For those struggling with understanding all the complexities of running a 503B compounding facility, a new resource is now available. The International Society of Pharmaceutical Engineers (ISPE) has a new guide coming out titled “503B Compounding – Regulatory Basis and Industry Good Practices for Outsourcing Facilities” (here).
Do you know why compounding exists? Shouldn’t all medications be purchased only after having been evaluated via the traditional ANDA/NDA, etc. regulatory pathways? Well, that’s not always possible for everyone. Compounders manufacture drug products to aid patients who can’t get the medications they need through traditional manufacturers. For example, the patient may be allergic to an excipient (non-active ingredient) or dye in a product, or they may need a dose that is different than those traditionally available. Compounding is also sometimes utilized to address drug shortages, create an alternate dosage form (tablet to oral solution, etc.), or to combine two commercially available drug products into one.
In 2012, there was a multistate outbreak of fungal meningitis among patients who had received contaminated preservative-free Methylprednisolone Acetate Injection from a compounding facility in Massachusetts. These injectable products were shipped across the country, and the outbreak resulted in more than sixty deaths and 750 cases of infection spread across twenty states. The investigation by the U.S. Centers for Disease Control and Prevention (CDC), along with state and local health departments and the FDA, found this to be due to poor compounding practices. This resulted in the enactment of the Compounding Quality Act, which added a new Section 503B to the Food, Drug, and Cosmetic Act (FD&C Act), and establishing a new voluntary category of compounders called 503B Outsourcing Facilities.
The ISPE Guide walks through the regulatory requirements of the Compounding Quality Act and the compounding guidances as well as practical advice for how to comply with those requirements. The most notable of the guidances is the Draft Guidance for Industry (GFI) “Current Good Manufacturing Practices – Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act Guidance for Industry” (draft GFICGMPs for 503Bs). 503B compounding facilities are not exempt from the requirement to follow CGMPs (in other words, they must follow CGMPs), though some requirements are slightly different for compounding facilities, as explained in the draft GFICGMPs for 503Bs and the ISPE Guide.
The FDA also established the Office of Compounding Quality and Compliance (OCQC), the aim of which is to protect patients from unsafe, ineffective, and poor-quality compounded drugs by evaluating incidents and compliance as well as regulatory and enforcement actions related to compounded drugs. The OCQC maintains a website, which serves as a key source of current information for 503B compounders, known as the Compounding Quality Center of Excellence (COE) (here). The COE includes information on training, including on-demand training, compounding laws and policies, risk alerts, inspections, recalls, and other actions. It also includes a plethora of additional information such as lists of registered outsourcing facilities, lists of bulk drug substances used in compounding, and compounding research, to name a few.
The ISPE Guide includes chapters on Quality Systems, Supply Chain and Materials, Facilities and Equipment, Manufacturing Controls for Compounding, and Product Storage, Packaging, and Labeling specific to compounding in a 503B facility. Additionally, there are chapters on Laboratory and Testing requirements and how to determine Stability and Beyond-Use Dates. The final chapter contains prompts to assist 503B compounding facilities with what to expect during FDA inspections for each of the above-mentioned chapters.
This ISPE Guide fills a gap in helping the 503B compounding industry to better understand the requirements and good industry practices for compounding to enable compounders to deliver safe drug products to patients whose needs cannot be met by commercial manufacturing.
