1What an SOP is under GMP.
EU GMP Chapter 4 says procedures, “otherwise known as Standard Operating Procedures, or SOPs”, “give directions for performing certain operations”. They sit among the instruction documents, alongside specifications, manufacturing formulae and processing, packaging and testing instructions, and protocols, and apart from the records that show what was done.¹ WHO defines an SOP as “an authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material”, such as equipment operation, maintenance and cleaning, validation, environmental control, and sampling and inspection.²
GMP calls for written procedures across the operation. 21 CFR 211 requires written procedures for production and process control, and for the quality control unit’s own responsibilities, among many others.³⁴ EU GMP lists examples that need written policies, procedures and records, including validation and qualification, calibration, technology transfer, maintenance and cleaning, training, environmental monitoring, pest control, complaints, recalls, returns, change control, investigations of deviations and non-conformances, internal audits and supplier audits.¹
2SOP or work instruction.
None of 21 CFR 211, ICH Q7 or WHO’s GMP text defines a work instruction.³⁵² EU GMP Chapter 4 names it once, in the rule that “Standard Operating Procedures, Work Instructions and Methods should be written in an imperative mandatory style”, so it holds all three to the same style rule.¹ In device production, MDSAP auditors check that “documented procedures, requirements, work instructions, and reference materials” are available for each production process they audit.⁶
The distinction GMP itself draws is between procedures for operations and product-specific instructions. WHO notes that certain SOPs “may be used to supplement product-specific master and batch production documentation”.² The product-specific directions are the master production and control record in the US,⁷ the manufacturing formula and processing and packaging instructions in the EU,¹ and master production instructions for APIs.⁵
| Document | What it does |
|---|---|
| Procedure (SOP) | Gives directions for performing certain operations, not necessarily specific to a product.¹² |
| Work instruction | Not defined in 21 CFR 211, ICH Q7 or WHO’s GMP text. Written in the same imperative style as SOPs and methods, and checked for in device production audits.¹⁶ |
| Processing and packaging instructions, master record | Product- and batch-size-specific directions: materials, equipment, steps, in-process controls and limits.¹⁷ |
| Protocol | Gives instructions for performing and recording certain discrete operations.¹ |
| Record | Provides evidence of the actions taken to comply with the instructions.¹ |
Whatever a company calls a document, if it directs GMP work it is controlled. EU GMP asks for all types of document to be defined and adhered to, and ICH Q7 for all documents related to manufacture to be prepared, reviewed, approved and distributed according to written procedures.¹⁵
3What a GMP SOP must do.
| Requirement | Source |
|---|---|
| Written “in an instructional form in clear and unambiguous language, specifically applicable to the facilities provided”. | EU GMP Chapter 1, 1.8(iv)⁸ |
| Laid out in an orderly fashion and easy to check, in a style and language that fit its intended use, in an imperative mandatory style. | EU GMP Chapter 4, 4.4¹ |
| Title, nature and purpose clearly stated; contents unambiguous. | WHO TRS 986 Annex 2, 15.4² |
| Approved, signed and dated by appropriate and authorised persons; uniquely identifiable; effective date defined. | EU GMP Chapter 4, 4.3¹ |
| Production and process control procedures are drafted, reviewed and approved by the appropriate organisational units, and reviewed and approved by the quality control unit, which approves or rejects every procedure affecting identity, strength, quality and purity. | 21 CFR 211.100(a), 211.22(c)³⁴ |
| Consistent with the relevant parts of the manufacturing and marketing authorisation dossiers. | EU GMP Chapter 4, 4.2¹ |
| Not handwritten, with enough space where data has to be entered. | EU GMP Chapter 4, 4.6¹ |
| Followed and documented at the time of performance, with any deviation recorded and justified. | 21 CFR 211.100(b)³ |
| Known to the people who use it: training covers the written procedures that apply to each person’s functions. | 21 CFR 211.25(a)⁹ |
| Regularly reviewed and kept up to date, with superseded versions kept out of use. | EU GMP Chapter 4, 4.5; WHO 15.5¹² |
4Writing one.
