83 FR 46121 - Repeal of Regulation Requiring an Approved New Drug Application for Drugs Sterilized by Irradiation
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 177 (September 12, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 177 (September 12, 2018)
| Page Range | 46121-46126 | |
| FR Document | 2018-19845 |
[Federal Register Volume 83, Number 177 (Wednesday, September 12, 2018)] [Proposed Rules] [Pages 46121-46126] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-19845] ======================================================================= ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 310 [Docket No. FDA-2017-N-6924] RIN 0910-AH47 Repeal of Regulation Requiring an Approved New Drug Application for Drugs Sterilized by Irradiation AGENCY: Food and Drug Administration, HHS. ACTION: Proposed rule. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is proposing to repeal a regulation that requires an FDA-approved new drug application (NDA) or abbreviated new drug application (ANDA) for any drug product that is sterilized by irradiation (the irradiation regulation). Repealing the irradiation regulation would mean that over- the-counter (OTC) drug products that are generally recognized as safe and effective, that are not misbranded, and that comply with all applicable regulatory requirements can be marketed legally without an NDA or ANDA, even if they are sterilized by irradiation. FDA is proposing to take this action because the irradiation regulation is out of date and unnecessary. The technology of controlled nuclear radiation for sterilization of drugs is now well understood, and our regulations require that OTC drugs be manufactured in compliance with current good manufacturing practices (CGMPs). Appropriate and effective sterilization of drugs, including by irradiation, is adequately addressed by the CGMP requirements. This action is part of FDA's implementation of Executive Orders (EOs) 13771 and 13777. Under these EOs, FDA is comprehensively reviewing existing regulations to identify opportunities for repeal, replacement, or modification that will result in meaningful burden reduction while allowing the Agency to achieve our public health mission and fulfill statutory obligations. DATES: Submit either electronic or written comments on the proposed rule by November 13, 2018. ADDRESSES: You may submit comments as follows. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before November 13, 2018. The https://www.regulations.gov electronic filing system will accept comments until midnight Eastern Time at the end of November 13, 2018. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date. Electronic Submissions Submit electronic comments in the following way:Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to [[Page 46122]] the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov. If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ``Written/Paper Submissions'' and ``Instructions''). Written/Paper Submissions Submit written/paper submissions as follows: Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ``Instructions.'' Instructions: All submissions received must include the Docket No. FDA-2017-N-6924 for ``Repeal of Regulation Requiring an Approved New Drug Application for Drugs Sterilized by Irradiation.'' Received comments, those filed in a timely manner (see ADDRESSES), will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday. Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ``confidential.'' Any information marked as ``confidential'' will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.thefederalregister.org/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Sudha Shukla, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5198, Silver Spring, MD 20993-0002, 301- 796-3345. SUPPLEMENTARY INFORMATION: Table of Contents I. Executive Summary II. Background and Discussion A. The History of the Irradiation Regulation B. Sterilization by Irradiation C. The OTC Drug Monograph System and Current Good Manufacturing Practices D. Conclusion III. Legal Authority IV. Proposed Effective Date V. Economic Analysis of Impacts VI. Analysis of Environmental Impact VII. Paperwork Reduction Act of 1995 VIII. Federalism IX. Consultation and Coordination With Indian Tribal Governments X. References I. Executive Summary This proposed rule would repeal the irradiation regulation, which provides that any drug sterilized by irradiation is a new drug. This action, if finalized, would mean that OTC drugs marketed pursuant to the OTC Drug Review that are generally recognized as safe and effective, that are not misbranded, and that comply with all applicable regulatory requirements can be marketed legally without an FDA-approved NDA or ANDA, even if the drugs are sterilized by irradiation. FDA is taking this action because the Agency no longer concludes that drugs sterilized by irradiation are necessarily new drugs. The technology of controlled nuclear radiation for sterilization of drugs is now well understood. In addition, drugs that are marketed pursuant to the OTC Drug Review must be manufactured in compliance with CGMPs. Appropriate and effective sterilization of drugs, including by irradiation, is adequately addressed by the CGMP requirements. Repealing the irradiation regulation would eliminate a requirement that is no longer necessary, and will not diminish public health protections. The estimated one-time costs of this rule range from $120 to $150. Avoiding the unnecessary preparation and review of a premarket drug application will generate an estimated one-time cost savings that range from about $395,000 to $2,076,000. Over 10 years with a 7 percent discount rate, the annualized net cost savings range from $0.05 million to $0.28 million, with a primary estimate of $0.06 million; with a 3 percent discount rate, the annualized net cost savings range from $0.04 million to $0.24 million, with a primary estimate of $0.05 million. Over an infinite horizon, we assume that one sponsor will benefit from this deregulatory action every 10 years; the present value of the net cost savings over the infinite horizon range from $0.83 million to $4.37 million with a 7 percent discount rate and from $1.58 million to $8.30 million with a 3 percent discount rate. II. Background and Discussion On February 24, 2017, E.O. 13777, ``Enforcing the Regulatory Reform Agenda'' (https://www.thefederalregister.org/fdsys/pkg/FR-2017-03-01/pdf/2017-04107.pdf) was issued. One of the provisions in the E.O. requires Agencies to evaluate existing regulations and make recommendations to the Agency head regarding their repeal, replacement, or modification, consistent with applicable law. As part of this initiative, FDA is proposing to repeal the irradiation regulation as specified in this rule. In addition, in a citizen petition dated August 14, 2014, Richard O. Wood of The Wood Burditt Group LLC requested that the irradiation regulation be revoked. FDA has responded to Mr. Wood's citizen petition. A copy of the response is available at: https://www.regulations.gov under Docket No. FDA-2014-P-1784. [[Page 46123]] A. The History of the Irradiation Regulation In the November 29, 1955, issue of the Federal Register, FDA issued a statement of interpretation relating to the sterilization of drugs by irradiation (20 FR 8747 to 8748).