For anyone who wishes to gain a better understanding of all the complexities of running a 503A compounding pharmacy, a new resource is now available. The International Society of Pharmaceutical Engineering (ISPE) recently published a new Guide titled “Guide: 503A Compounding – Regulatory Basis and Industry Good Practices for Pharmacies” (here).
Some of you reading this may be thinking – wasn’t there a recent ISPE Compounding Guide that already came out? Yes, there was a recent publication by ISPE on compounding; however, it was specific to 503B Compounding Facilities (see blog announcing its publication here). Perhaps you now have another question – what is the difference between 503A and 503B compounding? And the answer is “a lot” yet also “not a lot.”
At a high level, 503B compounding facilities generally operate at a larger scale and they must follow CGMPs (with a few exceptions). Unlike 503A compounding pharmacies (503A Pharmacies), a 503B compounding facility does not produce products for individual patients when the patient has a prescription written by a healthcare provider. Compounding under 503A must be connected to a prescription by a licensed pharmacist in a state-licensed pharmacy or federal facility, or by a licensed physician. As mentioned in the previous blog, compounding, per the regulations, can only be done if there is no approved marketed product available for someone to purchase that can meet the patient’s needs for 503A or 503B compounding, unless that drug product is currently listed on the Drug Shortage list.
Drug compounding in pharmacies has been a practice since the 1920s; however, Section 503A of the Food, Drug, and Cosmetics Act (FD&C Act) was enacted in 1997 to formally present the conditions that must be satisfied for human drugs to be compounded. In 2013, the Drug, Quality, and Security Act (DQSA) added a new Section 503B to the FD&C Act, which established a new, voluntary category of compounders known as 503B outsourcing facilities.
503A Pharmacies compound at a much smaller scale and must have a specific patient prescription for which they are compounding a preparation. They are able to compound products in advance of that prescription if they have a history of compounding on a monthly (or other regular) basis for a specific patient; however, they must receive the prescription before providing the compounded product to the patient. Additionally, licensed physicians are able to prepare compounded preparations to have as stock for their patients (e.g., if an ophthalmologist’s patient has a fungal eye infection, the ophthalmologist may have preparations in stock to treat the patient quickly to prevent loss of vision), but they cannot sell these compounded preparations outside of their practice (i.e., to another physician or a pharmacy).
503A Pharmacies generally are asked to compound because of patient-specific needs; the patient may be allergic to an excipient (an inactive ingredient) in an approved product, or perhaps they need an alternate dosage form (an oral solution for a product that is only available as a solid oral dosage form). 503A Pharmacies also compound Total Parenteral Nutrition (TPN) for patients who are unable to orally ingest food. 503A Pharmacies also conduct a significant amount of their work within a hospital setting, compounding IV solutions, etc. for patients based on orders or a prescription from a physician.
This 503A ISPE Guide provides an overview of the regulations that apply to 503A Pharmacies, including applicable FDA Guidance for Industry (GFI) documents. 503A Pharmacies are subject to federal regulation; however, the State Board of Pharmacy (SBOP) in the state in which the 503A Pharmacy operates is primarily responsible for regulatory oversight. However, if a 503A Pharmacy distributes product to a patient in a different state, they will need to adhere to the requirements in that state and may need to be licensed in that state (requirements vary from state to state). Unlike 503B Compounding Facilities, 503A Pharmacies are not required to operate under CGMPs. Also, 503A Pharmacies must have a Quality System and are required to adhere to specific chapters in the U.S. Pharmacopeia (USP), primarily the following, though other chapters do also apply (as discussed in the ISPE Guide):
- USP <795> Pharmaceutical Compounding – Nonsterile Preparations
- USP <797> Pharmaceutical Compounding – Sterile Preparations
- USP <800> Hazardous Drugs – Handling in Healthcare Settings
- USP <1163> Quality Assurance in Pharmaceutical Compounding
The ISPE guide walks the reader through the requirements, how to implement them, and offers suggestions and best practices for 503A Pharmacy compounding of preparations. The Guide includes chapters on types of preparations; general compounding requirements; Quality Management System; Training; Material Sourcing; Facilities and Equipment; Environmental Controls, Quality, and Maintenance; Testing; and Handling, Storage, Shipping and Transport. It also contains lists of Standard Operating Procedures (SOPs) that a firm should draft and comply with in order to help ensure compliance with regulations.
The FDA also established the Office of Compounding Quality and Compliance (OCQC), whose aim is to protect patients from unsafe, ineffective, and poor-quality compounded drugs by evaluating incidents, compliance, regulatory, and enforcement actions related to compounded drugs. The OCQC maintains a website that serves as a key source of current information for 503A and 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, and information on inspections, recalls, and other actions.
This ISPE Guide fills a gap in helping the 503A compounding pharmacies to better understand the requirements and good industry practices for compounding to enable compounders to deliver safe drug products to patients for whom a traditional approved product cannot meet their needs. If you need assistance in setting up or verifying that your compounding pharmacy is in compliance with federal and state regulations, please contact Lachman Consultants at LCS@LachmanConsultants.com.
