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EU Directive 2001/83/EC describes in Article 52 that member states must ensure the fulfilment of the duties of Qualified Person (QP) either by administrative measures or by subjecting QPs to a code of professional conduct.

These requirements have been extracted from the relevant documents and are summarized in the Good Practice Guide “EQPA Code of Practice for QPs – Duties and Responsibilities for Qualified Persons in the EU” and is available publicly on the European QP Association website.

The new version 9.0 launched in January 2023 comprises a new chapter “Ethics for the Qualified Person – A Professional Code of Conduct” in addition to general revisions and a revised Annex 1 with the national requirements.

As the European QP Association (EQPA) is not aware of a Code of Conduct being published by any EU/EEA authorities, it was decided to develop such a code until an official version becomes available by the EU regulatory or National Competent Authorities (NCAs).

The new code is specifically intended to define and ensure the ethical dimension for QPs. It might also be used in informing other groups (e.g. senior management) of the specific duties of the QPs. It is further intended to become a reference to QPs and NCAs.

The following ethical duties of the QP have been identified:

  • Selflessness
  • Integrity
  • Objectivity
  • Responsibility
  • Transparency
  • Honesty
  • Leadership
  • Knowledge
  • Prevent professional misconduct
  • Rigour and Robustness



EQPA Code of Practice for QPs – Duties and Responsibilities for Qualified Person

Compliance with Good Distribution Practice (GDP) by manufacturers and wholesale distributors is a key element in ensuring the quality and safety of medicinal products in the supply chain.

Possession of a manufacturing licence may include authorisation to distribute the medicinal products covered by the authorisation. Manufacturers performing any distribution activities consisting of procuring, holding, supplying, importing, or exporting medicinal products, should therefore comply with GDP.

PIC/S has developed an Aide Memoire “Aide-Memoire on the Inspection of Good Distribution Practice for Medicinal Products in the Supply Chain” (PI 044-1)”, which can be considered a good tool for improving the understanding and performance of inspectors and a “Questions & Answers (Q&A) document regarding the PIC/S GDP Guide” (PS/INF 22/2017).

These documents were drafted by the PIC/S Expert Circle on GDP and came into force on February 1, 2023.

The Aide-Memoire consists of ten tables containing general subjects and items to be investigated during the GDP inspection of manufacturers and wholesale distributors.

Some relevant references to the following PIC/S documentation are also included:

  • PICS Guide to Good Distribution Practice for medicinal products (PE 011- 1);
  • PIC/S Guide to GMP for medicinal products (PE 009-16 (Part I)).



Aide-Memoire, Inspection of Good Distribution Practice (GDP) for medicinal products in the supply chain

Questions & Answers document regarding the PIC/S GDP Guide (PE 011-1)

The current EU GMP Guidance Annex 11 “Computerised Systems” has been issued in 2011 and does not give sufficient guidance within several areas. There has been discussion for some time about revising this annex to meet current technological and regulatory developments. On 16 November 2022, the EMA (European Medicines Agency) published a “Concept-Paper on the revision of Annex 11 of the guidelines on Good Manufacturing Practice for medicinal products – Computerised Systems” that addresses the need to update Annex 11.


Proposed timetable until the publication of the new EU GMP Annex 11

  • Deadline for comments on the concept paper: 16 November 2023.
  • Publication and commenting of a draft of the new Annex 11: March 2025.
  • Approval and publication by the European Commission: June 2026.
  • Reasons for the revision of Annex 11.


Where is there a need for change and adaptation?

In 33 points, based on the structure and chapters of the current Annex 11, new points to be included and topics to be updated are presented.

Which topics should be included in the new Annex 11?

