mdi Consultants
FDA outlines new GMP rules for Medical Gases
IMPORTANT CHANGES
Please take notice FDA came out with a new proposed rule for certain Medical Gases titled “Current Good Manufacturing Practice, Certification, Postmarketing Safety Reporting, and Labeling Requirements for Certain Medical Gases.”. FDA estimates this ruling will affect approximately 1,696 firms in the medical gases industry and some combination products industries.
FDA is proposing to establish new parts 213 and 230 (21 CFR parts 213 and 230) and amend parts 4, 16, 201, 210, 211, 314, and 514 (21 CFR parts 4, 16, 201, 210, 211, 314, and 514).
The proposed rule would:
- Revise the labeling regulations specific to medical gases;
- Establish CGMP requirements specific to medical gases;
- Establish regulations governing the designated medical gas certification process under section 576 of the FD&C Act, including certain post-approval requirements; and
- Establish post-marketing safety reporting requirements specific to designated medical gases.
We provide a high level summary of changes for each of the above elements below:
- FDA proposes revisions to the labeling regulations in part 201 related to medical gases which requires the label of a prescription drug in package form to bear a declaration of net quantity of contents.
In paragraph (a), FDA proposes to clarify that the statement of quantity of designated medical gases and medically appropriate combinations thereof in a gaseous state shall be in terms of volume measure.
In paragraph (b), FDA proposes to clarify that the statement of liquid measure currently described in the regulation would not apply to designated medical gases or medically appropriate combinations thereof.
Rather, FDA proposes separate requirements for the declaration of net quantity in the labels of designated medical gases or medically appropriate combinations thereof in a:
Gaseous state in a high-pressure container;
Liquefied compressed gas state in a high-pressure container; or
Liquefied state in a portable cryogenic container.
FDA proposes that designated medical gases and medically appropriate combinations for animal use utilize the same labeling information as designated medical gases and medically appropriate combinations for human use. Accordingly, FDA proposes to amend § 201.105 to exempt designated medical gases and medically appropriate combinations from the misbranding requirements of section 502(f)(1) of the FD&C Act if they are in compliance with the labeling requirements of § 201.161.
This proposal is intended to allow manufacturers to have one set of labeling that can be utilized for both human and animal use of their designated medical gases. Manufacturers will not necessarily know at the time of manufacture, filling, or distribution how their gas will be used. Additionally, FDA expects that requiring two separate sets of labeling would create a significant burden on industry with little or no benefit to product safety or patient outcomes. Because FDA is not aware of any reason to require different information for animal use, the Agency believes utilization of the same labeling for both human and animal use is appropriate.
In addition, FDA also proposes revisions to warning statements for certain medical gases.
- FDA proposes a separate Current Good Manufacturing Practice provision for medical gases. FDA proposes the establishment of part 213, which would contain the CGMP requirements for preparation of medical gases, including designated medical gases, for administration to humans or animals. If finalized as proposed, medical gases proposed to be subject to part 213 would no longer be subject to part 211.
21 CFR Part 213 would apply to the entity that initially produces a medical gas and also to any downstream firms that manufacture, process, pack, or hold medical gases, including firms that combine, commingle, refill, or distribute designated medical gases and medically appropriate combinations thereof.
Part 213 is not intended to apply to entities further upstream in the supply chain from the entity that initially produces a medical gas. FDA seeks comment on the scope of these requirements, including the stage of product development at which they would apply and the entities that would be subject to the requirements.
- FDA proposes Certification and Annual Reporting Provisions for medical gases. The proposed rule would establish, within new part 230, regulations setting forth the requirements for obtaining certification of a designated medical gas. As proposed, part 230 would contain the requirements for filing a certification request for a designated medical gas for human use, animal use, or both.
Proposed Part 230 would outline the information that must be submitted in a certification request. In addition, though not a proposed requirement in this proposed rule, FDA recommends that the applicant include a cover letter describing the purpose of the submission (e.g., original certification, amendment to supply additional information requested by FDA).
Such cover letters often provide context and information that would be helpful to the Agency as it processes certification requests. The certification request would need to include the name, address, telephone number, and email address of the person or entity requesting certification. If the address of the entity requesting certification is not in the United States, the certification request would need to contain the name and address of, and be countersigned by, an attorney, agent, or other authorized official who resides or maintains a place of business within the United States.
The certification request would also need to include a description of the designated medical gas. Each designated medical gas certification request would need to include the name of the gas, as well as a certification statement that the designated medical gas meets the appropriate compendial standard. FDA intends to develop a designated medical gas certification form which would include a certification statement. The Agency anticipates the form would have OMB approval prior to the finalization of any proposed rule.
The applicants would also be required to include certain facility information in the certification request, including the name and address of the facility or facilities where the designated medical gas will be initially produced. The applicants must certify in its that their methods, facilities, and controls used in manufacturing, processing, packing, and holding of the designated medical gas, as applicable, are adequate to ensure the gas’s safety, identity, strength, quality, and purity.
- FDA proposes Post-marketing Quality and Safety Reporting Provisions within Part 230.
FDA is proposing new post-marketing safety reporting regulations for designated medical gases and general safety reporting requirements for all certified designated medical gases. They have also proposed adverse event reporting requirements related to the use of designated medical gases in humans and animals.
For designated medical gases that are certified for human use and deemed to have in effect an approved application under section 505 of the FD&C Act, FDA is proposing that applicants and nonapplicants be required to report serious adverse events within 15 calendar days from when the applicant or nonapplicant has both met certain reporting criteria and acquired certain minimum data.
There are requirements for the contents and format of submissions, including an electronic submission requirement, the process for requesting a waiver of the electronic submission requirement, recordkeeping requirements, written procedures requirements, and patient privacy provisions.
For designated medical gases that are certified for animal use and deemed to have in effect an approved application under section 512 of the FD&C Act (21 U.S.C. 360b), FDA is proposing that applicants and nonapplicants be required to submit serious adverse event reports to FDA within 15 calendar days from when the applicant or nonapplicant has met certain reporting criteria and that recordkeeping requirements related to adverse events are maintained.
FDA proposes that any final rule based on this proposal become effective 18 months after publication in the Federal Register. The Agency anticipates that some proposed requirements will result in changes to cylinders as they are returned from service, and that it may take some time for firms to make required changes to all cylinders. FDA believes that 18 months is an appropriate amount of time to enable firms to make such changes.
You can review the full text of the proposed rule here: https://public-inspection.federalregister.gov/2022-10458.pdf
If you wish to comment on the proposed regulation, please submit electronic comments at the Federal eRulemaking Portal: https://www.regulations.gov. Include reference to the Docket No. FDA-2021-N1333 for “Current Good Manufacturing Practice, Certification, Postmarketing Safety Reporting, and Labeling Requirements for Certain Medical Gases.”
Please contact mdi Consultants to discuss your questions and implementation assistance regarding these upcoming changes, [email protected] and RE: Medical Gases