First edition · v1.0 · regulatory verification 01/10/2026
Coverage is not cleaning, pressure is not cold-spot temperature, qualification is not validation: CIP and SIP systems designed, qualified and governed with the source next to every value.
An engineering and quality guide for those who specify, design, qualify and run the cleaning, CIP and SIP systems of pharmaceutical and biotech process equipment: requirements and cleaning strategy, CIP design and hygienic engineering, SIP and thermal process control, automation and monitoring, qualification and the cleaning validation interface, lifecycle and procurement. 24 chapters in six parts and 6 appendices, 281 pages in the Italian edition and 285 in the English one, and 24 editable tools in Word and Excel, for €199.
281 pages (ITA) · 285 (ENG) · PDF A424 chapters in six parts + 6 appendices24 tools: 12 Word + 12 Excel88 sources in the register116 tracked decisionsDigital product: download after payment
One language per purchase, chosen by the variant. The ITA - Italiano variant gives you the PDF guide and the 24 tools in Italian; the ENG - English variant gives them in English. Both editions have the same structure, the same tools and the same codes CS-TK-01…24. There are no files in French, German or Spanish.
The decisions it helps you make
Every chapter starts from a company decision and closes it with who decides, on what basis and where it is recorded: 116 decision codes, each linked to the tool where it is documented.
URS you can verify
Requirements for skids, circuits, spray devices and SIP with criticality, verification method and expected evidence, traced through to release.
Chapter 4 · CS-TK-04, CS-TK-18
Hygienic design
Which dead-leg definition and which measurement reference, which slopes and drainability tests, which materials, finishes, valves and elastomers, which ASME BPE edition in the contract.
Chapter 7 · CS-TK-06, CS-TK-07
CIP hydraulics and chemistry
Architecture, capacity and return; hydraulic criterion per section and per branch, flow per device, agents, concentrations, temperatures, times and water quality per step, defined for the system.
Chapters 5–6 · CS-TK-05, CS-TK-13
Spray coverage
Riboflavin test under recipe conditions, with pressure at the device, zone map and repeat triggers: it demonstrates coverage, not cleanliness.
Chapter 8 · CS-TK-08
Steam, air and condensate in SIP
Sterile boundary, steam quality at the point of use, air removal, condensate and traps, vent filters and vacuum risk after the cycle.
Chapters 9–10 · CS-TK-09, CS-TK-10
Cold spots and F0
Which event starts exposure, where the coldest point is, which lethality criterion with stated Tref and z, which role for biological indicators.
Chapters 11–12 · CS-TK-11, CS-TK-12
Recipes, interlocks and data integrity
Parameters with access level and limits, valve matrix, interlocks with negative testing, versions, audit trail and cycle reports: a validated recipe changes only through change control.
Chapters 13 and 15 · CS-TK-13, CS-TK-15
Rinse endpoints and trending
Critical instruments and calibration, conductivity compensation, conductivity and TOC endpoints, control charts whose limits are not acceptance limits.
Chapters 14 and 16 · CS-TK-14, CS-TK-16
Commissioning and qualification
C&Q approach, reuse of supplier testing, FAT, SAT, IQ and OQ, release for use with conditions of use and requalification triggers.
Chapters 17, 18 and 20 · CS-TK-17, CS-TK-20
Interface with cleaning validation
System worst case, sampling points tied to the design, hold times, number of runs defined in the protocol; residue limits stay in the sister guide.
Chapter 19 · CS-TK-19
Troubleshooting and changes
Investigation with a hypothesis matrix and CAPA with an effectiveness criterion; retrofits, periodic review and requalification with the rationale for every due date.
Chapters 21–22 · CS-TK-21, CS-TK-22
Supplier and TCO
RFP, supplier and integrator responsibilities, mandatory requirements kept apart from scores, NPV, scenarios and break-even price.
Chapters 23–24 · CS-TK-23, CS-TK-24
The myths it takes apart
Values that circulate as "requirements" and that the sources write differently. For each one the guide gives the document, clause, nature and object.
