(a) Who must submit a request for certification. (1) The certification process described in this subpart applies to designated medical gases for the indications described in section 576(a)(3)(A)(i) of the Federal Food, Drug, and Cosmetic Act. Any person who seeks to initially introduce or deliver for introduction a designated medical gas into interstate commerce shall file a request for certification. The certification process is the same for all designated medical gases, regardless of whether it is intended for human use, animal use, or both. The applicant must identify its intention to market its designated medical gas for human use, animal use, or both.

(2) Any person that proposes to market a medical gas that is a new drug for human use must obtain approval under part 314 of this chapter, and any person that proposes to market a medical gas that is a new animal drug for animal use must obtain approval under part 514 of this chapter, unless—

(i) The medical gas meets the definition of a designated medical gas; and

(ii) The medical gas is proposed to be marketed alone or in combination (as medically appropriate) with another designated medical gas or other designated medical gases, for which a certification or certifications have been granted, for a use described under section 576(a)(3)(A)(i) of the Federal Food, Drug, and Cosmetic Act.

(b) The applicant must include the following information in its certification request—(1) Applicant information. The applicant must identify the name, address, telephone number, and email address of the person requesting certification. If the address of the person requesting certification is not in the United States, the certification request is required 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.

(2) Type of submission. The applicant must indicate the type of submission as one of the following:

(i) Original certification request. An initial request submitted by an applicant for certification of a medical gas as a designated medical gas.

(ii) Amendment to a pending certification request. Any submission related to a pending submission that revises existing information or provides additional information, including responses to Information Request Letters.

(iii) Resubmission. Any submission that has been revised and submitted again following a previous denial. If an applicant chooses to resubmit its submission, it must provide a written response to the deficiencies identified in FDA's denial letter, along with other information required for certification requests.

(iv) Supplement to a granted certification. Any submission that contains a change to a granted certification.

(v) Other. Any submission that does not fit in one of the other categories.

(3) Description of medical gas. A separate certification request is required to be submitted for each designated medical gas for which certification is sought. Each designated medical gas certification request must include the name of the medical gas and a certification statement from the applicant that the designated medical gas meets the appropriate compendial standard.

(4) Facility information. Each certification request must include the name and address of the facility or facilities where the designated medical gas will be initially produced. For each facility, include a brief description of the manufacturing or processing activities performed, the FDA Establishment Identifier, if one exists, and the Unique Facility Identifier in accordance with the requirements of part 207 of this chapter and section 510 of the Federal Food, Drug, and Cosmetic Act. For amendments and supplements, only changes to the list of facilities are required to be included.

(5) Certification of adequate manufacture, processing, packaging, and holding of designated medical gas. The applicant must certify that the applicant's methods, facilities, and controls used for the manufacture, processing, packing, and holding of the designated medical gas, as applicable, are adequate to ensure its safety, identity, strength, quality, and purity.

(6) Additional information. The applicant must provide any other information which FDA deems appropriate to determine whether the medical gas is a designated medical gas. The applicant may also provide other information that the applicant believes will assist FDA in evaluating the request.

(c) Where and how to submit a request for certification. The applicant must submit a signed, completed request for certification form either in an electronic format that FDA can process, review, and archive, or in hard copy by submitting two paper copies to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705.

An applicant may at any time withdraw a certification request that is not yet deemed granted by notifying FDA in writing. A decision to withdraw the certification request is without prejudice to refiling. The Agency will retain the certification request and will provide a copy to the applicant on request under the fee schedule in § 20.45 of this chapter (FDA's public information regulations).

(a) The applicant must submit a supplement if any information in the certification request changes after the request has been deemed granted, including, but not limited to, the addition of a new facility manufacturing the designated medical gas, a change in contact information, or a change in the corporate name.

(b) Each supplement must include a signed, completed request for certification form with the updated information in accordance with § 230.50. The updated information must be submitted no later than 30 calendar days after the date the change occurred.

An applicant may transfer ownership of its certification. At the time of transfer the new and former owners are required to submit information to FDA as follows:

(a) The former owner must submit a letter or other document that states that all rights to the certification have been transferred to the new owner.

(b) The new owner must submit a supplement under § 230.70 signed by the new owner describing any changes in the conditions in the granted certification and a letter or other document containing the date that the change in ownership is effective.

(a) The applicant must submit each year within 60 calendar days of the new calendar year an annual report containing the information described in paragraph (b) of this section. The applicant must submit a signed, completed annual report form either in an electronic format that FDA can process, review, and archive, or in hard copy by submitting two paper copies to the Central Document Room, Center for Drug Evaluation and Research, Food and Drug Administration, 5901-B Ammendale Rd., Beltsville, MD 20705.

(b) The report must contain, for the prior calendar year, the following information in the order listed:

(1) Summary. A brief summary of significant new information that might affect the safety, effectiveness, or labeling of the designated medical gas, including any actions the applicant has taken or intends to take as a result of this new information.

(2) Distribution data. Information about the quantity of the designated medical gas distributed by the applicant. The information must include the National Drug Code (NDC) numbers, the quantities distributed for domestic use, and the quantities distributed for foreign use. Disclosure of financial or pricing data is not required.

(3) Administrative changes. Any changes to the applicant's name or contact information.

(4) Current facilities. A list of current facilities where the designated medical gas is initially produced, and a list of facilities that are no longer in use.

(a) In reviewing a submission pursuant to § 230.50, FDA will consider information provided with the submission along with any other available, relevant information of which FDA becomes aware, including information obtained from State or Federal officials, FDA inspection reports, or any other source.

