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Cleaning Cycle Sequences 89 into the processing system (2). The solvent laden with residue is transferred to a waste handling system capable of handling the solvents and potent compounds. Some dedicated product facilities perform very infrequent cleaning, and may use process reactors equipped with spray devices and transfer piping to perform the duties of the CIP unit. When aCIP unit is used, the design will likely include solvent headers to supply the necessary cleaning solvents, for example acetone, methyl alcohol, DMSO, and dimethyl formamide. Solvent-Based Cleaning Sequence Example The primary phases of asolvent-based cleaning sequence, for cleaning between Drugs “A” and “B” campaigns are presented in sequential order in Table 6. TABLE 6 Solvent Cleaning Sequence Phase Function Success criteria Process solvent Apre-flush To process compound recovery and to reduce soil load prior to cleaning All soiled process paths flushed clear Process gas blow nitrogen Solvent recovery, line clear Primary solvent and soil load pushed to solvent recovery Process drain (complete Release process for cleaning Residual solvent drained to process A operations) solvent recovery CIP program initiation Acquires CIP boundary, Boundary and utilities initiates nitrogen purge and blanket available, permissives met Chemical wash Expose all soiled surfaces to Chemical wash removes soil, recirculated cleaning solvent confirmed later in program Gas blow, intermediate drain Remove soiled solvent from Primary solvent and soil load circuit sent to solvent recovery Rinse process solvent flush Single pass flush of all soiled Circuit flushed clear of spent surfaces with cleaning solvent solvent Gas blow, intermediate drain Remove flush solvent from Primary solvent and soil load circuit sent to solvent recovery Chemical wash Recharge with solvent and Sampling for previous product recirculate for sampling soil reveals residual below acceptance criteria (less than _ppm) Gas blow, intermediate drain Solvent recovery, line clear Sampling solvent to solvent recovery Program complete Releases CIP boundary, Perform visual inspection or terminates nitrogen and equipment breakdown for blanket manual cleaning prior to release for processing Process solvent Bflush To remove residual solvent A All soiled process paths flushed clear Process gas blow and Solvent recovery, line clearing Primary solvent and soil load process drain sent to solvent recovery Ready for process B operations Release for process B
90 The pre-cleaning process flush with Solvent “A” is akey ingredient in the equipment cleanability. This post-process flush removes the primary soil load and will lessen the overall CIP cleaning load. Typically, the flush does not involve the CIP unit, but does use the equipment CIP spray devices and is considered aprocess, not acleaning function. As such, there isnocleaning performance “acceptance criteria” assigned to the operation. Combustion Concerns Due to the combustion concerns related to the CIP system solvent utilization it is essential to consider the potential hazards and ensure the required safeguards are inplace. Nonconductive solvents build up an electrical charge, and sprayed mist will be capable of containing sufficient total electrical charge to generate the spark energy needed to exceed the solvent’s minimum ignition energy (MIE). If the spray device piping is grounded and bonded adequately, then these charges will go off toground and cannot participate in the generation of aspark. An ignition source with air present could initiate an explosion, and that ignition source could potentially be the sprayed organic mist. The CIP program must ensure the exclusion of a fuel source below the minimum oxygen concentration. A CIP circuit nitrogen purge to create an inert atmosphere may be required to avoid an explosive atmosphere. The CIP unit should include a filtered nitrogen supply and vent on to permit purging of the CIP circuit, and active nitrogen blanketing may be considered over the course of the CIP program. To determine the impact on the instrumentation selection and wiring installation, the solvent(s) selected and their MIE, as well as the expected use conditions must be evaluated to determine how best to respond and adapt. Solvent-Assisted Cleaning Programs Solvent-assisted cleaning programs are being applied with greater frequency in bulk pharmaceutical chemical or API facilities with both solvents and aqueousbased cleaners playing arole. Again, these CIP operations typically occur between process campaigns and may be infrequently scheduled. The soils may be marginally vulnerable to aqueous cleaners, and asolvent process pre-flush is used to supplement the benefits of the alkaline and acid based aqueous cleaning programs. This approach reduces the solvent waste generated, minimizes the hazards associated with spraying solvents, and reduces the added cost for specifying and supplying a CIP unit capable of running supplying solvents under anitrogen blanket. PROCESS CONTROL TO ENSURE CLEANING PROGRAM SUCCESS Rush There are two (2) relevant timers associated with the control ofaCIP cleaning boundary which aid in ensuring the integrity of clean processing operations, or the success of avalidated CIP program under controlled soil conditions.
