Downloaded from http://www.everyspec.com
`
`FED. STD. NO. 285A
`October
`19, 1976
`SUPERSEDING
`ht.
`Fed. St&No.
`July 21,
`1971
`
`00285
`
`FEDERAL
`
`STANDARD
`
`CAPSULES
`
`(FOR MEDICINAL
`
`PURPOSES)
`
`by the Commissioner,
`standard was approved
`This
`Federal
`Supply Service,
`General
`Services
`Administra-
`tion,
`for
`the use of all Federal
`agencies.
`
`S1. Purpose
`and scope.
`capsules
`ments
`for
`filled
`for oral
`administration.
`
`standard
`This
`in the dispensing
`
`describes
`of medicinal
`
`the general
`substance(s)
`
`require-
`
`S2. Classification.
`numbers,
`shapes,
`
`shall be of the following
`Capsules
`grades,
`and classes:
`
`types,
`
`size,
`
`Types
`
`and size numbers
`
`of capsules.
`
`Type
`
`I
`
`- Hard.
`
`Size No. 000
`Size No.
`00
`Size No. O
`Size No.
`1
`Size No. 2
`Size No.
`3
`Size No.
`4
`Size No.
`5
`Special,
`as specified.
`
`Type II - Soft.
`
`in the
`specified
`shallbe
`type II capsules
`for
`Dimensions
`document.
`procurement
`When not specified,
`the dimensions
`shall be those which are
`commercially
`supplied
`for
`the item.
`
`FSC 6505
`
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`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 1/20
`
`

`

`Downloaded from http://www.everyspec.com
`
`~h2F~
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`2
`“.
`
`/-
`Convent ier]al.-—---.
`~..-
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`— -.,
`
`I -“-
`
`--1”
`
`.;])~rf[:.
`
`b.
`
`Bullet -1ike.
`
`Shape
`
`co
`
`Elliptical
`
`Shape
`
`d.
`
`Oblong .—
`
`Shape
`
`e.
`
`Round —-–
`
`(oval)-—–
`
`!
`
`LT;’—- .
`
`\
`1
`
`‘- ‘“
`D
`-----.. 0
`- K-n)
`
`Shape
`
`f.
`
`Tapered ends
`
`Shape
`
`13” Special, as
`
`Grades
`
`of’
`
`transparency.
`
`l
`
`specified.
`
`Grade A.
`Grade B.
`Grade C.
`Grade i).
`
`Opaque.
`Clear.
`Combination.
`Special, as
`
`specified.
`
`Classec (form
`
`of fill).
`
`Class 1.
`Class 2.
`Class 3.
`class 4.
`
`Powder.
`Liquid.
`Pellets.
`Special, as
`
`specified.
`
`53*
`
`Referenced documents.
`
`Star]dard. The following document, of’ the issue in
`S3.1
`effect on date of in’~itation for bide, or request for proposals,
`form a part of this standard:
`
`MILITARY STA1~DAH1~:
`
`MIL-STD-105
`
`Sampling
`Inspection
`
`and Tables
`Procedures
`by Attributes.
`
`for
`
`and Standards reqllired
`(Copies of Military Specifications
`by contractors ~n connection with specific procurement fUnctiOns
`should be obtair~ed from the procuring activity or as directed
`by the contractirjg officer. )
`
`Q
`
`?
`
`-
`
`—
`
`—
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 2/20
`
`

`

`‘\
`
`,’
`
`)
`
`Downloaded from http://www.everyspec.com
`
`—
`
`Fed.
`
`Stcje
`
`lie.
`
`b
`
`2Fl~A
`
`t
`
`u. s. :~p ARTMENT OF HEALTH, EDUCATION, AND WELFARE
`FOOD A;;Z DRLJG ADMINISTRATION
`
`~’ede:’alFood, Drug, and Cosmetic Act and
`Regulations
`Promulgated Thereunder.
`
`(Application for copies should be addressed to the Food
`and Drug Adrinistratiorl, U. S. Department of Health, Education,
`and Welfare, Washington, DC
`20204. )
`
`U. S. DEPARTMENT OF JUSTICE
`DRUG ENFORCEMENT ADMINISTRATION
`
`Implementing the Comprehensive Drug
`Regulations
`Abuse Prevention and Control Act of 1970.
`
`(Application for copies should be addressed to the Drug
`Enforcement Administration,
`Department of Justice
`P.O. Box 28083, Cent;al Station, Washirlgton, DC
`
`;0005.)
`
`U. S. PHARMACOPEIAL
`
`CONVENTION,
`
`INC.
`
`The United States Pharmacopoeia.
`
`(Application for copies should be addressed to the Mack
`18042.)
`Publishing Company, Easton, PA
`
`The National
`
`Formulary.
`
`(Application for copies should be addressed to the Mack
`Publishing Company, Easton, PA
`18042. )
`
`S4 . Definitions .
`
`S4
`Caosules.
`.1
`Cap
`one o
`s
`r mo~lnal
`with
`or without diluent
`solub
`le container (shel
`may c
`ontaln glycerin or
`propo
`rtion which may be
`hard
`capsule or the sof
`
`sules a
`,re solid dosage forms containing
`ubstanc
`e(s), except for placebo capsules,
`s,
`encl
`osed in either a hard or a soft,
`1)
`prep
`ared from a gelatin base which
`other
`suitable plasticizer in a
`varied
`in order to produce either the
`b capsu
`le.
`
`--
`
`)
`
`3
`
`...
`
`0
`
`-- -- . - -e.
`
`. .
`
`.
`
`--
`
`.
`
`.
`
`.
`
`-
`
`~,
`
`.
`
`,
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 3/20
`
`

