21M9
`
`Federal Register I Vol. 47, No. 96 / Tuesday,' May 18, 1982 1 Notices
`
`|
`
`American Bank of Arlington, Arlington,
`Texas. Comments on this application
`must be received not later than June 12,
`1982.
`C. Federal Reserve Bank of San
`Francisco (Harry W. Green, Vice
`President) 400 Sansome Street, San
`Francisco, California 94120:
`1. AmBank Holding Company,
`Phoenix, Arizona, to become a bank
`holding company by acquiring 99.3
`percent of the voting shares of American
`Bank, Phoenix, Arizona. Comments on
`this application must be received not
`later than June 12, 1982.
`2. MBC Corp., Modesto, California; to
`become a bank holding company by
`acquiring 100 percent of the voting
`shares of Modesto Banking Company,
`Modesto, California. Comments on this
`application must be received not later
`than June 9, 1982.
`3. Professional Bancorp, Santa
`Monica, California; to become a bank
`holding company by acquiring 100
`percent of the voting shares of First
`Professional Bank of Los Angeles, Santa
`Monica, California. Comments on this
`application must be received not later
`than June 9,1982.
`4. TriCo Bancshares, Chico,
`California; to become a bank holding
`company by acquiring 100 percent of the
`voting shares of Tri-Counties Bank,
`Chico, California. Comments on this
`application must be received not later
`than June 11, 1982.
`C. Secretary, Board of Governors of
`the Federal Reserve System,
`Washington. D.C. 20551:
`1. NBC Bancorporation, Inc., Newport,
`Minnesota; to become bank a holding
`company by acquiring 100 percent of the
`voting shares of National Bank of
`Commerce in Mankato, Mankato,
`Minnesota. Comments on this
`application must be received not later
`than June 11, 1982.
`2. Town & Country Bancshares, Inc.,
`Newport, Minnesota; to become a bank
`holding company by acquiring 100
`percent of the voting shares of Town
`and Country Bank-Maplewood,
`Maplewood, Minnesota. Comments on
`this application must be received not
`later than June 11, 1982.
`Board of Govemors of the Federal Reserve
`System, May 12, 1982.
`Dolores S. Smith,
`Assistant Secretary of the Board.
`[FR Dom. 82-13308 Filed 5-17-82; 4S aml
`BIL.NG COOl 6210-01-M
`
`DEPARTMENT OF HEALTH AND
`HUMAN SERVICES
`Food and Drug Administration
`Consumer Participation; Open
`Meetings
`AGENCY. Food and Drug Administration.
`ACTION: Notice.
`
`SUMMARY: The Food and Drug
`Administration (FDA) is announcing the
`following consumer exchange meetings:
`Atlanta District Office, Chaired by John
`Turner, District Director.
`DATE: Thursday, May 27, 1982,10:30 a.m.
`ADDRESS: Brighton Multipurpose Center,
`outside Birmingham, Alabama.
`FOR FURTHER INFORMATION CONTACT.
`Janice Moton, Consumer Affairs Officer,
`Food and Drug Administration, 1182 W.
`Peachtree St. NW., Atlanta, GA 30309,
`404-881-7355.
`Cincinnati District Office, Chaired by
`James C. Simmons, District Director.
`DATE: Wednesday, June 9, 1982, 1 p.m.
`ADDRESS: Rm. 504, The Federal Bldg.,
`200 W. Second St., Dayton, OH 45402.
`FOR FURTHER INFORMATION CONTACT.
`Ruth E. Weishelt, Consumer Affairs
`Officer, Food and Drug Administration,
`Rm. 463, 601 Rockwell Ave., Cleveland.
`OH 44114, 216-522-4844.
`Cincinnati District Office, Chaired by
`James C. Simmons, District Director.
`DATE: Thursday, June 10, 1982,1:30 p.m.
`ADDRESS: Rm. 5525A, Federal Bldg., 550
`Main St., Cincinnati, OH 45202.
`FOR FURTHER INFORMATION CONTACT.
`Ruth E. Weisheit, Consumer Affairs
`Officer, Food and Drug Administration,
`Rm. 463, 601 Rockwell Ave., Cleveland,
`OH. 44114, 216-522-4844.
`Philadelphia District Office, Chaired
`by Loren Johnson, District Director.
`DATE: Wednesday, June 16, 1982, 1 to 3
`p.m.
