Pharmaceutical packaging technology

pharmaceutical Packaging Requires A Greater Knowledge Of Materials And A Greater Intensity Of Testing Than Most Other Packed Products, Not To Mention A Sound Knowledge Of Pharmaceutical Products And An Understanding Of Regulatory Requirements. Structured To Meet The Needs Of The Global Market, This Volume Provides An Assessment Of A Wide Range Of Issues. It Covers The Entire Supply Chain From Conversion Of Raw Materials Into Packaging Materials And Then Assembled Into Product Packs. Integrating Information From Many Drug Delivery Systems, The Author Discusses Testing And Evaluation And Emphasizes Traceability And The Need To For Additional Safeguards. booknews the Capsules, Pills, And So On That Hold The Drugs Together Are Not The Topic Here Of The Mostly British Scientists In The Pharmaceutical Industry, But The Cardboard, Plastic, And What-not Of The Commercial Product Sitting On The Shelf. Like Others, The Pharmaceutical Industry Is Having To Respond To Increasing Concerns About The Environmental Impact Of Packaging, But Has To Pay More Attention Than Many Industries To The Preservation Of The Product During Shipping, Storage, And Shelf Life. Their Topics Include Regulatory Aspects, Materials Based On Paper And Board And Their Use In Pack Security Systems, Glass Containers, Plastic, Metal, Closures And Closure Systems, Sterile Products And The Role Of Rubber Components, And Printing And Decoration. Annotation C. Book News, Inc., Portland, Or (booknews.com) BOOK COVER......Page 1 HALF-TITLE......Page 2 TITLE......Page 4 COPYRIGHT......Page 5 CONTENTS......Page 6 CONTRIBUTORS......Page 8 PREFACE......Page 9 Integrity......Page 11 Route or mode of administration......Page 12 The pack......Page 13 Identification/information......Page 14 Protection......Page 15 Shock–impact......Page 16 Puncture......Page 17 Temperature......Page 18 Moisture......Page 19 The atmosphere and atmospheric gases......Page 20 Sunlight/light......Page 21 Contamination arising from physical actions......Page 22 Avoidance of electrostatic build-up......Page 23 EXAMPLE 2. IV SOLUTIONS......Page 24 Tamper resistance and adulteration......Page 25 MOULDS AND FUNGI......Page 26 Heat and irradiation......Page 27 Chemical hazards and compatibility......Page 28 Environmental issues......Page 29 Conclusions......Page 32 Marketing and sales......Page 34 Production engineering, maintenance and machinery purchasing......Page 35 Quality control and quality assurance, and specifications......Page 36 Transportation—direction and control......Page 37 Product and pack development......Page 38 Feasibility or investigational tests......Page 39 Packaging and stability (the formal estimation of shelf life)......Page 40 Example of use of incorrect material and lack of initial specification detail......Page 42 Shelf life......Page 43 Example......Page 44 Performance specifications......Page 47 Some pack assembly features......Page 48 Changes to product and pack (after initial launch)......Page 49 Likely conclusions......Page 50 Likely conclusions......Page 51 The expanding role of the pack (e.g. where pack acts as an administration aid or is used in a device)......Page 52 Some historical device-oriented products......Page 54 Closures......Page 55 Conclusion......Page 56 Examples of tests for specific materials......Page 59 Definition of the pack......Page 60 Incorporating a device into the pack......Page 61 Regulatory authorities—background......Page 62 Decentralised system (mutual recognition)......Page 64 Centralised system......Page 65 Product licence applications—data requirements on the package......Page 66 Notice to applicants......Page 67 MAA application section IIC3—control of starting materials......Page 68 Resin......Page 69 MAA application section IIF2—stability......Page 70 Expert reports......Page 71 FDA packaging guideline......Page 72 Packaging for clinical trials in the USA......Page 73 Pharmacopoeias......Page 74 Plastic material in contact with food (90/128 and amendments)......Page 75 The SmPC......Page 76 Leaflets......Page 78 Packaging waste......Page 79 Ozone layer depletion......Page 80 Classification, packaging and labelling of hazardous materials......Page 81 Summary......Page 82 Quality—a philosophy......Page 83 Quality of conformance......Page 84 Material specifications and quality standards......Page 85 The component specification......Page 86 Procedures/specification......Page 87 Identification......Page 88 MOULDED GLASS CONTAINERS......Page 90 GO/NO GO GAUGES......Page 91 Functional/performance tests......Page 92 Defect classifications......Page 93 Records......Page 94 Sampling......Page 95 Fixed percentage/number......Page 97 Sample size......Page 98 The