The following is an excerpt from the Concept Paper of some chapters in Annex 11 that have been identified as needing adaptation:

  1. Suppliers and Service Providers

The topic of cloud service providers should be addressed in particular:

  • [3,1] “For critical systems validated and/or operated by service providers (e.g. ‘cloud’ services), expectations should go beyond that “formal agreements must exist”. Regulated users should have access to the complete documentation for validation and safe operation of a system and be able to present this during regulatory inspections, e.g. with the help of the service provider.”
  1. Validation
  • [4.1] The meaning of the term ‘validation’ (and ‘qualification’), needs to be clarified. It should be emphasised that both activities consist of a verification of required and specified functionality as described in user requirements specifications (URS) or similar.
  • [4.1] Following a risk-based approach, system qualification and validation should especially challenge critical parts of systems which are used to make GMP decisions, parts which ensure product quality and data integrity and parts, which have been specifically designed or customised.

The topic of “agile methods” should be integrated here regarding deviations from previous classic development documents.

  • [4.5] It should be acknowledged and addressed that software development today very often follows agile development processes, and criteria for accepting such products and corresponding documentation, which may not consist of traditional documents, should be clarified.
  1. Audit Trails

Most of the new topics are mentioned here. What has been a very short chapter so far, topic should be described much more comprehensively in the new Annex 11. The points to be addressed include:

  • Audit trails must not be editable
  • Audit trails must not be able to be switched off for the “normal user” of a system.
  • Statements should be made about the frequency of audit trail reviews.
  • Audit trail data as GMP requirements are often created together with log data. It should be possible to be able to sort these data.
  1. Security

This topic should also be integrated more strongly under the aspect of external threats.

  • [12.1] The current section has only focus on restricting system access to authorised individuals; however, there are other important topics. In line with ISO 27001, a section on IT security should include a focus on system and data confidentiality, integrity and availability.

Security techniques, information security management systems and requirements are specifically mentioned here.

  • [12.1] The current version says that “Physical and/or logical controls should be in place to restrict access to computerised system to authorised persons”. However, it is necessary to be more specific and to name some of the expected controls, e.g. multi-factor authentication, firewalls, platform management, security patching, virus scanning and intrusion detection/prevention.
  • [12.1] It should be specified that authentication on critical systems should identify the regulated user with a high degree of certainty. Therefore, authentication only by means of a ‘pass card’ might not be sufficient, as it could have been dropped and later found by anyone.
  • [12.1] Two important expectations for allocation of system accesses should be added either here or elsewhere; i.e. ‘segregation of duties’, that day-to-day users of a system do not have admin rights, and the ‘least privilege principle’, that users of a system do not have higher access rights than what is necessary for their job function.



The current Annex 11 is partly superseded by technological and regulatory developments and that there is a corresponding need for adaptation.

The latest version (version 16) of the “How to do” document – Interpretation of ICH Q7 Guide and “Review form” for active pharmaceutical ingredients was finalised in July 2022 and published on the new website of the APIC (Active Pharmaceutical Ingredients Committee) at the end of October.

The document aims to facilitate the implementation of the ICH Q7 guideline and provides recommendations on how it can be interpreted.

In this new version, the responsible task force of the APIC Quality Group, has made formal changes, additions and updates in the chapters (1) Introduction, (6) Documentation and Records, (10) Storage and Distribution and (12) Validation.

Following are some examples of relevant changes:


Chapter 6 Documentation and Records

This chapter has been thoroughly revised and contains many adjustments and innovations as well as formal changes. For example, in the first paragraph 6.1 “Documentation System and Specification” the acronym ALCOA has been replaced by ALCOA+, and more attention has been paid to electronic documentation and hybrid documentation systems.

In section 6.14, the sub-heading “Electronic systems” has been added; in sections 6.15, 6.16 and 6.17 have been almost completely reworded.

The following paragraphs have also been updated and revised:

  • 2 “Equipment Cleaning and Use Record”,
  • 3 “Records of Raw Materials, Intermediates, API Labelling and Packaging Materials”,
  • 4 “Master Production Instructions (Master Production and Control Records)”,
  • 5 “Batch Production Records (Batch Production and Control Records)”,
  • 6 “Laboratory Control Records”,
  • 7 “Batch Production Record Review”.


