California State Board of Pharmacy sends revised compounding rules to 15‑day comment period after debate over glutathione access

The California State Board of Pharmacy on Feb. 5, 2025, voted 7‑2 to approve staff responses to comments and to release the board’s third modified text of proposed compounding regulations for an additional 15‑day public comment period.

The vote followed more than three hours of board discussion and hours of public testimony focusing largely on proposed requirements for sterile and nonsterile compounding, documentation and stability testing for so‑called bulk drug substances and patient access to compounded products such as nebulized glutathione and injectable methylcobalamin.

The board motion — made on the record by Maria Jacobs, a staff presenter, and seconded by Vice Chair Renee Barker — directs staff to publish the third modified text for 15 days, and delegates to members Maria Serpa and Barker authority to review and recommend responses to any additional comments received during that period. The motion also authorized the executive officer to make technical, non‑substantive edits. The final vote tally was 7 in favor, 2 opposed (Jeff Hughes and Nicole Thiebaud).

Why it matters: The rules would update Title 16 of the California Code of Regulations governing nonsterile and sterile compounding, hazardous drugs and radiopharmaceuticals and are intended to align state requirements with U.S. Pharmacopeia (USP) chapters and applicable federal guidance. Licensees, public commenters and board members said the changes could affect patient access to some compounded therapies and impose new testing and documentation duties on pharmacies.

What the board approved and what remains under discussion - Action taken: The board approved staff responses to comments and authorized publication of the third modified text for a 15‑day comment period for stakeholder input. Staff said the third modified text reflects changes based on public feedback and earlier board direction, and that many edits are non‑substantive (grammar/readability). Maria Jacobs presented the changes. - Key topics addressed in the draft text: reorganization and clarification of nonsterile compounding rules (e.g., labeling, SOP content), documentation and verification requirements when a compounded product is intended to produce a clinically significant difference, new language on consultation and counseling requirements, recording and reporting potential quality problems, and revisions to hazardous‑drug and radiopharmaceutical provisions. - Delegation: The board delegated to members Serpa and Barker authority to review any additional comments received during the 15‑day window and advise the board; the executive officer may make non‑substantive edits.

Board and legal staff context Board staff and counsel repeatedly emphasized that the proposed state provisions are intended to clarify how California requirements interface with federal law and USP standards finalized in 2022 and compendial on Nov. 1, 2023. Board counsel Corinne Claridge told members, "to the extent that any public comments seem to suggest that Category 1 substances such as glutathione and methylcobalamin are FDA approved or have been determined to be safe or effective by the FDA, that is not an accurate statement." She reiterated that FDA has taken an enforcement‑discretion approach for several bulk substances rather than granting full FDA approval.

Main points of debate - Bulk drug substances and patient access: The most contested issue at the public hearing was whether requirements for stability testing, source verification and lot testing for bulk drug substances (Category 1 substances in the board staff materials) would effectively block access to certain compounded therapies, especially nebulized glutathione and injectable methylcobalamin. Several public commenters — including firefighters and patients — said local access had already been restricted and urged the board not to finalize rules that would further limit availability. - Cost and feasibility of testing: Board staff said many stability studies already exist in the marketplace and would not require a pharmacy to commission a study in every case. Staff reported vendor estimates provided to the board indicating lot‑specific testing costs roughly $16.10 per 250 mg vial for glutathione and $8.06 per vial for methylcobalamin when testing an API lot for impurities and endotoxins; staff also cited an industry estimate that an initial stability study typically costs about $5,000–$10,000 (one‑time) for a formulation if no published data are available. - Pharmacist verification/documentation: Stakeholders raised questions about proposed language requiring a pharmacist to "verify and document" that a prescribed compounded drug would produce a clinically significant difference from a commercially available product. Board staff and members clarified this was not intended to replace prescriber judgment but to record the pharmacist’s clinical review in certain circumstances when federal law (for example, the legal framework around essentially a copy/503A compounding) requires documentation. - Consultation language: Members discussed whether to use the word "provide" versus "offer" when describing required patient counseling and whether consultative details should be standardized across the code. Staff proposed rewording the consultation requirement in the nonsterile, sterile and hazardous sections so consultation "shall include proper use, storage, handling and disposal of the CNSP and related supplies furnished," and reminded members existing Section 17.07.2 already contains a patient’s right to decline counseling. - Immediate use and remediation timelines: The draft gives facilities limited flexibility to continue using "immediate use" compounding provisions after a facility or equipment failure, provided remediation is under way. Staff said the new language (for example, a 48‑hour window after remediation attempts) is intended to give licensees time to remediate, but it does not remove the requirement to meet standards. - Reporting quality problems: The draft would require facilities to notify the board in writing within 96 hours of receipt of a complaint or a quality problem as defined in the regulation and consistent with facility SOPs. Members debated the meaning of the term "potential" in "potential quality problem" and discussed how SOPs should operationalize when a pharmacist should report an incident.