binomial distribution......Page 100 The Poisson distribution......Page 101 New project with a new supplier......Page 104 Quality capability......Page 105 Manufacture and qualification controls......Page 106 Process controls......Page 107 Finished product control......Page 109 Validation as part of packaging quality......Page 110 Conclusion......Page 111 Technical references......Page 114 Sources of cellulose fibre......Page 116 Bleaching......Page 117 Mixer stage......Page 118 Additives......Page 119 Fourdrinier system......Page 120 Machine conversion into board......Page 121 Millboard......Page 122 Strawboards (lined or unlined)......Page 123 Paper and board merchandising......Page 124 Labels and labelling......Page 125 Label fundamentals......Page 126 Types of paper labels......Page 127 Problems of curl......Page 128 Delayed action labels......Page 129 Pressure sensitive labels (created by RS Avery 1935)......Page 130 Leaflets......Page 131 Choice of design......Page 132 Pre-folding and gluing......Page 133 Automatic......Page 134 Contact printing techniques......Page 135 On-line or off-line printing?......Page 136 Corrugated fibreboard......Page 137 Manufacture of corrugated and solid-board cases......Page 138 Closing of cases......Page 139 Composite containers......Page 141 The security environment in pharmaceuticals......Page 142 Adulteration or tampering......Page 143 Producer liability......Page 144 Project objectives......Page 145 Key features......Page 146 The adhesion system......Page 147 Security in the packaging operations......Page 148 Warehousing codes, e.g. EAN 128 or traded unit outer codes......Page 150 Security codes......Page 151 Conclusions......Page 152 Appendix 5.2: General tests for paper and board......Page 153 Appendix 5.3: Specific tests for cartons......Page 155 Appendix 5.4: Specific tests for corrugated......Page 156 Introduction......Page 157 Composition of glass and types......Page 158 Properties......Page 159 Blown glass......Page 161 Annealing......Page 162 Vello process......Page 163 Design and decoration......Page 164 Strength......Page 168 Consumer convenience......Page 169 Design protection—registration and patents......Page 170 Quality control and quality assurance......Page 171 Bottles and production lines......Page 173 Filling......Page 174 Closuring......Page 176 Labelling......Page 177 Warehousing......Page 178 Tubular glass containers......Page 179 Vials......Page 180 Cartridge tubes, disposable syringes......Page 181 Closures, caps, seals and stoppers......Page 182 Heterogeneous liners......Page 183 Screw closures......Page 184 Pitch......Page 185 Closuring diameter—relationship with seal efficiency......Page 186 Clinching, crimping, swaging, spinning or rolling......Page 187 Intravenous solutions, multidose vials......Page 188 Summary......Page 189 Terms not involving fractures or cracks......Page 190 Annealing test......Page 192 Notes......Page 193 References......Page 194 Linear......Page 195 Thermoset polymers......Page 196 Phenol formaldehyde (originally Bakelite) (PF)......Page 197 The acrylics......Page 198 Ethylene vinyl alcohol copolymer (EVAL or EVOH)......Page 199 Ionomers (trade name Surlyn)......Page 200 The nylons (polyamides) (PA)......Page 201 Low density polyethylene (LDPE)......Page 202 Polypropylene (PP)......Page 203 Poly ethersulph one......Page 204 Polyvinyl acetate (PVA)......Page 205 Rubber hydrochloride (Pliofilm—trade name)......Page 206 Synthetic rubbers (thermoplastic elastomers, TPE)......Page 207 Melt flow index (MFI)......Page 208 Appearance—optical properties......Page 209 Flexural properties (flexural strength)......Page 210 Hardness......Page 211 Brittleness temperature......Page 212 Water absorption......Page 213 Regulatory clearance......Page 214 Symmetry and cohesion energy......Page 215 Organic vapour permeation......Page 216 Plasticisers......Page 217 Stabilisers......Page 218 Colourants......Page 219 Extenders......Page 220 Residues in plastics......Page 221 Detection of constituents in plastics......Page 222 Film and sheet forms......Page 223 Injection moulding......Page 224 Extrusion blow moulding......Page 226 Thermoforming and blister (bubble) packs......Page 227 Sterilisation of plastics......Page 228 Gaseous sterilisation—ethylene oxide......Page 229 Aseptic processing and preservation......Page 230 Possible disadvantages......Page 231 Setting the specification......Page 232 Injection moulding......Page 234 Extrusion and injection stretch blow moulding......Page 235 References......Page 236 Packaging aspects......Page 239 Process of manufacture......Page 240 Materials and their properties......Page 241 Plastic grades......Page 242 Converter, i.e. laminate, film, bottle manufacturer......Page 