The GIC (Common Interest groups)

Since August 22, 2022, the new version of the Annex 1 text of the EU GMP has been published. The members of the A3P Annex 1 working group (GIC) will continue their analysis work and share their experiences with the network. (Annex1 GMP EU 2022 .pdf)

• Dec. 2022: Publication of the A3P Annex 1 CCS GUIDE (pdf in the A3P member area)
• Oct. 2022 & 2021: Annex 1 Conferences & Workshops at the A3P International Congress (pdf presentations in the A3P member area)
• Jul. 2020: Comments submitted on the draft “Concept paper on the revision of annex 1 of the guidelines on good manufacturing practice – manufacture of sterile medicinal products” issued by the EMA in 2015) to the EMA
• Jan. 2019: Article La Vague: A3P International Congress 2018: Key messages from the round table on the revision of Annex 1.
• Mar. 2018: Article La Vague: EU Annex 1 draft: Proposals from the A3P Annex 1 GIC
• Apr. 2018: Article La Vague: EU Annex 1 draft: Proposals from the A3P Annex 1 GIC
• Mar. 2018: Comments submitted on the draft “Annex 1: Manufacture of Sterile Medicinal Products” by the EMA
• Sept. 2015: Article La Vague: Specific proposed amendments to Annex 1.

Due to the COVID-19 pandemic, remote audits and inspections have become more widespread. This new mode of evaluation presents advantages beyond health constraints, indicating that it will become more common and complementary to traditional practices. This evaluation format requires adopting new practices, which has raised numerous questions that the members of the working group (GIC) have attempted to address by creating a reference document for both auditors and auditees in the form of a Technical Guide:

• May 2023: A3P Technical Guide “Remote Audit: Recommendations”

The group has set a new objective to work on the publication of a manual on “Preparation Practices for Audits and Inspections.” This manual would not only describe generic best practices but also highlight specific areas of focus and provide tips, such as in the field of sterile manufacturing and the new Annex 1. (Publication coming soon)

The complexity and diversity of aseptic processes require tailored Barrier Technology solutions for each of them. The development of new therapeutic alternatives, especially in the field of Advanced Therapy Medicinal Products, necessitates the search for solutions for predominantly manual processes that require high dexterity. The work and sharing of best practices by the members of the Working Group are intended for professionals to optimize their production processes, including validation standards, maintenance standards, and operational standards related to the use of barrier technologies, incorporating international recommendations (Annex 1, ISPE 2005, PHSS 2010), and identifying different “Barrier Technology” solutions.

• Sept 2021: Technical Days (conferences) in Tours.
• Oct 2020: Publication of an article in La Vague: “There is everything to gain from working in campaign mode, a breakthrough in isolator productivity.“
• Nov 2019: Creation of a practical training module: “Visual Inspection of Gloves and Sleeves under Isolators.”
• March 2019: Technical Days (conferences) in Pau.
• March 2017: Technical Days (conferences) in Pau.
• January 2017: Publication of an article in La Vague: “Secure the containment of your gloves“
• March 2015: Technical Days (conferences) in Pau.

In a context of increasing health authority requirements regarding BFS (Blow-Fill-Seal) technology and the growing demand for vaccines, it is crucial to understand all the necessary steps for filling injectable solutions, to grasp critical parameters, and to set the sterility assurance level at an appropriate level in order to control manufacturing costs and timelines.

Therefore, A3P has decided to create a Working Group on this subject, enabling various concerned industry stakeholders to exchange information and reach common consensus. The ultimate goal is to develop a practical guide for future BFS operators who must manage this type of process, as well as to present the results of this collaborative work in various formats such as conferences and articles.

Objectives of the A3P BFS Working Group: Define a practical guide for industry professionals to understand and effectively manage this technology and its associated processes in the long term.

One of the objectives of the Working Group will be to propose a decision tree (methodology, rationale) to support all high-value projects by listing key steps, prerequisites, and points of vigilance throughout the development of a Biopharmaceutical product.

Prerequisites and points of vigilance (non-exhaustive list):

• Process reproducibility
• Characterization of standards
• Level of qualification of analytical methods
• Analytical process validation
• Stability testing program
• Identification of raw materials/suppliers
• Regulatory strategy
• Quality documentation
• …

Following the revision of Annex 15 published in 2015, A3P decided to create a Cleaning Validation Working Group to support industry professionals in understanding the expectations of Health Authorities and the aforementioned annex. The purpose of this working group was to address all major topics related to cleaning validation, including the selection of worst-case products, determination of acceptance criteria (with a significant focus on PDEs newly requested by Annex 15), equipment train, applicable sampling methods, personnel training, types of cleaning and levels of automation, and other parameters to consider in the cleaning validation exercise such as DHT, CHT, and batch sizes.

Since 2022, the working group has evolved to be called “Cleaning & Disinfection” in line with regulatory expectations. It continues its work for professionals in the industry.

• March 2022: A3P Cleaning Validation Conference (conference available on the A3P member area)
• March 2022: Practical GMP Guideline – Annex 15 Qualification & Validation Chapter 10 Cleaning Validation
• June 2021: A3P Cleaning Validation Conference (conference available on the A3P member area)
• June 2018: A3P Cleaning Validation Conference (conference available on the A3P member area)
• July 2017: Articles published in La Vague magazine:
  • The A3P Cleaning Validation Working Group is preparing a practical guide for autumn 2017 on Chapter 10 of Annex 15 of the European GMP: Presentation & Discussion
  • Biocidal regulations applied to the disinfectants used in the pharmaceutical industry: all you need to know…
  • Cleaning control strategy in the production of active pharmaceutical ingredients for clinical use Indirect visual inspection modernizes cleaning validation
  • Recovery rate determination as a preliminary step required in a cleaning validation exercise
  • Implementation of the “health-based approach” for setting limits in cleaning validation for Vaccines/Biotech

The work of this Working Group has been completed.