Chapter 10 Storage and Distribution

This chapter in the current version contains, in addition to formal changes, an adjustment in the second paragraph of section 10.11. All other steps in this chapter are left unchanged.


Chapter 12 Validation

In addition to numerous formal adjustments, this chapter has been fundamentally updated and reformulated.

In the first paragraph 12.1 “Validation Policy”, section 12.11 “Critical Parameters/Attributes General considerations” has been expanded to include the term Critical Quality Attribute (CQA) and its meaning has been described in detail.

In the same way, in paragraph 12.3 “Qualification” the term engineering has been added and in paragraph 12.8 “Validation of Analytical Methods” the sentence “The level of the validation required for in-process controls should be evaluated depending on the influence on the final API quality.” has been added.


The ICH Q5A(R2) Expert Working Group is working on the revision of the of the Guideline Q5A(R1) “Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin”, providing additional recommendations on the established and complementary approaches to control the potential viral contamination of biotechnology products:

  • selecting and testing cell lines and other raw materials;
  • assessing the capacity of the production process to clear infectious viruses;
  • testing the product at appropriate steps of production.

The draft guideline text is currently at step 2 of the ICH process and was endorsed on 29 September 2022.

On 10 October 2022, EMA published a revised version, which is open for comments until 10 February 2023.


The previous guidance refers to products derived from cell cultures obtained from characterised cell banks. It covers products derived from in vitro cell cultures, such as interferons, monoclonal antibodies and recombinant DNA products, including recombinant subunit vaccines. It also includes products derived from hybridoma cells grown in vivo as ascites, for which special considerations apply.

In the new guidance, the following statement can be found in comparison:

“This document covers products produced from in vitro cell culture using recombinant DNA technologies such as interferons, monoclonal antibodies, and recombinant subunit vaccines. It also covers products derived from hybridoma cells grown in vivo as ascites: special considerations apply for these products, and Annex 1 contains additional information on testing cells propagated in vivo. The document also applies to certain genetically-engineered viral vectors and viral vector-derived products, which can undergo virus clearance without a negative impact on the product. These products may include viral vectors produced using transient transfection or from a stable cell line, or by infection using a recombinant virus. It also includes viral vector-derived recombinant proteins, for example, baculovirus-expressed Virus-Like Particles (VLPs), protein subunits and nanoparticle-based vaccines and therapeutics. Furthermore, the scope includes Adeno-Associated Virus (AAV) gene therapy vectors that depend on helper viruses such as baculovirus, herpes simplex virus or adenovirus for their production. Specific guidance on genetically engineered viral vectors and viral vector-derived products is provided in Annex 7. Inactivated viral vaccines and live attenuated viral vaccines containing self-replicating agents are excluded from the scope of this document.”

Next Generation Sequencing (NGS) and Nucleic Acid Amplification Techniques (NATs) may be appropriate for broad and specific virus detection, respectively. The introduction of these tests may be done without a systematic head-to-head comparison with the currently recommended in vitro and in vivo assays.



All biotechnological products derived from cell lines are at risk of viral contamination, which could have serious side effects or clinical consequences for the patient. This can be due to viral contamination of the starting material or contamination during the manufacturing process.

It is assumed that the safety of these products with respect to potential viral contamination can be ensured by applying a virus analysis programme and evaluating the virus removal and inactivation achieved by the manufacturing process through the appropriate measures described in this guidance document.

Summarized is the purpose of this document to provide a general framework for viral testing, experiments for the assessment of viral clearance and a recommended approach for the design of viral testing and viral clearance studies.

The guideline mentions three different, complementary approaches to controlling the potential viral contamination of biotechnology products:

  • Selecting and testing cell lines and other raw materials, including media components, for the absence of undesirable infectious viruses;
  • Assessing the capacity of the production processes to clear infectious viruses;
  • Testing the product at appropriate steps of production for the absence of contaminating infectious viruses.

