1The site master file template, section by section.
The EU explanatory notes, PIC/S PE 008-4 and WHO’s guideline (TRS 961, Annex 14) set out the same nine sections and eight appendices (WHO calls them annexes), so one file can serve all three.¹²³ Copy the left column as your headings; the right column is where the facts usually live, so its owner can check that section.
Before section 1, give the file an edition number, the date it becomes effective and the date by which it must be reviewed. Keep it to 25 to 30 pages plus appendices where possible, readable on A4. PE 008-4 says “Simple plans, outline drawings or schematic layouts are preferred instead of narratives”; architectural drawings are not required.¹²
| Section | Fill in | Draw from |
|---|---|---|
| 1.1 Contact | Manufacturer’s name and address; site, building and unit addresses; a 24-hour defect and recall contact; a site identifier such as GPS or D-U-N-S, which EU authorities require for sites outside the EU and EEA | Company register; recall contacts |
| 1.2 Authorisations | Manufacturing authorisation (Appendix 1), or a statement that none is issued; activities each authority allows; product types (Appendix 2); GMP inspections in the last 5 years; GMP certificate (Appendix 3) | Licence; inspection log |
| 1.3 Other activities | Non-pharmaceutical activities on site | Site activity list |
| 2.1 Quality system | Brief description and standards used; responsibilities, senior management included; accreditations | Quality manual |
| 2.2 Release | Qualified Persons’ qualifications and role; certification and release procedure; how several QPs share the work; any PAT, real-time or parametric release | Release procedure |
| 2.3 Suppliers | Supply-chain knowledge and external audits; how contractors, API makers and critical suppliers are qualified; TSE and falsified-product measures; outside help; contractors (Appendix 4); responsibility split with contract givers | Approved suppliers; audit plan |
| 2.4 Risk management | Methods; what is done centrally and locally; use for continuity of supply | Risk procedure |
| 2.5 Quality reviews | Product quality review method | Review procedure |
| 3 Personnel | Organisation chart (Appendix 5); staff in quality management, production, quality control, storage and distribution | Headcount report |
| 4.1 Premises | Site size and buildings, with the markets each serves; a scaled plan; production layouts with room classes and pressure differentials (Appendix 6); warehouse layouts | Site and room drawings |
| 4.1.1 to 4.1.3 Utilities | HVAC principles, air changes and recirculation included; water quality and schematics (Appendix 7); steam, compressed air, nitrogen | Utility qualification reports |
| 4.2 Equipment | Major equipment, critical items marked (Appendix 8); cleaning of product-contact surfaces; GMP-critical computerised systems, not equipment PLCs | Equipment register; system inventory |
| 5 Documentation | Paper or electronic; off-site archives with address and retrieval time | Archive index |
| 6.1 Products | Dosage forms, human, veterinary and investigational, with any separate areas or staff; hazardous substances; dedicated or campaign production; PAT | Product list |
| 6.2 Validation | Process validation policy; reprocessing and rework policy | Validation master plan |
| 6.3 Materials | Sampling, quarantine, release and storage; handling of rejects | Warehouse procedures |
| 7 Quality control | Physical, chemical, microbiological and biological testing on site | QC test list |
| 8.1 Distribution | Recipient types and locations; entitlement checks; transport conditions; traceability; measures against the illegal supply chain | Customer list |
| 8.2 Complaints, recalls | The system for complaints, product defects and recalls | Complaint and recall procedures |
| 9 Self-inspection | How areas are selected and inspections arranged and followed up | Self-inspection plan |
The appendices are: 1, manufacturing authorisation; 2, dosage forms with the INN or common name of each API; 3, GMP certificate; 4, contract manufacturers and laboratories with supply-chain flow charts; 5, organisation charts; 6, production layouts with material and personnel flows and process flow charts for each dosage form; 7, water system schematics; 8, major equipment.¹
1.1For India: the revised Schedule M outline.