"1.5 m/s is a GMP requirement." It is a design convention of dairy origin (3-A 605-04, appendix, "should"), tabulated by ASME BPE; EU GMP and 21 CFR 211 set no velocity. Removal depends on local wall shear stress, complete flooding, air displacement, chemistry, temperature and time, and is demonstrated by testing (Chapter 6).
"6D, 3D, L/d ≤ 2: the GMP dead-leg rule." EU GMP Annex 1 defines a dead leg as a non-circulating length greater than 3 internal diameters; L/d ≤ 2 from the inner wall is a design target of ASME BPE, a voluntary standard; the six diameters from the axis come from the proposals cited by the 1993 FDA inspection guide for hot water systems. Every comparison states where it measures from (Chapter 7).
"SIP is done at 121 °C for 15 minutes." Annex 1 does not contain "121": clause 8.63 requires all parts to receive the required treatment, with monitoring at locations correlated with the slowest to heat. ≥ 121 °C for ≥ 15 minutes is the Ph. Eur. reference cycle for products and materials; for equipment SIP there is no prescribed F0 and the criterion is justified at the coldest point (Chapters 9 and 11).
"If the pressure is right, so is the temperature." Only for pure saturated steam and in absolute pressure: air and non-condensable gases lower the temperature at the same pressure. The temperature at the control point does not guarantee the cold-spot temperature, and exposure time alone does not measure lethality (Chapters 9–11).
"Three consecutive runs validate cleaning." No text in force in the EU sets a number of cycles: EU GMP Annex 15 (10.13) requires an appropriate number based on risk assessment and PIC/S PI 006-4 has it defined in the protocol. "At least three consecutive applications" was in PI 006-3, superseded since 01/10/2026 (Chapter 19).
"10 ppm and 0.1% of the dose are requirements." They appear neither in EU GMP nor in PI 006-4: under Annex 15 (10.6) limits come from a toxicological evaluation. The historical criteria remain in the 2006 WHO text, to be compared with the HBEL: that is the subject of the sister guide on cleaning validation (Chapter 19).
"The riboflavin test passed, so the tank is clean." The riboflavin test is a qualitative check of the accessibility and wetting of surfaces under test conditions: it demonstrates coverage, not cleanliness. Cleaning effectiveness is demonstrated with the actual soil in cleaning validation (Chapter 8).
"Biological indicators are mandatory to qualify SIP." Annex 1 provides for them "where appropriate" (8.36) as an additional method (8.42): validation rests first of all on physical measurements, and BI results alone do not override critical parameters and process design (Chapter 12).
The guide
24 chapters in six parts, named after the six areas of the Cleaning, CIP & SIP hub, and 6 appendices. Chapters 2–23 follow seventeen fixed sections, always in the same order: requirement → interpretation → risk → decision → action → evidence → audit readiness. Four status labels and seven nature labels say what each source is worth and in which jurisdiction.
The toolkit
24 editable tools: 12 Word templates and 12 Excel workbooks, each as a clean template and as a filled-in example. The workbooks have a Read_Me with the functional specification and Formulas, Error_Check and Assumptions_Limits sheets, and return only "Comparison with the entered criteria" or "Assessment required".
Four integrated cases
On the fictitious company Neravo Biologics: a new CIP skid from URS to OQ, tank coverage after a spray-device retrofit, a cold spot in the SIP of a transfer line, conductivity endpoint drift with a recipe changed without change control, plus the TCO of replacing a skid. Chapter 24 closes with 164 inspector questions in twelve macro-areas.
Regulatory status verified as of 01/10/2026
The guide describes the regulatory and technical framework as of 01/10/2026; documents published or amended after that date are not considered. Every source carries a status label (current, draft, in development, superseded) and a nature label, with the jurisdiction where it applies. The points that most often change how a source is read:
- PIC/S PI 006-4 'Recommendations on Qualification and Validation' has been in force since 01/10/2026 and replaces PI 006-3 (2007). It is a PIC/S recommendation for inspectors and industry: in the EU the binding reference remains EU GMP Annex 15.
- EU GMP Annex 1 (2022), operational since 25/08/2023: for SIP (8.63) it requires all parts to receive the required treatment, with temperature, pressure and time monitored at locations correlated with the slowest to heat, and the system to remain integral after SIP.