`ADDRESS: Win. H. Green, Federal Bldg.,
`Rm. 7306, 6th and Arch Sts.,
`Philadelphia, PA 19106.
`FOR FURTHER INFORMATION CONTACT.
`Theresa A. Young, Consumer Affairs
`Technician, Food and Drug
`Administration, 2d and Chestnut Sts.,
`Philadelphia, PA 19106, 215-597-0837.
`Chicago District Office, Chaired by
`Mary K. Ellis, District Director.
`DATE: Tuesday, June 22, 1982, 1:30-3:30
`p.m.
`ADDRESS: Food and Drug
`Administration, Rm. 1204, 433 W. Van
`Buren, Chicago, IL 60607.
`FOR FURTHER INFORMATION CONTACT.
`Darlene M. Bailey, Consumer Affairs
`Officer, Food and Drug Administration,
`
`433 W. Van Buren, Chicago, IL 60607,
`312-353-7126.
`SUPPLEMENTARY INFORMATION: The
`purpose of these meetings is to
`encourage dialogue between consumers
`and FDA officials, to identify and set
`priorities for current and future health
`concerns, to enhance understanding and
`exchange information between local
`consumers and FDA's District Offices,
`and to contribute to the agency's
`policymaking decisions on vital issues.
`Dated: May 13,1982.
`William F. Randolph.
`Acting Associate Commissioner for
`Regulatory Aflair.
`Fi Dm. 62-13472 Filed 5-17-42; &45 am]
`BILLING CODE 41601-U
`
`[Docket Nos. 79N-0339 and 79N-0340, DESI
`Nos. 8615,9152,9188,50168, and 102101
`
`Certain Ophthalmic Combination
`Drugs Containing a Steriod and Anti.
`Infective(s) for Human Use; Drug
`Efficacy Study Implementatlon;
`Amendment
`AGENCY: Food and Drug Administration
`(FDA).
`ACTION: Notice.
`
`SUMMARY: This notice amends two
`previous Federal Register notices
`concerning ophthalmic combination
`drug products containing a steroid and
`one or more anti-infective agents. This
`amendment requires revised labeling
`which more precisely states the
`conditions of use for which such drugs
`are safe and effective. The notice also
`states the rationale for regarding these
`drugs as safe and effective.
`DATES: Amendments or supplements to
`approved applications (NDA's, ANDA's,
`or antibiotic forms) due on or before July
`19, 1982. Revised labeling must be put
`into use on or before November 15, 1982.
`ADDRESSES: Communications in resonse
`to this notice should be identified with
`the appropriate DESI number, directed
`to the attention of the appropriate office
`named below, and addressed to the
`Food and Drug Administration, 5600
`Fishers Lane, Rockville, MD 20857.
`Supplements to full new drug
`applications (identify with NDA
`number); Division of Anti-Infective Drug
`Products (HFD-140), Rm. 12B-45, Bureau
`of Drugs.
`Supplements to approved abbreviated
`new drug applications (identify with
`ANDA number): Division of Generic
`Drug Monographs (HFD-530), Bureau of
`Drugs.
`
`APOTEX 1034, pg. 1
`
`

`

`Federal Register / Vol. 47, No. 96 / Tuesday, May 18, 1982 / Notices
`
`21297
`
`Amendments to approved antibiotic
`forms (identify with form number);
`Antibiotic Drug Review Branch (HFD-
`535), Bureau of Drugs.
`Request for opinion of the
`applicability of this notice to a specific
`product: Division of Drug Labeling
`Compliance (HFD-310), Bureau of Drugs.
`Requests for a copy of the Health
`Reserach Group comments and/or
`FDA's response (identify with Docket
`Nos.): Dockets Management Branch
`(HFA-305), Rm. 4-65.
`Other communications regarding this
`notice: Drug Efficacy Study
`Implementation Project Manager (I-FDM-
`501), Bureau of Drugs.
`FOR FURTHER INFORMATION CONTACT.
`Douglas I. Ellsworth, Bureau of Drugs
`(HFD-32], Food and Drug
`Administration, 5600 Fishers Lane,
`Rockville, MD 20857, 301-443-3650.
`SUPPLEMENTARY INFORMATION: In two
`notices published in the Federal Register
`of August 29, 1980 (45 FR 57776 and 45
`FR 57780), FDA announced its
`conclusion that certain ophthalmic
`combination drugs containing a steroid
`and one or more anti-infective agents
`are effective. The notices also set forth a
`general outline for labeling of the
`effective products as a condition for
`marketing and approval.
