FDA Guidance Regarding Compounding to Assist with Hurricane Helene Recovery and Related Guidance (for 503A Pharmacies)

Updated as of 10/17/2024

On October 11^th 2024 the FDA released Temporary Policies for Compounding Certain Parenteral Drug Products: Guidance for Industry to be immediately-in-effect.¹ Baxter’s facility in North Cove, North Carolina has been impacted by rain and storm surge from Hurricane Helene resulting in a shortage of IV fluids including Sterile Water for Irrigation, Sterile Water for Injection, Dextrose 5% and 10% IV solutions, and Sodium Chloride 0.9% for Irrigation and Injection.^2,3 Baxter is making efforts to increase manufacturing capacity at other sites to increase available supply for the US with a goal of returning to 90-100% allocation of certain IV products by the end of 2024 per a recent press release.³

In the meantime, in order to address critical shortages, FDA has released a guidance document detailing when FDA does not intend to take action against a state-licensed pharmacy that is not a 503B outsourcing facility for providing compounded drug to a hospital or health system without obtaining a patient-specific prescription or for compounding a drug that is essentially a copy of a commercially available drug. FDA encourages the sourcing of these products from outsourcing facilities where possible, but when this is not an option, FDA does not intend to take action against 503A pharmacies if the below conditions are met (note, the below points are summarized, please refer to the guidance document to review these conditions in their entirety)

1. The drug appears on FDA’s list of drugs: Temporary Policy for Certain Parenteral Drug Products Compounded by Pharmacy Compounders Not Registered as Outsourcing Facilities (fda.gov)
2. The compounded product is labeled with a default beyond use date consistent with the table below (a copy of the table provided in the guidance document in Appendix A).
3. If the pharmacy and the hospital or health system are not owned and controlled by the same entity, the pharmacy requests that the hospital or health system provide to the extent allowed by applicable laws the records that identify the patients to whom the drugs were administered and document such requests within 1 month of sending the compounded drug to the hospital or health system.
4. Before providing the drug to the hospital or health system, the pharmacy notifies the state authority (such as the board of pharmacy) that regulates pharmacy compounding in the state where the pharmacy is located and (if different) the state authority that regulates compounding in the state where the hospital or health system is located. The state authority must confirm that they do not object to the pharmacy providing drug products to the hospital or health system before the pharmacy may proceed.
5. All other conditions of section 503A and other requirements in the Food Drug and Cosmetic Act are met. FDA specifically mentions adulterated drugs, highlighting that a drug is adulterated “if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health.” The guidance notes that section 501(b) of the FD&C Act requires a drug recognized in USP to meet the standards specified in the monograph or to be clearly labeled to designate how it differs from USP standards.

Sterile Water for Injection is defined as sterile, nonpyrogenic, distilled water and has a pH range of approximately 5.5 (range 5-7).⁴ The USP monograph for Sterile water for Injection requires testing for:

• Total organic carbon <643> (value is contingent on container volume, see <643> for further details)
• Water conductivity <645> (value is contingent on temperature and pH, see <645> for further details)
• Particulate matter in injection <788> (value is contingent on container volume, see <788> for further details)
• Sterility testing <71>
• Bacterial endotoxin testing <85> (limit 0.25EU/mL)

The guidance document provided by FDA with regards to 503A pharmacies does not currently address testing beyond sterility testing and notes “section 501(b) of the FD&C Act requires a drug recognized in the United States Pharmacopeia (USP) to meet the standards of strength, quality, and purity in the official monograph or to be clearly labeled to designate how it differs from USP standards” indicating that any testing discrepancies must be addressed on the product label.

Wednesday, October 16^th USP released Operational Considerations for Sterile Compounding by Pharmacy Compounders Not Registered as Outsourcing Facilities During Public Health Emergencies and Natural Disasters also addressing the shortage of Sterile Water for Injection, Sodium Chloride Injection and other intravenous (IV) fluids currently impacted by the shortage as well as FDA approved drugs currently in shortage.⁵ Copies of compounded formula monographs can be downloaded from USP upon request even for those who do not currently have a membership including:

• Dexamethasone Sodium Phosphate Compounded Injection
• Sodium Bicarbonate Compounded Injection
• Potassium Phosphates Compounded Injection
• Morphine Sulfate Compounded Injection
• Sodium Phosphates Compounded Injection
• Fentanyl Citrate Compounded Injection
• Morphine Sulfate Compounded Suppositories
• Vancomycin Hydrochloride Compounded Oral Solution

USP further discusses fluid conservation strategies to help minimize the impact of IV fluid shortages and the differences between different types of pharmaceutical water. The document offers a flow chart of how to determine what type of water is appropriate for a given usage and clarifies that household reverse osmosis systems are not suitable as a starting source for water eventually intended for injection.

Copied from Operational Considerations for Sterile Compounding by Pharmacy Compounders Not Registered as Outsourcing Facilities During Public Health Emergencies and Natural Disasters on October 17th 2024.

Though the documents released by FDA and USP are helpful, uncertainty regarding specific protocols and procedures remains. The FACTS team will work to provide updates and clarification if made available from the FDA or other regulatory bodies.

References:

1. Temporary Policies for Compounding Certain Parenteral Drug Products Guidance for Industry. October 2024. Temporary Policies for Compounding Certain Parenteral Drug Products (fda.gov).

2. Hurricane Helene: Baxter’s Manufacturing Recovery in North Carolina. Hurricane Helene: Baxter's manufacturing recovery in North Carolina | FDA. Updated October 9th 2024. Accessed October 11th 2024. 3. Hurricane Helene Updates. Hurricane Helene Updates | Baxter. Updated October 9th 2024. Accessed October 11th 2024.

4. Sterile Water – water for injection, solution [package insert] Mississauga, ON. Baxter Healthcare Company. Updated May 2016.

5. Operational Considerations for Sterile Compounding by Pharmacy Compounders Not Registered as Outsourcing Facilities During Public Health Emergencies and Natural Disasters. United States Pharmacopeia. Published October 16th 2024. Accessed October 17th 2024.

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