- EU GMP Annex 15 (2015) is in force. Its revision is in development: EMA concept paper of 19/01/2026, draft planned for December 2026.
- Annex 11, Chapter 4 and Chapter 1: the 2025 revisions are drafts with closed consultations; the 2011 Annex 11 and Chapter 4 and the 2013 Chapter 1 remain in force.
- ASME BPE: BPE-2026 was issued on 01/05/2026 and becomes effective six months later (on 01/11/2026, by calculation); as of 01/10/2026 BPE-2024 remains effective. Contracts must state the applicable edition.
- Voluntary standards (ASME BPE, ISO 13408-4 and -5, ISO 17665:2024, EN 285, 3-A, EHEDG, ASTM E2500) become binding only if referenced in a contract, a URS, a specification or a quality agreement. Their texts are not reproduced.
- USA: 21 CFR 211, 600.11 and Part 11. For biologics, 21 CFR 600.11(b) sets an equivalence with 121.5 °C for 20 minutes of saturated steam against which the validated cycle is compared: it is not a mandatory cycle.
Updates included. Appendix F lists the events that trigger re-verification of the guide: final texts of the Annex 11, Chapter 4 and Chapter 1 revisions, the draft revision of Annex 15, ASME BPE-2026 becoming effective, Ph. Eur. Issue 13.1 becoming applicable. When the texts change, you receive the revised guide and toolkit at no extra cost. The guide does not announce release dates for its own revisions: the revision on sale is shown on this page.
The 24 tools, in six groups
One folder per part of the book, with the exact titles of the English edition. No operational value is preloaded: velocities and flow rates, pressures, temperatures, concentrations and times, conductivity and TOC endpoints, slopes and L/d, SIP phase conditions, lethality criteria, number and location of thermocouples, number of runs, acceptance criteria and frequencies remain <to be defined>, with the decision code.
01_Requirements · Requirements and Cleaning Strategy
WORDCS-TK-01 · Project Brief and RACI Matrix
Scope, regimes per system, boundaries with the sister guides, RACI and split between site, supplier and integrator.
EXCELCS-TK-02 · Equipment, Surface and Residue Register
Equipment, surfaces with a mandatory source, hard-to-clean parts, residue families, materials and data for validation.
EXCELCS-TK-03 · Cleaning and SIP Risk Assessment
Failure modes per system, chosen method, system worst case and residual risk: without entered scales, no priority.
WORDCS-TK-04 · CIP/SIP URS
Verifiable requirements for skids, circuits, devices and SIP, with criticality, verification method and expected evidence.
02_CIP_Design · CIP Design and Hygienic Engineering
EXCELCS-TK-05 · CIP Hydraulic Calculator — Velocity, Reynolds, Wall Shear, Flow and Volume
Velocity, Re, mean wall shear stress, flow per branch and per device, volumes, rinses, capacity and return.
EXCELCS-TK-06 · Dead-Leg and Drainability Register
Branches and low points with a stated measurement, L/d with the chosen measurement method and no default, slopes and approved exceptions.
WORDCS-TK-07 · Hygienic Design Review Checklist
Branches, materials, finishes, welds, segregation, return, valves, slopes and exceptions.
WORDCS-TK-08 · Spray Coverage Test Protocol (Riboflavin)
Test under recipe conditions, pressure at the device, zone map, criterion and repeat triggers.
03_SIP · SIP and Thermal Process Control
EXCELCS-TK-09 · Saturated Steam and F0 Lethality Calculator
P–T in absolute pressure, air, throttling, F0 with actual Δt and stated Tref and z, BI reduction, start-up condensate and vacuum forces.
WORDCS-TK-10 · SIP Design and Sterile Boundary Checklist
Sterile boundary, air, condensate and traps, steam at the point of use, filters, vacuum and routine probes.
WORDCS-TK-11 · SIP Cycle Development and Qualification Protocol
Lethality target, start of exposure, thermocouples, BIs, sterile hold, post-SIP checks and conditions of validity.
EXCELCS-TK-12 · SIP Temperature Mapping Data Analysis
Protected raw data, gaps flagged and never interpolated, F0 per probe within the window; a positive BI always leads to "Assessment required".
