Pharmacautical Componding Regulations

Before the U.S. Food and Drug Administration stepped in, drug pharmacies were overseen by state pharmacy boards that largely lacked regulatory oversight. As a result, there were numerous cases of contaminated medications being manufactured and administered to the patients they served. This ultimately led to serious infections and numerous deaths.

In an effort to prevent such tragedies from repeating, the FDA took over the regulatory process. Furthermore, they placed compound pharmaceutical companies into two classes of categories in a bid to enhance safety and quality,

The first class, called 503A, refers to smaller, traditional pharmacies where medicinal drugs are prepared in smaller batches and are customized as per the patient’s prescription requirements. These pharmacies are not subjected to cGMP requirements. The second, 503B, are larger pharmaceuticals that manufacture drugs either with or without a prescription. They sell to healthcare facilities and are required by the FDA to maintain higher standards in addition to following cGMP requirements.

The differences between the two categories vary. Some of them include the labeling of drugs, validation of processes, the role of pharmacists, and pharmacy registration, etc.

The sections that are mentioned below will explain their major differences in detail.

1.) Labeling

All medications must be labeled. It ensures ease of identification and use by the consumer.

503A pharmacies have a specialized labeling system. These include personal information because of the personalized nature of the drugs. The packaging is traced with details about the patient’s condition, company details, medication history, common uses and directions, cautions, and possible side effects.

All 503B pharmacies follow labeling requirements as per the Drug Quality and Security Act (DQSA).

2.) Environmental Monitoring

This essential step helps to identify potential sources of contamination.

503A pharmacies are allowed to operate with environmental monitorings being performed every six months. This is sufficient as production level is lower and possible contamination can easily be arrested and addressed.

503B compounding pharmacies are required to have a sturdy program in place for environmental monitoring on a continual basis. Monitoring must be done after every production cycle in primary compounding areas.

Furthermore, all processes must be approved for 503B pharmacies. They are required to test multiple batches of the product before releasing it into the market. Testing procedures are also subjected to inspection and validation. In this regard, suppliers of raw materials are vetted as part of the regulatory process.

3.) Role of the Pharmacist

The objective is to ensure that all medications meet the highest quality standard in the final stages. However, the roles a pharmacist play before that will differ to a great extent.

In 503A pharmacies, the pharmacist oversees the preparation process. He or she can also research compounded formulas for proper preparation and safety. They can even check their own work for issues and take the necessary measures to resolve it.

In 503B, pharmacists take a direct role in the supervision of the manufacturing and compounding process. At the same time, they are not allowed to review the work. This is designated to an independent department or institution put in place, which has full autonomy during its investigation for quality assurance.

4.) Product Dating

This is an important process because the medications will last for a set period of time before it is rendered inert or toxic. Short-term expirations dates are provided unless their stability has been assessed.

503A pharmacies use what is called ‘Beyond Use Dating’. This is a date derived from the analysis of the scientific narrative on stability at or past a certain time.

503B pharmacies use Beyond Use Dating as well but are also required to develop a very stringent and strict program for product dating. This program is subject to degradation variables like time and humidity.

5.) Registrations and Obedience

Both 503A and 503B pharmacies must adhere to the United States Pharmacopeia guidelines.

503A compounding pharmacies have more flexibility. They are only required to register with their state’s Board of Pharmacy and Drug Enforcement Administration.

503B compounding pharmacies are required to register with their state’s Board of Pharmacy, the DEA, and the FDA. They are required to report product lists twice every year to the FDA. These pharmacies follow the directions given by the Current Good Manufacturing Practices or cGMPs. They must employ the latest systems and technologies to comply with the given regulatory standards.

As witnessed in the 2012 tragedy that saw the deaths of over 60 people at the New England Compounding Center, it is clear that FDA and cGMP guidelines are set in place to ensure that compounded medications across the market are deemed effective and safe prior to patient use.