Revised Schedule M requires a site master file “prepared and maintained up to date as per the Appendix-I” (17.2.9), which has 12 headings of its own.⁴ Build an Indian file on them, borrowing PIC/S content where it maps:
| Schedule M heading | Nearest PIC/S section |
|---|---|
| 1 General information | 1.1 to 1.3, 2.1, 2.3, 2.4, 3, 6.1. Products registered abroad: not in PIC/S |
| 2 Personnel | 3, and 2.2 for Qualified Persons. Other key staff, training, health and hygiene: not in PIC/S |
| 3 Premises | 4.1 to 4.1.2. Construction and preventive maintenance: not in PIC/S |
| 4 Equipment | 4.2. Maintenance, qualification, calibration and computerised system validation: not in PIC/S |
| 5 Sanitation | 4.2.2, which covers product-contact surfaces only |
| 6 Documentation | 5 |
| 7 Production | 6.1 to 6.3 |
| 8 Quality assurance | 2.2, 2.5, 5, 6.2, 7. Change control: not in PIC/S |
| 9 Loan licence | Not in PIC/S; nearest is 2.3, contractors |
| 10 Distribution, recall | 8 |
| 11 Self-inspection | 9. Whether an outside expert took part: not in PIC/S |
| 12 Export of drugs | Not in PIC/S; nearest are 1.2, authorised activities, and 8.2 |
The rules were notified on 28 December 2023; small and medium manufacturers that applied under G.S.R. 127(E) had until 31 December 2025.⁴⁵
2Example: a site master file for a small CDMO.
Example, invented for illustration. Company A runs Site A, a UK contract manufacturer that fills sterile vials for clients in the UK, the EU and the US. The edition below is 6, effective 2 November 2026, to be reviewed by 1 November 2027: 24 pages plus 8 appendices. The QA compliance lead compiles it, each record owner checks their section, and the head of quality approves it.
| Section | Example entry |
|---|---|
| 1.1 Contact | Company A, Site A: Building 2, fill-finish; Building 3, QC laboratory. 24-hour quality line. D-U-N-S number given, as the UK is outside the EEA |
| 1.2 Authorisations | MHRA licence in Appendix 1. Inspections: MHRA routine, May 2024; FDA pre-approval for a client product, September 2025. GMP certificate in Appendix 3 |
| 1.3 Other activities | None |
| 2.1 Quality system | Quality manual QM-001, built on EU GMP Chapter 1 and ICH Q10; quarterly management review chaired by the site director |
| 2.2 Release | Two QPs; SOP-QA-021 sets how they divide certification. No PAT, real-time or parametric release |
| 2.3 Suppliers | One contractor gamma-sterilises stoppers, audited every two years; list and flow chart in Appendix 4. Each client quality agreement says who checks marketing authorisation compliance |
| 2.4 Risk management | ICH Q9 tools under SOP-QA-030, run on site; a supply-continuity risk register per client product |
| 2.5 Quality reviews | One product quality review a year per product, written with the client |
| 3 Personnel | Quality management 9, production 42, quality control 16, storage and distribution 6: 73 in all |
| 4.1 Premises | Building 2: one Grade A filling line in a restricted access barrier system in a Grade B room; two freeze-dryers. Layouts in Appendix 6 |
| 4.1.1 to 4.1.3 Utilities | Two air-handling units for Grade B and C rooms; water for injection by distillation, hot loop, schematic in Appendix 7; clean steam, compressed air, nitrogen |
| 4.2 Equipment | Filling line, freeze-dryers, autoclave and depyrogenation tunnel marked critical in Appendix 8. Systems: LIMS, ERP, environmental monitoring, building management |
| 5 Documentation | Electronic documents; paper batch records; closed records at an off-site archive, retrieved within 2 working days |
| 6.1 Products | Aseptically filled solutions and freeze-dried powders in vials, human use. Investigational batches on the same line and staff. One cytotoxic product, in campaigns |
| 6.2 Validation | Validation master plan; aseptic process simulations on each line twice a year. No reprocessing; rework only with client approval |
| 6.3 Materials | Sampled in a booth, held in ERP quarantine until QC release; rejects caged and destroyed |
| 7 Quality control | Chemical, sterility, endotoxin and container closure integrity testing on site; bioassays at a contract laboratory (Appendix 4) |
| 8.1 Distribution | Only to clients’ licensed warehouses in the UK, EU and US; 2 to 8 °C shipments carry loggers |
| 8.2 Complaints, recalls | Clients take complaints and lead recalls under their quality agreements; Site A supplies distribution records within 4 hours |
| 9 Self-inspection | Annual risk-ranked plan covering every area within 2 years; findings tracked as CAPAs |
Each appendix can carry its own effective date, so a new organisation chart does not reissue the file:¹ in this edition Appendix 1, the licence, dates from 3 March 2025, Appendix 5, the organisation chart, from 14 September 2026, and Appendix 8, the equipment list, from 2 November 2026.