`On December 4, 1980, the Health
`Research Group (HRG), 2000 P St. NW.,
`Washington, D.C. 20036, wrote to the
`Commissioner of Food and Drugs
`concerning the agency's conclusion for
`this class of combinaton drug products.
`HRG asked that the decision be
`reconsidered, alleging that no adequate
`and well-controlled clinical trials are
`available to support the effectiveness of
`all ingredients in these combinations.
`Copies of HRG's letter and the FDA
`response have been placed in the docket
`of these proceedings. Copies are
`available from the Dockets Management
`Branch (address given above)
`As a result of the HRG letter, the
`Bureau of Drugs reevaluated the August
`29, 1980 notices and the record of this
`proceeding. Based upon this
`reevaluation, the Director of the Bureau
`has concluded (1) that the basic finding
`stated in those notices that these drug
`products are safe and effective should
`be reaffirmed, (2) that the rationale for
`concluding that these combination
`products are effective was not stated in
`the notices and should be stated clearly
`to avoid further confusion, and (3] that
`the labeling for these drug products, as
`described in the 1980 notices, should be
`revised to state more precisely the
`conditions of use for which these
`products are safe and effective.
`
`Background
`As noted in the August 29, 1980
`notices, the ophthalmic steroid/anti-
`infective combination products covered
`by these notices were originally
`classified as possibly effective under the
`Drug Efficacy Study in a series of
`notices published in 1971 and 1972.
`Subsequently, the ophthalmic steroid/
`anti-infective combination drug products
`were exempted from the schedule
`established for completing the study (37
`FR 26643]. The products were exempted
`because of their potential effectiveness
`in the treatment of marginal keratitis
`secondary to staphylococcus
`blepharoconjunctivitis, vernal catarrh,
`and allergic conjunctivitis, and their
`frequent use postoperatively by
`ophthalmologists to reduce
`inflammatory reactions and prevent
`infection. The exemption was
`conditioned upon the commitment of
`manufacturers and distributors to
`conduct appropriate studies to establish
`which particular combinations and
`concentrations are effective for specific
`indications.
`In response to the exemption notice,
`several manufacturers submitted plans
`for studies. The agency determined that
`the studies as planned were inadequate
`to demonstrate that all active
`ingredients contributed to the
`effectiveness of the fixed-combination
`drug products. Because the sponsors
`were unable to develop appropriate
`protocols and because of controversy
`over the role of thse combination
`products in ophthalmology, the matter
`was presented to FDA's Ophthalmic
`Drugs Advisory Committee at a public
`meeting held May 8, 1973. Discussion
`centered on the safety of these products
`and the design of meaningful studies.
`The committee concluded that the data
`available to it were insufficient to make
`a decision on any of the issues
`presented and appointed a
`subcommittee to obtain additional
`information.
`The subcommittee then drafted a
`proposal for clinical studies. This
`proposal was sent to affected firms for
`comment, and on August 6, 1973, the
`Advisory Committee met in open
`session to discuss the proposal. In spite
`of extensive discussion and continued
`subcommittee deliberations, the
`Committee was unable to finalize a
`protocol.
`Therefore, the subcommittee proposed
`that manufacturers and distributors
`prepare a single document containing all
`available data pertaining to each
`indication outlined in the exemption
`notice. The subcommittee believed that
`this data search might provide sufficient
`
`evidence of effectiveness in lieu of new
`clinical studies. On November 2, 1973,
`the full Advisory Committee adopted the
`proposal, and representatives of the
`pharmaceutical industry agreed to
`conduct the joint data search. On
`September 27, 1974, the industry task
`force submitted its data, which
`consisted of.published studies (domestic
`and foreign with translations),
`unpublished studies, and domestic and
`foreign adverse reaction surveys.
`These data then underwent thorough
`review by agency staff with input from
`the Advisory Committee and the Bureau
`of Drugs' Combination Drugs
`Committee, an internal staff committee
`established to evaluate products with
`respect to the agency's combination
`drug policy. The Advisory Committee
`reviewed the data and made
`recommendations at public meetings
`held November 4, 1974, November 3,
`1975, August 2, 1976, and November 7,
`1977, and the Combination Drugs
`Committee considered the matter at its
`meetings of August 27, 1977 and January
`18, 1978.
