FAQs regarding changes to PIC/S GMP Guides Part I & II and to PIC/S Annexes

  • What updates to the PIC/S GMP Guides & Annexes do you need to comply with to meet the latest regulatory compliance requirements?
  • And what manufacturing changes should you implement before your next GMP audit or site inspection?

PIC/S GMP Guides & Annexes V16 (PE 009-16)

  • The latest PIC/S GMP Guides & Annexes is “Version 16′ (PE 009-16), published in early February 2022.
  • A majority of Regulatory Authorities have adopted these updated guidelines and no longer refer to previous versions (such as PIC/S Version 15).
changes to PIC/S GMP guide PICS Version16

Comparison of PIC/S Version 15 to PIC/S Version 16 (differences)

  • PIC/S GMP Guide Version 15 (PE 009-15/V15) was published on 1 May 2021.
  • It was replaced by PIC/S GMP Guide Version 16 (PE 009-16/V16) on 1 February 2022.

The major differences in the latest PIC/S GMP guidelines (PE 009-16), compared to previous publications (PE 009-15 and prior versions)) relating to the following two Annexes:

  • PIC/S Annex 13 – Manufacture of Investigational Medicines
    • Updated to align with [new] Regulation No. 536/2014 on Clinical Trials
  • PIC/S Annex 16 for Certification & Batch Release by the Authorised Person (AP)
    • Newly added Annex that generally aligns with European Union (EU) GMP regulations relating to Qualified Persons (QP) and EU batch release processes

Review the Annex 16 Batch Release Training Presentation.

You can also browse our other Certificate Courses for GMP education topics, including the updated Annex 13 – Manufacture of Investigational Medicinal Products.

PICS GMP changes PIC/S GMP GUIDE Version 16 vs Version 15

What you need to know about complying with new PIC/S GMP Guidelines in Version 16 (PE 009-16):

Personnel, manufacturers, and their suppliers are expected to comply with updates to GMP requirements as of the time these new GMP requirements are published and/or become ‘in force’ within that jurisdiction.

New GMP regulations can intensify existing pressures on manufacturing resources, especially for smaller or mid-sized companies; e.g. talent hours (personnel skills, labour hours), data governance (data integrity), and clinical evidence requirements (testing, data collection/analysis and safety reports – before and after release to market).

Transitional periods for GMP compliance with new guidelines

There may be transitional periods for compliance with updated PIC/S GMP Guides/Annexes, which can vary per jurisdiction. Refer to guidance from the Regulatory Authorities in the jurisdiction(s) in which you are a Marketing Authorisation Holder (MAH) or Manufacturing & Import Authorisation Holder (MIAH) to review which PIC/S version is being referenced during site inspections for GMP compliance (GMP audits).

Regional example: Therapeutic Goods Administration (TGA) GMP expectations

The TGA (Australia) now refers to PIC/S Version 15*, and expects GMP compliance with PIC/S PE 009-15 guidelines, as of 1 July 2022.

  • Prior to 1 July 2022, the Australian TGA were referencing PIC/S Version 14 (PE 009-14), which they adopted in September 2020.
  • PIC/S Version 14 (PIC/s V14) represented significant changes to PE 009-13 (V13) in terms of new V14 requirements for Premises and Equipment (Chapter 3); Production (Chapter 5); Complaints & Product Recalls (Chapter 8); and Real Time Release Testing and Parametric Release (Annex 17).

*Exceptions to updated PIC/S guidance in Australia include Annexes 4 & 5 (Veterinary Medicines) and Annex 14 (Blood & Plasma), which were not adopted by Australia, because other regulations/guidelines apply to those specific product types.

Who must comply with the latest PIC/S Guidelines being referenced by Competent Authorities/Regulatory Authorities and GMP Inspectors/Auditors?

PIC/S GMP guidelines apply to individuals, companies, personnel, contractors, active pharmaceutical ingredient (API) manufacturers, importers, distributors and other supply chain operators involved in pharmaceutical manufacturing, medical device manufacturing, & veterinary medicines manufacturing.

You must also meet all conditions of your Marketing Authorisation/Import Authorisation, and consult any region-specific & product-specific guidance to understand your GMP responsibilities and other legal requirements for product quality, safety, and efficacy/performance.

FAQ#1: What is the latest or current version of the PIC/S GMP Guide?

Answer: The latest version of PIC/S GMP Guides & Annexes = PIC/S Version 16 – PE 009-16. This version has been in effect since the 1st of February 2022.

To download the latest PIC/S GMP Guide (Version 16) – PE 009-16, Click on the links below:

PICS Version 16 updates to Annex 13 16

FAQ#2: When does PIC/S Version (PE 009-16) go into effect according to most Regulatory Authorities?

Some Regulatory Authorities immediately adopt updates and changes to the PIC/S GMP Guide & Annexes.

In other jurisdictions, such as Australia, longer transition periods may apply. This means adapting to updates/changes to GMP Guidance can be done over time (but procrastination in the face of a looming ‘in force’ date is definitely not recommended).

Note: The Australian TGA only recently adopted PIC/S Version 15 (PE 009-15) on 1 July 2022.

It is not yet clear when Australia will adopt PIC/S PE 009-16, published in February 2022 (e.g. when the TGA will refer to PIC/S Version 16 instead of PIC/S Version 15 for GMP compliance inspections). TGA = Therapeutic Goods Administration

FAQ#3: What were the major changes between PIC/S Version 15 and PIC/S Version 16?

As noted in the prelude to this article, the main changes in the updated PIC/S guideline related to:

The major differences in the latest PIC/S GMP Guide (PE 009-16/V16), compared to the previous PIC/S GMP Guide (PE 009-15/V15) relating to the following two Annexes:

However, with the new European Union Annex 1 (EU Annex 1) published on 25 August 2022and going into force on 25 August 2023 (1 year after its publication in Eudralex Volume 4), its important manufacturers of sterile medicinal products stay up to date on Annex 1.

Is there a PIC/S Version 17 (PIC/S GMP GUIDE – PE 009-17) in the works?

News about EU Annex 1 guidance updates for the manufacture of sterile products/medicines

With the European Union’s updated Annex 1 (EU Annex 1) for sterile medicinal products going into force in less than a year’s time, it appears likely we’ll see a revised PIC/S GMP Guide (Version 17) in the not-so-distant future.

Here’s what you need to know about the updated EU Annex 1 publication (August 2022) going into force in August 2023:


Learn from the experts: Attend Annex 1 training presentations/course sessions with the GMP compliance experts at PharmOut – click here for schedules or contact PharmOut for facilitated training of large groups of personnel.

You can also download the EU Annex 1 guidelines (PDF version) here.  

For assistance updating your sterile manufacturing processes and PQS documentation, validation and data storage systems, and/or pharmaceutical technical writing (SOP updates, new procedures, updated Work Instructions, design specifications, etc), click here for PharmOut’s highly-respected, best-practice GMP consultants.

PQS template packages are also available.

Review the Annex 16 Batch Release Training Presentation.

Browse other Certificate Courses for GMP education topics and best-practice manufacturing, including the updated Annex 13 – Manufacture of Investigational Medicinal Products.

Last updated on November 16th, 2022 at 07:30 am

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