The U.S. pharmaceutical sector holds over 45 percent of the world’s pharmaceutical market. It plays a key role in the healthcare system and public health issues.
There are approximately 56,000 community-based pharmacies in the United States according to the International Academy of Compounding Pharmacists. An estimated 7,500 compounding pharmacies provide advanced compounding services of which 3,000 of them provide sterile compounding.
Regulations for Compound Pharmacies:
Regulatory oversight has been taken up by various governmental and state boards that consider the various processes that go about within the pharmacy sector. Compounding pharmaceutical companies are heavily regulated to ensure they are complying with federal and state safety laws. Drugs are tested for efficacy, safety, and minimal side effects. Testing, (which include three clinical trials) can span from 10 to 15 years before being approved and marketed to the public.
Regulating agencies in the U.S. has been taken up by two different authorities:
- The US FDA or the Food and Drug Administration.
- The State Boards of Pharmacy.
These agencies enforce regulations to reduce risks such as incorrect dosing, contamination, or compounds that are injurious to health.
Events That Changed Everything:
Despite the safety measures that were taken up by the government, there were numerous tragedies that occurred that involved compounding facilities.
These incidents led to the infection of numerous people and the deaths of several more across the country. The cause of these mishaps was attributed to contaminated drugs that were manufactured at these facilities.
As a result, the US FDA has divided compounding pharmacies into two sectors: 503A and 503B.
503A pharmacies compound drugs for patients based on receipts of a valid prescription. These facilities must be licensed. They are not allowed to compound large batches thereby lowering product costs. These facilities are subject only to the USP<797> standards.
503B pharmacies compound drugs with or without a prescription. Licensing is not a requirement for these facilities. They are allowed to compound larger batches thereby lowering manufacturing costs. These facilities are subject to both the USP <797> and GMP/cGMP standards. Both are used in tandem with each other for the purpose of ensuring that 503B facilities are preparing sterile medications in a sterilized and safe environment.
The term, GMP, stands for Good Manufacturing Practices, which places regulation on ways that drugs are manufactured at compound facilities. This includes all materials used, the cleanliness of production facilities, and everything in between. It is a regulatory practice that is followed in several countries including the United States, the United Kingdom, China, Canada, Europe, etc.
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Van Norman, Gail A. M.D. (2016). Drugs, Devices and the FDA: Part 1: An Overview of Approval Processes For Drugs. Science Direct. JACC: Basics to Translational Science, Vol. 1. (PDF file) (3) 170-179. Retrieved from https://www.sciencedirect.com/science/article/pii/S2452302X1600036X.
Myers, Charles. (2013). Sterile Compounding: History of Sterile Compounding in U.S. Hospitals: Learning from the tragic lessons from the past. American Society of Health-System Pharmacists. Vol. 70. (PDF file). Bethesda, MD. Retrieved from http://www.cspinsourcing.org/files/ajhp-myers-2013.pdf..
The cGMP and the Pharmacy Sector
The cGMP (Current Good Manufacturing Practices) is a summary of regulatory standards introduced by the US FDA in 1996 to modernize the regulation of pharmaceutical manufacturing and product quality. The term may vary, but the requirements are the same.
The US FDA is slowly guiding 503B facilities toward cGMP regulations over the USP<797> guidelines. The reason is that both regulations are essentially outlining the same requirements. The FDA would benefit from the change which will simplify the inspection and assessment process. Compounding pharmacies would benefit by reducing the amount of paperwork and other challenges involved in maintaining dual regulatory standards.
Listed below is a summary of the cGMP regulations that 503B facilities must follow:
- Unidirectional flow of personnel and materials.
- Only one product per cleanroom hood – which includes full cleaning between products.
- Beyond-Use-Dating (BUD) is required for all products. Stability testing is conducted. This test will provide evidence on how the quality of a drug product varies with time.
- Final containers for all drug batches must be sterile.
- Temperature level monitoring should be conducted on a continual basis.
- Environmental monitoring of the air, surface, and the personnel is conducted daily during production.
- Full sterile garbing (head to toe) is required.
- Rotation of disinfectants and sporicidal agents – which must be validated.
- Good Documentation Practice (GDP) is required for all drug batches which include the manufacturing process, testing, and validation.
- The following are also required:
- Material testing
- Usage of equipment
- The manufacturing process
- IT systems
- Cleaning validation
- Change control
- Adverse drug events
- Quality control
Steps are being taken to help ensure full compliance with the current FDA expectations. Not only will it help in the oversight process, it will also enable compound facilities to better manage their resources, ensure adequate quality control standards, and ultimately offer the highest level of safety and service to all their end users.