• November 2017: Publication of an A3P Scientific and Technical Guide: “Control of supplier risks and cross contamination Survey and summary of regulatory changes EU-GMP Part.1 Chap. 3 and 5“
• October 2016: Response to the public consultation on “Guidance on the sterilisation of the medicinal product, active substance, excipient and primary container: EMA/CHMP/CVMP/QWP/BWP/850374/2015”

The management of the lifecycle of analytical methods emerged in the Pharmacopeia Forum in 2013 (PF39(5)) and has received several stimuli related to the concepts of ATP (Analytical Target Profile), method performance (measurement uncertainty, Chapter <1210> of the USP), and control strategy.

The objective is to replace the traditional trilogy of method development/validation/transfer with a continuous approach that allows for iterative steps based on the knowledge and control of the analytical technique implemented to monitor critical attributes of products.

The objectives of the A3P Analytical Method Lifecycle Working Group are:

• Contribute to the drafting of comments, for example, on the revision of the USP Chapter <1220> “Analytical Procedure Life Cycle.”
• Define a practical guide for industry professionals that will help them understand the expectations of this phenomenon and manage it in the long term.
• Continue the work based on future ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) texts (ICHQ14 and ICHQ2(R2)).

This group first allows for an assessment of the methods proposed, considered, evaluated, adopted, and rejected by all pharmaceutical industry laboratories, along with their proven advantages and disadvantages. This group is currently working on the creation of a validation guide.

This group aims to create a practical and technical guide to demystify the concepts presented in regulations, such as establishing the QTPP (Quality Target Product Profile), defining critical process parameters and critical quality attributes of the product, and the design space, in order to develop and validate a robust and capable process with an effective and appropriate control strategy. This GIC will complement the “CPV Continued Process Verification” and “statistical methodology for the comparative assessment of quality attributes in development” GICs.

• February 2022: Technical and Scientific Guide “QbD: An approach to better understand the process, to better control it rather than being subject to it (Stages 1 & 2).“

The main objectives of the A3P Rouging / Dérouging working Group (GIC) are:

• Define a practical guide for industrial professionals that will help them understand and manage this phenomenon in the long term.
• Presentations during a themed day and other A3P events.
• Provide a space for technological watch and innovation through scientific articles and synthesis files for members, via certain existing media.
• May 2023: A3P Rouging & Dérouging Webinar (PDF conferences A3P member area)
• Sept 2022:
  • A3P Rouging & Dérouging Conference Day (PDF conferences A3P member area)
  • Publication of the Practical guide on Rouging / Derouging management
• Sept 2019: A3P Rouging & Dérouging Conference Day (PDF conferences A3P member area)

Particulate Risk Management in Injectable Products

The Particles GIC is the first one created within A3P. It served as a model, and the statutes were drafted to function as other GICs, with the collaboration of experts and the possibility to create sub-working groups. The GIC delivered various outputs, including recommendations, technical documents, and monographs.

The Particles GIC was established in 2013 and was led by Alain EUZEN until 2017. Throughout its existence, the GIC obtained the real collaboration of over 70 experts, whom we sincerely thank for their contributions. They were willing to share their practices, engage in technical discussions, and review and work on tests related to standardization. It was a substantial and beneficial effort for the entire A3P community and beyond. Participants from different European countries (France, Belgium, Switzerland, Germany) showed great commitment.

Given the magnitude of the task and numerous requests following regulatory inspections, the GIC structured itself into four sub-working groups:

• Sub-Group 1: Primary packaging and transportation, distinguishing between glass articles, elastomers, and disposables or single-use systems (led by François FONVIELLE – Sanofi Pasteur and Benoît LUX – Lilly France).
• Sub-Group 2: Manufacturing and distribution (led by Alain EUZEN – Sanofi Pasteur).
• Sub-Group 3: Visual inspection (Romain VEILLON – GSK Vaccines).
• Sub-Group 4: Complaints, market recalls, and overall statistical data (Patrick TURLIER – GSK).

Thus, the GIC developed a comprehensive understanding of the particulate issue in injectable products.

Knowledge and progress sharing by the GIC took place during four Particles Forums in Le Vaudreuil (Eure) and Lyon between 2013 and 2016, as well as through numerous publications in La Vague and conference presentations (Biarritz Congress, Pharmaceutical Industry Days in Lille, SFSTP seminar in Paris).

In a context of increasing regulatory requirements for defect detection, providing producers with the tools to enhance the value of visual inspection processes in the middle of the injectables production chain.

• Oct. 2022: Publication of A3P Guideline : Good practices for the implementation of an automatic visual inspection process for injectable products
• Oct. 2022: A3P Annual Congress (PDF conferences workshops A3P member area)

This group works on the topic of pharmaceutical water in order to facilitate exchanges among the various concerned industrial stakeholders and reach common consensus to facilitate the implementation of this guideline.

• December 2020: Conducted two webinars on the latest regulatory developments, their impacts on the design and maintenance of production and distribution systems, as well as the latest trends in monitoring (PDF materials available in the A3P member area)
• May 2019: Response to the public consultation on the draft issued by the EMA titled “Guideline on the quality of water for pharmaceutical use”