CRITICAL SELECTION OF PRIMARY PACKAGING

1 CRITICAL SELECTION OF CRITICAL SELECTION OF PRIMARY PACKAGINGPRIMARY PACKAGINGS hams RustomShams RustomLabopharmLabopharmSr. Director, Product Development & ManufacturingSr. Director, Product Development & ManufacturingOutlinesOutlinesWhat is PRIMARY PACKAGING ?What is PRIMARY PACKAGING ?Types of PRIMARY PackagingTypes of PRIMARY PackagingSelection criteria of PRIMARY pack mat for oral SELECTION criteria of PRIMARY pack mat for oral solid dosage formsolid dosage formPackaging materials variablesPackaging materials variablesPackaging process variables & troubleshootingPackaging process variables & troubleshootingPackaging process validation strategyPackaging process validation strategyAntiAnti--counterfeit packagingcounterfeit packagingGlobal strategy & Regulatory requirementsGlobal strategy & Regulatory requirementsPrimary PACKAGING DefinitionPrimary PACKAGING DefinitionRefers to PACKAGING that immediately Refers to PACKAGING that immediately envelopes a product.

2 It provides most of the envelopes a product. It provides most of the strengthstrength and and barrierbarrier needed to safeguard a needed to safeguard a productproduct s purity, potency and integrity from s purity, potency and integrity from the time it leaves the assembly line until itthe time it leaves the assembly line until it s s used by the by the of PRIMARY PACKAGING include Bottles, Examples of PRIMARY PACKAGING include Bottles, blister packs, etc. blister packs, etc. Healthcare PACKAGING & ProductsHealthcare PACKAGING & ProductsPharmaceutical PackagingPharmaceutical PackagingBottlesBottlesBlister Films and FoilsBlister Films and FoilsClosure LinersClosure LinersAerosol/Pump System Aerosol/Pump System ComponentsComponentsPharma Rubber ComponentsPharma Rubber ComponentsTypes of PRIMARY PackagingTypes of PRIMARY PackagingGlass Bottles (colored / transparent)Glass Bottles (colored / transparent)

3 Polymer Bottles & Closures PET, Polymer Bottles & Closures PET, HDPE etcHDPE etcTubes & Pump System componentsTubes & Pump System componentsBlistersBlisters PVC film with Aluminum foilPVC film with Aluminum foil PVC/PVDC film with Aluminum foilPVC/PVDC film with Aluminum foil Aclar/ PVC or Aclar/PVC/PE with Al. FoilAclar/ PVC or Aclar/PVC/PE with Al. Foil Cold Form Foil (CFF)Cold Form Foil (CFF) COC (PVC free barrier film)COC (PVC free barrier film) Aluminum / Aluminum blistersAluminum / Aluminum blistersSelection CriteriaSelection CriteriaCompany Strategy & Goal (global or National?)Company Strategy & Goal (global or National?) Trouble free global submissions (USA, EU, Japan) Trouble free global submissions (USA, EU, Japan) Global acceptance of supplier (DMF) & materials Global acceptance of supplier (DMF) & materials Product stability & Required BarrierProduct stability & Required Barrier ICH conditions for zoneICH conditions for zone--I to II or Zone II to II or Zone I--IVIVR egulatory & Patient Compliance Regulatory & Patient Compliance Child resistant, Senior friendly resistant, Senior friendly & BenefitCost & Benefit Price, Advantages & Compliances of the specific Price, Advantages & Compliances of the specific PACKAGING & Advantages of BottlesProperties & Advantages of BottlesGlass BottlesGlass Bottles Convenience:Convenience.

4 Glass is a perfect barrier to atmospheric oxygen, avoiding ranciGlass is a perfect barrier to atmospheric oxygen, avoiding rancidness, dness, changes of colour & of colour & is inert. No migration of components Glass is inert. No migration of components Inconvenience: Fragile & heavy weightInconvenience: Fragile & heavy weightPET bottlesPET bottles Convenience: Light weight & not fragileConvenience: Light weight & not fragile Inconvenience: Not a good barrier & migration of components may Inconvenience: Not a good barrier & migration of components may BottlesHDPE Bottles Convenience:Convenience:Light weight & UnbreakableLight weight & UnbreakableComparatively better barrierComparatively better barrier Inconvenience:Inconvenience.

5 Migration of components may happen & may affect on product stabMigration of components may happen & may affect on product stability,ility,Types of Polymer BottlesTypes of Polymer Bottles*Type 1 *Type 1 -- PETE Polyethylene Terephthalate (PET) PETE Polyethylene Terephthalate (PET) *Type 2 *Type 2 -- HDPE HighHDPE High--Density Polyethylene Density Polyethylene *Type 3 *Type 3 -- Polyvinyl Chloride (PVC) blistersPolyvinyl Chloride (PVC) blisters*Type 4 *Type 4 -- LDPE LowLDPE Low--Density Polyethylene, Density Polyethylene, *Type 5 *Type 5 -- PP Polypropylene Most bottles caps. PP Polypropylene Most bottles caps. *Type 6 *Type 6 -- PS Polystyrene Throwaway utensils,. PS Polystyrene Throwaway utensils,. *Type 7 *Type 7 -- OTHER Usually layered or mixed plastic.