`

`Downloaded from http://www.everyspec.com
`
`b
`
`,
`
`Fed. Std. l~o. 285A
`
`~4.~.~ T:j’pe1, hard . Type 1, hard capsules consist or 2
`pieces
`ca~~). liard capsules are those
`(i.e., the base and tkJe
`which cor~tain powder(s), granulaticm(+
`Or Pelkts.
`
`s4.1.2
`Type 11 capsules consist of two
`II, soft.
`~pe
`flexible pieces formed into a body and permanently sealed.
`Soft capsules are those which contain liquids, powder(s),
`or semi-solid ingredient(s).
`
`34.1.3
`Sizes of hard capsules.
`Ha~d capsules are manufactured
`under standard size numbers ranging from Size No. 000 to Size
`1{0. 5.
`When special size capsules are required, the size shall
`be specified in the procurement document.
`
`Sizes of’ soft capsules.
`S4.1.4
`Soft capsules are manufactured
`in various sizes (dimensions) . When not specified, the
`dimensions shall be those which are commercially supplied for
`the item.
`
`S4.1.5 Shapes of capsules.
`
`S4.1.5.1
`Conventional,
`round, and tapered ends.
`
`elliptical (oval), oblon~,
`bullet-like,
`(See appropriate illustration in S2.)
`
`Special capsules.
`Special capsules shall be of the
`S4.1.5.2
`capsule shape specified in the procurement document.
`
`-1 [
`J’
`
`s4.1.6 Grades cf trar~sparency.
`
`s4.1.6.1 Grade A
`Grade A, opaque capsules
`opaque capsules.
`are those which protect contents from light rays.
`
`Grade B, clear capsules
`Grade B, clear capsules.
`s4.1.6.2
`are those in =hich the contained ingredient(s) may be seen
`Such capsules may be colored or uncolored.
`through the capsule.
`
`Grade C, combination capsules
`Grade C, combination.
`s4.L6.3
`are those in which the shells of the capsule are of different
`grades of transparency,
`i.e., one shell clear (colored or
`uncolored) and the other shell, of the same caPsule, opaque=
`Grade C capsules shall be in accordance with manufacturer’s
`commercial prad~ice, wl]en such is not specified in the procure-
`ment document.
`
`4
`
`I
`
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`

