Injections and Implanted Drug Products (Parenterals ...

1 Injections and Implanted drug Products (Parenterals) product Quality tests Type of Posting Revision Bulletin Posting Date 25 Mar 2016 Official Date 01 May 2016 Expert Committee General Chapters Dosage Forms Reason for Revision Compliance In accordance with the Rules and Procedures of the 2015-2020 Council of Experts, the Dosage Forms Expert Committee has revised General Chapter <1> Injections and Implanted drug Products (Parenterals) product Quality tests . General Chapter <1> Injections and Implanted drug Products (Parenterals) product Quality tests , which will become official May 1, 2016, was intended to support existing monographs, as well as, the development of new monographs. Comments were received indicating that the dual purpose of this General Chapter could lead to confusion and application of the General Chapter requirements to Products not intended by the Expert Committee. In response to these comments the Expert Committee has revised the General Chapter <1> to narrow its scope to clarifying its purpose and application to eliminate potential compliance issues.

2 Furthermore, USP will be reviewing all of the product Quality General Chapters ( Injections and Implanted drug Products <1>, Oral drug Products product Quality tests <2>, Topical and Transdermal drug Products product Quality tests <3>, Mucosal drug Products product Quality tests <4>, and Inhalation and Nasal drug Products General Information and product Quality tests <5>) to determine whether the current format and content is appropriate. The <1> Injections and Implanted drug Products (Parenterals) product Quality tests Revision Bulletin supersedes the version published in USP 39 NF 34, which was scheduled to become official May 1, 2016. The Revision Bulletin will be incorporated in the USP 40 NF 35. Should you have any questions, please contact Desmond Hunt, (301-816-8341, C169380_151208-M98730-GCDF2015, , 20160325 Revision BulletinOfficial May 1, 2016 1 Injections1in addition to Universal tests ; and (RB 1-May-2016) (3) product 1 Injections ANDquality tests for specific dosage forms, which lists (RB 1-May-2016) applicable tests (universal and specific) for the specificIMPLANTED drug Products dosage form.)

3 This chapter applies, in whole or in part, when refer-(PARENTERALS) product enced in a drug product monograph (see General Notices, Applicability of Standards). (RB 1-May-2016)QUALITY TESTSThe pharmacopeial definitions for sterile preparations forparenteral use may not apply to some biologics because oftheir special nature and licensing requirements (see Biologics 1041 ). However, some biological finished drug productscontaining injection in the monograph title must meetChange to read:the requirements of 1 or indicated chapter subparts,where it is specified in the monograph. (RB 1-May-2016)(Chapter to become official May 1, 2016)(Current chapter name is 1 Injections ) Change to read:INTRODUCTIONPRODUCT QUALITY tests COMMON TO PARENTERALDOSAGE FORMSU niversal TestsPRODUCT QUALITY tests COMMON TOSpecific TestsPARENTERAL DOSAGE FORMSPRODUCT QUALITY tests FOR SPECIFIC PARENTERALDOSAGE FORMSS olutionsSterile Powders for SolutionsUniversal TestsSuspensionsLiposomesUniversal tests are listed below and are applicable to par-Sterile Powders for Suspensionsenteral dosage (RB 1-May-2016)ImplantsIdentification:Identi fication tests are discussed in GeneralDrug-Eluting StentsNotices and Requirements (RB 1-May-2016) (RB 1-May-2016)Assay:A specific and stability-indicating test should beused to determine the strength (content) of the drug prod-uct.

4 In cases where the use of a nonspecific assay is justi-Change to read:fied, other supporting analytical procedures should be usedto achieve overall specificity. A specific procedure should beused when there is evidence of excipient interference withINTRODUCTIONthe nonspecific : tests for impurities are discussed in GeneralParenteral drug Products include both Injections and im-Notices and Requirements (RB 1-May-2016)planted drug Products that are injected through the skin orForeign and particulate matter:Articles intended forother external boundary tissue, or Implanted within theparenteral administration should be prepared in a mannerbody to allow the direct administration of the active drugdesigned to exclude particulate matter as defined in Sub-substance(s) into blood vessels, organs, tissues, or Particulate Matter in Therapeutic Protein InjectionsInjections may exist as either immediate- or extended-re- 787 , Particulate Matter in Injections 788 , or (RB 1-May-2016)lease dosage forms.

5 Implanted parenteral drug Products areParticulate Matter in Ophthalmic Solutions 789 , as well aslong-acting dosage forms that provide continuous releaseexcluding other foreign matter as appropriate for the dos-of the active drug substance(s), often for periods of monthsage form. Each final container of all parenteral preparationsto years. For systemic delivery, they may be placed subcu-should be inspected to the extent possible for the presencetaneously; for local delivery, they may be placed in a spe-of observable foreign and particulate matter (hereaftercific region of the body. Routes of administration for paren-termed visible particulates) in its contents. The inspectionteral drug Products include intravenous, intraventricular,process should be designed and qualified to ensure thatintra-arterial, intra-articular, subcutaneous, intramuscular,every lot of all parenteral preparations is essentially freeintrathecal, intracisternal, and visible particulates, as defined in Visible Particulates inParenteral dosage forms include solutions, suspensions, Injections 790.

