TGA Regulatory Affairs Consultants

PIC/S GMPs vs WHO GMPs – what’s the difference?

t]As many are aware, the Pharmaceutical Inspection Co-operation Scheme (PIC/S) develops and provides standards and guidelines for the harmonisation of Good Manufacturing Practice(GMP) in the global pharmaceutical industry.

Those who fall under the umbrella of participating countries, often take for granted the fact that PIC/S is the go-to for compliance (i.e. Part 1, Part 2 (API), and the accompanying Related Annexes). However, non-members often use a different standard, namely, the World Health Organisation (WHO) standard – Annex 2 WHO good manufacturing practices for pharmaceutical products: main principles.

Because they are both “GMP” standards, common questions that follow are:

“Can’t I just use the WHO GMPs?”

“Aren’t the WHO and PIC/S GMPs the same?”

Answers depend on who your target market is. For example, if you are a non-participating country supplying your own country with products, then you could argue that you don’t need the PIC/S GMPs.

However, if you are a non-participating country who either:

  1. Wants to become a PIC/S member, or
  2. Wants to export products to PIC/S member countries

– then, you will need to update your GMP codes.

While it’s all well and good to say: “Yes there is a difference between PIC/S GMPs vs WHO GMPs,” it’s not particularly useful if you don’t know exactly where they differ.

So, here at PharmOut, we decided to do the heavy lifting for you and did a clause by clause comparison of the following standards for PIC/S GMPs vs WHO GMPs:

Where relevant, PIC/S Guide to Good Manufacturing Practice for Medicinal Products Annexes (PIC/S Annexes) were also consulted.

So, what is the difference between PIC/S GMPs vs WHO GMPs?

Firstly, the references to the main compliance standards in the WHO GMPs are not up to date:

  • Pharmaceutical Inspection Convention, Pharmaceutical Inspection Co-operation Scheme (PIC/S). In: Guide to good manufacturing practice for medicinal plants. Geneva, PIC/S Secretariat, 2000.
  • EudraLex – Volume 4. Good manufacturing practice (GMP) Guidelines. European Commission.

Current PIC/s is at PE 009-14 (Part I) as of 1 July 2018. While a comparison to EudraLex is out of scope for this blog, it should be noted that EudraLex has since had other updates since the WHO publication in 2014 and can be seen here.

An overview of the related chapters in the PIC/S GMPs vs WHO GMPs is provided below, specifically where they overlap:

SectionWHO GMPsCorresponding PIC/S Part I Chapters
1Pharmaceutical Quality System


  • Quality risk management
  • Product Quality review

Good manufacturing practices for pharmaceutical products

Chapter 1- Pharmaceutical Quality System


  • Principle
  • Pharmaceutical Quality System
  • GMP for Medicinal Products
  • Quality Control
  • Product Quality Review
2Sanitation and hygieneChapter 5- Production (Prevention of cross-contamination in production)


Chapter 2 – Personnel (Personnel Hygiene)

3Qualification and validationChapter 5 – Production (Validation)


Chapter 3 – Premises and Equipment



Product recalls

Chapter 8 – Complaints and Product Recall


  • Principle
  • Personnel and organisation
  • Procedures for handling and investigating complaints including possible Quality Defects
  • Investigation and Decision-making
  • Root Cause Analysis and Corrective and Preventative Actions
  • Product Recalls and other potential risk-reducing actions
 5Contract production, analysis and other activities


  • General
  • The contract giver
  • The contract acceptor
  • The contract
Chapter 7  –Outsourced activities


  • Principle
  • General
  • The contract giver
  • The contract acceptor
  • The contract
6Self-inspection, quality audits and suppliers’ audits and approval


  • Items for self-inspection
  • Self-inspection team
  • Frequency of self-inspection
  • Self-inspection report
  • Follow-up action
  • Quality audit
  • Suppliers’ audits and approval
Chapter 9 – Self-inspection





  • General
  • Key personnel
Chapter 2 – Personnel


  • Principle
  • General
  • Key Personnel
  • Training Personnel Hygiene Consultants.
8TrainingChapter 2 – Personnel (Training)
9Personal hygieneChapter 2 – Personnel (Personnel Hygiene)


  • General
  • Ancillary areas
  • Storage areas
  • Weighing areas
  • Production areas
  • Quality control areas
Chapter 3 – premises and equipment


  • Principle
  • Premises
  • General
  • Production area
  • Storage area
  • Quality control area
  • Ancillary areas
11EquipmentChapter 3 – premises and equipment


  • Principle
  • Premises
  • General
  • Production area
  • Storage area
  • Quality control area
  • Ancillary areas