3How to prepare a site master file and keep it current.
The manufacturer prepares the file, and it belongs to the quality system, “kept updated accordingly” like any controlled document.¹ None of the texts names an owner or an approver, so name both in your document control procedure, as the example does. Health Canada asks importers for “the most recent, signed and dated SMF”.⁶
Review it on the date the file sets, and reissue the section or appendix concerned when one of these changes:
- A building, room grade or utility (4.1, Appendices 6 and 7).
- A dosage form, product type or hazardous substance (6.1, Appendix 2).
- A contractor added or dropped (2.3, Appendix 4).
- An inspection or a new GMP certificate (1.2, Appendix 3).
- An organisation chart or Qualified Person (2.2, 3, Appendix 5).
- A GMP-critical computerised system (4.2).
- The licence (1.2, Appendix 1).
The Philippine FDA asks for an updated file when a plant moves, adds a product line or changes its activities.⁷ FDA dropped its own site file partly because it went stale: the first reason it gave for abolishing the Type I drug master file was that “The information contained in Type I DMF’s was often outdated.”⁸
Before issuing, check two points regulators raise. MHRA’s pre-inspection report asks for principal computerised systems such as ERP, LIMS, eBMR and MES, and accepts a reference to the file if it holds the detail.⁹ Health Canada treats a building address that does not match the site master file as a deficiency in a licence application, so copy the address exactly from the licence.¹⁰
4Who requires a site master file, and does FDA?
| Authority | Position | Source |
|---|---|---|
| EU | Listed in EU GMP Chapter 4 as required GMP documentation; inspectors may assess it when preparing an inspection | Chapter 4;¹¹ EU inspection procedure 3.3¹² |
| EU, ATMPs | A site master file “should be prepared for every site involved in manufacturing of authorised ATMPs” | Part IV, 6.31¹³ |
| UK | MHRA points to EudraLex Volume 4, Chapter 4 included; licence applicants “provide a site master plan”, in MHRA’s words | MHRA GMP guidance;¹⁴ licence guidance¹⁵ |
| PIC/S, WHO | Guidance; manufacturers check national rules “to establish whether it is mandatory” | PE 008-4, 4;² TRS 961, Annex 14, 3³ |
| India | Required, in the Appendix-I outline above | Schedule M 17.2.9⁴ |
| Philippines | Presented to FDA inspectors when a drug manufacturer applies for a licence to operate | FDA citizen’s charter⁷ |
| Canada | Filed by importers for each foreign building; a quality manual may do for a site that only tests, does secondary packaging or sterilises packaging | GUI-0080⁶ |
| Australia | A site master file or equivalent, such as a plant file or quality manual, supports GMP clearance of an overseas site by compliance verification | TGA clearance guidance¹⁶ |
| FDA | Not required. Parts 210 and 211 contain no mention of a site master file; FDA can instead require records “in advance of or in lieu of an inspection” | 21 CFR 210, 211;¹⁷¹⁸ FD&C Act 704(a)(4)¹⁹ |
Health Canada’s notes, GUI-0005, published 10 April 2026, follow PE 008-4 with changes: a file for each location that fabricates, packages, labels or tests drugs, letter-size paper, no D-U-N-S, and any regulator’s database, not only EudraGMP, in place of licence and certificate copies.²⁰ TGA asks for the PIC/S content plus cross-contamination controls for high-risk or highly sensitising products.¹⁶
The nearest US equivalent, the Type I drug master file, held “manufacturing site, facilities, operating procedures, and personnel information”; a final rule of 12 January 2000 removed it.⁸ FDA asks for records instead. Its June 2025 guidance on remote regulatory assessments lists examples such as SOPs, periodic product reviews and “a summary of batches manufactured and their disposition, or a summary of discrepancies and investigations related to manufacturing and testing”.²¹ Keep those summaries current; a US site supplying the EU may still be asked for the file by EU inspectors.¹²
The EU requirement stays: the Commission’s draft Chapter 4, consulted on from 7 July to 7 October 2025, lists the site master file first among required master documents (4.27). The 2011 text still applies.²²²³²⁴
5Site master file vs other master files.
