Why Outsourcing Facilities and Compounding Manufacturers Should Go Beyond USP
Never settle for mediocrity: it’s a phrase that rings true on the sports field, in the classroom and in every area of life. It’s particularly true in pharmacology. Mediocrity in our profession endangers patients, which is unacceptable. Compounding pharmacists have a responsibility to their patients to not only meet the basic safety standards, but exceed them.
For traditional pharmacists, safety standards are well-established through the United States Pharmacopeia General Chapter <797>. Pharmacists must be vigilant, well-trained and working within proper systems to meet and exceed these standards, but the guidance is aimed at these pharmacists who are compounding to specific patient prescriptions.1
But what about pharmaceutical operations that the Food and Drug Administration classifies as manufacturers, or those who choose to classify themselves as outsourcing facilities? Since they are regulated under the same state boards of pharmacy as traditional compounding pharmacies, they are also held to the USP <797> standard, but the problem is that USP <797> simply does not work well at that scale. That leaves outsourcing facilities and manufacturers little choice but to formulate their own more robust quality assurance programs and standards if they want to ensure patient safety and high quality.
USP <797> Isn’t the Right Standard for Sterile Outsourcing Facilities and Manufacturers
USP <797>, which governs sterile compounding practices, was not formulated or intended for large-scale sterile compounding.
The General Chapter leaves quite a bit of room for discretion on the part of individual pharmacists when creating a compounded sterile product (CSP), and rightly so. When a pharmacist is compounding medication for a specific patient, he or she will have access to information that will affect exactly how that drug will be compounded. Within a strict quality assurance program, there is still room for and should be a degree of latitude for the pharmacist to use his or her expertise to create the best possible CSP for his or her patient.2
This becomes much more difficult at the scale of production seen at an outsourcing facility or compounding manufacturer. These formulations are often being made to a general specification, and not for any patient prescription. They are made at volumes that make a quality assurance program the most important element of the compounding equation, far outweighing the pharmacist’s ability to make patient-specific decisions. Even for facilities that work by aggregating large numbers of prescriptions for compounding en masse, USP <797> falls short. The General Chapter simply doesn’t adequately address these types of operations.3
Looking to the CGMP for Building Blocks for Better Quality Assurance and Quality Control
Under the FDA’s Compounding Quality Act, section 503B, manufacturers and large-scale drug compounders who self-classify as outsourcing facilities must follow the FDA’s Current Good Manufacturing Practices (CGMP). These are by nature stricter standards than USP <797>, and compounders can start with these codes for indications of how to structure quality assurance and quality control programs.
The relevant CGMPs for quality in manufacturers and outsourcing facilities are Parts 210 and 211 of the 21 Code of Federal Regulations, and several FDA-released guidance documents. Some of the elements required by the CGMP that are either not addressed or not required by USP <797> include:
- inbound component ID tests
- stability tests for methods to assign beyond-use dates
- validation of cleanliness
- continuous particle count
- environmental monitoring of air, surface and personnel during production
- use of sterile disinfectants (USP <797> requires only isopropyl alcohol)
- use of sterile garb (USP <797> requires only sterile gloves)
Meeting compliance standards should be about more than simply earning the right to keep operating under the current regulatory framework. For compounding pharmacies who meet 5 definition of a traditional compounding pharmacy under the FDA’s Compounding Quality Act section 503A, these measures are well-defined and have been practiced for many years.
For pharmacies and operations who qualify as manufacturers or have elected to be classified as outsourcing facilities—due to their production volume or practice of compounding without patient-specific prescriptions—meeting and exceeding the standards of the USP <797> should be a matter of course. According to a notice dated September 25, 2015, USP intends to revise <797> in the near future. Although none of the planned updates specifically address larger-scale compounders, hopefully more guidance will be forthcoming. In the meantime, we should all hold ourselves to the highest possible standards, not merely the ones we are legally required to follow.4
Pharmacy has always been a science and practice with the high ability to influence health outcomes for patients. Compounding pharmacists must always work with regulatory agencies in order to make sure that all regulatory frameworks do the work of promoting safety and quality but do not burden pharmacies to the point of potentially disrupting the crucial work they do. But with that in mind, safety and the highest possible standards of manufacturing should be at the heart of all pharmacies’ practices, whether they are classified as traditional compounding pharmacies, outsourcing facilities or manufacturers.
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- “USP-NF General Chapters for Compounding,” accessed Jan. 18, 2016, http://www.usp.org/usp-healthcare-professionals/compounding/compounding-general-chapters ↩
- “Quality Standards for Large Scale Sterile Compounding Facilities,” accessed Jan. 18, 2016, http://www.clinicaliq.com/images/stories/clinicaliq_compounding%20quality%20standards.pdf ↩
- “Regulating Compounding Pharmacies,” May 1, 2014, http://www.healthaffairs.org/healthpolicybriefs/brief.php?brief_id=114 ↩
- “General Chapter <797> Pharmaceutical Compounding–Sterile Preparations,” Sept. 25, 2015, http://www.usp.org/usp-nf/notices/general-chapter-797-proposed-revision ↩