FDA Compliance

7/1/14 - Changes to policies on filling open mouthed dewars

Q – What is the latest information about filling liquid nitrogen in open topped dewars for dermatologists? 

A – This issue has been interpreted in contradictory ways in the past. Recently, the CGA Medical Gases Committee published a position statement about open topped dewars (PS-38-2014, Registration of Facilities Filling Open Topped Medical Nitrogen Dewars For Device Use).

The small open topped container should not contain a medical label but should include a product identification label. The position statement includes other clarifying information about container filling, personnel training and written procedures. The conditions under which you may fill these open topped containers without FDA registration are detailed in the position statement.

If you fill open topped dewars with medical liquid nitrogen, we recommend that you download the position statement from CGANet.com. Of course, this is available at no cost for participating GAWDA members.

The GAWDA Medical Gas SOP’s are being revised to recognize this new industry position.

6/1/14 – NADA Submissions Part 2

Q – What is the latest information regarding New Animal Drug Application (NADA) submissions for drug listings (June 2014)?

A – Since last month, the FDA has revised the animal drug listing procedures to reverse their prior procedures regarding Active Pharmaceutical Ingredients (API’s). You may now submit your drug animal listings is exactly the same manner as your human drug listings. The only differences are that you use the NDA number for human drugs and NADA numbers for animal drugs. You also select the type of drug listing you are submitting… human or animal. 

We recommend that you review and submit your human and animal drug listings to remove the “unapproved medical gas” statement from your online FDA drug listings. The following resources are available on the GAWDA.ORG website:
-    An 18 minute recorded teleconference about how to remove the “unapproved medical gas” statement from your online FDA drug listings: http://www.aws.org/GAWDA/audio/Medical_Gas_Update_20140131.WAV
-    Handouts and sample forms for the recorded teleconference: http://www.gawda.org/uploadedFiles/Site_Framework/Home_Page/FDA_Medical_Gas_Certification_Compliance_Alert_20140131.pdf

If you have any questions about this process or would like us to re-submit your drug listings, please contact amy@asteriskllc.com.

5/1/14 - NADA Submissions Part 1

Q – What is the latest information regarding New Animal Drug Application (NADA) submissions for drug listings?

A – The Center for Veterinary Medicine (CVM) has implemented additional validation procedures on medical gas drug listings for animal drugs. The agency believes that listings with NADA numbers should be classified as an Active Pharmaceutical Ingredient (API). We disagree with the Agency’s position and have formally notified the agency of our objections.

The API requirements cause significant disruptions in the listing process for animal drug gases. After resolving this issue with the FDA, we will let you know how to proceed.

Interestingly, this does not seem to affect the human drug listings. We recommend that you continue to re-list your medical gases with the NDA (for humans) number in order to remove the “unapproved medical gas” statement from your drug listings

4/1/14 - What are the FDA issues around security?

A – The FDA does not have the same type of security regulations as the DOT. However, there are several security related issues.

Drug Storage
The 2003, Draft Guidance for Industry - Current Good Manufacturing Practice for Medical Gases summarizes the FDA thinking and regulations about medical gas security:

B.    Security

Medical gas manufacturers are wholesale distributors who are subject to the requirements of § 205.50 - Minimum requirements for the storage and handling of prescription drugs and for the establishment and maintenance of prescription drug distribution records.

All facilities used for medical gas distribution must be secure from unauthorized entry (§ 205.50(b)(1)).

Entry into areas where medical gases are held must be limited to authorized personnel (§ 205.50(b)(1)(iii)).  We recommend areas where nitrous oxide is held be especially secure.

The security requirements of § 205.50(b) apply to all facilities used for medical gas distribution.  FDA interprets this regulation to include all facilities where loaded medical gas delivery trucks are parked prior to making deliveries, including at an employee's home when a loaded medical gas delivery truck is driven there and parked overnight for early morning runs.

A manufacturer could use an alarm system to secure the building and keep loading docks secure, rather than open and easily accessible.

Keep in mind that the Draft Guidance does not carry the same authority as the underlying regulations. However, it does represent the last published agency thinking about security and medical gases.

Nitrous Oxide
The FDA does not define “especially secure” storage areas for nitrous oxide. The Compressed Gas Association has published excellent guidelines for storing and securing nitrous oxide. GAWDA members can sign up for free access to these CGA resources. For further details, see:
•    CGA G-8.3, Safe Practices for Storage and Handling of Nitrous Oxide
•    CGA P-50, Site Security Standard
•    CGA P-51, Transportation Security Standard for the Compressed Gas Industry
•    CGA P-52, Security Standard for Qualifying Customers Purchasing Compressed Gases

Though not all items will apply in all cases, consider the following:
•    Inventory control systems to detect theft or loss
•    Access controls
•    Property fencing
•    Secondary fencing for nitrous cylinders and bulk storage
•    Lockout devices to secure valves on bulk storage
•    Security systems, alarms, etc.
•    Procedure to determine if a customer is legitimate