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`
`)
`
`Fed. Std. !:o.
`*
`t
`~/4*1*~.4 Grade D, special.
`Grade D, special capsules shall be
`of’ the grade specified in the procurement document.
`
`>35/4
`
`S4.1.7
`
`Classes
`
`(forms of fill).
`
`Class 1.
`S4.1.7.1
`granulation{ s>.
`
`Class 1 shall be dry powder(s), including
`
`Class 2.
`Sh.1.7.2
`Class 2 shall be liquid(s) encapsulated
`a suspension or solution.
`
`as
`
`S4.1.7.3
`Class 3.
`sustained act~med)
`
`Class 3 shall be pellets which release
`substance(s).
`
`S4.1.7.4
`be as
`specified
`may contalr]
`specified
`
`or
`
`Class 4. Class 4, special fill capsules,
`in the
`procurement
`document.
`These
`a paste
`(semi-solid)
`other
`form of
`above.
`
`shall
`capsules
`not
`
`fill
`
`S4.2
`For purposes of this document, a lot, batch, or
`Lot.
`control
`is that single, uniform, and homogeneous quantity of
`filled capsules produced from one compounding formulation,
`.in one manufacturing
`and filling operation, and which quantity
`has received entirely the same processing and treatment.
`
`Lot, batch, or control number.
`s4.2.1
`Lot, batch, or control
`number is a series of ntimbers and/or letters that Identify
`the lot.
`
`\,
`
`)
`
`.
`
`~
`
`S4~3
`defined
`
`of manufacture.
`Date
`as
`follows:
`
`The date
`
`of manufacture
`
`Is
`
`S4.3.1 For those capsules that are submitted to Federal
`(FDA)
`for
`certification
`prior
`Food and Drug Administration
`to
`release,
`the
`date
`of manufacture
`is
`the
`date
`the
`official
`of
`certification
`notice.
`This
`certification
`shall
`be not
`later
`than
`6 months after the date of filllng the capsules.
`
`For those capsules that are manufactured under
`S4.3.2
`Bureau of Biologics, FDA, (B of B),
`license, the date of
`manufacture
`conforms to the definition established by the
`B of B.
`
`~4,3*3
`For other capsules not covered by S4.3.1 and s4.3.2,
`the date of manufacture
`is the date of’ filling of the capsules,
`or the date of manufact~drer’s or contractor’s final qquality
`approval, which shall be not later than one month after the
`date of filling the capsule.
`
`;
`
`5
`
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`QUALICAPS EX. 2005 - 5/20
`
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`
`‘).
`
`The expiration dating
`da Lin~; perio~.
`Expiration
`S4.4
`period s)hal.ibe designated by the prc)curi,ng,activity and
`represents tile periQd ‘Deycnd wl]ich the c~psules cannct be
`expected, beyond reasonable doubt, to yield their specific
`results, or retain their required potency.
`~4.401 For those capsules that are submitted to FDA for
`certification prier to release, the expiration dating period
`shall be based upon the first or original FDA certification.
`This certification
`shall be not later than 6 months after the
`date of enca~sulation.
`
`,
`‘
`
`For those capsules that are manufactured under
`R4.4.2
`B o; B license, the expiration dating period shall be as
`established by tli~ B of B, and shall be as specified in the
`procurement document.
`
`S4.5 ExpiT’ation date.
`The expiration date is the date of
`termination of the expiration dating period.
`
`s?). GerAeI’alrequirements.
`
`hard capsules and
`The unfilled
`s~.1 Unfilled capsules.
`from
`the gelatin mix for soft capsules shall be manufactured
`type A or type B gelatin, or a suitable mixture of both, and
`shall be in accordance with the requirements of the USP for
`gelatin used in the manufacture of capsules.
`
`S5.2 The ingredients
`entering into the preparation or
`manufacture of the filled capsules shall comply with the tests,
`of the USP or NF, and the
`standards , and. requirements
`The descriptions
`included in the USP
`procurement dccument.
`and NF monograp]ls that pertajn to appearance or other attributes
`determined, by organoleptic examination
`which can be specifically
`shall be considered part of the
`or simple manipulations,
`If’ the in~redients are not monographed
`req[jirements :or the item.
`in the USP or iJF, and the standards for the ingredients
`are not included in the procurement document, the ingredients
`shall be of high quality and purity suitable for use in capsules
`\/henever water is required
`to
`be
`used
`in
`a
`Step
`(See s6.4. 1).
`@ithcr as part of the formulation
`~“-t~rin~ process, .
`of the manuld~
`or as a vehicle ~or adding other ingredient (s) , purified hrater,
`USP, shall be required.
`
`6
`
`,.
`
`<.4
`
`.
`
`.
`
`. ‘
`
`)
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 6/20
`
`