`With respect to safety, these reviews
`showed that the data from adverse
`reaction surveys and unpublished
`studies reveal a low number of adverse
`reactions, particularly when judged
`against the extensive use of these
`products. Adverse reaction rates, as
`estimated by the number of adverse
`reaction reports divided by the
`distribution of these drugs, were, if
`anything, lower for steroid/anti-
`infective combination products than for
`single-ingredient anti-infective
`ophthalmological products, possibly
`because of a therapeutic or prophylactic
`effect of the steroid component on
`sensitivity reactions to the anti-infective
`component. The safety data supported
`the conclusions that the most serious
`adverse reactions resulting from the
`combinations are those related to the
`steroid component (e.g., increase in
`intraocular pressure, scleral perforation,
`and exacerbation of certain infections),
`that these reactions are most commonly
`associated with long-term use, that they
`are best prevented by periodic
`examinations during treatment, and that
`the only incremental risk added by the
`anti-infective component is occasional
`sensitivity reactions.
`With respect to effectiveness, the
`Advisory Committee recommended that
`the agency review five potential
`indications for these combination
`.products: marginal keratitis secondary
`to Staphylococcus aureus,
`staphylococcal blepharoconjunctivitis,
`phylctenular keratoconjunctivitis, vernal
`catarrh, and allergic conjunctivitis
`
`APOTEX 1034, pg. 2
`
`

`

`21298
`
`Federal Register / Vol. 47, No. 96 / Tuesday, May 18, 1982 / Notices
`
`secondary to infection. These
`indications and their supporting
`evidence resulted from the Advisory
`Committee review and industry data
`search conducted In 1973 and 1974. The
`Bureau of Drugs' staff and its
`Combination Drugs Committee reviewed
`the submitted information and
`concluded that there were not at least
`two adequate and well-controlled trials
`demonstrating that both the steroid
`component and the anti-infective
`component contribute to the
`effectiveness of the combination in
`these conditions. There are studies
`showing that the combination is more
`effective than the antibiotic component
`alone. However, of two studies designed
`to show whether the combination is
`more effective than the steroid
`component alone, one failed to show
`any such advantage and the other
`suggested only a marginal advantage of
`the combination, namely in providing
`more rapid resolution of symptoms. The
`Combination Drugs Committee thus
`concluded that the effectiveness of these
`combinations in the above conditions
`can be attributed to the steroid
`component alone.
`The Combination Drugs Committee
`also noted, however, that these steroid-
`responsive conditions can be
`accompanied by bacterial infection or
`risk of infection, that bacterial
`overgrowth in the eye is catastrophic
`although fortunately rare, that animal
`studies using techniques to make the eye
`more susceptible to infection
`demonstrate that steroids can reduce
`resistance to infection and anti-infective
`agents can counteract this effect, and
`that it is medically reasonable to include
`both ingredients in a single preparation
`so that one drug does not wash out the
`other. For these reasons, the Committee
`recommended that steroid/anti-infective
`combination products should remain
`available under appropriate labeling
`and that the requirement for adequate
`and well-cohitrolled trials to
`demonstrate the contribution of each
`ingredient should be waived.
`This recommendation was discussed
`with the Advisory Committee at its
`meeting of November 7, 1977. The
`Advisory Committee believed that the
`specific indications noted previously
`were appropriate although it
`acknowledged that adequate and well-
`controlled trials showing that the anti-
`infective component contributes to the
`therapeutic effect in the routine
`management of these conditions are not
`available. After considerable discussion
`the Advisory Committee recommended
`a more general labeling indication for
`consideration by the Combination Drugs
`
`Committee: "For use in the treatment of
`ocular Inflammation where concurrent
`use of anti-infectives and steroids are
`indicated."
`This indication was considered by the
`Bureau staff and by the Combination
`Drugs Committee on January 18,1978.
`The conclusion was announced in the
`1980 notices that ophthalmic steroid/
`anti-infective combination products are
`considered safe and effective under a
`slightly modified general indication as
`follows: "A steroid/anti-infective
`combination is indicated in ocular
`inflammation when concurrent use of an
`antimicrobial is judged necessary." The
`notices also set forth class labeling that
`contained specific contraindications,
`warnings, and precautions. It is this
`decision and labeling statement that
`was challenged by the Health Research
`Group.