Source: “ICH Guideline Q5A(R2) on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin”


The United States Pharmacopeia (USP) is making important changes to series of chapters on Good Storage and Distribution Practices <1079> that will impact risk mitigation strategies for storage and transportation of finished pharmaceuticals.

This chapter focuses on packaging, storage, and transportation processes that maintain drug product quality and supply chain integrity. The proposed revision identifies common risks in the storage and transportation of drug products and recommends appropriate mitigation strategies.

The new USP <1079> changes are significant and highlight the need for companies who will store, handle or transport products with label temperature requirements to meet a thorough Quality Management System (QMS). USP <1079> defines good storage and distribution practices for temperature sensitive drugs during all stages of the cold chain.

The existing chapter is titled “Good Storage and Distribution for Drug Products.” The new proposed chapter title will be – “Risks and Mitigation Strategies for the Storage and Transportation of Finished Drug Products.

The <1079> Series

The current plan for the expanded series is as follows:

Chapters <1079> and <1079.2> are already effective. For <1079.3>, a draft is available for comments.

USP <1079.2>

The sub-chapter <1079.2> addresses the utility and application of mean kinetic temperature (MKT) for the evaluation of temperature excursion in controlled room temperature (CRT) and controlled cold temperature (CCT) products.

USP <1079.3>

Is a new sub-chapter. It provides background information about the science and technology of temperature and humidity monitoring over time. It also describes the available technologies and performance characteristics and provides recommendations for qualifying performance.

Sub-chapter <1118> “Monitoring Devices—Time, Temperature, and Humidity” will be omitted, as the information will be included in the new sub-chapter <1079.3>.

USP <1079.4>

<1079.4> is also a new chapter, which was first published for comments in the Pharmacopeial Forum, PF 48(5), in September 2022.

The draft versions of all proposed new chapters are available in PF Online.


GAMP®5, now supplemented by several Good Practice Guides, is a globally accepted standard for the validation of computerised systems.

The progress of IT environments in recent years has made it necessary to revise and extend the guide, although the basic structure is still well suited to the current IT landscape and to the validation of computer systems.

The new edition “GAMP®5 2nd Edition” is not a new guideline but a revision of the existing guide. It was published at the end of July 2022 and can be ordered on the ISPE website. (


What are the news in the GAMP®5 2nd edition?

The structure, divided into 8 chapters, has remained unchanged:

  • 1-Introductio
  • 2-Key Concepts
  • 3-Life Cycle Approach
  • 4-Life Cycle Phases
  • 5-Quality Risk Management
  • 6-Regulated Company Activities
  • 7-Supplier Activities
  • 8-Efficiency Improvements


  • In the chapter 3-Life Cycle Approach, the subsection “Critical Thinking Through the Life Cycle” has been added,
  • in the chapter 8-Efficiency Improvements, the subsection “Using Tools and Automation” has been included in addition to some wording adjustments.
  • In the Management Appendices, the appendices M 11 “Infrastructure” and M 12 “Critical Thinking” have been added as well as some minor changes in the wording.
  • In the Development Appendices, in addition to some wording changes, Appendix D2 “Functional Specifications” has been removed and for new Appendices have been introduced:
    • D8 “Agile Software Development“,
    • D9 “Software Tools“,
    • D10 “Distributed Ledger Systems (Blockchain)“,
    • D11 “Artificial Intelligence and Machine Learning (AL/ML)“.
  • In the Operation Appendices, besides some wording adjustments, the Appendix O7 “Repair Activity” has been removed.
  • In the Special Topics Appendices, Appendix S5 “Managing Quality within an Outsourced IS/IT Environment” has been removed.
  • In the General Appendices, the previous Appendix G1 “GAMP Good Practice Guide Summary” has been removed.