`

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`
`Fed. ‘Std. IJo. 265A
`
`# ,
`
`s5e3 Capsules that are official articles in the USp or
`lJF shall cemplj~ with tl]e tests, standards, and requirements
`of the USP or lJF, and the procurement document.
`The
`capsules shall also comply with all specifications of the USP
`or NF, relating to the article, whether incorporated in the
`monograph itself, in the General Notices, or in the section
`on General Tests, Processes, and Apparatus (see s6.4.3).
`
`Capsules that are not official articles in the USP
`SY.Q
`or NF shall comply with all re~ui.remf?ntsof the procurement
`document (see S6.4.3).
`
`~5.5 Capsules that require from FDA either a Certification
`or an Approved New Drug Application shall comply with the
`applicable requirements
`of the FDA and the procurement
`document.
`
`S5.6 Sealing.
`The base and cap segments of the hard capsule
`shall so fit that a tight friction closure is maintained.
`Capsules
`may be
`sealed
`by a band
`or
`a spot
`seal.
`
`shall be first class throughout.
`Workmanship
`Workmanship.
`S5.7
`The materials shall be free from any defects which detract from
`their appearance or may impair their usefulness.
`
`Labeling,
`s5.8
`Labeling, packaging, and packing of capsules.
`packaging, and packirig of capsules shall be as specified In
`the procurement document.
`
`s6. Detail
`
`requirements.
`
`Note:
`
`Attention is directed to paragraphs s6.4, S6.6,
`and s6.7 for inprocess and final product testing
`and examination.
`
`s6.1 ~njzredients entering into the DreD aration or manufacture
`of capsules.
`
`s6.1.1 All ingredients shall conform to the requirements
`Each ingredient, and all ingredients combined, shall
`of S5.2.
`The gelatin used In
`be nontoxic in the amounts administered.
`the capsules shall comply with S5.1.
`
`7
`
`I
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`QUALICAPS EX. 2005 - 7/20
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`
`‘7
`
`~b,],p
`Diluents
`co2cr:r.~3 and Gt her materials
`Tl”l.,.aw-p
`.
`U14. U* AI UL),
`(I]]cluding excipients,
`bulking a~ents, absorbents, disintegrants,
`binders, adhesives, and lubricants),
`coloring, and ether materials
`used in the medicarnent in the capsules shall be t]]erapeutically
`innocuous in the amounts used,and shall not in any way adversely
`affect the stability nor the therapeutic efficacy of the capsules.
`The diluents, coloring, and other materials shall not interfere
`with the applicable
`tests and assays.
`
`s6.1.2.1
`Coloring material.
`For capsules that are required
`to have added color(s), the coloring agent(s) used in the
`formula shall be a color additive certified or listed as
`harmless and suitable for coloring drugs under the terms of
`the Federal Food, Drug, and Cosmetic Act and Color Additive
`Regulation~.
`
`36.2
`
`Characteristics
`
`of’ capsules.
`
`Appearance.
`s6.2.1
`Capsules within one lot, and within
`one contractl~al quantity, shall be of the same color, transparency,
`size, and shape.
`If one capsule bears identifying marking,
`all capsules shall bear the identical marking.
`
`.
`
`I
`
`Capsules shall be smooth and uniform
`capsules.
`s6.2.1.1
`in size, shape, and color.
`Capsules shall show no evidence
`of spots, breaks, excess powder in the containers, mottling,
`cracks, splitting, ~oreign particulate
`contamination
`(foreign
`matter) and embedded or adhering surface spots, or foreign
`material contained in the capsule not visible through the
`capsule shell, exceedin~ the limits permitted in the classifi-
`cation of’ defects (see s6.7.1), within the applicable acceptable
`quality level (AQL).
`Unless otherwise specified, any coloring
`material employed in the capsules shall be uniformly and
`homogeneously distributed, with the possible exception of the
`pellets in capsules and special capsules.
`
`s6.2.2 color.
`Color of the capsules and of the fill shall
`be specified in the procurement document.
`If the color is not
`specified, capsules and fill shall be the same as that which
`is
`commercially
`supplled
`for
`the
`item.
`
`specified
`number
`size
`the
`of
`be
`shall
`Capsules
`Size.
`s6.2.5
`—.—
`document.
`procurement
`in the
`If the specific size for capsules
`document, the size shall
`is Il(Jt# specified in the procurement
`Qhe item.
`be the same a: ?hat which is ~ornmcrcia~l.y
`supplied
`for
`When spccj.al size capsules are supplied, the size shall be of
`sufficient ca~:~city to contain the prescribed amount of medicinal
`substance(s).
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 8/20
`
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`