\1\ In the statement, FDA explained that there was an interest in the utilization of newly developed sources of radiation for the sterilization of drugs. The Agency went on to state that it was necessary in the interest of protecting the public health to establish by adequate investigations that the irradiation treatment does not cause the drug to become unsafe or otherwise unsuitable for use. For this reason, all drug products sterilized by irradiation would be regarded as new drugs within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which would mean that an effective new drug application would be required for such products. --------------------------------------------------------------------------- \1\ Available at: https://www.loc.gov/item/fr020231/. A month later, this provision was included at Sec. 3.45 in the republication of chapter 21 of the Code of Federal Regulations in the Federal Register. See 20 FR 9525 at 9554 (December 20, 1955), available at: http://cdn.loc.gov/service/ll/fedreg/fr020/fr020246/fr020246.pdf. In 1975, FDA republished and re-codified the rule at 21 CFR 200.30. See 40 FR 13996 at 13997 (March 27, 1975), available at: https://www.loc.gov/item/fr040060/. --------------------------------------------------------------------------- In 1996, FDA proposed to revise the statement and consolidate it with similar provisions into a single list of drugs that have been determined by previous rulemaking procedures to be new drugs within the meaning of section 201(p) of the FD&C Act (61 FR 29502 at 29503 to 29504 (June 11, 1996)). The Agency proposed to remove any existing background information describing the Agency's basis for determination of new drug status from the regulatory text. In 1997, FDA finalized these provisions, now located in 21 CFR 310.502, entitled ``Certain drugs accorded new drug status through rulemaking procedures.'' (62 FR 12084 at 12084 (March 14, 1997).) Paragraph 310.502(a) sets forth a list of drugs that have been determined by rulemaking procedures to be ``new drugs'' within the meaning of section 201(p) of the FD&C Act. Included on the list is sterilization of drugs by irradiation (Sec. 310.502(a)(11) (21 CFR 310.502(a)(11)). Because this regulation reflects an FDA determination that the drugs on the list are ``new drugs,'' an NDA or ANDA must be submitted and approved by FDA before they can be marketed legally. For a non-prescription drug that could otherwise be legally marketed without an approved NDA or ANDA in effect pursuant to the OTC Drug Review, the effect of Sec. 310.502(a)(11) is that, if the drug is sterilized by irradiation, an approved NDA or ANDA is necessary. B. Sterilization by Irradiation Since the paragraph now reflected at Sec. 310.502(a)(11) was published in 1955, the technology of controlled nuclear radiation for sterilization of drugs has become well understood. Gamma ray irradiation has been recognized as a method of sterilizing drug products for half a century (Refs. 1 and 2). Electron beam and x-ray irradiation are also recognized methods for sterilizing drugs (Ref. 1). Information and data on whether a particular drug can safely and effectively be sterilized by irradiation are available in the scientific literature (Ref. 1). The United States Pharmacopeial Convention (USP) has provided guidance on irradiation sterilization of drug products since 1965 (Refs. 1 and 3). This includes chapter <1229> on ``Sterilization of Compendial Articles,'' which sets forth principles that may be applied to the sterilization of compendial and non-compendial drug products, and chapter <1229.10> on ``Radiation Sterilization,'' which sets forth guidelines on validation of sterilization by irradiation (Refs. 3 and 4). The American National Standards Institute, the Association for the Advancement of Medical Instrumentation, ASTM International, and the International Organization for Standardization (ISO) have also published standards on the irradiation of medical products, including drugs (Ref. 1). ISO standard 11137, which sets forth several methods that can be used to determine the appropriate radiation dose for health care products, was first published in 1984 \2\ (Ref. 1). --------------------------------------------------------------------------- \2\ ISO 11137-1 specifies standards for the development, validation, and routine control of a radiation sterilization process for medical devices, while ISO 11137-2 specifies dose establishment and dose audit methods and defines product family approaches for dose establishment and dose audits. Additional target sterilization doses are covered in ISO Technical Information Report (TIR) 13004. Neither ISO 11137-2 nor TIR 13004 is explicitly limited to medical devices. In addition, both ISO 11137-2 and ISO TIR 13004 reference ISO 11137-1 as ``indispensable for the application of this document.'' This implies that the concepts in ISO 11137-1 may be applied to sterilization of drug products. --------------------------------------------------------------------------- USP chapter <1229.10> states that the methods set forth in ISO 11137 typically guide the choice of radiation dose (Ref. 3). Relevant factors include a drug's pre-sterilization level of microbial contamination (sometimes referred to as its bioburden) and the desired sterility assurance level (Ref. 1). Once the dose is selected, USP General Chapter <1229.10> states that all materials exposed to radiation, especially the drug product and its primary container, should be evaluated for immediate and long-term effects, and ``[p]roduct stability, safety, and functionality should be confirmed over the product's intended use period'' (Ref. 3). Among the advantages of sterilizing drug products by irradiation is that due to radiation's high penetrability, drug products can be irradiated after they are placed in their final containers (Ref. 1). Known as terminal sterilization, this provides a greater degree of sterilization assurance than aseptic processing and, where feasible, its use is preferable to relying solely on aseptic processing to ensure sterility (Ref. 5). Other advantages to irradiation sterilization of drugs include low chemical reactivity; the very low rise in temperature associated with radiation, which allows for its use on heat-sensitive products; that irradiation sterilization has fewer process variables than other methods, which translates into fewer sterility rejections; and that radiation does not leave behind any sterilant residuals (Refs. 1 and 6). C. The OTC Drug Monograph System and Current Good Manufacturing Practices The OTC Drug Review was established to evaluate the safety and effectiveness of OTC drug products marketed in the United States before May 11, 1972. As set forth in 21 CFR 330.10, it is a multiphase public rulemaking process (each phase requiring a Federal Register publication) resulting in the establishment of monographs for OTC therapeutic drug classes. OTC drug monographs, which can be found in Title 21, chapter I, subchapter D of the Code of Federal Regulations, cover acceptable ingredients, doses, formulations, other conditions, and labeling for certain OTC drugs. A company can legally make and market an OTC product that meets each of the conditions contained in an applicable monograph and, in addition, each of the general conditions set forth in Sec. 330.1. Among the general conditions that apply to all drug products marketed under the OTC Drug Review is the requirement set forth in Sec. 330.1(a) that they be manufactured in compliance with current good manufacturing practices, as established by parts 210 and 211 of this chapter. The CGMP requirements in parts 210 and 211 [[Page 46124]] encompass sterilization, including by irradiation.