243 Stage 3— product/pack compatibility and investigational testing......Page 244 Stage 4— formal product—pack stability tests......Page 245 Additional discussion......Page 246 Closure efficiency......Page 247 Use and misuse by the patient......Page 248 Panelling or cavitation......Page 249 Pretreatments for printing (and labelling)......Page 250 Conclusion......Page 251 Infusions and injections......Page 252 Appendix 8.2: Programme evaluation example......Page 253 France (Pharmacopoeia Francaise Xth edn 1982)......Page 254 Appendix 8.5: Bibliography......Page 255 Appendix 8.7: The plastics industry and GMP including traceability......Page 256 Appendix 8.8: Risk versus intensity ,of testing......Page 257 The elderly patient......Page 258 Support documentation for company and regulatory clearance (of products, packs and devices)......Page 259 Appendix 8.10: Other articles by author......Page 260 Gamma irradiation......Page 261 Summary—plastics and pharmaceutical packaging......Page 262 Absorption and adsorption of preservatives......Page 263 Extractives and general compendial tests......Page 264 Packaging material (primary or immediate packaging)......Page 265 Appendix 8.14: Summary of ICH guidelines on stability and possible influences on the ‘pack’......Page 266 Appendix 8.15: Future polymers for pharmaceuticals......Page 267 Shrink wrapping......Page 268 Oriented polypropylene......Page 269 Shrink terminology......Page 270 Stretch bundling......Page 271 Combination materials covering flexible and rigid applications (or multilayer materials)......Page 272 Printing processes......Page 273 Regenerated cellulose film (RCF) (Cellophane, Rayophane, Diophane, etc.)......Page 274 Films and coatings based on plastics......Page 275 Protective properties......Page 276 The polyolefins......Page 277 Polystyrene (PS, density 1.05)......Page 278 Polyacrylonitrile (PAN, trade name—Barex)......Page 279 Lacquers and waxes......Page 280 Extrusion coatings......Page 281 Vacuumised treatment, e.g. metallisation......Page 282 Foil strength......Page 283 Adhesives—traditional......Page 284 Heat sealing—peelable, semi-permanent, permanent......Page 287 Lamination selection......Page 288 Other points......Page 289 Metallisation......Page 291 Silicon oxide (SiOx) coated materials (thickness 1500–3000 Å)......Page 292 Appendix 9.1: Packing material specification......Page 293 Introduction......Page 295 Manufacture of tinplate......Page 296 Specification of steel and tinplate......Page 297 Can enamels and lacquers......Page 298 Decorating metal containers......Page 299 Offset lithography......Page 300 Types of metal containers......Page 301 Deep drawn containers......Page 302 Rigid impact extruded aluminium containers......Page 303 Closures......Page 304 Impact extruded collapsible metal tubes......Page 305 Closures and closuring......Page 306 Built-up containers......Page 307 Container fabrication—the open-top can......Page 308 Talcum powder containers......Page 309 Liquid containers......Page 310 Shipping containers......Page 312 Components and types of aerosols......Page 313 Filling and packaging......Page 314 Conclusion......Page 315 The properties of aluminium foil......Page 316 Supported foil......Page 317 Pinholes and pinhole theory......Page 318 Cold forming......Page 319 Conclusions......Page 320 Introduction......Page 321 Closure evaluation and performance against egress and ingress for reclosables......Page 322 Closure assessment and control: some general factors......Page 323 Environment......Page 324 Initial approach to closure assessment and control......Page 325 Atmospheric pressure......Page 326 Combined pressure and vacuum tests......Page 327 Ingress to product......Page 328 Other tests and considerations......Page 329 Thermoplastic-based closures......Page 331 Wadless closure systems......Page 332 Torque......Page 333 Thread engagement—turn to release......Page 334 Multi-start versus single start threading......Page 335 Metal vacuum seals......Page 336 Conclusions—reclosables......Page 337 Metal......Page 338 Impact extruded aluminium cans......Page 339 Reel factors (or sheet factors)......Page 340 Heating methods and cooling......Page 341 Other factors......Page 342 Terminology associated with adhesion......Page 343 Methods of adhesive application......Page 344 Observation of visual defects, e.g. pinholes, capillaries.......Page 345 Crack, pinhole, capillary detection......Page 346 Tamper-evidence and tamper-resistance......Page 347 Child-resistance, tamper-evidence/resistance and OPD (original pack dispensing)......Page 348 Closure systems involving product delivery or administration......Page 349 Intravenous (IV) solutions......Page 350 Appendix 11.2: References—sterile