(b) FDA will deny a submission if FDA finds that:

(1) The medical gas that is the subject of the submission is not a designated medical gas;

(2) The submission does not contain the required information or otherwise appears to lack sufficient information to determine that the medical gas is a designated medical gas;

(3) The applicant's methods, facilities, and controls used for the manufacture, processing, and handling of the designated medical gas, as applicable, are not adequate to ensure its safety, identity, strength, quality, and purity; or

(4) Denying the request is otherwise necessary to protect the public health.

(c) Within 60 calendar days of filing of a submission, FDA may contact the applicant to request additional information regarding the submission if it determines that required information is not included in the submission, that FDA needs such information to determine whether the medical gas is a designated medical gas, or that FDA determines such information is necessary to protect the public health. Upon receipt of an amendment to a pending certification request, this 60-day review period will restart. If FDA is not able to contact the applicant to obtain and evaluate the information within the 60-day review period, FDA may find that the submission lacks sufficient information to permit a determination that the medical gas is a designated medical gas and deny the submission. If FDA is able to contact the applicant but is not provided with the additional information requested within the 60-day review period, FDA may find that the request lacks sufficient information to permit a determination that the medical gas is a designated medical gas and deny the submission.

(d) Within 60 calendar days of filing of a submission, if FDA makes one of the findings described in paragraph (b) of this section, FDA will notify the applicant in writing that the submission is denied and provide the basis for FDA's determination.

Unless FDA makes one of the findings described in § 230.100(b) and notifies the applicant within 60 calendar days of filing that the submission is denied, the certification is deemed to be granted and the designated medical gas will be deemed to have in effect an approved application under section 505 or section 512 of the Federal Food, Drug, and Cosmetic Act, or both, as applicable, for the indications described in section 576(a)(3)(A)(i) of the Federal Food, Drug, and Cosmetic Act. FDA will notify the applicant in writing.

(a) Withdrawal. (1) FDA will notify the applicant, and afford an opportunity for a hearing on a proposal to withdraw approval of the application under the procedure in § 314.200 of this chapter, § 514.200 of this chapter, or both, as applicable, if any of the following apply:

(i) The Secretary of Health and Human Services has suspended the approval of the application for a designated medical gas on a finding that there is an imminent hazard to the public health. FDA will promptly afford the applicant an expedited hearing following summary suspension on a finding of imminent hazard to health.

(ii) FDA finds:

(A) That clinical or other experience, tests, or other scientific data show that the designated medical gas is unsafe for use under the conditions of use upon the basis of which the application was approved; or

(B) That new evidence of clinical experience not available to FDA until after the application was approved, or tests by new methods, or tests by methods not deemed reasonably applicable when the application was approved, evaluated together with the evidence available when the application was approved, reveal that the designated medical gas is not shown to be safe for use under the conditions of use upon the basis of which the application was approved; or

(C) Upon the basis of new information before FDA with respect to the designated medical gas, evaluated together with the evidence available when the application was approved, that there is a lack of substantial evidence from adequate and well-controlled investigations as defined in § 314.126 of this chapter, that the designated medical gas will have the effect it is purported or represented to have under the conditions of use prescribed, recommended, or suggested in its labeling; or

(D) That the application contains any untrue statement of a material fact.

(2) FDA may notify the applicant, and afford an opportunity for a hearing on a proposal to withdraw approval of the application under the procedure in § 314.200 of this chapter, § 514.200 of this chapter, or both, as applicable, if the Agency finds:

(i) That the applicant has failed to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain required records or to make required reports applicable to designated medical gases, including under sections 505(k) and 512(l) of the Federal Food, Drug, and Cosmetic Act and this part, part 213 of this chapter, and § 314.81(b)(3) of this chapter, or that the applicant has refused to permit access to, or copying or verification of, its records.

(ii) That on the basis of new information before FDA, evaluated together with the evidence available when the application was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of the designated medical gas are inadequate to ensure and preserve its identity, strength, quality, and purity and were not made adequate within a reasonable time after receipt of written notice from the Agency.

(iii) That on the basis of new information before FDA, evaluated together with the evidence available when the application was approved, the labeling of the designated medical gas, based on a fair evaluation of all material facts, is false or misleading in any particular, and the labeling was not corrected by the applicant within a reasonable time after receipt of written notice from the Agency.

(iv) That the applicant has failed to comply with the notice requirements of section 510(j)(2) of the Federal Food, Drug, and Cosmetic Act.

(3) FDA will withdraw approval of an application if the applicant requests its withdrawal because the designated medical gas subject to the application is no longer being marketed, provided none of the conditions listed in paragraphs (a)(1) and (2) of this section applies to the designated medical gas. FDA will consider a written request for a withdrawal under this paragraph (a)(3) to be a waiver of an opportunity for hearing otherwise provided for in this section. Withdrawal of approval of an application under this paragraph (a)(3) is without prejudice to refiling.

(4) FDA may notify an applicant that it believes a potential problem associated with a designated medical gas is sufficiently serious that the designated medical gas should be removed from the market and may ask the applicant to waive the opportunity for hearing otherwise provided for under this section, to permit FDA to withdraw approval of the application for the product, and to remove voluntarily the product from the market. If the applicant agrees, the Agency will not make a finding under paragraph (a)(1) or (2) of this section, but will withdraw approval of the application in a notice published in the Federal Register that contains a brief summary of the Agency's and the applicant's views of the reasons for withdrawal.

(5) If FDA withdraws an approval, FDA will publish a notice in the Federal Register announcing the withdrawal of approval.

(b) Revocation. FDA may revoke the grant of a certification if FDA determines, after providing the applicant with notice and opportunity for an informal hearing in accordance with part 16 of this chapter, that the request for certification contains any material omission or falsification.