Start from the operation as it is done in your facility and from the authorisations it has to match, since EU GMP expects procedures to be specific to the facilities provided and consistent with the dossiers.⁸¹ State the title and purpose, then write the steps as instructions in the imperative, in the order they are done, with the checks and limits that apply and space for any data to be recorded.²¹ Where a step depends on a product, put it in the product’s master instructions and have the SOP refer to them.²
Route the draft for review by the units that do the work and approval by the quality unit, and set an effective date.³¹ Train the people who will use it in the procedure as it relates to their functions.⁹ Once it is effective, change it only through change control, which revises every document the change affects.⁵
5How it runs in Seal.
In Seal a procedure is linked to the forms, training and execution rules it governs, so a revision carries its reason, impact assessment and verification through change control, and once it is effective the next run follows the new version (document system). Document control keeps one effective version per document, with review, approval, change impact, training, effective dates and controlled copies in one governed workflow.
Neil, Seal’s AI agent, can turn an SOP into a process: it proposes the steps, capture fields, checks and approval gates mapped to the clauses of the source procedure, and leaves open any decision the procedure doesn’t settle. Your team checks intended use, resolves ambiguities, tests the configuration and releases it under change control. Neil can also compare procedure revisions, tracing a revised requirement into the configured process; the process and quality owners assess the impact, training and verification it needs.
References
- 1EudraLex Volume 4, Chapter 4: Documentation, European Commission, January 2011. https:/
/ health. ec. europa. eu/ system/ files/ 2016- 11/ chapter4_ 01- 2011_ en_ 0. pdf (read 6 November 2026) - 2WHO good manufacturing practices for pharmaceutical products: main principles, WHO Technical Report Series No. 986, Annex 2, glossary and section 15, World Health Organization, 2014. https:/
/ cdn. who. int/ media/ docs/ default- source/ medicines/ norms- and- standards/ guidelines/ inspections/ trs986annex2. pdf (read 6 November 2026) - 321 CFR 211.100, Written procedures; deviations, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- F/ section- 211. 100 (read 6 November 2026) - 421 CFR 211.22, Responsibilities of quality control unit, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- B/ section- 211. 22 (read 6 November 2026) - 5ICH Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, sections 6 and 13, ICH, 10 November 2000. https:/
/ database. ich. org/ sites/ default/ files/ Q7%20Guideline. pdf (read 6 November 2026) - 6MDSAP AU P0002.009, MDSAP Audit Approach, chapter 6, Production and Service Controls, task 3, Medical Device Single Audit Program, revision date 6 August 2024, on FDA’s MDSAP audit procedures page. https:/
/ www. fda. gov/ media/ 166672/ download (read 6 November 2026) - 721 CFR 211.186, Master production and control records, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- J/ section- 211. 186 (read 6 November 2026) - 8EudraLex Volume 4, Chapter 1: Pharmaceutical Quality System, section 1.8, 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 6 November 2026) - 921 CFR 211.25, Personnel qualifications, eCFR. https:/
/ www. ecfr. gov/ current/ title- 21/ chapter- I/ subchapter- C/ part- 211/ subpart- B/ section- 211. 25 (read 6 November 2026)
AQuestions and answers
How often should SOPs be reviewed and updated?
EU GMP and WHO ask for documents to be regularly reviewed and kept up to date, but neither they nor 21 CFR 211 or ICH Q7 set a fixed interval. Set the interval in your document control procedure, and revise a procedure whenever an approved change affects it rather than waiting for the next scheduled review.
What is the difference between an SOP and a policy?
A policy states intent and direction; ICH Q10 describes the quality policy as the overall intentions and direction of an organisation related to quality, as formally expressed by senior management. An SOP gives directions for performing an operation. EU GMP lists policies and procedures as separate kinds of document.
What is the difference between an SOP and a protocol?
EU GMP says a protocol gives instructions for performing and recording certain discrete operations, while an SOP gives directions for performing certain operations. A validation protocol is one example, and ICH Q7 asks for it to be reviewed and approved by the quality unit.
Who should approve a GMP SOP?
In the US, production and process control procedures are drafted, reviewed and approved by the appropriate organisational units and reviewed and approved by the quality control unit. ICH Q7 asks the quality unit to approve all procedures that affect the quality of intermediates or APIs, and EU GMP asks for approval, signature and date by appropriate, authorised persons.
Does everyone need training before an SOP takes effect?
The people who perform the operation must be trained in the written procedures that apply to their work, so plan the effective date to leave time for that training. EU GMP also expects procedures to be carried out correctly and operators to be trained to do so.