\3\ --------------------------------------------------------------------------- \3\ We note that sterilization is not generally a condition specifically covered by OTC monographs. Currently, the monograph for ophthalmic drug products at 21 CFR part 349 is the only monograph that incorporates a sterility condition. There are, however, OTC products covered by a monograph or tentative final monograph that are not required to be sterile, but which manufacturers may choose to sterilize. These may include consumer and healthcare antiseptics, such as consumer hand washes, body washes, and hand rubs, first aid antiseptics, health care personnel hand washes and hand rubs, surgical hand scrubs and rubs, and patient preoperative skin preparations. In 2013, FDA asked manufacturers to voluntarily revise the product labels for topical antiseptics to indicate whether the product is manufactured as a sterile or nonsterile product (Ref. 7). --------------------------------------------------------------------------- In 1955, when the determination with respect to drugs sterilized by irradiation (now reflected in Sec. 310.502(a)(11)) was made, neither the OTC drug monograph system nor the CGMP requirements existed. The authorizing legislation that the CGMP regulations implement, section 501(a)(2)(B) of the FD&C Act (21 U.S.C. 351(a)(2)(B)), was enacted in 1962 (Drug Amendments of 1962, October 10, 1962, Pub. L. 87-781, Title I, sec. 101), and the first CGMP regulations followed in 1963 (Part 133--Drugs; Current Good Manufacturing Practice in Manufacture, Processing, Packing, or Holding, 28 FR 6385 (June 20, 1963) available at: https://www.loc.gov/item/fr028120/). The regulations creating procedures for establishing OTC drug monographs were issued in 1972 (37 FR 9464 (May 11, 1972)) available at: https://www.loc.gov/item/fr037092/). Because of these subsequent statutes and regulations, Sec. 310.502(a)(11) can be revoked and manufacturers will still be obligated to ensure that, if they use radiation: (1) The drug products that they purport to be sterile are in fact sterile and (2) their use of radiation does not have a detrimental effect on their drug products' identity, strength, quality, purity, or stability. CGMP regulations require manufacturers to take steps to ensure that sterile drug products are free of objectionable microorganisms. (See, e.g., 21 CFR 211.28(a), 211.42(b) and (c), 211.67(a), 211.84(c), 211.110(a), 211.113(b), 211.165(b), 211.167(a).) The CGMP regulations also include provisions that ensure that irradiation or any other sterilization processes do not have a detrimental effect on a drug product's identity, strength, quality, purity, or stability. (See, e.g., 21 CFR 211.22, 211.25(b), 211.68, 211.100, 211.160(b), 211.165, 211.166.) Numerous records relating to the manufacture of the drug product must be maintained and made available for inspection (21 CFR part 211, subpart J). FDA conducts inspections at manufacturing facilities, including irradiation facilities, to ensure that the CGMP regulations are followed. Inspection findings are reviewed and, when appropriate, action may be recommended against manufacturers observed to be out of compliance. Choosing the sterilization process that is suitable for a particular drug product is the responsibility of the manufacturer and is an important part of pharmaceutical development. To guide them in choosing an appropriate method of sterilization and otherwise complying with the CGMP requirements, manufacturers can turn to voluntary consensus standards that are widely-known by industry and recognized by FDA for the development, validation, and routine control of the sterilization of drugs by irradiation. As noted previously in this document, ISO publishes standards that address the different doses of radiation that are appropriate depending on the type and amount of microbiological contamination and the necessary degree of sterility assurance (Ref. 3). These include the following: ISO 11137-1:2006: Sterilization of health care products-- Radiation--Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices; ISO 11137-2:2013: Sterilization of health care products-- Radiation--Part 2: Establishing the sterilization dose; ISO 11137-3:2006: Sterilization of health care products-- Radiation--Part 3: Guidance on dosimetric aspects; and ISO/TS 13004:2013: Sterilization of health care products-- Substantiation of selected sterilization dose: Method VDmaxSD. The USP also provides guidance on irradiation sterilization, including in chapter <1229.10>, which specifically addresses the topic (Ref. 3). D. Conclusion We propose the repeal of Sec. 310.502(a)(11) because the Agency no longer concludes that drugs sterilized by irradiation are necessarily new drugs. The technology of controlled nuclear radiation for sterilization of drugs is now well understood and sterilization is a manufacturing process that is adequately addressed by the regulations governing the OTC drug monograph system and CGMPs. III. Legal Authority FDA is issuing this proposed rule under the drugs and general administrative provisions of the FD&C Act (sections 201, 301, 501, 502, 503, 505, 510, 701, 702, and 704 (21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 371, 372, and 374)) and under section 361 of the Public Health Service Act (PHS Act) (42 U.S.C. 264). The FD&C Act gives us the authority to issue and enforce regulations designed to help ensure that drug products are safe, effective, and manufactured according to current good manufacturing practices, while section 361 of the PHS Act gives us the authority to issue and enforce regulations designed to prevent the introduction, transmission, or spread of communicable diseases. IV. Proposed Effective Date Any final rule that results from this proposed rule will be effective 30 days after the date of the final rule's publication in the Federal Register. V. Economic Analysis of Impacts We have examined the impacts of the proposed rule under E.O. 12866, E.O. 13563, E.O. 13771, the Regulatory Flexibility Act (5 U.S.C. 601- 612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 104-4). EOs 12866 and 13563 direct us to assess all costs and benefits of available regulatory alternatives and, when regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety, and other advantages; distributive impacts; and equity). E.O. 13771 requires that the costs associated with significant new regulations ``shall, to the extent permitted by law, be offset by the elimination of existing costs associated with at least two prior regulations.'' We believe that this proposed rule is not a significant regulatory action as defined by E.O. 12866. The Regulatory Flexibility Act requires us to analyze regulatory options that would minimize any significant impact of a rule on small entities. Because few entities will be affected and the net effect will be cost savings to affected firms, we propose to certify that the proposed rule, if finalized, will not have a significant economic impact on a substantial number of small entities. The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires us to prepare a written statement, which includes an assessment of anticipated costs and benefits, before proposing ``any rule that includes any Federal mandate that may result in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted annually for inflation) in any one year.'' The current threshold after [[Page 46125]] adjustment for inflation is $150 million, using the most current (2017) Implicit Price Deflator for the Gross Domestic Product. This proposed rule would not result in an expenditure in any year that meets or exceeds this amount. Table 1 summarizes our estimate of the annualized costs and benefits of the proposed rule. Table 1--Summary of Benefits, Costs and Distributional Effects of the Rule [$ million] -------------------------------------------------------------------------------------------------------------------------------------------------------- Units ------------------------------------ Category Primary Low High Period Notes estimate estimate estimate Year Discount covered dollars rate (%) (years) -------------------------------------------------------------------------------------------------------------------------------------------------------- Benefits: Annualized, Monetized $millions/ $0.06 $0.05 $0.28 2016 7 10 Benefits are cost savings. year. 0.05 0.04 0.24 2016 3 10 Benefits are cost savings. Annualized Quantified.............. .......... .......... .......... 