`Downloaded from http://www.everyspec.com
`
`Fed . Std. Jdo. 28fj A
`.
`.
`Shape,
`S6. 2.4
`The shape of the capsule shall be s~,ecified
`the procurement document.
`When the shape of the capsule
`net tipec~fled, the shape sl]all conform to that commercially
`accepted as standard in the pl~armaceu~ical industry for the
`“
`capsules being supplied.
`
`s6.2.5
`Upon opening a sealed bottle, the filled
`Odor.
`capsules shall be odorless if they (a) are not flavored, or
`(b) do not contain ingredient(s) which normally have a
`characteristic
`odor.
`Capsules shall have no foreign odor or
`odor resulting from decomposition
`or deterioration.
`The
`term “odorless” applies to examination of capsules in the
`freshly-opened
`immediate container, with the cotton or other
`filler removed.
`After exposure to the air at room temperature
`(in room free from drafts) for the period specified herein, the
`contents of a freshly-opened
`immediate container shall have no
`odor.
`For containers labeled to contain 100 capsules, or less,
`exposure to air shall be 5 minutes; for containers labeled to
`contain between 101 and 500 capsules, exposure to air shall be
`10 minutes; for containers labeled to contain between 501 and
`minutes; and for
`1000 capsules, exposure to air shall be
`containers labeled to contain more than
`exposure
`1000 capsules,
`to air shall be 25 minutes.
`or
`other
`filler
`shall
`The cotton
`be removed from the immediate container
`during
`the
`exposure
`to air.
`
`15
`
`s6.2.6
`and volubility.
`Disintegration
`When a disintegration
`and volubility time is required
`(other than specified in
`s6.2.15), it shall be as specified in the procurement document.
`
`s6.2.7
`Moisture content.
`The limit of moisture content
`shall be specified in the procurement
`document. When the
`limit
`not-
`specified,
`the medication
`in the
`of moisture content is
`capsules
`shall
`contain
`a minimum amount
`of moisture,
`so as
`to
`insure
`maximum stability
`of
`the
`capsules.
`The moisture
`of
`content
`the
`capsule
`(hard
`or
`soft
`gelatin)
`Itself,
`shall
`such as to prevent brittleness and cracking.
`
`be
`
`s6.2.8 Marking
`other
`designation
`
`or
`
`on capsules.
`distinctive
`
`may bear
`Capsules
`of
`the manufacturer’s
`
`a trademark
`item.
`
`s6.2.9 Wel~ht
`
`variation.
`
`s6.2.9.1
`Type I and Typ e II.
`Unless otherwise specified,
`filled capsules shall conform to the USP Weight Variation
`Test for Capsules.
`Hard and soft capsules shall be tested in
`accordance with the applicable procedure.
`
`.
`
`,.
`
`.’t.
`
`, .
`.
`
`)..
`
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`QUALICAPS EX. 2005 - 9/20
`
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`1
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`
`F~~
`
`, Std. jdO.
`
`285A
`
`#
`~nif’ormi~yOf’pel~e~~o
`S6.2.1O
`The peliets in each capsule
`shall be of’ u~lif’ormsize(s) and not less than 95 percent of
`the pellets in each capsule shall fall within the numbered
`mesh ran~e specified in the procurement document, when tested
`in accordance with the USP, using U.S. Standard Mesh Sieves”
`
`,
`
`Capsules shall be so compounded as to
`Stability.
`s6.2.11
`provide physical stability of’ capsules and chemical stability
`Capsules that are designated as having an
`of the ingredients.
`expiration dating period shall comply with all applicable
`requirements
`for the full expiration dating period under
`normal storage and handling, or storage as specified in the
`procurement document.
`
`The number
`s6.2.12
`Net contents and variations in count.
`(count) of capsules in the immediate containers shall average
`not lens than that quantity specified in the item identification
`The figure (number) representing
`of’ the procurement document.
`the average count shall be adjusted to the nearest whole number.
`In addition, the following shall apply:
`
`(a)
`
`(b)
`
`(c)
`
`IJo immediate container shall contain
`97 percent of the required amount of
`the specified number of capsules per
`container is 100 or more.
`
`less than
`capsules when
`immediate
`
`than two (2)
`No immediate container shall be more
`capsules short of the required amount when the
`specified number of capsules per immediate container
`is between 50 and 99.
`
`No immediate container shall be more than one (1) .-..
`capsule short of the required amount when the specll’lea
`number of’ capsules per immediate container is less
`than 50.
`
`s6.2.12.1 For
`capsules contain~ng narcotics or barbiturate%
`and capsules subject to the Regulations
`Implementing the
`Comprehensive Drug Abuse Prevention and Control Act, the number
`of capsules in the immediate container shall comply with the
`preceding, except that the average count shall be not less
`than 99.& ]~ercent and not more than 100.5 percent of the
`number of capsules specified in the item identification
`procurement document.
`
`of the
`
`10
`
`9
`
`-
`
`)
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 10/20
`
`

`

`Downloaded from http://www.everyspec.com
`
`Fed . Std. No. 285A
`,
`
`s6.2.12.2
`FCP capsules
`packaged in blister
`number of capsules in each
`immediate container
`percent of the n’:mber of’ capsules specified in
`document.
`No tolerances shall be allowed.
`
`packets, ‘the
`shall be 100.0
`the procurement
`
`Volume occupied by capsules.
`s6.2.13
`capsules shall meet the test requirements
`document for volume occupied by capsules.
`
`When
`specified, the
`in the psocmement
`
`S6.2.14 Water resistance.
`Unless otherwise specified,
`the capsule shell shall show no signs of disintegration when
`tested as follows:
`
`The capsules shall be immersed in purified water at 25°C. +
`10C. for 15 minutes.
`A sample of 20 capsules shall be
`–
`tested for compliance with this test.
`
`Acid volubility.
`s6.2.15
`Unless otherwise specified, the
`Type I capsule shell shall completely fall apart, dissolve, or
`disintegrate,
`when tested as follows:
`
`. “ The capsules shall be immersed in 0.5 percent, by weight,
`aqueous hydrochloric acid solution at 360c. to 38°C. and
`allowed to remain at this temperature for 15 minutes.
`A
`sample of 20 capsules shell shall be tested for complianc~
`with this test.
`
`Unless otherwise specified, the Type 11 capsule shell shall
`dissolve within 15 minutes in artificial gastric fluid,
`Test Method
`for
`Tablets.
`using the USP Disintegration
`
`s6.2.16 Foreign material inside filled capsules.
`Capsules
`shall be free of foreign material inside the capsule, when
`examined using either method (a) or method (b) without accessory
`magnification
`(except for such optional correction as may be
`required to establish normal vision).
`The capsules shall comply
`with the limits permitted in the classification
`of defects (see
`table IV and table V), and the applicable AQL.
`
`Method (a).
`
`Type I capsules.
`Take one (1) capsule and
`open carefully.
`Empty the contents of the
`capsule onto a clean, dry surface.
`Examine
`the contents (powder, granulations, or pellets)
`for foreign material . Record the number of
`capsules found to contain foreign material.
`
`11
`
`I
`
`[fin
`
`1
`
`nxvnnnurm
`
`lt~
`
`[hr
`
`1111111
`
`Hill
`
`Xl
`
`IIJJ1
`
`.>VIIIIKU.
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 11/20
`
`