  • General
  • Starting materials
  • Packaging materials
  • Intermediate and bulk products
  • Finished products
  • Rejected, recovered, reprocessed and reworked materials
  • Recalled products
  • Returned goods
  • Reagents and culture media
  • Reference standards
  • Waste materials
  • Miscellaneous
Chapter 4 – Documentation (Specifications)


Chapter 5 – Production

  • Starting Materials
  • Processing Operations – Intermediate and Bulk Products
  • Packaging Materials
  • Finished Products
  • Rejected, Recovered and Returned Materials

Chapter 6 – Quality Control

  • Sampling
  • Testing


  • General
  • Documents required
Chapter 4 – Documentation


  • Principle
  • Required GMP Documentation (by type)
  • Generation and Control of Documentation
  • Good Documentation Practices
  • Retention of Documents
  • Specifications
    • Specifications for starting and packaging materials
    • Specifications for intermediate and bulk products
    • Specifications for finished products
  • Manufacturing Formula and Processing Instructions
    • Packaging Instructions
    • Batch Processing Records
    • Batch Packaging Records
  • Procedures and Records
    • Receipt
    • Sampling
    • Testing
14Good practices in production


  • General
  • Prevention of cross-contamination and bacterial contamination during production
  • Processing operations
  • Packaging operations
Chapter 5 – Production


  • Principle
  • General
  • Prevention of cross-contamination in Production
  • Validation
  • Starting Materials
  • Processing operations – intermediate and bulk products
  • Packaging Materials
  • Packaging Operations
  • Finished Products
  • Rejected, Recovered and Returned Materials
  • Product Shortages due to Manufacturing Constraints
15Good practices in quality control


  • Control of starting materials and intermediate, bulk and finished products
  • Test requirements
  • Batch record review
  • Stability studies
  • References
Chapter 6 – Quality Control


  • Principle
  • General
  • Good Quality Control Laboratory Practice
  • Documentation
  • Sampling
  • Testing
  • On-going Stability Programme
  • Technical Transfer of Testing Methods

From this, it is clear that while there are definitely sections that overlap in the PIC/S GMPs vs WHO GMPs, PIC/S has structured the information differently and has also provided far more detail for certain sections.

10 main discrepancies between PIC/S GMPs vs WHO GMPS

The comparison revealed 10 sections in the WHO GMPs that did not align with current PIC/S GMPs:

  1. Quality Risk Management(QRM) –  mentioned only twice in WHO GMPs, however, there is an entire annex dedicated to QRM in PIC/S Annex 20.
  2. Sanitation and hygiene – PIC/S Part 1 has additional detail that is not covered, specifically around premises, personal hygiene and cross-contamination.
  3. Qualification and validation – section is outdated, there is no mention of Factory Acceptance Testing or Site Acceptance Testing, nor User Requirements Specifications. Limited details on what constitutes IQ, OQ, PQ. Details from PIC/S Annex 15 Qualification and Validation are also missing.
  4. Customer complaints – sparse and does not go into detail on the level of the required investigation.
  5. Product recall – spare, PIC/S Part 1 has much more detail on requirements in chapter 8.
  6. Self-inspection – does not match what is in PIC/S Part I, however, PIC/S Part I guidance is limited. For more practical guidance, the following regulations are recommended:
  • PI 040-1 PIC/S Guidance on Classification of GMP Deficiencies
  • ISO 9001: 2015Quality Management systems – Requirements, specifically section 9.2 Internal audit.
  1. Personnel – section does align but is missing a few crucial details, WHO GMPs also has more detail on Qualified person and batch release however this is covered more in the EU GMP Guide rather than PIC/S Part I and Annexes.
  2. Materials – insufficient detail around material handling, especially starting material selection and qualification of vendors as well as information from PIC/S Annex 8 Sampling of Starting and Packaging Materials.
  3. Quality control – section not sufficient, majority of PIC/S Part I information missing (especially around documentation, testing, tech transfer, and ongoing stability). What guidance is given does not always align. Details required from Annex 19 Reference and Retention Samples.
  4. Documentation – major details missing, specifically requirements in processing and packaging instructions, and the list of recommended written procedures. Batch record review also insufficient.

Want more?

PharmOut has been involved with helping countries in the past with PIC/S compliance, including non-member countries, read more read here about one of our colleagues help the Suadi Arabian health authorities.

If you would like more information or advice on compliance with PIC/S GMPs, or even to see the spreadsheets of WHO and PIC/S GMPs clause-by-clause comparison, feel free to contact us at one of our offices around the world and we will try help.

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