04_Automation_Monitoring · Automation and Process Monitoring
WORDCS-TK-13 · Recipe, Sequence and Interlock Functional Specification
States, parameters with level and limits, valve matrix, interlocks with negative testing, versions, cycle reports and alarms.
EXCELCS-TK-14 · Instrument and Calibration Register
Critical instruments and calibrations with as-found error; for every out-of-tolerance as-found, the cycles run since the last valid calibration.
EXCELCS-TK-15 · CIP/SIP Data Integrity and Audit Trail Assessment
Primary record, cycle report, controls per requirement of Annex 11 and 21 CFR Part 11 and 211, access, recipes, audit trail and alarms.
EXCELCS-TK-16 · Rinse Endpoint Trending (Conductivity/TOC)
End-of-step measurements, reference window and run rules; control limits are not acceptance limits.
05_Qualification · Qualification and Cleaning Validation
WORDCS-TK-17 · C&Q Plan and FAT/SAT/IQ/OQ/PQ Framework
Approach, classification, reuse of supplier testing, sequence and phase releases, FAT, SAT, IQ and OQ frameworks.
EXCELCS-TK-18 · Requirements Traceability Matrix
Requirement → risk → test → evidence → deviation → status, with descriptive statuses and no percentages.
WORDCS-TK-19 · Cleaning PQ Protocol — Cleaning Validation Interface
Boundary, system worst case, sampling points tied to the design, hold times, number of runs and triggers.
WORDCS-TK-20 · Qualification Report and Release for Use
Criterion-by-criterion comparison, traceability status, deviations, released recipes, conditions of use and requalification triggers.
06_Lifecycle · Lifecycle and Procurement
WORDCS-TK-21 · CIP/SIP Deviation Investigation and CAPA
Containment, timeline, hypothesis matrix, root cause, impact and CAPA with an effectiveness criterion.
EXCELCS-TK-22 · Maintenance, Periodic Review and Requalification Planner
History, changes, activities with the rationale for every due date, triggers, reviews and the inspector question bank.
WORDCS-TK-23 · RFP Checklist and Supplier Responsibilities
Technical request, deliverables, responsibilities, service, spare parts, obsolescence, data and topics for quality agreements.
EXCELCS-TK-24 · Technical Bid Evaluation and TCO
Mandatory requirements kept apart from scores, NPV, scenarios and break-even, non-monetary criteria; no bid is flagged as the winner.
In the ITA - Italiano variant the same 24 tools carry the titles of the Italian edition and the same codes CS-TK-01…24. Every tool also exists as a filled-in example on the Neravo Biologics case, in the 07_Examples folder.
Use it tomorrow morning
| The situation | What you use |
|---|
| A new CIP skid to specify and qualify | Chapters 4, 6, 17, 18 and 20 + CS-TK-04, CS-TK-05, CS-TK-17, CS-TK-18 and CS-TK-20: verifiable URS, hydraulic calculation, FAT, SAT, IQ and OQ, requirement → evidence traceability and release for use. This is Case A in Chapter 24. |
| After a spray-device change, the riboflavin test finds shadow zones | Chapters 8 and 21 + CS-TK-05, CS-TK-08 and CS-TK-21: test under recipe conditions, pressure at the device, diverted flow, cause, remedy and repeat test. This is Case B. |
| A low point does not reach temperature while the PLC completes the SIP normally | Chapters 10, 11 and 12 + CS-TK-09, CS-TK-10, CS-TK-11 and CS-TK-12: air and condensate, the event that starts exposure, thermocouple mapping, F0 per probe, BIs, investigation and requalification. This is Case C. |
| The conductivity endpoint drifts and a recipe was changed without change control | Chapters 13, 15, 16 and 21 + CS-TK-13, CS-TK-15, CS-TK-16 and CS-TK-21: recipe versions and audit trail, trending with control limits that are not acceptance limits, investigation and CAPA. This is Case D. |
| The cleaning PQ protocol to write with the validation team | Chapter 19 + CS-TK-19 and CS-TK-02: system worst case, sampling points tied to the design, hold times, number of runs defined in the protocol; limits and MACO in the sister guide. |