`

`Downloaded from http://www.everyspec.com
`
`*
`
`capsule i;,
`one U)
`1; capsules.
`F’iace
`Type
`-.—
`a depress
`of’ a clean, porcelain spotplate.
`i~ri
`I.lsinga slla~’~.~c[l~ting ~nstrumer]t (scalpel, etc. )
`:Il:t or cut t.hjecapsule into twc or more pieces.
`“i~~i~li]~etl]c contents (liquid, powder, semi-solids,
`etc. ), for foreign material.
`Reco~d the
`number of capsules found to contain foreign
`material .
`
`IJC)TL:
`
`Method (a) or Method (b), as
`Ilethod(s), other tl]an
`shall be submitted for approval and
`specified
`acceptance by the Government, prior to use.
`If
`the method(s) are approved by the Government, such
`method(s) shall be employed in testing of the
`capsules to determine foreign material inside the
`capsules.
`
`s6.3 Delivery.
`
`S6 .3.1 Expiration dated capsules requiring certification
`— —
`tlyF]-)Aor manllf’ac~ureunder ~ of B lic~
`Delivery
`for expiration dated capsules that requir~h certification by FDA
`license, shall be in
`or are-manufactured
`under B of B
`Column no. 1 represents the specified
`accordance with table 1.
`expiration dating period, and columrlno. 2 represents the
`allowable minimum expiration dating period remaining at the time
`that the material is delivered to the Goverr]ment.
`
`Column no . 2
`(months
`)
`
`2-1/2
`
`50
`
`10
`16
`21
`27
`33
`44
`56
`
`Column no . 1
`(months)
`
`TABLE I.
`
`Delivery
`
`369
`
`12
`18
`24
`30
`36
`48
`60
`
`I
`
`12
`
`“
`
`--
`,.
`
`,*.-“)..,.
`
`b
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 12/20
`
`

`

`Downloaded from http://www.everyspec.com
`
`~t~,
`I
`,
`capsules
`dated
`Expiratio]l
`S6 .3.2
`other
`than those complying
`with S6 .3.1. ~~l~y,~mlJ schedule for expiration dated capsules,
`other than those complying with s6.3.], shall be in accordance
`with table 11.
`Column no. 1 represents the specified expiration
`dating period and column no. 2 represents the maximum number
`of months that may elapse from the date of manufacture
`(defined
`in S4.3) of the capsules to the date that the material is
`delivered to the Government.
`
`]jcc 265A
`
`~e,j
`
`.
`
`Column no. 1
`(months )
`
`TABLE 11.
`
`Delivery
`
`Column no. 2
`(months)
`
`122334Q
`
`12
`18
`24
`30
`36
`48
`60
`
`.-‘)
`
`Unless otherwise
`Non-expiration dated capsules.
`s6.3.3
`, not more than 6 months shall elapse from the date
`specified
`of manufacture
`(defined in S4.3) of non-expiration
`dated
`capsules, to the date of’delivery to the Government.
`
`s6.4
`
`Tests.
`
`s6.4.1
`Testin
`~.
`Ingredients
`that are official
`in the USP or NF shall be tested by the methods
`described in
`the USP or NF and the ~rocurement document. and
`the ingredients
`shall comply with S5.2.
`Ingredients that are not official
`in the USP or NF shall be tested by the methods specified in the
`procurement document, or if not specified therein, the nonofficial
`ingredients shall be tested by suitable methods to determine
`their identity and compliance with S5.2.
`
`Inprocess testing.
`s6.4.2
`During the encapsulating operation
`of hard gelatin capsules, not less than 10 capsules from each
`lot shall be drawn from each capsulating machine, at regular
`intervals of 30 minutes or less, and tested for weight.
`For
`soft gelatin capsules, not less than 10 capsules shall be drawn
`from each lot at the beginning of the filling operation and tested
`f’or fill weight.
`If filling pumps are adtjusted or changed, the
`fill weight test shall be repeated.
`In addition, for soft
`gelatin capsules, the seal thickness shall be verified at the
`beginning and during the encapsulating
`(filling) operation.
`The
`seal thickness shall be within required limits.
`The inprocess
`testing shall be applicable to capsules from each capsulating
`machine.
`The test results shall be recorded for each capsulating
`machine used for each lot to confirm uniformity of weight.
`
`13
`
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`QUALICAPS EX. 2005 - 13/20
`
`

