The United States Pharmacopeia (USP) is a scientific nonprofit organization, originally founded by physicians; it sets public standards for the identity, strength, quality, and purity of medication. The first USP book was published in 1820 as a “recipe” book to promote uniformity in drugs prepared and dispensed by practitioners to their patients. The USP’s commitment to help ensure the quality of compounded medicines is ongoing. USP standards are recognized in law and play a prominent role in federal and state compliance and enforcement activities.
In September 2015, USP issued a proposed revision of the compounding section of Chapter 797. While an ongoing debate continues, for now, allergy extract preparation is considered compounding although obviously on a different scale from commercial compounding manufacturers, marketing mass quantities of albuterol or injectables. It is important to note, in 2018 the FDA decided to call allergy compounding, allergy “mixing.”
USP Chapter 797 was previously updated in 2007 with input from our former Joint Council of Allergy, Asthma and Immunology (JCAAI). JCAAI was able to negotiate an allergy exception whereby allergy antigen mixing was carved out under certain delineated standards. However, in 2015 USP was proposing to put us all back under general, non-specific industry-wide guidelines and regulation which would probably prevent small practice allergists from mixing allergy antigens in their offices. The College’s Advocacy Council was notified almost immediately and sprang into action.
We hired an outside consultant, a former AMA executive who also had excellent USP connections. The consultant helped us summarize the problem, identify the key contact people at USP and outline an action plan. At about the same time, we also enlisted the help of former Congressman Steven Kagen (a practicing allergist), who had his own USP and FDA connections. FDA became involved as they moved to implement regulations for the Drug Quality and Security Act with proposed regulations pertaining to Insanitary Conditions.
Finally, working our contacts together with the political influence of Dr. J. Allen Meadows, Alabama U.S. legislators, and joining with our sister organizations (AAAAI, ENT Allergy and the U.S. Military Allergists), we were able to organize an Allergy Steering Committee. The steering committee held many conference calls with USP and had a face-to-face meeting with FDA staff.
In June of 2016, these allergy organizations took the compounding issue to the AMA with Resolution 204 (A-16) written by Drs. George Green and Stephen Imbeau. It was passed with overwhelming support in the AMA House of Delegates: Resolved, that our AMA undertake to form a coalition with affected physician specialty organizations such as allergy, dermatology, immunology, otolaryngology, oncology, ophthalmology, neurology and rheumatology to jointly engage with USP, FDA and the U.S. Congress on the issue of physician office-based compounding preparations and the proposed changes to USP Chapter 797.
The AMA reaffirmed this Resolution at their 2017 Annual Meeting. Once the 2016 Resolution was AMA Policy, AMA staff then began to help us with both USP and FDA. A coalition was formed that included allergy, ophthalmology, plastic surgery, endocrinology, anesthesiology, facial surgery, ENT, dermatology, oncology and rheumatology. This group participated in conference calls and at least one listening session with USP and FDA and wrote a formal letter to the FDA in August 2016.
The AMA continues to hold important leverage with USP and the FDA. In October 2017, AMA convened a meeting with USP and our coalition. Through the AMA, the Advocacy Council has also formed an important alliance with a few board members of the Federation of State Medical Licensing Boards, who also have an interest in the compounding issue and have become more supportive of the allergy viewpoint. In early 2017, the College and AAAAI made a formal commitment to coordinate and cooperatively work on USP/FDA compounding issues.
All these efforts led to an in-person meeting with USP in Baltimore in February 2017. Allergists were well-represented. USP heard us and our key argument that change from the 2007 version was unnecessary due to the lack of reported adverse cases or problems, together with our efforts to train and monitor our member physicians. In the fall of 2017, we learned that the USP Chapter 797 was still under revision.
The draft was delayed until July of 2018 because of a large amount of public comment. We were all pleased the revised set of proposed standards on sterile compounding that specifically addressed safety and sterility of allergen extract preparation, were favorable and along the lines of our suggestions and input. Those new standards set forth 19 requirements specific to allergen extract preparation that comprehensively address safety and sterility of allergen extract preparation.
They include requirements for hygiene and garbing of personnel, establishment of ISO Class 5 primary engineering controls or a dedicated allergenic extract compounding area, cleaning and disinfecting standards, and training and competency evaluations for personnel, among other standards. Our organizations support the USP’s new standards published in 2019. We believe these new USP standards are sufficient to ensure that allergen extracts are prepared in a way that does not violate the provisions of the Food Drug and Cosmetic Act. The original implementation date has been postponed, but a new implementation date has not been announced.
The FDA has stated, in its revised draft Insanitary Guidelines, that it would not take action under the adulteration provision of the Food Drug and Cosmetic Act [(section 501(a)(2)(A)] against physicians who are compounding a drug product – or mixing, diluting or repackaging a biological product – when those activities occur in the physician’s office where the products are administered or dispensed.
We support this policy and urge it be included in the final Insanitary Guidance. We request the FDA honor the new USP standards for allergy mixing of antigen vials in Section 21 of the 2019 USP Standards.
The Advocacy Council and College have developed an Allergen Extract Mixing Toolkit, available to help guide members to USP compliancy. We have you covered!