| Velocity, dead legs and slopes to justify in a design review | Chapters 6 and 7 + CS-TK-05, CS-TK-06 and CS-TK-07: criterion per section and per branch, stated measurement reference, drainability test, approved exceptions with their mitigations. |
| An end-of-life skid to replace, or bids to compare | Chapters 23 and 24 + CS-TK-23 and CS-TK-24: supplier and integrator responsibilities, mandatory requirements kept apart from scores, NPV, scenarios and break-even. This is the TCO in Chapter 24. |
| A GMP inspection with CIP/SIP systems in scope | Chapters 20, 22 and 24 + CS-TK-18, CS-TK-20 and CS-TK-22: traceability, release for use, periodic review and 164 inspector questions built for training, with expected evidence and red flags. |
What the guide does not do
It gives no universal numbers. No universal value for velocities, flow rates, pressures, temperatures, concentrations, contact times, number of rinses, endpoints, slopes, L/d, SIP hold times, target F0, number and location of thermocouples, number of runs or requalification frequencies. Where a source states a value, the guide reports it with document, clause, nature and object; numerical examples are marked [DEMONSTRATION EXAMPLE].
It never declares a system validated, clean or released. No tool returns a validated, clean or sterile outcome: the only outcomes are "Comparison with the entered criteria" or "Assessment required", and a missing data point always leads to the latter. Releasing the system for use and accepting a cycle rest with the quality function, on the basis of data and a documented assessment.
It does not calculate residue limits. HBEL, PDE, MACO, limits, sampling, recovery and analytical methods are covered in the sister guide Cleaning Validation in GMP Facilities – Operational Guide to HBEL, MACO and Defensible Limits (Second Edition + Toolkit); this guide describes only how the CIP/SIP system connects to those requirements.
It is not legal advice and does not reproduce subscription texts. It describes the texts, status and force of the sources. ASME, ISO, EN, EHEDG, 3-A, USP–NF, Ph. Eur., PDA, ISPE and ASTM are cited by title, number, edition and status, without tables or numerical criteria.
Contents: six parts, 24 chapters
Chapter titles of the English edition. Every chapter closes with a checklist, related tools and articles, decisions and the chapter's sources.
Part I — Requirements and Cleaning Strategy
- 1. Governance, responsibilities and regulatory basis of CIP/SIP
- 2. Equipment, surfaces, products and residues
- 3. Cleaning and sterilisation strategy and QRM
- 4. URS for cleaning, CIP and SIP systems
Part II — CIP Design and Hygienic Engineering
- 5. CIP system architecture
- 6. Hydraulics, chemistry and cycle parameters
- 7. Hygienic design
- 8. Spray devices and coverage testing
Part III — SIP and Thermal Process Control
- 9. Steam sterilisation fundamentals for SIP
- 10. SIP design
- 11. SIP cycle development
- 12. SIP qualification
Part IV — Automation and Process Monitoring
- 13. Control architecture, recipes and interlocks
- 14. Instrumentation and measurement
- 15. Data integrity of CIP/SIP systems
- 16. Rinse endpoints, routine monitoring and trending
Part V — Qualification and Cleaning Validation
- 17. C&Q strategy
- 18. FAT, SAT, IQ and OQ of CIP/SIP systems
- 19. Interface with cleaning validation
- 20. Report, deviations and release for GMP use
Part VI — Lifecycle and Procurement
- 21. Troubleshooting CIP and SIP cycles
- 22. Change control, retrofit, periodic review and requalification
- 23. Supplier selection, RFP and quality agreement
- 24. TCO and integrated cases
Appendices A–F. A ITA/ENG glossary · B Source matrix · C Chapter, toolkit and article matrix · D Toolkit instructions · E Register of assumptions and limitations · F Revision and change log.
What the package contains
After payment you download a ZIP file with the guide and the toolkit in the language of the chosen variant.
- The complete PDF guide. 281 A4 pages in the Italian edition, 285 in the English one; clickable table of contents and bookmarks.
