of drug products, related regulations are decidedly more extensive. Sterile as well as non-sterile medications can be mass-produced in a facility that is designated as 503B.
Regulations required of 503B compounders are much more rigorous than for 503A pharmacies. Like 503A pharmacies, compliance with USP 795, 797 and respective state boards of pharmacy are required. Most notably, 503B facilities must also strictly adhere to cGMP requirements
The major difference between 503A and 503B drug manufacturing processes are the requirements as instructed in Current Good Manufacturing Practices (cGMP). A central tenet of cGMP is that quality assurance is built into the drug product development life-cycle: from receipt of raw materials to patient administration
It falls upon the 503B compounding facility to confirm the pedigree of all ingredients, packaging, materials, and supplies. Procedures must be established to obtain Certificates of Analysis (COA). All testing methods must be validated prior to any active testing to assure compliance with USP testing standards. A product list must be provided biannually to the FDA.
503B outsourcing facilities are required to develop standard operating procedures and implement environmental monitoring that complies with standards of laboratory cleanliness according to the International Organization for Standardization (ISO). Different types of pharmacy compounding areas require different levels of air cleanliness to prevent potentially fatal contamination of drug products. This specialized type of monitoring must occur much more often than in 503A facilities. Indeed, environmental monitoring must be performed (and of course documented) at minimum each production shift for ISO 5 areas. If compounding areas are designated as ISO 7 or 8, environmental monitoring must be carried out weekly to meet these critical requirements of air cleanliness.