| Document | What it describes | Source |
|---|---|---|
| Site master file | One site’s GMP activities, for an inspectorate planning an inspection | EU explanatory notes 1.2¹ |
| Drug master file | A drug substance, product, packaging or excipient, which an applicant can reference with the holder’s written authorisation | 21 CFR 314.420²⁵ |
| Quality manual | The company’s pharmaceutical quality system, management responsibilities included | ICH Q10 1.8;²⁶ EU GMP 1.7²⁷ |
| PV system master file | A marketing authorisation holder’s pharmacovigilance system, kept at an EU site | GVP Module II²⁸ |
The site master file asks only for a “brief description” of the quality system, so it can refer to the quality manual rather than repeat it.¹ A drug master file describes a material or product, not a site.
6How it runs in Seal.
In Seal, a site master file is a controlled document like any other: under document control each document has one effective state, and where procedure requires periodic review, the interval, reminders and escalation belong to the document record. The review draws on deviations, audit findings, CAPAs and changes, and ends in a recorded decision to continue, revise, consolidate, replace or retire.
When inspectors ask for the file or the records behind it, inspection readiness keeps the request log, the package delivered and the observations that follow linked, so the team can show what was asked and exactly what was shared.
References
- 1EudraLex Volume 4, Part III, Explanatory Notes on the preparation of a Site Master File, European Commission, 2011, sections 1 to 4 and annex. https:/
/ health. ec. europa. eu/ document/ download/ 95af86f8- c82d- 4ad0- 85cb- 27c7f56531b4_ en?filename=2011_ site_ master_ file_ en. pdf (read 8 November 2026) - 2PE 008-4, Explanatory Notes for Pharmaceutical Manufacturers on the Preparation of a Site Master File, PIC/S, 1 January 2011, sections 2 to 6 and annex. https:/
/ picscheme. org/ docview/ 3463 (read 8 November 2026) - 3WHO guidelines for drafting a site master file, WHO Technical Report Series No. 961, Annex 14, World Health Organization, 2011, sections 1 to 4 and appendix. https:/
/ www. who. int/ docs/ default- source/ medicines/ norms- and- standards/ guidelines/ distribution/ trs961- annex14- guidelinesdraftingsitemasterfile. pdf?sfvrsn=29ee9d0_ 2 (read 8 November 2026) - 4G.S.R. 922(E), Drugs (Amendment) Rules, 2023, revised Schedule M, Gazette of India, Ministry of Health and Family Welfare, 28 December 2023, Part I 17.2.9, Appendix-I and rule 6. https:/
/ www. cdsco. gov. in/ opencms/ resources/ UploadCDSCOWeb/ 2018/ UploadGazette_ NotificationsFiles/ 2023. 12. 28_ DR_ Final%20G. S. R. %20922(E)_ Notification%20of%20Schedule%20M%20of. pdf (read 8 November 2026) - 5G.S.R. 127(E), Drugs Amendment Rules, 2025, Gazette of India, Ministry of Health and Family Welfare, 11 February 2025. https:/
/ www. cdsco. gov. in/ opencms/ resources/ UploadCDSCOWeb/ 2018/ UploadGazette_ NotificationsFiles/ 2025. 02. 11_ G. S. R. %20127(E). pdf (read 8 November 2026) - 6How to demonstrate foreign building compliance with drug good manufacturing practices (GUI-0080): Recommended full GMP evidence, Health Canada, modified 2 July 2025, site master file. https:/
/ www. canada. ca/ en/ health- canada/ services/ drugs- health- products/ compliance- enforcement/ good- manufacturing- practices/ guidance- documents/ guidance- evidence- demonstrate- drug- compliance- foreign- sites- 0080/ recommended- full- gmp- evidence. html (read 8 November 2026) - 7Citizen’s Charter, License to Operate (LTO), section 1.1 initial application for drug manufacturers and major variations, Food and Drug Administration Philippines, April 2024. https:/
