The month of September has been a busy one with regards to compounding in the U.S. USP held an open forum with Expert Compounding Committee in regard to the appeals to BUD tables for revised USP <795> and USP <797> chapters and FDA held it first stakeholder meeting with Outsourcing Facilities (503Bs) and healthcare providers.
USP Open Forum September 15, 2020
In accordance with the March 12, 2020 USP Appeals Panel decisions on the appeals to General Chapters USP <795>, <797> and <825>, the Compounding Expert Committee held an open forum on September 15, 2020 for the Beyond-Use Date (BUD) provision in General Chapters <795> and <797>. There were many practice sites represented on the call to discuss the appeals of the BUD standards. USP assembled members of the Compounding Expert Committee (CEC) including folks from past and current members of the USP CEC, academia, FDA, hospital pharmacy and compounding/retail pharmacy to provide the rationale behind the proposed BUD tables.
A brief background of information was presented on the development of proposed revised BUD tables Table 3. Maximum BUD by Type of Preparation in the Absence of a USP-NF Compounded Preparation Monograph or CNSP Specific Stability Information for USP <795> and Table 10. BUDs for Category 1 CSPs / Table 11. BUDs for Category 2 CSPs for USP <797>. During the presentation the Compounding Expert Committee members were provided with constructive feedback with the limitations of the proposed revisions to the BUD tables, namely limiting the BUD for non-sterile preparations to 180 days and disallowing the use of stability and sterility studies to establish BUDs for compounded preparations. Interestingly, John Metcalfe from FDA was part of the panel discussion and provided an FDA perspective noting that patient safety is their top concern. FDA also noted that due to the varying practices at sites providing these drugs, limiting the BUD also limits the ability for microorganisms to grow.
A key statement made multiple times from members of the USP CEC centered around sterility testing; where sterility testing through a sampling program does not guarantee that all products are sterile and the only way to assure sterility would be sample each and every product.
Key Points:
- All comments from the forum will be reviewed and taken into consideration
- FDA is intimately involved with providing feedback on behalf of public safety on BUDs for both chapters: refer to the link/attachment of the letter FDA sent to the Expert Compounding Committee on BUDs
- No timelines were announced, however multiple scenarios exist
- No change to the proposed BUD tables and USP sets a date for expected compliance (6 months from notice like the case for USP <825>)
- Possible federal lawsuit by appellants (timeline?)
- Change to the BUD tables are made which will then be put out to the public to provide comments leading to a comment and setting an expected compliance date (estimated timeline based on historical 9 months events)
- Rewrite of both chapters (timeline?)
- No change to the proposed BUD tables and USP sets a date for expected compliance (6 months from notice like the case for USP <825>)
The current status of USP compounding chapters
2014 USP <795> Pharmaceutical Compounding – Non-sterile Preparations – Active
2008 USP <797> Pharmaceutical Compounding – Sterile Preparations – Active
*2019 USP <825> Radiopharmaceuticals – Dec 01, 2020
2019 USP <795> Pharmaceutical Compounding – Non-sterile Preparations – Postponed
2019 USP <797> Pharmaceutical Compounding – Sterile Preparations – Postponed
2019 USP <800> Handling Hazardous Drugs in Healthcare Settings – check state regulatory groups
* Of note, the March 12, 2020 USP Appeals Panel denied the appeal to General Chapter <825> Radiopharmaceuticals – Preparation, Compounding, Dispensing, and Repackaging and set forth the official date for compliance of December 1, 2020; https://www.usp.org/sites/default/files/usp/document/our-work/compounding/2020-03-24_revision_bulletin_notice_gc825_.pdf
USP has done a nice job chronicling this evolving process on their website: https://www.usp.org/compounding. As this ‘battle’ continues to evolve, Visante recommends sites providing compounded products to patients continually strive to do what best and safest for your patients and ensure that your employees feel safe.
FDA Compounding Quality Center of Excellence: Working Together for Patient Safety; September 21 – 22, 2020
FDA held its first Compounding Quality Center of Excellence Program on September 21 to 22, 2020 and was open to outsourcing facilities (503Bs) and healthcare providers. The Administration created the Compounding Quality Centers of Excellences in 2019 to foster collaboration in safety.
Stephen Hahn, MD FDA Commissioner opened the session by first acknowledging the importance of Outsourcing Facilities for providing critical medications. Dr. Hahn followed that statement with ‘compounded drugs are not reviewed by FDA prior to marketing and can pose serious risks, but it is important to patient care.’ He emphasized working together we can achieve patient safety.
Experts in each division of the FDA who have responsibility to ensuring compounded medications are safe for the public presented information. Information ranged from the application of existing/pending regulations, inspection expectations, 483 Observations resolution, instilling a culture of quality and safety. Non-agency experts spoke on the integration of technology into compounding processes, Boards of Pharmacy differences for inspecting/licensing and Group Purchasing Organizations auditing processes and expectations.
Key Points:
- Final Draft of the “Insanitary Conditions at Compounding Facilities: Guidance Document for Industry” will be coming out prior to the end of the year and applies to every site that handles drugs including hospitals.
- Final Draft of the “Hospital and Health System Compounding Under the Federal Food, Drug and Cosmetic Act: Guidance for Industry” will be coming out. We will need to see how FDA navigates addressing the 1-mile distribution rule especially important for large IDNs with centralized compounding services that cross state lines.
- Final Draft of the “Current Good Manufacturing Practice – Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act; Guidance for Industry” is in development and will be released soon.
- FDA now offers a service to review facility plans, SOPs, etc. prior to registration
- FDA may start to conduct on-site and virtual site visits especially in the current time.
- FDA has revised its Memorandum of Understanding (MOU) with states to partner with administration and share information when concerns arise regarding compounded products. States must sign the MOU to be active and no specific information regarding the new MOU was shared.
- Currently there are 74 registered 503Bs and since 2013, 216 outsourcing inspections have taken place which equivalates out to approximately 30 inspections for year.
Gregg Jones, NABP provided some interesting statistics on state licensing of 503B facilities adding to onerous processes 503B Outsourcing Facilities must endure.
- 21 States have a ‘503B Outsourcing Facilities’ license Designation
- 9 States license Outsourcing Facilities as ‘Manufacturers’
- 3 States license 503B Outsourcing Facilities as ‘Drug Wholesale Distributors’
- 5 States license in-state 503B Outsourcing Facilities as ‘Manufacturers’ and out-of-state 503B Outsourcing Facilities as ‘Drug Wholesale Distributors’
- NABP is working on establishing accrediting arm for 503B Outsourcing Facilities
Gail Bormel, Associate Director, Compounding FDA provided closing statements and re-emphasized FDA’s role is public safety and providing a voluntary agency for compliance with regulations. Overall, the program was well executed provided a wealth of information on FDA and the 503B Outsourcing Facility industry.
For more information go to the FDA’s Compounding Quality Center of Excellence: https://www.fda.gov/drugs/human-drug-compounding/compounding-quality-center-excellence
With the noted, pharmacy leaders and compounding experts should closely follow the status of all compounding chapters with special attention to USP <800>, noting that some state boards of pharmacy have taken the stance to enforce USP <800> now versus waiting for the dust to settle on the revised USP <795> and USP <797> chapters. In addition, keep an eye on state boards of Pharmacy’s and the FDA MOU process and the continuing evolution of FDA Guidance documents that will impact acute care settings.