`

`Downloaded from http://www.everyspec.com
`
`)
`
`d
`
`.)
`
`s6.!],3 !’e sting of finished capsulcc. ‘
`
`Each lot
`S6.4.3.1 Capsules official in the USP or NF.
`of capsules that are official in the USP or NF shall be
`tested by the methods described in the USP or NF and the
`procurement document to determine compliance with S5.3~
`
`Each
`Capsules r]u~ uf~icial in the USP or NF.
`S6.4.3.2
`lot of capsules that are not official irl the USl? or NF shall
`be tested bj~ the methods described in the procurement document.
`
`s6.5 Test records.
`Recorlds of all tests performed shall
`be maintained for not less than 3 years from date of delivery
`Upon request, records
`of the supplies to the Government.
`Fox’
`shall be available to the Government for examination.
`inprocess testing, such test records shall include the
`capsulating machine number or the permanent capsulating station
`For capsules that bear
`number, lot number, and test findings.
`an expiration date, the records shall be maintained and shall
`be available during the full expiration dating period and for
`6 months after the expiration date.
`
`S(5.6 Sampljng.
`Unless otherwise specified in the procurement
`document, sampling shall be in accordance with MIL-STD-105.
`
`Examination shall be conducted in
`Examination.
`s6.6.1
`accordance with the following inspection level:
`
`TAB
`
`For examination
`
`Examination. ~
`)E 111.
`AQL (percent
`Inspection
`defective)
`level
`
`of
`Unit
`product
`
`Ma~or A
`Major B
`
`Minor
`
`11
`s-2
`
`II
`
`I
`
`I
`
`1.0
`1.0
`
`2.5
`
`capsule
`Filled
`immediate
`Filled
`container
`Filled
`capsule
`
`—“
`
`is
`characteristics
`of mafior A and minor
`examination
`1/ When the
`not
`performed prior to filiing of final (immediate) containers,
`and such examination
`is necessary on the filledj final
`(immediate) containers, the sample size for capsules shall
`The required number of capsules for
`r’emaln the same.
`examination
`shall then be selected at random from filled,
`final (immediate) containers sampled in accordance with
`level S-29 minimum sample of 5 immediate containers
`MIL-STD-105,
`except where the immediate container is a transparent blister
`packet . The sample size shall then be based on the lot size
`Whenever the capsules are placed in the
`of the capsules~
`packets, only a visual (physical) examination of the capsules
`
`14
`
`
`
`———----.—-.————=_._—_=______.. __-
`
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`QUALICAPS EX. 2005 - 14/20
`
`

`

`&,
`
`)
`
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`
`.-
`
`I
`
`(without destruction of the blister) shall be required; using
`three (3) times the sample size of’ each lot of capsules.
`If
`the number of immedi~te containers selected does not give
`the required number of capsules for examination, randomly
`select
`additional immediate containers to give the required number of
`capsules.
`Those defects that are annotated “#1~in the
`classification
`of defects must be determined on capsules from
`filled, final (immediate) containers.
`Results of examination
`for those defects
`obtained prior to filling of final (immediate)
`containers
`shall not be acceptable.
`
`s6.6.2
`Testin
`Shall be conducted as f’oll~ws: For end
`item testing
`unit of product - filled immediate container
`+“
`
`~/’
`
`.
`
`(a)
`
`(b)
`
`Sampling of each lot for the tests required in
`table IV shall be in accordance with level S-1,
`except as indicated by ~/.
`Minimum sample size
`is three (3) inmedf..te contalner:s. The acceptance
`number for each test shall t~e zero (0).
`
`As an alternate to the above procedure, each lot shall
`be tested, as required in table IV, on
`capsules
`taken from bulk stock (prior to packaging of capsules).
`A minimum of 300 capsules shall be utilized.
`The
`acceptance number shall be zero (0).
`In addition,
`a minimum of one (1) Identification
`test shall be
`performed on each lot of filled immediate containers.
`The identity test shall be specific for the products.
`For products containing more than one active ingredient,
`a minimum of two ingredients shall be identified by
`specific tests.
`
`TABLE IV.
`
`Testing.
`
`Characteristic
`Testing of finished capsules (assays, identities,
`and other tests app licable for the item)
`Color
`and volubility
`Disintegration
`Weight variation
`Moisture
`Capsule
`Shape
`Volume (when specified)
`Water resistance 2/
`Acid volubility
`2/
`
`(when specified)
`
`size
`
`Requirement
`paragraph
`s6.4.3
`
`S6.2.2
`S6.2.6
`s6.2.9
`s6.2.7
`s6.2.3
`S6.2.4
`s6.2.13
`S6..2.14
`s6.2.15
`
`v
`b!here the unit of issue being examined is other than ‘immediate
`container” substitute
`the
`terminology
`of
`the
`unit
`of’
`issue
`(:oe
`package,
`can,
`tube,
`etc.),
`wherever
`the words
`~limm~~iate
`container”
`appear.
`use
`sample size in s6.2.14
`
`----
`
`~/
`
`)
`~ 2,/
`
`and s6.2.15, as applicable.
`
`15
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 15/20
`
`

