SOP on Site Master File (SMF) Preparation

In short: This illustrative SOP describes how a pharmaceutical manufacturer can prepare, review and control a Site Master File (SMF). For an Indian licensed site, use the current Schedule M Appendix-I and verify that the description matches the site’s licensed activities and actual operations.

This is a template for adaptation within a site’s approved quality system. It does not replace the applicable licence, regulations, marketing authorisations or the site’s document-control procedure.

Objective

Describe a controlled method for compiling, checking, approving and updating an SMF that gives an accurate overview of the GMP activities performed at a manufacturing site.

Scope

Use this procedure for the licensed manufacturing premises and the operations carried out there. In India, Drugs Rules, 1945, Schedule M Part I §17.2.9 requires the licensee to prepare and keep the SMF up to date in line with Appendix-I, as substituted by G.S.R. 922(E) (28 December 2023). WHO TRS No. 961, Annex 14 (2011) explains that the SMF should describe the site’s GMP-related operations; national or regional requirements determine whether an SMF is mandatory in other jurisdictions.

Responsibility

Example in-house criterion (not a pharmacopoeial requirement): QA coordinates the document, functional owners provide and verify information for their areas, and authorised site management approves it under the site’s document-control procedure.

Procedure

1. Initiate the SMF

Identify the legal entity, licensed site and activities to be described. Define the intended regulatory or inspection use, applicable markets, document owner and review route. Include an adjacent or nearby building only when its operation is integrated with the named site; describe only the operation performed on site when the manufacturer carries out only part of a process there, consistent with WHO TRS No. 961, Annex 14 §§1.1–1.2 (2011).

2. Collect and verify site information

Request current information from the accountable department owners. Compare it with the manufacturing licence, approved procedures, site plans, product and process lists, organisation chart, inspection records and current contracts or technical agreements, as applicable. Resolve differences with the responsible owner before using the information. Do not include confidential operational detail that is unnecessary for the SMF’s purpose.

3. Draft the content

For an Indian licensed site, organise the document around the content in Schedule M Part I, Appendix-I (G.S.R. 922(E), 28 December 2023):

1. General information: firm profile, licensed manufacturing activities, other activities at the premises, licensed product types and process-flow charts, relevant employee numbers, external scientific or technical support, foreign product registrations, a short QMS description and quality risk assessment. WHO TRS No. 961, Annex 14 Appendix §§1.2 and 2.1 (2011) also recommends listing site GMP inspections from the preceding five years, with dates and authority details, and noting relevant certifications or accreditations.
2. Personnel: organisation chart for quality assurance, production and quality control; key personnel’s qualifications, experience and responsibilities; training arrangements and records; personnel health and hygiene requirements, including clothing.
3. Premises: scaled plans or descriptions of manufacturing areas, construction and fittings, ventilation and relevant contamination-control layouts, sterile-room classification where applicable, special handling areas, water systems and premises-maintenance arrangements.
4. Equipment: major production and QC laboratory equipment, preventive-maintenance arrangements, qualification and calibration, and validation arrangements for computerised systems.
5. Sanitation: the availability of written specifications and procedures for cleaning manufacturing areas and equipment.
6. Documentation: how manufacturing and product-quality documents are prepared, revised and distributed, including relevant quality monitoring documentation.
7. Production: process descriptions or flow diagrams; material and product handling from receipt through sampling, quarantine, release and storage; rejected-material controls; and the general process-validation policy.
8. Quality assurance and control: the documentation system, change control, validation policy or master plan, product-quality review, QC activities and finished-product release procedure.
9. Loan-licence manufacture: how GMP compliance by the loan licensee is assessed, when applicable.
10. Distribution, complaints and product recall: distribution arrangements and records, and the complaint and recall-handling systems.
11. Self-inspection: a brief description of the self-inspection programme and whether an independent external expert has taken part.
12. Exports: products exported by country and any relevant export-related complaint or recall information.

Keep the description factual and representative of current operations. WHO recommends a concise SMF, as far as possible no longer than 25–30 pages plus appendices, with simple plans or diagrams where useful and legible A4 printing; this is WHO guidance, not a page limit in Schedule M (WHO TRS No. 961, Annex 14 §1.3, 2011).

4. Attach and control supporting material

Use current, legible appendices for information better presented as a list, plan, flow chart or diagram. Index each appendix and identify its title, owner, revision or effective date, where applicable. Check that the main text points to the right appendix and that no appendix contradicts the body. Include a current contact route for product-defect or recall matters where appropriate; WHO TRS No. 961, Annex 14 Appendix §1.1 (2011) recommends a 24-hour contact number for that purpose.