- 24 editable tools. 12 Word templates and 12 Excel workbooks, in folders 01_Requirements…06_Lifecycle.
- 24 filled-in examples and demonstration datasets. The examples on the Neravo Biologics case in the 07_Examples folder, with datasets DS-01…DS-06 (hydraulics, SIP mapping, endpoint trend, TCO, test cases) in .csv and .xlsx.
- Support files. README, navigable toolkit index, field glossary and guide–toolkit–article matrix in the 00_Read_Me folder.
- Verification. Test Log with one row per tool, test case and language, language parity report, check of example values and a manifest with the SHA-256 hash of every file, in the 08_Verification folder.
Read the excerpt before you buy
The free excerpt is made of real pages: 16 pages in the Italian edition, 16 in the English one. It contains the presentation with the regulatory status box and the labels, the full table of contents, dead legs and drainability from Chapter 7, the event that starts SIP exposure from Chapter 11, the complete Case C from Chapter 24, real pages of three tools (CS-TK-06, CS-TK-08 and CS-TK-12) and the list of what the purchase includes.
Specifications
| Format | A4 PDF with clickable table of contents and bookmarks; tools in .docx and .xlsx |
| Pages and chapters | 281 pages (ITA edition) · 285 pages (ENG edition) · 24 chapters in six parts + 6 appendices (A–F) |
| Toolkit | 24 editable tools: 12 Word + 12 Excel, codes CS-TK-01…24, plus 24 filled-in examples |
| File languages | One language per purchase: ITA - Italiano or ENG - English. There are no files in French, German or Spanish. |
| Edition and revision | First edition, October 2026 · v1.0 · tools rev. 1.0 |
| Regulatory verification | 01/10/2026 (status of every source as of that date) |
| References | EU (EudraLex, EMA) · PIC/S · WHO · USA (21 CFR, FDA guidance) · United Kingdom (essential status) · voluntary technical standards |
| Sources and decisions | 88 sources in the Appendix B register · 116 decisions tracked in Appendix D |
| Free excerpt | 16 pages (ITA edition) · 16 pages (ENG edition) |
| Updates | When the texts change, you receive the revised guide and toolkit at no extra cost. |
| Delivery | Digital product: download of the ZIP file after payment. No shipping: the 3D image of the volume is a graphic rendering; there is no printed book. |
| Software requirements | A PDF reader; Microsoft Word and Excel or compatible programs: the Excel workbooks were recalculated with LibreOffice in the Test Log runs. No macros, no external links; calculated cells protected without a password. |
| Licence | Individual use and internal use within the purchasing company: a personal, non-exclusive, non-transferable licence under the site's Legal Notice; printing for internal use only; sharing the files with third parties is prohibited. |
| Price | €199.00 per variant (guide + toolkit in the chosen language) |
Limits of use
- The Excel workbooks are calculation templates with specification, tests and limits, not validated software: before GMP use, the company verifies them in its own quality system by repeating the relevant Test Log cases.
- Simulated case: Neravo Biologics S.r.l. is a fictitious company and the data are hypothetical. Example values are not acceptance criteria or parameters of a real system.
- No sheet declares a system validated, clean or released: the only outcomes are "Comparison with the entered criteria" or "Assessment required". The guide does not replace the assessment of the quality function.
- The guide does not replace the official texts cited and is not personalised legal, regulatory or quality advice.
- The inspector questions are built for training and do not reproduce real findings. No guarantee of audit or inspection outcomes, which depend on context and application.
- The numerical examples were recalculated independently by the editorial team; the guide and the toolkit have not undergone independent third-party validation.
Who it is for. Process and project engineering, CQV and validation, QA, production (process owners), automation and OT, maintenance and utilities, procurement, skid suppliers and system integrators. It is written for those who specify, design, qualify or run CIP and SIP circuits on tanks, transfer lines, bioreactors, media and buffer preparation, filtration and chromatography skids, and need to know which text every value comes from, with what force and in which jurisdiction.
Who it is not for. It is not a guide to cleaning validation (limits, HBEL, MACO, sampling and methods stay in the sister guide), to pharmaceutical water systems and pure steam generation, to autoclaves and terminal sterilisation, or to full computerised system validation. Single-use systems, chromatography resin sanitisation and room disinfection are out of scope or covered only as interfaces.