The European Commission has decided to revise Annex 1 of the EU GMP “Manufacture Of Sterile Medicinal Products” to cover the current regulatory and technological developments in the manufacture of sterile medicinal products. In particular, the integration concerns some aspects addressed in ICH guidelines Q9 (Quality Risk Management) and Q10 (Pharmaceutical Quality System).

The Final Version of Annex 1 was published on 25 August 2022.



  • New Annex 1 will come into force on 25 August 2023
  • Chapter 8.123 “Lyophilizers and associated product transfer and loading/unloading areas” will come into force on 25 August 2024


Changes compared to the second draft version of 2020

The basic structure of Annex 1 has remained unchanged.

In this final version, are broadened topics such as:

  • “Barrier Technologies” – subchapter of the chapter “Premises”
    • The topics of background environment, gloves and decontamination methods have been dealt with separately for Isolators and RABS: “18 Isolators or RABS, which are different technologies, and the associated processes, should be designed to provide protection through separation of the grade A environment from the environment of the surrounding room. […]”
  • “Form-Fill-Seal (FFS)” (8.96) and “Blow-Fill-Seal” (8.105) – subchapter of the chapter “Production and Specific Technologies” go into much more detail.
  • In addition, there are new insertions in many chapters, as well as deletions and rewording.

The EDQM informs that the 11th Edition of the European Pharmacopoeia (Ph. Eur.) is now available.

The latest version comprises some updated monographs which will be implemented on 1 January 2023.

Holders of Certificates of suitability to the monographs of the Ph. Eur. (CEPs) are required to align their applications and thus the respective CEPs according to the revised monographs.



According to Directives 2001/83/EC and 2001/82/EC, as amended, it is the responsibility of the manufacturer to comply with the current version of a Ph. Eur. monograph, and therefore to update the specification when a revised monograph is issued.

In addition, the European Directorate for the Quality of Medicines & HealthCare (EDQM) ensures that CEPs always reference the latest version of the pharmacopoeia.

Besides the web notice, EDQM will contact CEP holders to provide more details on how to proceed. However, it remains the responsibility of the CEP holder to comply with the requirements of the monograph and, if necessary, to update their respective applications no later than the implementation date of the revised monograph, regardless of whether they have been contacted by EDQM.

The EDQM listed the substances covered by a CEP and for which a revised monograph will be implemented on January 1, 2023, classifying them into two categories, A and B, based on the required information

Case A:

The specification of the substance should be updated according to the revised monograph. The updated specification should be included in the next request for revision that is submitted to the EDQM.

Case B:

This case concerns amendments to the monograph which require the submission of data to the EDQM. An updated dossier demonstrating that the substance complies with the requirements of the revised monograph should be provided within three months of the EDQM contacting the CEP holder.

Where the required information has already been submitted in the approved dossier, a self-declaration is considered to be sufficient.

Source: EDQM Newsroom

The second revision of the “Guideline for Elemental Impurities Q3D(R2)” has achieved “step 4” (adoption by the Regulatory Members of the ICH Assembly) on April 26, 2022 and is available on the ICH website.

Compared with the draft dated September 2020, the final version of this second revision includes some revisions and adaptations:

§  Appendix 2: Established PDEs for Elemental Impurities PDEs (Permitted Daily Exposure) values for Gold, Silver and Nickel have been adjusted

§  Appendix 3: Individual Safety Assessments Gold and Silver monographs were revised

§  Appendix 5: Limits for Elemental Impurities by the Cutaneous and Transcutaneous Route was added in the second revision of the guideline and contains information on the limits for impurities for cutaneously or transcutaneously applied medicinal products.

The appendix focuses on the forms of impurities most likely to be detected following the application of pharmaceuticals to human skin. It also considers both local and systemic toxicities.

“[…] ICH decided to adopt a “generic approach” instead of an element-by-element one.

The reason for the choice is due to the results of the studies consulted. Indeed, these would tend to report a “disappearance” of impurities in the skin rather than transcutaneous absorption.”

The “Harmonized Guideline for Elemental Impurities Q3D(R2)” can be found on the ICH website.