/ www. fda. gov. ph/ wp- content/ uploads/ 2024/ 04/ 15. - License- to- Operate- LTO. pdf (read 8 November 2026) - 8New Drug Applications; Drug Master Files, final rule, 65 FR 1776, FDA, 12 January 2000, summary and background. https:/
/ www. govinfo. gov/ content/ pkg/ FR- 2000- 01- 12/ pdf/ 00- 648. pdf (read 8 November 2026) - 9GMP pre-inspection compliance report, MHRA, GOV.UK, question on principal computerised systems. https:/
/ assets. publishing. service. gov. uk/ media/ 5ef09176d3bf7f6c06ec3938/ PreInspection_ Compliance_ Report_ document. doc (read 8 November 2026) - 10Deficiencies: Applications and service standards for drug establishment licences (GUI-0127), Health Canada, modified 4 December 2024. https:/
/ www. canada. ca/ en/ health- canada/ services/ drugs- health- products/ compliance- enforcement/ establishment- licences/ directives- guidance- documents- policies/ management- applications- performance- drug- establishment- licences- 0127/ deficiencies. html (read 8 November 2026) - 11EudraLex Volume 4, Part I, Chapter 4: Documentation, required GMP documentation, European Commission, in operation since 30 June 2011. https:/
/ health. ec. europa. eu/ system/ files/ 2016- 11/ chapter4_ 01- 2011_ en_ 0. pdf (read 8 November 2026) - 12Conduct of inspections of pharmaceutical manufacturers or importers, Compilation of Union Procedures, European Commission and EMA, in force from 1 January 2024, section 3.3. https:/
/ www. ema. europa. eu/ en/ documents/ regulatory- procedural- guideline/ conduct- inspections- pharmaceutical- manufacturers- or- importers_ en. pdf (read 8 November 2026) - 13EudraLex Volume 4, Part IV, Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products, European Commission, 22 November 2017, section 6.31. https:/
/ health. ec. europa. eu/ document/ download/ ad33d9dd- 03f0- 4bef- af53- 21308ce2187d_ en?filename=2017_ 11_ 22_ guidelines_ gmp_ for_ atmps. pdf (read 8 November 2026) - 14Medicines: good manufacturing practice and good distribution practice, MHRA, GOV.UK, last updated 13 May 2024, overview. https:/
/ www. gov. uk/ guidance/ good- manufacturing- practice- and- good- distribution- practice (read 8 November 2026) - 15Apply for manufacturer or wholesaler of medicines licences, MHRA, GOV.UK, last updated 12 September 2025, inspection process. https:/
/ www. gov. uk/ guidance/ apply- for- manufacturer- or- wholesaler- of- medicines- licences (read 8 November 2026) - 16How to obtain GMP clearance through inspection reliance, Version 18.6, Therapeutic Goods Administration, May 2025, CV pathway documentation, site master file. https:/
/ www. tga. gov. au/ sites/ default/ files/ 2024- 11/ How- to- obtain- GMP- clearance- through- inspection- reliance. pdf (read 8 November 2026) - 1721 CFR Part 210, Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; general, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 210 (read 8 November 2026) - 1821 CFR Part 211, Current good manufacturing practice for finished pharmaceuticals, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211 (read 8 November 2026) - 1921 U.S.C. 374(a)(4), Inspection (FD&C Act section 704), United States Code, govinfo. https:/
/ www. govinfo. gov/ content/ pkg/ USCODE- 2023- title21/ html/ USCODE- 2023- title21- chap9- subchapVII- partA- sec374. htm (read 8 November 2026) - 20Annex 1 to the Good manufacturing practices guide: Explanatory notes for industry on the preparation of a site master file (GUI-0005), Health Canada, published 10 April 2026. https:/
/ www. canada. ca/ en/ health- canada/ services/ drugs- health- products/ compliance- enforcement/ establishment- licences/ directives- guidance- documents- policies/ annex- 1- explanatory- notes- industry- preparation- site- master. html (read 8 November 2026) - 21Conducting Remote Regulatory Assessments, Questions and Answers, guidance for industry, FDA, June 2025, question 12. https:/