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Clean-In-Place for Biopharmaceutica
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Informa Healthcare USA, Inc. 52 Van
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iv Preface period, the industry rec
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Preface iii Contents Acknowledgment
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Contributors Barry J. Andersen Seib
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2 the last step of abatch manufactu
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4 Seiberling The vessel capacity ma
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6 Seiberling any two ports. For pur
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8 AWFI (or Any Water) Supply If the
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10 Seiberling program, and through
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12 Seiberling (380 L) for the solut
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14 AWFI CIP skid Drain When steam a
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16 Seiberling products in asingle f
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18 Seiberling The literature began
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2 Project Planning for the CIPable
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Project Planning for CIPable Facili
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Page 62 and 63: 3 Water for the CIP System Jay C. A
Page 64 and 65: Water for the CIP System 43 FIGURE
Page 66 and 67: Water for the CIP System 45 of clea
Page 72: Water for the CIP System 51 WATER U
Page 75 and 76: 54 Time Temperature FIGURE 2 The cl
Page 77 and 78: 56 Classification of Cleaners by pH
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Page 81 and 82: 60 + - Na O O C CH 2 CH 2 (CH 2 ) n
Page 83 and 84: 62 CH3 -(CH2 ) n -CH2 -O -CH2 -CH2
Page 85 and 86: 64 B C D E FIGURE 17 Capability of
Page 87 and 88: 66 pH 13 pH 7 pH, %, Excess water h
Page 89 and 90: 68 dramatically increased rinsing t
Page 91 and 92: 70 desorption. If the affinity is v
Page 93 and 94: 72 & Cleaning procedure inthe case
Page 95 and 96: 74 effort being performed relativel
Page 97 and 98: 76 Rush & A1000 Lmixing vessel, hav
Page 99 and 100: 78 TABLE 2 Typical Single-Pass Chem
Page 101 and 102: 80 Rush Rinse Volume (Duration) The
Page 103 and 104: 82 Rush Intermediate Drain Objectiv
Page 105 and 106: 84 Rush Final Drain Phase (Gravity)
Page 107 and 108: 86 TABLE 4 Recirculated Chemical Wa
Page 109: 88 Rush type of soil include fermen
Page 113 and 114: 92 REFERENCES Rush 1. Howard T, Wie
Page 115 and 116: 94 CIP return (CIPR)-piping to conv
Page 117 and 118: 96 Seiberling provided, generally o
Page 119 and 120: 98 Single-Tank CIP Skid Operational
Page 121 and 122: 100 Single-Tank Bypass or Recycle O
Page 123 and 124: 102 Seiberling Single-Tank Single P
Page 125 and 126: 104 Seiberling installation of an e
Page 127 and 128: 106 Chemical loop AB FE Chemical bl
Page 129 and 130: 108 Chemical loop AB FCV FE Steam C
Page 131 and 132: CIP supply Transfer line (typical)
Page 133 and 134: 112 Seiberling FIGURE 14 This singl
Page 135 and 136: 114 Seiberling FIGURE 15 This large
Page 137 and 138: 116 Seiberling FIGURE 17 This mini-
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Page 142 and 143: CIP System Instrumentation and Cont
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CIP System Instrumentation and Cont
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146 Lebowitz should be considered f
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148 Lebowitz barrels and the chemic
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150 Lebowitz Electromagnetic-Operat
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152 Lebowitz FIGURE 5 The venturi o
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154 Chemical pump enclosure Acid AL
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156 Steam Facility acid header Faci
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158 Lebowitz That is to say aweak a
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160 CIP Philosophy The production p
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162 Franks and Seiberling the numbe
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164 Franks and Seiberling Similar s
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166 Franks and Seiberling FIGURE 3
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170 (A) (B) Franks and Seiberling F
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174 The variables that impact the r
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176 There are two guiding concepts
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178 Mezz. Floor(ref.) V-5 1000L CIP
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180 return line piping, substantial
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182 Lebowitz U-bend transfer panels
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184 Lebowitz oriented vertically. T
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186 Lebowitz suction-side port on T
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CIPS loop Primary CIPS CIPSPS CIPS
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190 Lebowitz FIGURE 10 Photo of sma
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192 Drain CIP return Drain Recycle
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11 Materials of Construction and Su
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Materials of Construction and Surfa
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12 Cleanable In-Line Components INT
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Cleanable In-Line Components 213 &
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Cleanable In-Line Components 215 Al
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Cleanable In-Line Components 217 Ex
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Cleanable In-Line Components 219 FI
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Cleanable In-Line Components 221 Tr
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Cleanable In-Line Components 223 it
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Cleanable In-Line Components 229 eq
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Cleanable In-Line Components 231 Th
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Cleanable In-Line Components 233 co
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13 Cleanable Liquids Processing Equ
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Cleanable Liquids Processing Equipm
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1-9 CIPS 2 Plant steam CIPS valves
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258 8. Projectile-type thermometer
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260 Forder control of the drying pr
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262 Forder FIGURE 5 Pharmaceutical
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264 Forder FIGURE 7 Pharmaceutical
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266 FIGURE 9 Pleated filter cartrid
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268 FIGURE 12 Disassembledstainless
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270 The acid wash of 85% phosphoric
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272 FIGURE 17 Sanitary Vbenders. So
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274 one each for the upper, central
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276 CIP VS. TRADITIONAL BOIL-UP MET
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278 Cerulli were not designed to be
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280 by large flanged connections fo
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282 CIP header Once thru CIP soluti
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284 Nozzle Use A Manway B Agitator
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286 3" Stub end w/150# flange 2A 1
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288 In most cases, the pressure dro
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290 CIP fluids Process fluids 1 2 3
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292 A Vent to atm. B M Conical drye
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294 One of the designer’s first t
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16 CIP System Troubleshooting Guide
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CIP System Troubleshooting Guide 29
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17 Waste Treatment for the CIP Syst
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Waste Treatment for the CIP System
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18 Commissioning and Qualification
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Commissioning and Qualification 329
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348 & Sterilization refers to the r
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350 Lankford All analytical methods
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352 should be based upon scientific
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354 Lankford acleaning validation p
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356 In summary, TOC analysis is are
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358 In-Situ In-situ measurement tec
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360 15. Karen A. Clark, Product Man
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362 Actually, most countries revise
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364 §211.100 Written procedures; d
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366 §211.186 Master production and
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368 Equipment Regulation C.02.005 T
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370 … C.02.004 … 4. Pipework sy
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372 5.20 Schedules and procedures (
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374 TABLE 1 Directives of the Europ
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376 TABLE 5 Cleanability Performanc
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Index Accessibility, 28 Acid cleane
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Index 381 CIP supply flow troublesh
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Index 383 [Cleaning cycle sequences
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Index 385 Flow alarm, no-return, 30
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Index 387 Off skid instrumentation,
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Index 389 Rising stem valves, 223-2
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Index 391 [Troubleshooting] spray c
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