There has been a lot of discussion regarding the use of bulk drug substances in compounding. On July 23, 2018, the FDA announced that it updated the Category 1 list of bulk drug substances for 503Bs. Many newly nominated ingredients were approved for Category 1 and are approved by the FDA for use in compounded formulations. See press release below.
The point of this article is to provide in a summary format what a bulk drug is, why it is important in compounding, and why this is such a hot topic. The goal is to provide the reader with enough background so that they may speak intelligently on the subject and be able to dispel any inaccuracies or myths that have been floating about in the medical community.
A bulk drug substance is also known as an API (Active Pharmaceutical Ingredient). It is the pure form of a substance used in a finished pharmaceutical product, intended to furnish pharmacological activity or to otherwise have a direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or have a direct effect in restoring, correcting or modifying physiological functions in human beings. In laymen’s terms it is the pure form of the drug.
When compounding, there are two choices to use for the starting substance.
- Commercially available drug
- Bulk drug substances
Sincerus Florida has argued aggressively for the use of bulk drug substances. It is well documented in the scientific literature that using bulks as the starting material in compounding results in a more reliable end product. Since you are starting with the pure form of the active, it has been cited that it is easier to measure and requires fewer manipulations. Since the FDA restricts Outsourcing facilities to purchase bulks from only FDA approved manufacturers with an accompanying Certificate Of Analysis, the quality of the starting material is verified. Lastly, and perhaps most important, is that by using the pure bulk, Outsourcing facilities can better customize the end product to be free of the excipients, fillers, buffers, and preservatives that may come as part of a commercially available drug.
There has been a lot of dialogue as to how the FDA will rule on the subject of bulks. These latest nomination approvals signal that they are true to their word- provided the bulks are nominated with sufficient clinical evidence to support their utilization, they will be placed on category 1 and approved for use.
Below is a quick summary on the differences between 503A Compounding Pharmacies and FDA 503b Outsourcing facilities:
State-licensed physicians and pharmacists seeking to operate under section 503A of the Federal Food, Drug & Cosmetic Act (“FFDCA”), may only use bulk drug substances in compounding drug products that:
- comply with an applicable United States Pharmacopeia (USP) or National Formulary (NF) monograph if one exists, and the USP chapter on pharmacy compounding; or
- are components of FDA-approved drug product if an applicable USP or NF monograph does not exist; or
- appear on FDA’s list of bulk drug substances that a traditional pharmacy (the 503A) can use in compounding if such a monograph does not exist and the substance is not a component of an FDA-approved drug product.
Outsourcing facilities, which register with FDA, compound under section 503B of the FFDCA, and may only use bulk drug substances in compounding that:
- Are used to compound drug products that appear on FDA’s drug shortage list at the time of compounding, distribution, and dispensing; or
- Appear on the FDA’s list of bulk drug substances for which there is a clinical need (the 503B bulks list).
The 503B bulks list is formulated by the FDA based on clinical need. For example, when a patient has an allergy or is irritated by an ingredient in an FDA-approved drug, a state-licensed pharmacist or physician, or an outsourcing facility, might compound a drug product using a bulk drug substance that does not contain the allergen or irritant. In the case of an outsourcing facility that is producing drugs in bulk without a patient-specific prescription, the facility is required to collect a statement of clinical difference from the ordering physician. This allows the doctors the necessary flexibility to customize medications. It also satisfies the FDA’s requirement of “Essentially A Copy”. By providing this affirmation, both the doctor and the outsourcing facility are afforded the opportunity to better treat patients.
So, how does a bulk drug substance make the FDA list? As aforementioned, it must be nominated with sufficient clinical evidence to satisfy the clinical need threshold. Sincerus Florida is pleased and proud to report that all of the bulk drug substances that it has nominated and have been evaluated, have been approved!