Public comment highlights Hundreds of verbal and written comments were submitted during and before the meeting; several hundred people spoke during public comment. Testimony included firsthand accounts from firefighters, patients with chronic conditions, clinicians and pharmacy representatives. - Firefighting/first‑responder pleas: Multiple firefighters and representatives of the Volunteer Fire Foundation told the board compounded nebulized glutathione had been used in pop‑up clinics after recent wildfires and said it provided rapid symptomatic relief. Jackie Jorgensen of the Volunteer Fire Foundation said, "Most importantly, if you take 1 thing away from this meeting, please know that nebulized glutathione is not available to firefighters." Several firefighter speakers said they had been unable to obtain the compound because pharmacies are unwilling to make it under the current enforcement environment. - Patient community and petition: Commenters said many patients (long COVID, chronic Lyme, others) use compounded therapies, often out of pocket, and asked the board to avoid rules that would push access out of California. The board received a petition circulated by organizers that staff said contained 10,005 signatures opposing the proposed rules as written. - Pharmacy and industry commenters: CVS Health (Mark Johnston) sought clarification on the proposed flavoring provisions and whether a pharmacy performing routine nonsterile compounding would fit the exemption the draft creates for facilities that only add flavoring. Outsourcing facility counsel and compounding industry groups urged clarity that certain notations or prescriber instructions would meet verification and documentation requirements.

Direct quotes on the record - Maria Jacobs, board staff presenter: "Some seek to lessen standards of existing federal law. Some seek to lessen USP standards, and some seek to lessen the regulations proposed." (Jan. 30, 2025 staff summary of comment themes.) - Corinne (board counsel): "To the extent that any public comments seem to suggest that Category 1 substances such as glutathione and methylcobalamin are FDA approved or have been determined to be safe or effective by the FDA, that is not an accurate statement." (Board counsel clarification during public comment summary.) - Jackie Jorgensen, Volunteer Fire Foundation (public commenter): "The firefighters in the room can tell you [nebulized glutathione is not available to firefighters]." (public comment)

Clarifying details captured in the record - Last 15‑day comment period closed Jan. 27, 2025; staff produced a third modified text dated Jan. 30, 2025. (Staff presentation.) - Staff cited vendor quotes indicating API lot screening at approximately $16.10 per 250 mg glutathione vial and $8.06 per vial for methylcobalamin in one cost example; staff also noted that the typical one‑time stability‑study cost ranges from about $5,000 to $10,000 when no published data exist. (Staff presentation summarizing vendor responses.) - Proposed reporting timeline: board notification in writing within 96 hours of the facility’s receipt of a complaint or a (potential) quality problem; language and operational details were discussed at length.

What happens next Board staff will publish the third modified text for a 15‑day public comment period. Members Serpa and Barker were delegated authority to review any additional comments received during that interval and to advise the board. After the 15‑day period concludes, staff will bring a recommendation back to the board; any further substantive changes could require another public notice and may affect the rulemaking timeline.

Background The board began revising compounding regulations in 2019 after USP updated compounding chapters and court/appeal processes delayed action. USP chapters were finalized in 2022 and became compendial Nov. 1, 2023. Board staff said the proposed regulations are intended to clarify California’s compounding requirements in light of those USP changes and related federal guidance.