5. Review and approve

Ask each information owner to confirm their section. QA checks completeness against the applicable Schedule M Appendix-I headings, consistency between text and appendices, correct citations, and alignment with current site-controlled information. Route the final document for approval according to the site’s controlled-document procedure. Record approvals and the effective date in the controlled copy.

Example in-house criterion (not a pharmacopoeial requirement): the older template assigns preparation to the QA Head and calls for signatures from QA, the Head of Quality and the Plant Head. Confirm the current roles and approval route in the site’s document-control procedure.

6. Review, revise and issue

Schedule M Part I §17.2.4 requires documents to be regularly reviewed and kept up to date, with controls to prevent unintended use of superseded versions; §17.2.9 specifically requires the SMF to be maintained up to date (G.S.R. 922(E), 28 December 2023). Review the SMF when site operations, licensed activities, products, facilities, responsibilities or relevant systems change, and at the interval set in the site’s approved procedure. Record revisions and control issue of the current approved copy under that procedure.

Example in-house criterion (not a pharmacopoeial requirement): the older template schedules an annual review in January, sets the next review date one year after the effective date, allows review within ±30 days of the due date, and recertifies continued use if a review finds no revision is needed.

Example in-house criterion (not a pharmacopoeial requirement): the older template uses the document number XX/SMF/YYYY/ZZ, starts the revision sequence at 00, allows annexes to be updated separately from the main SMF, and resets an annex revision suffix to 00 when the main SMF is revised. It records review history from the initial revision.

Example in-house criterion (not a pharmacopoeial requirement): the older format specifies a white A4 sheet with company logo; top, bottom, left and right margins of 0.7, 0.5, 1.2 and 0.5 inches; header and footer offsets of 0.8 and 0.5 inches; Times New Roman 14-point company heading and 12-point subheadings; page numbering as “Page X of Y”; new-page starts for sections; date fields handwritten on each page; and separate pagination for annexes and revision history. It uses a cover sheet for title, document and section numbers, issue/effective/next-review dates and superseded version, with separate indexes for annexes and amendments.

Example in-house criterion (not a pharmacopoeial requirement): the older template sets section-length caps of 250 words/one A4 page for company profile and site description; 100 words/half a page for external technical assistance; 750 words/three pages for QMS and qualification/validation/calibration; 500 words/two pages for personnel, construction/finishes, ventilation and documentation; 250 words/half a page for premises and utility maintenance and sanitation; and 250 words/one page for equipment maintenance.

The older template also asks for a list of products recalled during the previous two years, or “none” if there were no recalls. Keep that look-back only if it remains suitable for the site’s intended submission and applicable requirements.

Example in-house criterion (not a pharmacopoeial requirement): the older template requires the SMF to be prepared by the QA Head, approved by QA, the Head of Quality and Plant Head, distributed as a controlled copy to the Factory Head, and sent to an outside authority only by the Head of Quality or a designee as an “uncontrolled copy”; the issue is logged. It calls for superseded copies to be marked obsolete and handled under the document-control procedure, and uses amendments for changes between full revisions.

7. Records and retention

Control SMF drafts, approvals, change history and issued copies under the site’s records-management procedure. Batch-associated GMP records must be retained at least one year after the expiry date of the respective product batch under Schedule M Part I §17.2.7 and 21 CFR §211.180(a). For EU batch documentation, retain it for one year after batch expiry or five years after Qualified Person certification, whichever is longer (EudraLex Volume 4, Part I, Chapter 4 §4.11). Apply any longer period required by the applicable local law or marketing authorisation.

8. Related procedures

See also: SOP for corrective and preventive actions, SOP on change control and SOP for risk management.

Abbreviations

• GMP: Good Manufacturing Practice
• QMS: Quality Management System
• QC: Quality Control
• QA: Quality Assurance
• SMF: Site Master File

References

1. Government of India, Ministry of Health and Family Welfare. Drugs Rules, 1945, Schedule M Part I §§17.2.4, 17.2.7, 17.2.9 and Appendix-I, substituted by G.S.R. 922(E), 28 December 2023. Official Gazette PDF.
2. World Health Organization. WHO Technical Report Series No. 961, Annex 14: WHO guidelines for drafting a site master file (2011), §§1.1–1.4 and Appendix. Official WHO document.
3. European Commission. EudraLex, Volume 4, Part I, Chapter 4: Documentation, revision 1 (January 2011; effective 30 June 2011), §4.11. Official European Commission PDF.
4. United States, 21 CFR §211.180(a), current eCFR text (2026). Official eCFR.