3/1/14 – Unapproved Medical Gas Part 2

Q – Why does my Drug Listing have the “Unapproved Medical Gas” warning statement? How can I remove this statement?
A – Medical gases, like oxygen, have been in use for well over a hundred years…. Even before the creation of the FDA. The FDA has approved many drugs over the years… but the common medical gases were never actually formally approved.
Several years ago, we began to see statements on our medical gas listings that said “unapproved medical gas”. Other safety warnings were also placed on the listings that could have been a concern to consumers. 
Just recently, the FDA has established a process to remove these “unapproved” statements and warnings. On January 31, 2014, we conducted an 18-minute teleconference explaining how to remove the “unapproved medical gas” warning statement from your listing. You can get the teleconference handout and sample forms/letter from: http://www.gawda.org/uploadedFiles/Site_Framework/Home_Page/FDA_Medical_Gas_Certification_Compliance_Alert_20140131.pdf

You can also listen to a recording of the consultants teleconference about Medical Gas Certification on the GAWDA home page. You can reach it here: http://www.aws.org/GAWDA/audio/Medical_Gas_Update_20140131.WAV

2/1/14 – Colors of Medical Gas Cylinders

Q – Where is the regulation that specifies the color of medical gas cylinders? Must the color of Nitrogen, NF cylinder be black?
A – There is no actual “regulation” that specifies the color of medical gas cylinders… however there are at least two published requirements:
1.    In 2003, the FDA published it’s latest thinking on Current Good Manufacturing Practices in the “Draft Guidance”. On page 16, the document states:
Color code examination: The following colors are used by the medical gas industry in the United States to aid in identifying a medical gas.  We recommend manufacturers use them.
•    Carbon Dioxide - gray;
•    Helium - brown;
•    Medical Air - yellow;
•    Nitrogen - black;
•    Nitrous Oxide - blue;
•    Oxygen - green; and
•    Blends of medical gases use a combination of the corresponding color for each component gas.  For example, oxygen and carbon dioxide would be green and gray.
2.    In addition, in 1989, the FDA published the “Compressed Medical Gases Guideline”. This document is still official, though in many cases, the 2003 Draft Guidance has replaced it as the latest agency thinking. In 1989, the FDA specified the pre-fill inspection requirements:
Page 7….. A check to determine that each container is of the proper color to correspond to any color-coding system employed, such as that recommended by the CGA in its pamphlet C-9, Standard Color Marking of Compressed Gas Cylinders Intended for Medical Use in the United States. 
We highly recommend that GAWDA members download the latest copy of CGA C-9 and carefully review the proper colors for medical gases. The CGA pamphlets are available at no charge to GAWDA members.

1/1/14 – Unapproved Medical Gas Part 1

The FDA has developed a process to remove the “unapproved medical gas” label from certain drug listings. 


1.     Who does this process apply to? Only the “original manufacturer” of the medical gas can be certified and receive the New Drug Application number from the FDA.

2.     Who is the “original manufacturer”? The first company to produce the drug is the original manufacturer. For oxygen and nitrogen, this will be the bulk air separation plant. For carbon dioxide, helium and nitrous oxide, the original manufacturer will be the validated plant that produced the product from the non-medical raw material.

3.     What about Medical Air, USP? It’s a little more complicated for medical air. If you produce medical air from the atmosphere with an air compressor, you are the “original manufacturer” of the medical air. If you blend Oxygen, USP and Nitrogen, NF together to make medical air, you are not the “original manufacturer”.

4.     What is a “subsequent manufacturer”? Each company that processes the medical gas after the original manufacturer is the subsequent manufacturer. Most independent distributors who fill medical gases are subsequent manufacturers. If you fill medical oxygen cylinders and you do not own the ASU, you are a subsequent manufacturer.

5.     What’s the regulatory basis for all this? Congress passed the Medical Gas Safety Act about 18 months ago as a part of the FDA reauthorization (FDASIA). One of the provisions of the Act was to remove the “unapproved” status from medical gases.

6.     I fill medical air with a compressor (as the original manufacturer). What do I need to do to remove the “unapproved medical gas” label from my drug listing?

a.     In the Spring of 2013, you should have completed the medical gas certification application. (If you still need to complete the application, let us know.)

b.     The FDA should have sent you a letter titled “Acknowledge – Medical Gas Certification Request”. This letter should have included an NDA number.

c.     Resubmit your listing for medical air and add the NDA number in the pull down menu. If you listing submission fails due to data validation issues, contact the SPL office and give them your “coreid” for the submission. The SPL office can override the data validation error and process your submission. If there are other errors on the X-Form, these errors should be corrected before contacting the SPL office for an override.

d.     If AsteRisk, or another company, processed your FDA Drug Listing, have them resubmit your listing with the NDA number to remove the unapproved medical gas distinction.

7.     How does a subsequent manufacturer (most independent distributors) remove the unapproved medical gas from it’s listing? The FDA is implementing a process to allow subsequent manufacturers to have the benefits of the “New Drug Application” without going through the certification process of the original manufacturer. Here are the steps:

a.     Ask your bulk medical gas supplier for their NDA number on each bulk medical gas that you buy.

b.     Update your drug product listing with their NDA number.

c.     Handle data validation errors as above.

8.     How can I verify that my FDA drug listing is not an unapproved medical gas?

a.     Log on to: http://dailymed.nlm.nih.gov/dailymed/search.cfm 

b.     Enter your labeler code in the search window and all of your drug listings will be displayed.


If you have questions about this, or other FDA issues, please contact Tom Badstubner: tom@asteriskllc.com.


1/1/14 – Micro Audit

1.     Quality Control Unit Training – Verify that your QCU has received CGMP training within the last year. This training should be documented. The monthly online training sessions are examples of CGMP training.

2.     Personnel Training – Verify that your operations personnel and drivers have received documented CGMP and function specific training.