6 Qualification of the inspection processemulsions, sterile powders for solutions and suspensions (in-should be performed with reference to particulates in thecluding liposomes), implants (including microparticles), andvisible range and those particulates that might emanateproducts that consist of both a drug and a device such asfrom the manufacturing or filling process. Every containerdrug-eluting stents. The definitions and descriptions ofin which the contents show evidence of visible particulatesthese dosage forms, and brief information about their com-must be rejected. The inspection for visible particulates mayposition and manufacturing processes, are found in Phar-take place during examination for other (RB 1-May-2016) de-maceutical Dosage Forms 1151 . [NOTE All references tofects such as cracked or defective containers or seals, orchapters above 1000 are for informational purposes only,when characterizing the appearance of a lyophilized prod-for use as a helpful resource.]

7 These chapters are unless explicitly called out for application.] (RB 1-When the nature of the contents or the container closureMay-2016)system permits only limited inspection of the total con- (RB 1-May-2016)This chapter is divided into three (RB 1-May-tents, the 100% inspection of a lot should be supple-2016) main sections: (1) universal product quality tests thatmented with the inspection of constituted ( , dried) orare applicable to parenteral dosage forms; (2) specific prod-uct quality tests , which are tests that should be considered 2016 The United States Pharmacopeial ConventionAll Rights , , 20160325C169380_151208-M98730-GCDF2015, , 20160325 Revision Bulletin2 1 InjectionsOfficial May 1, 2016withdrawn ( , from a dark amber container) contents ofcussed below. All vehicles should be suitable for their in-a sample of containers from the use and should not impact drug product Injections for single-dose infusion, small-Aqueous vehicles Aqueous vehicles must meet the require-volume Injections , and pharmacy bulk packages (PBPs) arements of 151 or 85 , whichever is specified in the mono-subject to the light obscuration or microscopic proceduresgraph.

8 Water for injection is generally used as the limits for subvisible particulate matter set forth inSodium chloride or dextrose may be added to render the 788 , unless otherwise specified in the chapter or in theresulting solution isotonic, and sodium chloride injection orindividual monograph. An article packaged as both a large-Ringer s injection may be used in whole or in part insteadvolume and a small-volume injection meets the require-of water for set forth for small-volume Injections where the con-Nonaqueous vehicles Fixed oils are classified under Non-tainer is labeled as containing 100 mL or less. It meets theaqueous vehicles. Fixed oils used as vehicles are of vegetablerequirements set forth for large-volume Injections for single-origin and are odorless. They meet the requirements in thedose infusion where the container is labeled as containingtest for Solid Paraffin in the Mineral Oil monograph with themore than 100 bath maintained at 10.

9 Sterility:The sterility of all drug Products intended for Nonaqueous vehicles should (RB 1-May-2016) also meet theparenteral administration should be confirmed by the userequirements of the following tests :of methods described in Sterility tests 71 or by an ap- Fats and Fixed Oils 401 , Saponification Value: Betweenproved alternative and 200 bacterial endotoxins :All articles intended for parenteral Fats and Fixed Oils 401 , Iodine Value: Between 79 andadministration should be prepared in a manner designed to141limit bacterial endotoxins as defined in bacterial endotoxins Fats and Fixed Oils 401 , Unsaponifiable Matter: NMTTest 85 or Pyrogen Test 151 . Fats and Fixed Oils 401 , Acid Value: NMT content:Container content should be deter- Fats and Fixed Oils 401 , Peroxide Value: NMT when appropriate (see Container Content for Injec- Water Determination 921 , Method Ic: NMT 697 ). Limit of Copper, Iron, Lead, and Nickel: [NOTE The test Packaging systems: (RB 1-May-2016)The packaging systemfor nickel is not required if the oil has not been sub-should not interact physically or chemically with the prepa-jected to hydrogenation, or a nickel catalyst has notration to alter its strength, quality, or purity beyond thebeen used in processing.]

10 ] Proceed as directed in Fatsofficial or established requirements. The packaging systemand Fixed Oils 401 , Trace Metals or Elemental Impuri-should meet the requirements in Elastomeric Closures for In-ties Procedures 233 . Meet the requirements in Ele-jections 381 , Packaging and Storage Requirements 659 ,mental Impurities Limits 232 .Containers Glass 660 , Plastic Packaging Systems andSynthetic mono- or diglycerides of fatty acids may be usedtheir Materials of Construction 661 (CN 1-May-2016), Plasticprovided they are liquid and remain clear when cooled toMaterials of Construction , and Plastic Packaging Sys-10 and have an iodine value of NMT for Pharmaceutical Use . Further information re-Added substances Suitable substances may be added togarding packaging systems testing may be found in Assess-preparations in order to increase stability or usefulness un-ment of Extractables Associated with Pharmaceuticalless they are proscribed in the monograph.