Frequently asked questions
Which language are the files in?
The language of the chosen variant: ITA - Italiano or ENG - English. Each purchase includes the guide and the toolkit in one language. There are no files in French, German or Spanish.
Is it a printed book?
No. It is a digital product: after payment you download a ZIP file with the PDF and the tools. No shipping; the 3D image is only a rendering of the volume.
Does the guide give velocities, temperatures, times or F0 values that apply to everyone?
No, because no regulation sets them. It reports the values the sources state, with their nature (1.5 m/s is a convention, L/d ≤ 2 an ASME BPE target, F0 ≥ 8 minutes an EMA criterion for the medicinal product in the dossier), and the method for deciding the company's own, each with its decision code (Chapters 6, 7, 9 and 11).
Do the tools say whether a system is clean, sterile or validated?
No. They return only "Comparison with the entered criteria" or "Assessment required"; missing data, exceedances or criteria not entered always lead to the latter, with the reason. The decision rests with the quality function.
Does it calculate MACO and residue limits?
No. Chapter 19 and CS-TK-19 describe how the CIP/SIP system connects to cleaning validation (system worst case, sampling points, hold times, number of runs); HBEL, PDE, MACO, limits, recovery and analytical methods are in the sister guide on cleaning validation linked on this page.
Does it take PIC/S PI 006-4 into account?
Yes. PI 006-4 has been in force since 01/10/2026 and replaces PI 006-3: the guide treats it as a PIC/S recommendation, with EU GMP Annex 15 as the binding reference in the EU. The PI 006-3 statements on three consecutive applications and on the 10 ppm and 0.1% of dose criteria are not carried over into the current version (Chapters 1, 17 and 19).
Does it apply to the United States?
The main reference is the EU, with PIC/S and WHO as guidance; for the United States the guide covers 21 CFR 211, 600.11 and Part 11, the relevant FDA guidance and inspection guides, and informational USP chapters such as <1229.13>, which set no requirements or acceptance criteria, without reproducing their text.
Are the Excel workbooks validated?
They are not validated software. Each one has a Read_Me with the functional specification, readable formulas, error checks and a Test Log of the tests run: the company verifies them in its own system before GMP use.
What happens when the reference texts change?
Appendix F lists the events that trigger re-verification of the guide: final texts of the Annex 11, Chapter 4 and Chapter 1 revisions, the draft revision of Annex 15, ASME BPE-2026 becoming effective, Ph. Eur. Issue 13.1. When the texts change, you receive the revised guide and toolkit at no extra cost. The revision on sale is shown on this page, with the regulatory verification date.
Can I share the files with colleagues, suppliers or integrators?
The licence is for individual use and internal use within the purchasing company, personal, non-exclusive and non-transferable: sharing the files with third parties, including suppliers, integrators and external consultants, is prohibited. Printing is allowed for internal use only.
Before you buy: the Cleaning, CIP & SIP hub
The 12 technical articles of the Cleaning, CIP & SIP Systems hub introduce the six areas of the guide, from the URS to supplier selection.
Go to the Cleaning, CIP & SIP hub →Do you have a CIP or SIP circuit to design, qualify or bring back under control?
Describe the system, the products, the project stage and where you are stuck. GuideGxP will review the request and, where appropriate, may put you in touch with a specialist suited to your technical needs and your geographical area.
Describe your situation →No purchase obligation. The request is reviewed before any referral to a specialist.
GuideGxP guides do not replace official legislation or the guidance and standards cited (European Commission, EMA, PIC/S, WHO, ICH, FDA, MHRA, EDQM, USP, ASME, ISO/EN, 3-A, EHEDG, ASTM): they are operational support tools, do not constitute legal advice, and users remain responsible for the correct application of the rules in force in their own company context. Subscription texts are not reproduced. Numerical examples are for demonstration and are not acceptance criteria; releasing the system for use and accepting a cycle rest with the quality function. Regulatory status verified as of 01/10/2026. Neravo Biologics S.r.l. is a fictitious company. Digital product: no physical shipping.