`Decision and Rationale
`The Dh-ector of the Bureau of Drugs
`has reviewed the record of this
`proceeding. On the basis of this review,
`the Director reaffirms that these
`combination products are safe and
`effective if properly labeled and that
`they meet the agency's policy with
`respect to combination drug products.
`The rationale for this conclusion was
`not published in the 1980 notices, nor is
`it adequately and completely articulated
`in the minutes of agency or advisory
`committee meetings. Furthermore, the
`Director finds that the labeling
`indication published in the 1980 notices
`is vague and does not adequately
`describe the conditions for which these
`products are considered safe and
`effective. Accordingly, the Director is
`announcing the rationale that supports
`the conclusion that these combination
`products are safe and effective and is
`also announcng a requirement for
`revised labeling.
`The Director concludes that the
`available data indicate that the
`effectiveness of combination steroid/
`anti-infective products in
`ophthalmologic inflammatory conditions
`is, in most cases, due to the steroid
`component. If the anti-infective
`component contributes to the
`effectiveness of the combination in the
`treatment of these conditions, e.g.,
`staphylococcal blepharoconjunctivitis or
`marginal keratitis, this alleged effect is
`sufficiently small or unpredictable that it
`has proven difficult to document in
`adequate and well-controlled trials. In
`some cases, however, steroid-responsive
`inflammatory conditions in the eye may
`be accompanied by frank bacterial
`infection or the risk of such infection. In
`such cases the safety of treatment with
`the steroid is increased by concomitant
`
`administration of an effective anti-
`infective agent to either treat or prevent
`accompanying bacterial infection.
`The addition of an anti-infective
`component to an ophthalmic steroid
`preparation is thus done to enhance the
`safety of the product when bacterial
`infection is present or possible. Such
`addition of an ingredierit to enhance the
`safety of a product is permitted under
`FDA's combination policy (21 CFR
`300.50(a)(1)).
`While clinical trials to demonstrate
`the contribution of each active
`ingredient are ordinarily required for
`combination drugs, clinical trials to
`prove the increased safety of the
`combination in the presence of bacterial
`infection are not feasible for both
`technical and ethical reasons. An
`extremely large trial would be necessary
`to determine the incidence of eye
`infections in patients undergoing
`treatment with steroids because such
`infections are relatively rare. It would
`also be ethically impossible to obtain a
`valid control group of patients with eye
`infections treated with steroids alone
`because of the risk of serious damage to
`the eye. For these reasons clincial trials
`to prove the increased safety of the
`combination in such circumstances are
`not deemed feasible or necessary.
`Labeling
`While the labeling indication in the
`1980 notices implied this rationale, the
`Director concludes that modification of
`that indication is necessary to reflect
`more accurately the appropriate
`indication. Furthermore, because the
`anti-infective component is added to
`treat or prevent specific infections, the
`labeling should state those common eye
`pathogens that are -generally sensitive to
`the particular anti-infective drug and
`those that are not. Accordingly, a
`requirement for revised labeling for
`combination steroid/anti-infective drug
`products is included in this notice.
`Manufacturers and distributors of the
`following drug products, which were
`evaluated as effective in the 1980
`notices, are required to revise their
`labeling in accordance with this
`amendment (antibiotic form numbers
`are stated as NDA numbers below):
`DESI 8615
`1. NDA 50-169; Cortisporin
`Ophthalmic Suspension containing
`neomycin sulfate, polymyxin B sulfate,
`and hydrocortisone; Burroughs
`Wellcome & Co., Inc., 3030 Cornwallis
`Rd., Research Triangle Park, NC 22709.
`2. NDA 50-202; Chloromycetin
`Hydrocortisone Ophthalmic Suspension
`containing chloramphenicol and
`
`APOTEX 1034, pg. 3
`
`

`

`Federal Register / Vol. 47, No. 96 / Tuesday, May 18, 1982 / Notices
`
`21299
`
`I
`
`hydrocortisone acetate; Parke-Davis,
`Division of Warner-Lambert Co., Morris
`Plains, NJ 07950.
`3. NDA 50-272; Achromycin
`Ophthalmic Ointment with
`Hydrocortisone containing tetracycline
`hydrochloride and hydrocortisone;
`Lederle Laboratories Division, American
`Cyanamid Co., Pearl River, NY 10965.
`4. NDA 50-362; Metimyd with
`Neomycin Ophthalmic Ointment
`containing neomycin sulfate,
`prednisolone acetate, and sodium
`suflacetamide; Schering Corp., Galloping
`Hill Rd., Kenilworth, NJ 07033.