2016 7 10 .......... .......... .......... 2016 3 10 ....................................... ---------------------------------------------------------------------------------------------------------------- Qualitative -------------------------------------------------------------------------------------------------------------------------------------------------------- Costs: Annualized Monetized $millions/year 0.00 0.00 0.00 2016 7 10 Costs total less than $100. 0.00 0.00 0.00 2016 3 10 Costs total less than $100. Annualized Quantified.............. .......... .......... .......... 2016 7 10 .......... .......... .......... 2016 3 10 -------------------------------------------------------------------------------------------------------------------------------------------------------- Qualitative -------------------------------------------------------------------------------------------------------------------------------------------------------- Transfers: Federal Annualized Monetized 0.14 0.14 0.14 2016 7 10 User Fee. $millions/year. 0.12 0.12 0.12 2016 3 10 User Fee. ---------------------------------------------------------------------------------------------------------------- From: To: ---------------------------------------------------------------------------------------------------------------- Other Annualized Monetized .......... .......... .......... 2016 7 10 $millions/year. .......... .......... .......... 2016 3 10 ---------------------------------------------------------------------------------------------------------------- From: To: -------------------------------------------------------------------------------------------------------------------------------------------------------- Effects: -------------------------------------------------------------------------------------------------------------------------------------------------------- State, Local or Tribal Government: None............................................................................................................. Small Business: None................................................................................................................................ Wages: None......................................................................................................................................... Growth: None........................................................................................................................................ -------------------------------------------------------------------------------------------------------------------------------------------------------- Because the proposed rule will repeal an outdated regulation and generate net cost savings, we consider this action a deregulatory action under E.O. 13771. Table 2 presents a summary of the E.O. 13771 impacts of the proposed rule over an infinite horizon. For this estimate, we assume that one sponsor will benefit from this deregulatory action every 10 years. Table 2--E.O. 13771 Summary [In $ millions 2016 dollars, over an infinite horizon] -------------------------------------------------------------------------------------------------------------------------------------------------------- Lower bound Upper bound Lower bound Upper bound Primary (7%) (7%) (7%) Primary (3%) (3%) (3%) -------------------------------------------------------------------------------------------------------------------------------------------------------- Present Value of Costs.................................. $0.00 $0.00 $0.00 $0.00 $0.00 $0.00 Present Value of Cost Savings........................... 0.97 0.83 4.37 1.84 1.58 8.30 Present Value of Net Costs.............................. (0.97) (0.83) (4.37) (1.84) (1.58) (8.30) Annualized Costs........................................ $0.00 $0.00 $0.00 $0.00 $0.00 $0.00 Annualized Cost Savings................................. $0.07 $0.06 $0.31 $0.06 $0.05 $0.25 Annualized Net Costs.................................... (0.07) (0.06) (0.31) (0.06) (0.05) (0.25) -------------------------------------------------------------------------------------------------------------------------------------------------------- We have developed a comprehensive Economic Analysis of Impacts that assesses the impacts of the proposed rule. The full analysis of economic impacts is available in the docket for this proposed rule (Ref. 8) and at: https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm. VI. Analysis of Environmental Impact We have determined under 21 CFR 25.30(h) and 25.31(a) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required. VII. Paperwork Reduction Act of 1995 This proposed rule refers to previously approved collections of information that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501- 3520). The collections of information resulting from compliance with CGMPs have been [[Page 46126]] approved under OMB control number 0910-0139. VIII. Federalism We have analyzed this proposed rule in accordance with the principles set forth in E.O. 13132. We have determined that this proposed rule does not contain policies that have substantial direct effects on the States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various levels of government. Accordingly, we conclude that the rule does not contain policies that have federalism implications as defined in the E.O. and, consequently, a federalism summary impact statement is not required. IX. Consultation and Coordination With Indian Tribal Governments We have analyzed this proposed rule in accordance with the principles set forth in E.O. 13175. We have tentatively determined that the rule does not contain policies that would have a substantial direct effect on one or more Indian Tribes, on the relationship between the Federal Government and Indian Tribes, or on the distribution of power and responsibilities between the Federal Government and Indian Tribes. The Agency solicits comments from tribal officials on any potential impact on Indian Tribes from this proposed action. X. References The following references are on display in the Dockets Management Staff (see ADDRESSES) and are available for viewing by interested persons between 9 a.m. and 4 p.m., Monday through Friday; they are also available electronically at https://www.regulations.gov. FDA has verified the website addresses, as of the date this document publishes in the Federal Register, but websites are subject to change over time. 1. Jacobs, G., ``Validation of the Radiation Sterilization of Pharmaceuticals.'' In: J. Agalloco and F. J. Carleton (eds.), Validation of Pharmaceutical Processes (3rd Ed.) Informa USA, New York, 2007. 