/ www. fda. gov/ media/ 160173/ download (read 8 November 2026) - 22EudraLex Volume 4, Chapter 4: Documentation, draft for consultation, European Commission, July 2025, section 4.27. https:/
/ health. ec. europa. eu/ document/ download/ fa336a6e- 753b- 46fc- b53b- 9178bacd8878_ en?filename=mp_ vol4_ chap4_ consultation_ guideline_ en. pdf (read 8 November 2026) - 23Stakeholders’ Consultation on EudraLex Volume 4: Chapter 4, Annex 11 and New Annex 22, European Commission, 7 July to 7 October 2025. https:/
/ health. ec. europa. eu/ consultations/ stakeholders- consultation- eudralex- volume- 4- good- manufacturing- practice- guidelines- chapter- 4- annex_ en (read 8 November 2026) - 24EudraLex Volume 4, Good Manufacturing Practice guidelines, European Commission, list of Part I chapters and Part III documents. https:/
/ health. ec. europa. eu/ medicinal- products/ eudralex/ eudralex- volume- 4_ en (read 8 November 2026) - 2521 CFR 314.420, Drug master files, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ section- 314. 420 (read 8 November 2026) - 26ICH Q10, Pharmaceutical Quality System, section 1.8, ICH, 4 June 2008. https:/
/ database. ich. org/ sites/ default/ files/ Q10%20Guideline. pdf (read 8 November 2026) - 27EudraLex Volume 4, Part I, Chapter 1: Pharmaceutical Quality System, section 1.7, European Commission, in operation since 31 January 2013. https:/
/ health. ec. europa. eu/ system/ files/ 2016- 11/ vol4- chap1_ 2013- 01_ en_ 0. pdf (read 8 November 2026) - 28Guideline on good pharmacovigilance practices (GVP), Module II, Pharmacovigilance system master file (Rev 2), EMA/816573/2011 Rev 2, European Medicines Agency, in effect from 31 March 2017, section II.A. https:/
/ www. ema. europa. eu/ en/ documents/ scientific- guideline/ guideline- good- pharmacovigilance- practices- module- ii- pharmacovigilance- system- master- file- rev- 2_ en. pdf (read 8 November 2026)
AQuestions and answers
Does FDA require a site master file?
No. FDA’s drug GMP regulations in 21 CFR Parts 210 and 211 do not mention one. FDA can instead require specific records in advance of or in place of an inspection, such as summaries of batches and their disposition or of investigations. A US site that supplies Europe or other PIC/S markets may still need one for those authorities.
What is the purpose of a site master file?
It gives a regulator a short, factual description of one site’s GMP activities, so inspectors can plan an inspection and decide where to spend their time. It is written for the inspectorate rather than for staff, which is why it favours plans and lists over narrative and aims to stay within 25 to 30 pages plus appendices.
How often should a site master file be updated?
None of the EU, PIC/S or WHO texts sets an interval. You set the review-by date in the file itself, and you update the affected section or appendix whenever something it describes changes, without waiting for that date.
How does India’s site master file differ from the PIC/S format?
Revised Schedule M sets out 12 headings rather than the nine PIC/S sections. Most content maps across, but India also asks for staff training, health and hygiene arrangements, construction and preventive maintenance of premises, equipment qualification and calibration, change control, loan licence manufacture, products registered or exported abroad, and whether an outside expert took part in self-inspection.
Does a contract testing laboratory need a site master file?
Where the authority requires one, yes, but it covers only what the site does. The texts say a site doing only part of a pharmaceutical operation, such as analysis or packaging, describes only those operations, so a laboratory’s file centres on quality control, equipment, documentation and its clients.