`

`Downloaded from http://www.everyspec.com
`... ——
`
`——...—. _—~
`
`.
`
`-——
`
`,
`
`(d
`
`The net content and variation in count (s6.2.12
`and S6. 2.12.1) shall be sampled in accordance with
`ir~s~~ectior~level S-2.
`Acceptance number shall be
`zero (0).
`
`s6.7
`The capsules shall be examined to
`Examination.
`determine compl~anc= with all requirements
`of’ this document.
`Nonconformance
`with these requirements
`will be permitted to
`the extent indicated in S6.6.
`
`s6.7.1
`of defects.
`Classification
`shall be
`Examination
`conducted in accordance with the following classification] of’
`defects:
`
`TABLE V.
`
`l{ard Capsules.
`Defects 1/—
`
`(i.e., hard shell).
`Capsule not type-specified
`Capsule not free of cracks, breaks, pinholes, or
`sr’lits where leakage of contents may occur.
`Capsules not uniform, in appearance.
`Base and/or cap of capsule not as specified.
`Capsule
`not uniform in color(s).
`-
`Capsule empty.
`Capsule not free of embedded surface spots
`contamination
`(definition (a), S6.701.1).
`Capsule fill not free from foreign matter.
`
`and
`
`Categories
`
`#Major A
`
`101
`#lo2
`
`103
`104
`105
`#lo6
`#lo7
`
`108
`
`2/—“
`
`Major
`
`B— y
`
`#151
`
`#152
`#153
`#154
`
`#155
`
`#156
`
`#157
`
`tight closure or
`or during normal
`
`in
`seal
`handling,
`
`Capsule does not maintain
`the
`immediate
`container,
`,
`I or dispensing.
`lImmediate container not free from extraneous matter.
`cap
`separated
`from body).
`!Capsule
`not
`intact
`(i.e.,
`odor,
`~CaP~ule
`not
`l~ree
`of
`other than
`foreign
`: characteristic
`odor.
`lImrnediate container not internally and externally
`
`Void space of immediate container not filled, when
`
`I clean.
`
`Irequired.
`
`Ir.mediate container not free of excess ingredient
`t
`(capsule contents).
`
`16
`
`-.8 AL.;..
`
`-*.-.-.J.3..
`
`.1
`
`“-. ..a,l.a,l
`
`1...
`
`,.,
`
`...
`
`t..
`
`ofibms.
`
`. .
`
`.
`
`.
`
`,..
`
`.
`
`.
`
`.
`
`‘\)
`
`)
`
`Mylan v. Qualicaps, IPR2017-00203
`QUALICAPS EX. 2005 - 16/20
`
`

`

`Downloaded from http://www.everyspec.com
`
`TABLS V.
`
`llard capsules (cent’d)
`Defects 1/
`
`f
`)
`
`Fed.
`
`Std.
`
`No. Z85A
`
`‘7
`
`Categories!
`I
`,!
`
`Minor
`
`I
`
`201
`202
`203
`#2o4
`
`205
`#206
`
`,Capsule
`not free of
`not free of
`,Capsule
`not free of
`Capsule
`not free of
`Capsule
`one another.
`Capsule not smooth.
`Capsule not free Or
`s6.7.1.1).
`‘ (b),
`I
`
`pits or dents.
`thin areas.
`specks, spots, or blemishes.
`cap and/or body cutting into
`
`adhering surface spots (definition
`
`1/
`—
`
`~/
`
`~/
`
`Inspection is not restricted to classified possible defects
`listed above.
`For opaque capsules use a sample size of 20 capsules to
`No capsule shall show evidence of
`examine contents.
`foreign matter.
`Capsules obtained from the bottles used for examination of
`Major B defects may be used for examination of Major A
`Thus , no additional capsules
`and Minor defects annotated “#”.
`# Applies to examination of capsules in
`need be selected.
`filled, final (i~ediate)
`containers.
`
`.
`
`TABLE VI.
`
`Soft Capsules.
`Defects 1/
`
`(i.e., soft shell).
`not type specified
`Capsule
`not free of cracks, breaks, pinholes~ or
`Capsule
`where leakage of contents may occur.
`splits
`Capsules not uniform in appearance.
`Capsule not uniform in color(s).
`Capsule empty.
`Capsule not free of embedded surface spots and
`s6.7.1.1),
`contamination
`(definition
`(a),
`Capsule
`fill
`free
`from foreign
`matter.
`
`not
`
`IIC
`
`apsule does not maintain tight
`I immedi