2. Microbiology Sub-Committee, Radiation Sterilization Task Force, Parenteral Drug Association, Technical Report No. 11, ``Sterilization of Parenterals by Gamma Radiation,'' Journal of Parenteral Science and Technology, 42 (3S), 1988, available at: https://store.pda.org/ProductCatalog/Product.aspx?ID=1170. 3. United States Pharmacopeial Convention (USP 40), Radiation Sterilization <1229.10>, 2017. 4. United States Pharmacopeial Convention (USP 40), Sterilization of Compendial Articles <1229>, 2017. 5. FDA Guidance for Industry on ``Sterile Drug Products Produced by Aseptic Processing--Current Good Manufacturing Practice,'' September 2004; available at https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070342.pdf. 6. United States Pharmacopeial Convention (USP 40), Sterilization and Sterility Assurance of Compendial Articles <1211>, 2017. 7. FDA Drug Safety Communication, ``FDA Requests Label Changes and Single-Use Packaging for Some Over-the-Counter Topical Antiseptic Products to Decrease Risk of Infection,'' November 13, 2013; available at https://www.fda.gov/Drugs/DrugSafety/ucm374711.htm. 8. FDA Preliminary Regulatory Impact Analysis, Repeal of Regulation Requiring an Approved New Drug Application for Drugs Sterilized by Irradiation; https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm. List of Subjects in 21 CFR Part 310 Administrative practice and procedure, Drugs, Labeling, Medical devices, Reporting and recordkeeping requirements. Therefore, under the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act and under authority delegated to the Commissioner of Food and Drugs, it is proposed that 21 CFR part 310 be amended as follows: PART 310--NEW DRUGS 0 1. The authority citation for part 310 continues to read as follows: Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f, 360j, 360hh-360ss, 361(a), 371, 374, 375, 379e, 379k-1; 42 U.S.C. 216, 241, 242(a), 262. 0 2. In Sec. 310.502, revise paragraph (a) introductory text and remove and reserve paragraph (a)(11) to read as follows: Sec. 310.502 Certain drugs accorded new drug status through rulemaking procedures. (a) The drugs listed in this paragraph have been determined by rulemaking procedures to be new drugs within the meaning of section 201(p) of the Federal Food, Drug, and Cosmetic Act. An approved new drug application under section 505 of the Federal Food, Drug, and Cosmetic Act and part 314 of this chapter is required for marketing the following drugs: * * * * * (11) [Reserved] * * * * * Dated: September 7, 2018. Scott Gottlieb, Commissioner of Food and Drugs. [FR Doc. 2018-19845 Filed 9-11-18; 8:45 am] BILLING CODE 4164-01-P
![Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 46121
be kept within the amount authorized in USDA has not identified any relevant SUMMARY: The Food and Drug
the Order. Federal rules that duplicate, overlap, or Administration (FDA, the Agency, or
A review of historical information and conflict with this proposed rule. we) is proposing to repeal a regulation
preliminary information pertaining to A small business guide on complying that requires an FDA-approved new
the upcoming fiscal year indicates that with fruit, vegetable, and specialty crop drug application (NDA) or abbreviated
the average grower price for the 2018– marketing agreements and orders may new drug application (ANDA) for any
2019 season should be approximately be viewed at: http://www.ams.usda.gov/ drug product that is sterilized by
$296 per ton of pears for processing. rules-regulations/moa/small-businesses. irradiation (the irradiation regulation).
Therefore, the estimated assessment Any questions about the compliance Repealing the irradiation regulation
revenue for the 2018–2019 fiscal period guide should be sent to Richard Lower would mean that over-the-counter
as a percentage of total grower revenue at the previously mentioned address in (OTC) drug products that are generally
would be about 2.4 percent ($7.15 per the FOR FURTHER INFORMATION CONTACT recognized as safe and effective, that are
ton assessment divided by $296 per ton section. not misbranded, and that comply with
grower price). List of Subjects in 7 CFR Part 927 all applicable regulatory requirements
This proposed action would decrease can be marketed legally without an NDA
the assessment obligation imposed on Marketing agreements, Pears, or ANDA, even if they are sterilized by
handlers for the 2018–2019 and Reporting and recordkeeping irradiation. FDA is proposing to take
subsequent fiscal periods. Assessments requirements. this action because the irradiation
are applied uniformly on all handlers, For the reasons set forth in the regulation is out of date and
and some of the costs may be passed on preamble, 7 CFR part 927 is proposed to unnecessary. The technology of
to producers. However, decreasing the be amended as follows: controlled nuclear radiation for
assessment rate would reduce the sterilization of drugs is now well
burden on handlers, and may reduce the PART 927—PEARS GROWN IN understood, and our regulations require
burden on producers. OREGON AND WASHINGTON that OTC drugs be manufactured in
The Committee’s meetings were ■ 1. The authority citation for 7 CFR compliance with current good
widely publicized throughout the part 927 continues to read as follows: manufacturing practices (CGMPs).
Oregon and Washington processed pear Appropriate and effective sterilization
Authority: 7 U.S.C. 601–674. of drugs, including by irradiation, is
industry. All interested persons were
invited to attend the meetings and ■ 2. In § 927.237 revise the intro adequately addressed by the CGMP
participate in Committee deliberations paragraph text and paragraph (a) to read requirements. This action is part of
on all issues. Like all Committee as follows: FDA’s implementation of Executive
meetings, the May 30, 2018, meeting Orders (EOs) 13771 and 13777. Under
§ 927.237 Assessment rate. these EOs, FDA is comprehensively
was a public meeting and all entities,
both large and small, were able to On and after July 1, 2018, the reviewing existing regulations to
express views on this issue. Finally, following base rates of assessment for identify opportunities for repeal,
interested persons are invited to submit pears for processing are established for replacement, or modification that will
comments on this proposed rule, the Processed Pear Committee: result in meaningful burden reduction
(a) $7.15 per ton for any or all while allowing the Agency to achieve
including the regulatory and
varieties or subvarieties of pears for our public health mission and fulfill
information collection impacts of this
canning classified as ‘‘summer/fall’’ statutory obligations.
action on small businesses.
excluding pears for other methods of
In accordance with the Paperwork DATES: Submit either electronic or
processing;
Reduction Act of 1995 (44 U.S.C. written comments on the proposed rule
chapter 35), the Order’s information * * * * * by November 13, 2018.
collection requirements have been Dated: September 6, 2018. ADDRESSES: You may submit comments
previously approved by OMB and Bruce Summers, as follows. Please note that late,
assigned OMB No. 0581–0189. No Administrator, Agricultural Marketing untimely filed comments will not be
changes in those requirements would be Service. considered. Electronic comments must
necessary because of this action. Should [FR Doc. 2018–19683 Filed 9–11–18; 8:45 am] be submitted on or before November 13,
any changes become necessary, they BILLING CODE 3410–02–P 2018. The https://www.regulations.gov
would be submitted to OMB for electronic filing system will accept
approval. comments until midnight Eastern Time
This proposed rule would not impose DEPARTMENT OF HEALTH AND at the end of November 13, 2018.
