Vol. 5 •Issue 1 • Page 26
The FDA and Oxygen Transfilling
Make sure you follow these FDA regulations for oxygen transfilling and delivery.
T he Food and Drug Administration considers anyone who moves medical grade oxygen from one container to another a manufacturer. Whether you’re moving liquid to liquid (cryogenic), liquid to gaseous, or gaseous to gaseous, if you’re transfilling oxygen, you must comply with FDA guidelines.
This includes registering with the FDA and complying with Current Good Manufacturing Practice (CGMP) regulations. Hospital pharmacies that provide oxygen solely for inpatient use are exempt from FDA registration only.
FRESH AIR GUIDELINES
All drugs, including medical gases, must comply with the general CGMP regulations, Title 21, Code of Federal Regulations, Parts 210 and 211 (The Federal Food, Drug, and Cosmetic Act) with some exceptions. This Act outlines the requirements for any over-the-counter or prescription drug’s manufacture and quality control. But while these rules are logical for the manufacturer of a bottle of pills, they sometimes translate poorly when it comes to medical gases.
To clarify the guidelines, Duane Syvia, consumer safety officer at the center for drug evaluation and research at the FDA, developed a workshop and handout called “Fresh Air.” This handout is the primary resource for FDA inspectors and medical gas manufacturers. For a copy, go to www.fda.gov/ cder/dmpq/freshair.htm.
To ensure that oxygen transfillers comply with the Fresh Air guidelines and their own written policies, the FDA tries to inspect all registered manufacturers at least once every two years. Each inspection can take several days while an inspector reviews your written policies and procedures and accompanying documentation.
The following are just a few of the items an FDA inspector would look for.
TEST YOUR OXYGEN
Manufacturers must test all oxygen for purity, strength and quality with FDA-approved oxygen analyzers. Calibrate analyzers within eight hours of use with a certified calibration-grade oxygen tank. If you’re checking the identity of a concentrator, you can use a medical-grade tank. Document your findings on an analyzer calibration log.
If you purchase liquid oxygen from a bulk supplier, you must witness the product testing and obtain a valid certificate of analysis (COA) that contains the supplier’s name, name of the product (oxygen), an air liquification statement, lot number, actual analytical results obtained for identity and strength, test method used for analysis and the supplier’s handwritten signature and date. If you don’t witness the testing that is documented on the COA, you must perform and document an identity test yourself.
Establish the reliability of the supplier’s strength analyses at least once a year if you are accepting COA’s at face value. Be sure to document this. If you have your own stand tank that is filled by a tanker truck, you must perform a strength test after every supplier refill because oxygen from the old lot and new lot have co-mingled in the bulk tank. Test a direct sample from the vessel’s co-mingled lot or from the first container filled.
The plant providing oxygen assigns new lot numbers each time it fills a liquid or gaseous oxygen bulk vessel. Use this as your company lot number, which will appear on the tags or stickers attached to the home liquid oxygen container. If you swap fill you must be able to identify the lot number of each customer’s oygen refills.
Before transfilling liquid oxygen, do the following:
• Inspect the cylinders for grease and oil, damage or soil.
• Inspect all volume and contents gauges.
• Inspect inlet and outlet connections.
• Inspect the label. All labels are required to state: “For emergency use only when administered by properly trained personnel for oxygen deficiency and resuscitation. For all other medical applications, Caution: Rx only.” Document initial number of labels and account for each removal. Liquid oxygen reservoir or cylinder labels must contain your company’s name and address, and state that your company filled and distributed the oxygen.
• Look for Department of Transportation (DOT) markings.
• Verify that the pressure relief device on the unit is appropriate for its intended use.
• Make sure the storage/transfilling area is secure, dry, cool and well ventilated.
If you’re transfilling compressed medical gases, make sure the tank is green. Further, CMG manifolds must be dedicated to a single gas and equipped with fill connections that correspond only to the container valve connection for oxygen. Medical gas cylinders must be properly secured, separated into full and empty, and grouped by size and gas type.
Before you begin the transfill process, empty any residual gas from the tank. If the tank is completely empty, purge it with nitrogen. Attach tanks to the manifold and apply the vacuum to 25 mm Hg. Begin cascading, increasing oxygen pressure from progressive tanks up to 1800-2200 psi. Monitor for any temperature changes in the cylinder and spray for leaks. After recording temperature and pressure, remove the tank from the manifold.
Perform a strength test on at least one cylinder. Any time the batch/lots are changed on the source gas manifold, additional testing is required. Attach new lot numbers to the filled tanks. Expiration dates are no longer required for oxygen.
Document every step and make sure a supervisor reviews all documentation and signs all forms.
Maintain separate files for FDA information. Keep all records for three years plus the current year, unless otherwise noted. Include the following items:
• bulk delivery tags or distributor shipping papers
• FDA quality assurance logs
• patient oxygen lot numbers (in case of recall)
• batch production and control records signed and dated by a supervisor
• analyzer equipment calibration logs
• equipment function check logs
• all COA tags, labels and documents that contain lot numbers
• customer complaint file (must be maintained even if there have been no complaints)
• staff training records, including initial quality control training and retraining
• written recall procedure. Enter the lot number on delivery paperwork and transfer it to a log or computer file.
There are additional rules addressing equipment storage, labeling, gauge calibration, traceability and recalls. Be sure to carefully review “Fresh Air” to verify that you comply. n
Vianna Zimbel is president of Vianna Zimbel Consulting, Glastonbury, Conn. Contact her at (860) 657-9530 or [email protected]. For more information about FDA regulations, go to www.fda. gov/cder/dmpq/freshair.htm.