The College, the American Academy of Allergy, Asthma and Immunology (AAAAI) and the American Academy of Otolaryngic Allergy (AAOA) have provided comments to the United States Pharmacopeia (USP) acknowledging that proposed standards for the in-office compounding of extracts for allergen immunotherapy are reasonable and acceptable, and have committed to supporting our members’ efforts to implement the standards through education and outreach.
The current USP Chapter 797 on sterile compounding had three levels of safety protocols for compounding reflecting increasing levels of potential risk to patients. Aside from high, medium and lower risk categories, a separate section detailed standards for compounding of allergen immunotherapy, reflecting both how allergen immunotherapy is fundamentally different in nature from other compound administration processes and the comparative safety of the allergen extract compounding and administration.
The draft issued in 2015 abandoned the risk-relational approach and characterized all compounding for human injection as equally and inherently dangerous, thus treating allergen immunotherapy the same as radioactive and high-risk compounds. The extraordinary measures required would have made in-office compounding of allergen essentially impossible.
The College, AAAAI, AAOA and others immediately responded by submitting thousands of comments expressing concern for both the patient safety and patient access to allergen immunotherapy unless in-office compounding remained feasible. Extensive feedback focused on the increased risk of anaphylactic shock presented by lack of control of source material, the necessity of extended beyond use dates to make allergen immunotherapy feasible, and the likelihood of significantly increased patient costs and delays of treatment if control over compounding in the office setting was lost. Ongoing efforts by the allergy/immunology specialty to promulgate its own rigorous patient safety standards, educate providers and support continuous data collection on adverse events were stressed as important mechanisms to help support the specialty’s commitment to patient access and patient safety.
An updated draft Chapter 797 provides standards unique to allergen extract compounding for individual patients. These standards include updated requirements for personnel qualifications and training; personnel hygiene and garbing; facilities; cleaning and disinfecting; and documentation and labeling. Under the proposed standards, to continue in-office compounding for individual prescription sets for patients, allergy practices must conduct compounding activities in either a (1) ISO Class 5 Primary Engineering Control chamber (PEC), or (2) in a dedicated Allergenic Extracts Compounding Area (AECA). Standards are provided for the set-up, use and maintenance of either approach. In addition to these requirements for the physical space, there are additional requirements for personnel, including having their garbing and hand hygiene evaluated, including fingertip and thumb sampling, at least three times before beginning compounding and at least annually thereafter.
The College, AAAAI and AAOA find the standards proposed to be a reasonable compromise to protect both patient access to allergen immunotherapy and patient safety with allergen extract compounded in the in-office setting. We encourage members to review the proposed standards and submit comments by Nov. 30 if you wish to do so. The final version of Chapter 797 will be published on June 1, 2019, and becomes official as of December 1, 2019.
Proposed standards for allergen extract compounding under USP Chapter 797
Under the proposed standards, to continue in-office compounding of individual treatment sets for allergen immunotherapy, allergy practices will need to comply with the following:
1. Personnel qualifications
- Designate one person to oversee and evaluate compounding personnel.
- Provide training and testing on principles and procedures for new staff – and annual evaluation for others – for sterile compounding, garbing, hygiene, gloved fingertip and thumb sampling, and media fill tests.
- Compounding personnel must wear powder-free sterile gloves; non-cotton, low-lint sleeved garments that gather at the wrist and close at the neck; face mask, and disposable cover for head and facial hair.
- Compounding must occur in an ISO Class 5 PEC or in a dedicated Allergenic Extracts Compounding Area (AECA), either of which must not be within one meter from a sink and can’t be near unsealed windows, doors to the outside, or high traffic or other areas that present environmental control challenges such as bathrooms or kitchens.
- If used, a PEC must be certified every six months, cleaned and disinfected before and after each compounding, and surfaces must be disinfected between each prescription set.
- An AECA must have a visible perimeter, and meet the following conditions:
- Access restricted to authorized personnel.
- No other activity permitted during compounding.
- All surfaces must be cleanable and kept clean.
- No carpet.
- No surfaces that can be damaged by cleaning and sanitizing agents.
- Surfaces must be smooth, impervious, non-shedding, and free of cracks or crevices.
- Overhangs should be avoided or must be easily cleaned.
- Well lit, and temperature and humidity controlled for comfort of compounding personnel.
- Work surfaces must be cleaned and disinfected before and after each compounding session, and disinfected between each new set, as well as at the time of any spill or contamination.
- Vial stoppers on packages of conventionally manufactured sterile ingredients must be disinfected with 70% IPA wipes before each use.
All facilities where allergen extracts are prepared must have and maintain written or electronic documentation to demonstrate compliance with the requirements USP Chapter 797. This documentation must include, but is not limited to, the following:
- Labels on prescription sets must include patient name, type and fractional dilution with corresponding vial number, beyond use date, identity of compounder, date extract was compounded, and required storage conditions.
- Standard operating procedure manuals describing required compounding process.
- Training, assessment results, evaluations, and qualification records for all compounding personnel, including any corrective actions following assessments and evaluations.
- Certification reports for PEC, if used.
- Cleaning logs.
- Temperature logs for refrigeration.
- Compounding records for individual extract prescription sets.
- Information on any complaints and adverse events.
- Investigations and corrective actions following any complaints and adverse events.
If you wish to view the full Chapter 797 proposed draft, it’s available as a downloadable PDF.