`5. NDA 60-310; Neomycin Sulfate with
`Hydrocortisone Acetate Ophthalmic
`Ointment; Biocraft Laboratories, Inc., 92
`Route 42, East Patterson, NJ 07407.
`6. NDA 60-452; Isopto P-H-N
`Ophthalmic Suspension containing
`neomycin sulfate, polymyxin B sulfate,
`and hydrocortisone acetate; Alcon
`Laboratories, Inc., 2601 South Freeway,
`Fort Worth, TX 76134.
`7. NDA 60-464; Neo-Deltef Eye Drops
`containing neomycin sulfate and
`prednisolone; The Upjohn Co., 7171
`Portage Rd. Kalamazoo, MI 49001.
`8. NDA 60-788; Di-Hydrin Ophthalmic
`Solution containing neomycin sulfate,
`polymyxin B sulfate, and
`hydrocortisone; Broemmel
`Pharmaceuticals, 1235 Sutter St., San
`Francisco, CA 94109.
`9. NDA 60-790; Neo-Polycin HC
`Ophthalmic Ointment containing
`bacitracin, neomycin sulfate, polymyxin
`B sulfate, and hydrocortisone acetate;
`Pitman-Moore Co., Division of the Dow
`Chemical Co., 55 West Sheffield,
`Englewood, NJ 07631.
`10. NDA 60-925; Florinef-S
`Ophthalmic Ointment and Suspension
`containing neomycin sulfate, gramicidin,
`and fludrocortisone acetate; E. R. Squibb
`& Sons, Inc., P.O. Box 4000, Princeton, NJ
`08540.
`11. NDA 61-045; Neosone Ophthalmic
`Ointment containing neomycin sulfate
`and cortisone acetate; The Upjohn Co.
`12. NDA 61-075; Hydrocortisone-
`Neomycin Ophthalmic Ointment
`containing neomycin sulfate and
`hydrocortisone acetate; Day-Baldwin,
`Inc., 1460 Chestnut Ave., Hillside, NJ
`07205.
`13. NDA 61-107; Neomycin Sulfate
`with Hydrocortisone Acetate
`Ophthalmic Ointment; Kasco
`Laboratories, Inc., Cantiaque Rd., P.O.
`Box 73, Hicksville, NY 11802.
`DES1 9152
`1. NDA 61-016; Terra-Cortril
`Ophthalmic Suspension containing
`oxytetracycline hydrochloride and
`hydrocortisone acetate; Pfizer
`Laboratories, Division of Charles Pfizer
`
`& Co., Inc., 235 East 42d St., New York,
`NY 10017.
`DES! 9188
`1. NDA 50-322; Neo-Decadron
`Ophthalmic Solution containing
`dexamethasone sodium phosphate and
`neomycin sulfate; Merck Sharp &
`Dohme, Division Merck & Co., Inc., West
`Point, PA 19486.
`2. NDA 50-324; Neo-Decadron
`Ophthalmic Ointment containing
`dexamethasone sodium phosphate and
`neomycin sulfate; Merck Sharp &
`Dohme.
`3. NDA 50-378; Neo-Hydeltrasol
`Ophthalmic Ointment containing
`prednisolone sodium phosphate and
`neomycin sulfate; Merck Sharp &
`Dohme.
`4. NDA 50-379; Neo-Hydeltrasol
`Ophthalmic Solution containing
`prednisolone sodium phosphate and
`neomycin; Merck Sharp & Dohme.
`5. NDA 60-188; Cor-Oticin Ophthalmic
`Suspension containing hydrocortisone
`acetate and neomycin sulfate; Maurry
`Biological Co., Inc., 6109 South Western
`Ave., Los Angeles, CA 90047.
`6. NDA 60-442; Neo-Aristocort
`Ophthalmic Ointment containing
`triamcinolone acetonide and neomycin
`sulfate; Lederle Laboratories.
`7. NDA 60-610; Neo-Cortef
`Ophthalmic Ointment containing
`hydrocortisone acetate and neomycin
`sulfate; The Upjohn Co.
`8. NDA 60-612; Neo-Cortef Eye Drops
`containing hydrocortisone acetate and
`neomycin sulfate; The Upjohn Co.
`9. NDA 60-645; Neo-Medrol
`Ophthalmic Ointment containing
`methylprednisolone and neomycin
`sulfate; The Upjohn Co.