6 OTHER Usually layered or mixed plastic. The number indicates the class of resin. Types 1 and 2 are The number indicates the class of resin. Types 1 and 2 are commonly recycled. Type 4 is less commonly recycled. commonly recycled. Type 4 is less commonly recycled. The ``Other`` types are generally not recycled because of The ``Other`` types are generally not recycled because of harmful chemicals, except perhaps in small test chemicals, except perhaps in small test programs. Common plastics polycarbonate (PC) and acrylonitrileCommon plastics polycarbonate (PC) and acrylonitrile--butadienebutadiene--styre ne (ABS) do not have recycling numbers. styrene (ABS) do not have recycling numbers. Identification SymbolsIdentification SymbolsPETC larity, strength, toughness, barrier to gas and Soft drink, water, peanut butter Soft drink, water, peanut butter , strength, toughness, resistance to moisture, permeability to gas.

7 Widely used for widely used for pharmaceuticalsPVCV ersatility, ease of blending, strength, widely used for blister widely used for blister filmLDPEEase of processing, strength, toughness, flexibility, ease of sealing, barrier to moisture. squeezable bottles & squeezable bottles & , toughness, resistance to heat, chemicals, grease and oil, versatile, barrier to moisture bottle bottle caps, caps, PSVersatility, clarity, easily Egg cartons, disposable cup & plates Egg cartons, disposable cup & plates on polymers or combination of Beverage bottle , baby milk bottles Beverage bottle , baby milk bottles etcNon PACKAGING uses: Compact PACKAGING uses: Compact of Polymer Bottle propertiesComparison of Polymer Bottle propertiesResinDensity (g/ml)MVTR1 Oxygen2 Stiffness3 Impact ResistHot Fill Max (F) (hot fill) (polypropylene) ,500200 Fair200O-PP (oriented) ,500250 Good220 PVC (high density polyethylene) ,000150 Excellent1601 g/mil/100 sq in - 24 hrs, 2 cc/mil/sq m - 24 hrs, 3 Flexural modulus (jpsi x 1000)Source.

8 WestbridgeBlister Films and FoilsBlister Films and FoilsMono PPMono PPMono PVCMono PVCPVdCPVdC--coated PVCcoated PVCPCTFE laminationPCTFE laminationCOCCOC coco--extrusionsextrusionsPETG/PCTFE laminationPETG/PCTFE laminationCFFCFF Cold Form Foil (Alu / Alu)Cold Form Foil (Alu / Alu)PTA film for aggressive liquids (Tekniflex)PTA film for aggressive liquids (Tekniflex)Lidding foilLidding foilFilm Layers Vs Product ContactFilm Layers Vs Product ContactSame product contact layer:Same product contact layer:Mono PVCMono PVCPVdCPVdC--coated PVCcoated PVCPCTFE laminations (Aclar or Vaposhield)PCTFE laminations (Aclar or Vaposhield)ColdCold--Form FoilForm FoilPVC Puretherm 1001 LHDPVDCPCTFEAluoPAProperties & Advantages of PVC Properties & Advantages of PVC Pharmaceutical and Food grade onlyPharmaceutical and Food grade onlyHomopolymer type (more inert).

9 Homopolymer type (more inert).Gauge range 125 Gauge range 125 -- 500500 (5mil to 20mil).(5mil to 20mil).Common gauges: 200 Common gauges: 200 -- 250250 ( & 10mil).( & 10mil).Colors: Clear, UVColors: Clear, UV--blocker, White, , White, adhesion with lidding foil Better adhesion with lidding foil Cheapest PACKAGING optionCheapest PACKAGING optionLimited barrierLimited barrierProperties & Advantage of PVDCP roperties & Advantage of PVDCPVDC Coated Film:PVDC Coated Film: PVC Gauges 200 PVC Gauges 200 & 250& 250 ( & 10mil).( & 10mil). PVDC coatings: 40gsm, 60gsm, 90gsm & PVDC coatings: 40gsm, 60gsm, 90gsm & Duplex or Triplex (25 Duplex or Triplex (25 PE)PE) Colors: Clear and WhiteColors: Clear and White Medium barrier for moisture and oxygenMedium barrier for moisture and oxygenDuplex & Triplex PVDC coatingsDuplex & Triplex PVDC coatingsTriplex (example: VDC 250 Triplex (example: VDC 250--2525--60) 60) Duplex (example: VDC 250 Duplex (example.))

10 VDC 250--40)40)PVC 250 micronAdhesivePVDC 60gsmPE 25 micronPVDC 40gsmPVC 250micronPCTFE is a flexible thermoplastic film made from PCTFE is a flexible thermoplastic film made from ((polyolycchlorohlorottririffluoroluoroe ethylene) fluoropolymer resin thylene) fluoropolymer resin F CFFC ClnHomopolymer PCTFE filmHomopolymer PCTFE film-- 100% PCTFE (additive free)100% PCTFE (additive free)-- Less shrinkageLess shrinkage-- More cost effectiveMore cost effective CopolymerCopolymer PCTFE filmPCTFE film-- Historically firstHistorically first-- ~ 40 ~ 40 -- 50 % less barrier 50 % less barrier (vs. Homopolymer)(vs. Homopolymer)-- ~95% PCTFE content~95% PCTFE contentProperties ofProperties of PCTFE FilmPCTFE FilmPCTFE LaminationsPCTFE LaminationsTriplex LaminationTriplex LaminationDuplex LaminationDuplex LaminationPVC or alternativeAdhesivePCTFEPEA dhesivePCTFEPVC, PETG, BAREX , PPOr even LDPEA dvantage of PCTFE LaminationAdvantage of PCTFE LaminationTriplex lamination (PVC/PE/PCTFE )Triplex lamination (PVC/PE/PCTFE ) More forgiving in thermoformingMore forgiving in thermoforming Historically material of choiceHistorically material of choiceDuplex lamination (PVC/PCTFE )Duplex lamination (PVC/PCTFE ) Higher yield (more area per unit weight)Higher yield (more area per unit weight) Lower cost (source reduction)