any additional reporting or HUMAN SERVICES Comments received by mail/hand
recordkeeping requirements on either delivery/courier (for written/paper
small or large Oregon and Washington Food and Drug Administration submissions) will be considered timely
processed pear handlers. As with all if they are postmarked or the delivery
Federal marketing order programs, 21 CFR Part 310 service acceptance receipt is on or
reports and forms are periodically before that date.
reviewed to reduce information [Docket No. FDA–2017–N–6924]
requirements and duplication by RIN 0910–AH47 Electronic Submissions
daltland on DSKBBV9HB2PROD with PROPOSALS
industry and public sector agencies. Submit electronic comments in the
AMS is committed to complying with Repeal of Regulation Requiring an following way:
the E-Government Act, to promote the Approved New Drug Application for • Federal eRulemaking Portal: https://
use of the internet and other Drugs Sterilized by Irradiation www.regulations.gov. Follow the
information technologies to provide AGENCY: Food and Drug Administration, instructions for submitting comments.
increased opportunities for citizen HHS. Comments submitted electronically,
access to Government information and including attachments, to https://
ACTION: Proposed rule.
services, and for other purposes. www.regulations.gov will be posted to
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![Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 46123
A. The History of the Irradiation ANDA in effect pursuant to the OTC is selected, USP General Chapter
Regulation Drug Review, the effect of <1229.10> states that all materials
In the November 29, 1955, issue of the § 310.502(a)(11) is that, if the drug is exposed to radiation, especially the drug
Federal Register, FDA issued a sterilized by irradiation, an approved product and its primary container,
statement of interpretation relating to NDA or ANDA is necessary. should be evaluated for immediate and
the sterilization of drugs by irradiation B. Sterilization by Irradiation long-term effects, and ‘‘[p]roduct
(20 FR 8747 to 8748).1 In the statement, stability, safety, and functionality
Since the paragraph now reflected at
FDA explained that there was an should be confirmed over the product’s
§ 310.502(a)(11) was published in 1955,
interest in the utilization of newly intended use period’’ (Ref. 3). Among
the technology of controlled nuclear
developed sources of radiation for the the advantages of sterilizing drug
radiation for sterilization of drugs has
sterilization of drugs. The Agency went products by irradiation is that due to
become well understood. Gamma ray
on to state that it was necessary in the radiation’s high penetrability, drug
irradiation has been recognized as a
interest of protecting the public health products can be irradiated after they are
method of sterilizing drug products for
to establish by adequate investigations placed in their final containers (Ref. 1).
half a century (Refs. 1 and 2). Electron
that the irradiation treatment does not Known as terminal sterilization, this
beam and x-ray irradiation are also
cause the drug to become unsafe or provides a greater degree of sterilization
recognized methods for sterilizing drugs
otherwise unsuitable for use. For this (Ref. 1). assurance than aseptic processing and,
reason, all drug products sterilized by Information and data on whether a where feasible, its use is preferable to
irradiation would be regarded as new particular drug can safely and relying solely on aseptic processing to
drugs within the meaning of section effectively be sterilized by irradiation ensure sterility (Ref. 5). Other
201(p) of the Federal Food, Drug, and are available in the scientific literature advantages to irradiation sterilization of
Cosmetic Act (FD&C Act), which would (Ref. 1). The United States drugs include low chemical reactivity;
mean that an effective new drug Pharmacopeial Convention (USP) has the very low rise in temperature
application would be required for such provided guidance on irradiation associated with radiation, which allows
products. sterilization of drug products since 1965
In 1996, FDA proposed to revise the for its use on heat-sensitive products;
(Refs. 1 and 3). This includes chapter that irradiation sterilization has fewer
statement and consolidate it with <1229> on ‘‘Sterilization of Compendial
similar provisions into a single list of process variables than other methods,
Articles,’’ which sets forth principles which translates into fewer sterility
drugs that have been determined by that may be applied to the sterilization
previous rulemaking procedures to be rejections; and that radiation does not
of compendial and non-compendial leave behind any sterilant residuals
new drugs within the meaning of drug products, and chapter <1229.10>
section 201(p) of the FD&C Act (61 FR (Refs. 1 and 6).
on ‘‘Radiation Sterilization,’’ which sets
29502 at 29503 to 29504 (June 11, forth guidelines on validation of C. The OTC Drug Monograph System
1996)). The Agency proposed to remove sterilization by irradiation (Refs. 3 and and Current Good Manufacturing
any existing background information 4). The American National Standards Practices
describing the Agency’s basis for Institute, the Association for the
determination of new drug status from Advancement of Medical The OTC Drug Review was
the regulatory text. Instrumentation, ASTM International, established to evaluate the safety and
In 1997, FDA finalized these and the International Organization for effectiveness of OTC drug products
provisions, now located in 21 CFR Standardization (ISO) have also marketed in the United States before
310.502, entitled ‘‘Certain drugs published standards on the irradiation May 11, 1972. As set forth in 21 CFR
accorded new drug status through of medical products, including drugs 330.10, it is a multiphase public
rulemaking procedures.’’ (62 FR 12084 (Ref. 1). ISO standard 11137, which sets rulemaking process (each phase
at 12084 (March 14, 1997).) Paragraph forth several methods that can be used requiring a Federal Register
310.502(a) sets forth a list of drugs that to determine the appropriate radiation publication) resulting in the
have been determined by rulemaking dose for health care products, was first establishment of monographs for OTC
procedures to be ‘‘new drugs’’ within published in 1984 2 (Ref. 1). therapeutic drug classes. OTC drug
the meaning of section 201(p) of the USP chapter <1229.10> states that the monographs, which can be found in
FD&C Act. Included on the list is methods set forth in ISO 11137 typically
sterilization of drugs by irradiation Title 21, chapter I, subchapter D of the
guide the choice of radiation dose (Ref. Code of Federal Regulations, cover
(§ 310.502(a)(11) (21 CFR 3). Relevant factors include a drug’s pre-
310.502(a)(11)). Because this regulation acceptable ingredients, doses,
sterilization level of microbial
reflects an FDA determination that the formulations, other conditions, and
contamination (sometimes referred to as
drugs on the list are ‘‘new drugs,’’ an its bioburden) and the desired sterility labeling for certain OTC drugs. A
NDA or ANDA must be submitted and assurance level (Ref. 1). Once the dose company can legally make and market
approved by FDA before they can be an OTC product that meets each of the
marketed legally. For a non-prescription 2 ISO 11137–1 specifies standards for the conditions contained in an applicable
drug that could otherwise be legally development, validation, and routine control of a monograph and, in addition, each of the
marketed without an approved NDA or radiation sterilization process for medical devices, general conditions set forth in § 330.1.