`10. NDA 61-037; Neo-Delta-Cortef
`Ophthalmic Ointment containing
`hydrocortisone acetate and neomycin
`'sulfate; The Upjohn Co.
`11. NDA 61-039; Neo-Delta-Cortef
`Ophthalmic Ointment containing
`prednisolone acetate and neomycin
`sulfate; The Upjohn Co.
`DESI 10210
`1. NDA 10-210; Metimyd Ophthalmic
`Susension, each milliliter containing 5
`mg prednisolone acetate and 100 mg
`sodium sulfacetamide; Schering Corp.
`The following drug products were
`listed in one notice (45 FR 57776) as
`lacking substantial evidence of
`effectiveness because they contained
`less than 10,000 units of polymyxin B.
`The notice provided that if the
`manufacturers reformulated these
`products to contain no less than 10,000
`units of polymyxin B, the products
`would be regarded as effective when
`labeled as described in thie notice.
`
`These products have since been
`reformulated and the reformulated
`products are regarded as effective.
`Manuafacturers and distributors of
`these reformulated products are also
`required to revise their labeling in
`accordance with this amendment.
`
`DESI 8615
`1. NDA 50-081; Predmycin-P Liquifilm
`Ophthalmic Suspension containing
`neomycin sulfate, polymyxin B sulfate,
`and prednisolone acetate; Allergan
`Pharmaceuticals, 1000 South Grand
`Ave., Santa Ana, CA 92705.
`2. NDA 50-201; Ophthocort
`Ophthalmic Ointment containing
`chloramphenicol, polymyxin B sulfate,
`and hydrocortisone acetate; Parke-
`Davis.
`3. NDA 60-731; Bacitracin-Polymyxin.
`Neomycin with Hydrocortisone
`Ophthalmic Ointment containing zinc
`bacitracin, neomycin sulfate, polymyxin
`B sulfate, and hydrocortisone acetate;
`Kasco Laboratories, Inc.
`
`DESI 50168
`1. NDA 50-416; Cortisporin Ointment
`containing polymyxin B sulfate, zinc
`bacitracin, neomycin sulfate, and
`hydrocortisone; Burroughs Wellcome &
`Co.
`Manufacturers or distributors of the
`following drug products, which were not
`listed in either of the 1980 notices, are
`also required to revise their labeling in
`accordance with this amendment:
`1. NDA 50-023; Maxitrol Suspension
`containing neomycin sulfate, ploymyxin
`B sulfate, and dexamethasone, Alcon
`Laboratories, Inc.
`2. NDA 50-065; Maxitrol Ointment
`containing neomycin sulfate, ploymyxin
`B sulfate, and dexamethasone; Alcon
`Laboratories, Inc.
`3. NDA 61-188; Chloroptic-P Ointment
`containing chloramphenicol and
`prednisolone; Allergan Pharmaceuticals.
`4. ANDA 87-547; Isoptocetapred
`containing prednisolone acetate and
`sodium sulfacetamide; Alcon
`Laboratories, Inc.
`All Steroid/anti-infective combination
`drug products recommended for
`ophthalmic use that are the subject of an
`approved new drug application or are
`eligible for certification or release,
`whether or not listed above, are subject
`to this notice. All manufacturers and
`distributors are required to revise the
`labeling of such products in accordance
`with this amendment.
`
`APOTEX 1034, pg. 4
`
`

`

`2130U
`
`Federal Register / Vol. 47, No. 96 / Tuesday, May 18, 1982 / Notices
`
`CONDITIONS FOR MARKETING AND
`APPROVAL
`The conditions for marketing and
`approval stated in the August 29, 1980
`notices are amended to read as follows:
`I. Steroid/Anti-Infective Combination
`Drug Products for Ophthalmic Use
`Containing One or More Antibiotic
`Components
`[Subject to Section 507 of the Federal
`Food, Drug, and Cosmetic Act (21 U.S.C.
`357)) (see 45 FR 57776) (DESI Nos. 8615,
`9152, 9188, and 50168).
`Batches of such drugs with labeling
`not in accordance with the "Labeling
`Requirement" listed below will no
`longer be acceptable for certification or
`release after November 15, 1982.
`II. The Combination of 5 mg
`Prednisolone Acetate and 100 mg
`Sodium Sulfacetamide for Ophthalmic
`Use
`(Subject to Section 505 of the Act (21
`U.S.C. 355)) (see 45 FR 57780) (DESI
`10210).