products......Page 351 Appendix 11.4: Closure systems and stress cracking......Page 352 Pressure sensitive tapes......Page 353 Appendix 11.7: US finishes......Page 354 Introduction......Page 355 The history of injectables......Page 356 Moist heat......Page 357 Packaging materials......Page 358 Rubber and elastomers......Page 359 Natural rubber......Page 360 Cure ingredients......Page 361 Plasticisers......Page 362 Ampoules and vials......Page 363 Lyophilised products......Page 364 Two-component drug system......Page 366 Compatibility with the drug......Page 367 Seal integrity......Page 368 Self-sealing and fragmentation......Page 369 Ready to sterilise (RTS) closures......Page 370 Conclusions......Page 371 References......Page 372 Basic equipment principles......Page 373 Feeding and filling......Page 374 Lidding and heat sealing......Page 375 Curl of trays (particularly relevant with hard foil)......Page 376 Machine summary......Page 377 Protection against moisture......Page 378 Blister materials—trays and lids......Page 379 Blister lidding materials (push-through)......Page 380 Cold forming (or mechanically formed blisters)......Page 381 Costs......Page 382 Controlled or monitored dosage systems for the elderly......Page 383 Strip packaging process......Page 384 Strip designs......Page 385 Conclusions......Page 386 Pinholes and foil (aluminium)......Page 387 Tamper-evidence, tamper-resistance and child-resistance......Page 388 Semi-automatic blister packaging equipment......Page 389 Materials......Page 390 September 23rd—24th 1998......Page 392 Introduction......Page 395 Bringing the materials to the packaging line......Page 396 Packaging line services......Page 397 Gas......Page 398 Container-based filling......Page 399 Form fill and seal packaging systems......Page 400 Sachets......Page 401 Ampoules......Page 402 Closing the package......Page 403 Collation, casing and palletisation......Page 404 Operators and training......Page 405 Physical or mechanical damage......Page 408 Hazards the product creates......Page 409 Nature of primary pack......Page 410 Environmental changes during storage, handling and distribution......Page 411 Palletised and non-palletised loads......Page 412 Pallet types......Page 413 Incorporation of low slip materials......Page 414 Height stacked and stack configuration......Page 415 Containerisation......Page 416 Storage and handling of packaging materials and components......Page 417 Costs......Page 418 UN certification......Page 419 Conclusions......Page 420 Introduction......Page 421 Key......Page 422 Print terminology......Page 423 Decoration/printing—general processes......Page 424 Graphic reproduction (‘origination’)......Page 425 Line artwork—multicolour print......Page 426 Desktop publishing (DTP) and digital artwork and reproduction (DAR), i.e. preprint to press (PTP) systems.......Page 427 PRECIPITATION......Page 428 Printing machine terminology......Page 429 Flexographic......Page 430 Hot die stamping and gold blocking......Page 431 Planographic......Page 432 Dry offset lithography......Page 433 Intaglio......Page 434 Letraset......Page 435 Embossing and debossing......Page 436 Vacuum metallising......Page 437 Security systems......Page 438 Print adhesion......Page 439 Special considerations—pharmaceutical and cosmetics......Page 440 Printing and printing inks......Page 441 Conclusions......Page 442 Introduction......Page 444 Product trends influencing pack trends......Page 445 Other medicinal products which influence packaging trends......Page 446 Films, foils and laminates, including coextrusions and metallisation......Page 447 Faster lines, pregauging on-line or pregauged components and tighter specifications......Page 448 Child-resistance......Page 449 In-house printing......Page 450 Controlled dosage systems (also called monitored dosage systems)......Page 451 Conclusions......Page 452 Appendix 17.1: Packaging and medical devices......Page 453 INDEX......Page 454 & Quot;This volume reviews the current status of product-pack relationships both as a multi-disciplinary activity and in the expanding role of the pack as a drug delivery system. Extensive coverage is given to the supplier chain, the means by which raw materials are converted into packaging materials, components etc. and then assembled into product packs. Testing and evaluation is therefore discussed from raw materials through to ongoing product sale, use and disposal. Particular emphasis is placed on traceability and the need to safeguard both the user and the producer in issues of product liability. All types of product and pack are considered, from those of low risk (e.g. solid dose forms) to those of greater risk (IV solutions, sterile products). & quot;--BOOK JACKET