while ISO 11137–2 specifies dose establishment
and dose audit methods and defines product family
Among the general conditions that
daltland on DSKBBV9HB2PROD with PROPOSALS
1 Available at: https://www.loc.gov/item/ approaches for dose establishment and dose audits. apply to all drug products marketed
fr020231/. A month later, this provision was Additional target sterilization doses are covered in under the OTC Drug Review is the
included at § 3.45 in the republication of chapter 21 ISO Technical Information Report (TIR) 13004. requirement set forth in § 330.1(a) that
of the Code of Federal Regulations in the Federal Neither ISO 11137–2 nor TIR 13004 is explicitly
Register. See 20 FR 9525 at 9554 (December 20, limited to medical devices. In addition, both ISO they be manufactured in compliance
1955), available at: http://cdn.loc.gov/service/ll/ 11137–2 and ISO TIR 13004 reference ISO 11137– with current good manufacturing
fedreg/fr020/fr020246/fr020246.pdf. In 1975, FDA 1 as ‘‘indispensable for the application of this practices, as established by parts 210
republished and re-codified the rule at 21 CFR document.’’ This implies that the concepts in ISO
200.30. See 40 FR 13996 at 13997 (March 27, 1975), 11137–1 may be applied to sterilization of drug
and 211 of this chapter. The CGMP
available at: https://www.loc.gov/item/fr040060/. products. requirements in parts 210 and 211
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![Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules 46125
adjustment for inflation is $150 million, Product. This proposed rule would not Table 1 summarizes our estimate of
using the most current (2017) Implicit result in an expenditure in any year that the annualized costs and benefits of the
Price Deflator for the Gross Domestic meets or exceeds this amount. proposed rule.
TABLE 1—SUMMARY OF BENEFITS, COSTS AND DISTRIBUTIONAL EFFECTS OF THE RULE
[$ million]
Units
Primary Low High
Category Discount Period Notes
estimate estimate estimate Year rate covered
dollars (%) (years)
Benefits:
Annualized, Monetized $millions/year .................. $0.06 $0.05 $0.28 2016 7 10 Benefits are cost savings.
0.05 0.04 0.24 2016 3 10 Benefits are cost savings.
Annualized Quantified ........................................... .................. .................. .................. 2016 7 10
.................. .................. .................. 2016 3 10
Qualitative
Costs:
Annualized Monetized $millions/year ................... 0.00 0.00 0.00 2016 7 10 Costs total less than $100.
0.00 0.00 0.00 2016 3 10 Costs total less than $100.
Annualized Quantified ........................................... .................. .................. .................. 2016 7 10
.................. .................. .................. 2016 3 10
Qualitative
Transfers:
Federal Annualized Monetized $millions/year ...... 0.14 0.14 0.14 2016 7 10 User Fee.
0.12 0.12 0.12 2016 3 10 User Fee.
From: To:
Other Annualized Monetized $millions/year ......... .................. .................. .................. 2016 7 10
.................. .................. .................. 2016 3 10
From: To:
Effects:
State, Local or Tribal Government: None
Small Business: None
Wages: None
Growth: None
Because the proposed rule will repeal Table 2 presents a summary of the E.O. from this deregulatory action every 10
an outdated regulation and generate net 13771 impacts of the proposed rule over years.
cost savings, we consider this action a an infinite horizon. For this estimate,
deregulatory action under E.O. 13771. we assume that one sponsor will benefit
TABLE 2—E.O. 13771 SUMMARY
[In $ millions 2016 dollars, over an infinite horizon]
Primary Lower bound Upper bound Primary Lower bound Upper bound
(7%) (7%) (7%) (3%) (3%) (3%)
Present Value of Costs ............................ $0.00 $0.00 $0.00 $0.00 $0.00 $0.00
Present Value of Cost Savings ................ 0.97 0.83 4.37 1.84 1.58 8.30
Present Value of Net Costs ..................... (0.97) (0.83) (4.37) (1.84) (1.58) (8.30)
Annualized Costs ..................................... $0.00 $0.00 $0.00 $0.00 $0.00 $0.00
Annualized Cost Savings ......................... $0.07 $0.06 $0.31 $0.06 $0.05 $0.25
Annualized Net Costs .............................. (0.07) (0.06) (0.31) (0.06) (0.05) (0.25)
We have developed a comprehensive VI. Analysis of Environmental Impact VII. Paperwork Reduction Act of 1995
Economic Analysis of Impacts that
assesses the impacts of the proposed We have determined under 21 CFR This proposed rule refers to
daltland on DSKBBV9HB2PROD with PROPOSALS
rule. The full analysis of economic 25.30(h) and 25.31(a) that this action is previously approved collections of
impacts is available in the docket for of a type that does not individually or information that are subject to review by
this proposed rule (Ref. 8) and at: cumulatively have a significant effect on the Office of Management and Budget
https://www.fda.gov/AboutFDA/ the human environment. Therefore, (OMB) under the Paperwork Reduction
ReportsManualsForms/Reports/ neither an environmental assessment Act of 1995 (44 U.S.C. 3501–3520). The
EconomicAnalyses/default.htm. nor an environmental impact statement collections of information resulting from
is required. compliance with CGMPs have been
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![46126 Federal Register / Vol. 83, No. 177 / Wednesday, September 12, 2018 / Proposed Rules
approved under OMB control number 5. FDA Guidance for Industry on ‘‘Sterile Dated: September 7, 2018.
0910–0139. Drug Products Produced by Aseptic Scott Gottlieb,
Processing—Current Good Commissioner of Food and Drugs.