`Such drugs are regarded as new drugs
`(21 U.S.C. 321(p)). Supplemental new
`drug applications are required to revise
`the labeling in and to update previously
`approved applications providing for
`such drugs. An approved new drug
`application is a requirement for
`marketing such drug products.
`In addition to the product specifically
`named above, this notice applies to any
`drug product that is not the subject of an
`approved new drug application and is
`identical to the product named above. It
`may also be applicable, under 21 CFR
`310.6, to a similar or related drug
`product that is not the subject of an
`approved new drug application. It is the
`responsibility of every drug
`manufacturer or distributor to review
`this notice to determine whether it
`covers any drug product that the person
`manufactures or distributes. Such
`person may request an opinion of the
`applicability of this notice to a specific'
`drug product by writing to the Division
`of Drug Labeling Compliance (address
`given above).
`A. Effectiveness classification. The
`Food and Drug Administration has
`reviewed all available evidence and
`concludes that the drug product is
`effective for the indication described in
`the "Labeling Requirement" listed
`below.
`B. Conditions for approval and
`marketing. The Food and Drug
`Administration is prepared to approve
`abbreviated new drug applications and
`abbreviated supplements to previously
`approved new drug applications under
`conditions described herein.
`
`1. Form of drug. The drug product
`contains 5 mg prednisolone acetate and
`100 mg sodium sulfacetamide, and is in a
`form suitable for ophthalmic
`administration.
`2. Labeling conditions, a. The label
`bears the statement, "Caution: Federal
`law prohibits dispensing without
`prescription."
`b. The drug is labeled to comply with
`all requirements of the act and
`regulations, and the labeling bears
`adequate information for safe and
`effective use of the drug. The labeling
`conforms to the "Labeling Requirement"
`listed below.
`3. Marketing status, a. Marketing of
`such drug products that are now the
`subject of an approved or effective new
`drug application may be continued
`provided that, on or before July 19, 1982,
`the holder of the application has
`submitted (i) a supplement for revised
`labeling as needed to be in accord with
`the labeling conditions described in this
`notice, and complete container labeling
`if current container labeling has not
`been submitted, and (ii) a supplement to
`provide updating information with
`respect to items 6 (components), 7
`(composition), and 8 (methods, facilities,
`and controls) of new drug application
`form FD-356H (21 CFR 314.1(c)) to the
`extent required in abbreviated
`application (21 CFR 314.1(f)), if such
`information has not previously been
`submitted. Revised labeling in accord
`with the labeling conditions described in
`this notice must be put into use on or
`before November 15, 1982. The revised
`labeling may be put into use before
`approval of the supplemental new drug
`applications, as provided for in 21 CFR
`314.8(d) and (e).
`b. Approval of an abbreviated new
`drug application (21 CFR 314.1(f)) must
`be obtained before marketing such
`products. An abbreviated application
`will be acceptable only for the
`formulation containing 5 mg
`prednisolone acetate and 100 mg sodium
`sulfacetamide. Any new combination
`requires a full new drug application and
`appropriate studies. Marketing before
`approval of a new drug application will
`subject such products, and those
`persons who caused the products to be
`marketed, to regulatory action.
`III. Labeling Requirement
`A. The indication is as follows:
`For steroid-responsive inflammatory
`ocular conditions for which a
`corticosteroid is indicated and where
`bacterial infection or a risk of bacterial
`ocular infection exists.
`Ocular steroids are indicated in
`inflammatory conditions of the
`palpebral and bulbar conjunctiva,
`
`cornea, and anterior segment of the
`globe where the inherent risk of steroid
`use in certain infective conjunctivitides
`is accepted to obtain a diminution in
`edema and inflammation. They are also
`indicated in chronic anterior uveitis and
`corneal injury from chemical radiation,
`thermal bums, or penetration of foreign
`bodies.
`The use of a combination drug with an
`anti-infective component is Indicated
`where the risk of infection is high or
`where there is an expectation that
`potentially dangerous numbers of
`bacteria wkll be present in the eye.
`The particular anti-infective drug(s) in
`this product is [are] active against the
`following common bacterial eye
`pathogens: [insert appropriate
`organisms from the list in the Appendix
`to this notice].
`I The product does not provide
`adequate coverage against: [insert
`appropr