VIII. Federalism Manufacturing Practice,’’ September
[FR Doc. 2018–19845 Filed 9–11–18; 8:45 am]
We have analyzed this proposed rule 2004; available at https://www.fda.gov/
downloads/drugs/guidance BILLING CODE 4164–01–P
in accordance with the principles set
forth in E.O. 13132. We have complianceregulatoryinformation/
determined that this proposed rule does guidances/ucm070342.pdf.
not contain policies that have 6. United States Pharmacopeial Convention ENVIRONMENTAL PROTECTION
(USP 40), Sterilization and Sterility AGENCY
substantial direct effects on the States,
Assurance of Compendial Articles
on the relationship between the <1211>, 2017. 40 CFR Part 261
National Government and the States, or 7. FDA Drug Safety Communication, ‘‘FDA
on the distribution of power and Requests Label Changes and Single-Use [EPA–R10–RCRA–2018–0538; SW–FRL–
responsibilities among the various Packaging for Some Over-the-Counter 9982–05—Region 10]
levels of government. Accordingly, we Topical Antiseptic Products to Decrease
conclude that the rule does not contain Risk of Infection,’’ November 13, 2013; Hazardous Waste Management
policies that have federalism available at https://www.fda.gov/Drugs/ System; Proposed Exclusion for
implications as defined in the E.O. and, DrugSafety/ucm374711.htm. Identifying and Listing Hazardous
consequently, a federalism summary 8. FDA Preliminary Regulatory Impact Waste
impact statement is not required. Analysis, Repeal of Regulation Requiring
an Approved New Drug Application for
AGENCY: Environmental Protection
IX. Consultation and Coordination With Drugs Sterilized by Irradiation; https:// Agency (EPA).
Indian Tribal Governments www.fda.gov/AboutFDA/ ACTION: Proposed rule and request for
We have analyzed this proposed rule ReportsManualsForms/Reports/ comment.
EconomicAnalyses/default.htm.
in accordance with the principles set SUMMARY: The Environmental Protection
forth in E.O. 13175. We have tentatively List of Subjects in 21 CFR Part 310 Agency (also, ‘‘the Agency’’ or ‘‘we’’ in
determined that the rule does not this preamble) is proposing to grant a
contain policies that would have a Administrative practice and
procedure, Drugs, Labeling, Medical petition submitted by Sandvik Special
substantial direct effect on one or more Metals (Sandvik), in Kennewick,
Indian Tribes, on the relationship devices, Reporting and recordkeeping
requirements. Washington to exclude (or ‘‘delist’’) up
between the Federal Government and
to 1,500 cubic yards of F006 wastewater
Indian Tribes, or on the distribution of Therefore, under the Federal Food, treatment sludge per year from the list
power and responsibilities between the Drug, and Cosmetic Act and the Public of federal hazardous wastes.
Federal Government and Indian Tribes. Health Service Act and under authority The Agency is proposing to grant the
The Agency solicits comments from delegated to the Commissioner of Food petition based on an evaluation of
tribal officials on any potential impact and Drugs, it is proposed that 21 CFR waste-specific information provided by
on Indian Tribes from this proposed
part 310 be amended as follows: Sandvik. This proposed decision, if
action.
finalized, conditionally excludes the
X. References PART 310—NEW DRUGS petitioned waste from the requirements
The following references are on of hazardous waste regulations under
display in the Dockets Management ■ 1. The authority citation for part 310 the Resource Conservation and
Staff (see ADDRESSES) and are available continues to read as follows: Recovery Act.
for viewing by interested persons Authority: 21 U.S.C. 321, 331, 351, 352, We conclude that Sandvik’s
between 9 a.m. and 4 p.m., Monday 353, 355, 360b–360f, 360j, 360hh–360ss, petitioned waste is nonhazardous with
through Friday; they are also available 361(a), 371, 374, 375, 379e, 379k–1; 42 U.S.C. respect to the original federal listing
electronically at https:// 216, 241, 242(a), 262. criteria and that there are no other
www.regulations.gov. FDA has verified factors (including additional
■ 2. In § 310.502, revise paragraph (a) constituents) other than those for which
the website addresses, as of the date this introductory text and remove and
document publishes in the Federal the waste was listed that would warrant
reserve paragraph (a)(11) to read as retaining the waste as a hazardous
Register, but websites are subject to follows:
change over time. waste. Subject to state-only
§ 310.502 Certain drugs accorded new requirements within the state of
1. Jacobs, G., ‘‘Validation of the Radiation
Sterilization of Pharmaceuticals.’’ In: J. drug status through rulemaking Washington, or federally-authorized or
Agalloco and F. J. Carleton (eds.), procedures. state-only requirements in other states
Validation of Pharmaceutical Processes where the subject wastes may be
(3rd Ed.) Informa USA, New York, 2007.
(a) The drugs listed in this paragraph disposed of, Sandvik’s petitioned waste
2. Microbiology Sub-Committee, Radiation have been determined by rulemaking may be disposed of in a Subtitle D
Sterilization Task Force, Parenteral Drug procedures to be new drugs within the landfill which is permitted, licensed, or
Association, Technical Report No. 11, meaning of section 201(p) of the Federal registered by a State to manage
‘‘Sterilization of Parenterals by Gamma Food, Drug, and Cosmetic Act. An industrial solid waste.
Radiation,’’ Journal of Parenteral Science approved new drug application under
daltland on DSKBBV9HB2PROD with PROPOSALS
and Technology, 42 (3S), 1988, available DATES: Comments must be received on
section 505 of the Federal Food, Drug,
at: https://store.pda.org/ProductCatalog/ and Cosmetic Act and part 314 of this or before October 12, 2018. Requests for
Product.aspx?ID=1170. an informal hearing must reach the EPA
3. United States Pharmacopeial Convention chapter is required for marketing the
following drugs: by September 27, 2018.
(USP 40), Radiation Sterilization
<1229.10>, 2017. ADDRESSES: Submit your comments,
* * * * *
4. United States Pharmacopeial Convention identified by Docket ID No. EPA–R10–
(USP 40), Sterilization of Compendial (11) [Reserved] RCRA–2018–0538 by one of the
Articles <1229>, 2017. * * * * * following methods:
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Document Created: 2018-09-12 02:07:13
Document Modified: 2018-09-12 02:07:13
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Proposed Rules | |
| Action | Proposed rule. | |
| Dates | Submit either electronic or written comments on the proposed rule by November 13, 2018. | |
| Contact | Sudha Shukla, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5198, Silver Spring, MD 20993-0002, 301- 796-3345. | |
| FR Citation | 83 FR 46121 | |
| RIN Number | 0910-AH47 | |
| CFR Associated | Administrative Practice and Procedure; Drugs; Labeling; Medical Devices and Reporting and Recordkeeping Requirements |
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