pharma Tag

08 Apr

Posted at 16:46h in Blog

In January 2025, the Task Force “Data Integrity” of the Quality Group of APIC (CEFIC), has published the version 2.0 of the document “Data Integrity Frequently Asked Questions (FAQ)“.

This document contains a collection of frequently asked questions that have been submitted by the industry to the Data Integrity taskforce. Since this is a living document, it is updated as new questions are posed to the group.

Updated questions are written in red: the new questions and answers can be found in the “Password management” and “Access management” sections.

  1. Password management

Q1: When I logged into a system, do I need to re-authenticate myself for every data entry?

A: No, it depends upon the criticality of the data/action. This criticality should be based upon process mapping and a risk assessment as explained in the guide. Criticality of the data and/or responsibility associated with the action should be taken into account when evaluating electronic signature requirements.

Q2: What are the requirements for e-signature components? (This question in version 1 of the FAQ was worded differently whereas it has now been revised as above)

A: This practice is described in 21CFR11, chapter 11.200 “e-signature and components”:

(i) When an individual executes a series of signings during a single, continuous period of controlled system access, the first signing shall be executed using all electronic signature components (= user ID and password or biometrics); subsequent signings shall be executed using at least one electronic signature component that is only executable by, and designed to be used only by, the individual.

(ii) When an individual executes one or more signings not performed during a single, continuous period of controlled system access, each signing shall be executed using all of the electronic signature components

  1. Access management

Q2: Can we extend the time of a user session before this is automatically locked for inactivity because of a HSE (health-safety-environment) concern?

A: The inactive time of a user session should be managed by the user locking their computer station when they move away for an extend period of time to prevent unauthorised actions been taken by other persons. The automatic lock is a security measure. A reasonable amount of time should be supported by a risk assessment. This type of HSE concern should be managed independently of the GXP system with an emergency stop button as an example. If this is approach is not feasible, the computerized system should be designed as such that a fast intervention is possible. It is best practice for a system like a DCS to be configured in such a way that the screen does not completely goes into operating system lock and actions can be taken by clicking on the valve or object and entering a password to confirm the action.

 

SOURCES:

https://apic.cefic.org/wp-content/uploads/2025/01/FAQ-DI-APIC-TF-Version-2-Jan-25-1.pdf

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08 Apr

Posted at 16:44h in Blog

The Version 17 of the “How to do” document – Interpretation of ICH Q7 Guide and “Review form” for APIs was finalized last November and published on the Active Pharmaceutical Ingredients Committee (APIC) website in early 2025.

The document aims to facilitate the implementation of the ICH Q7 guideline and provides recommendations for its interpretation.

In this version, additions and updates have been made in the following chapters:

  • Chapter 2 Quality Management
    • the changes were made in the subsections 2.1 Principles (10, 2.12, 2.14) and 2.2 Responsibilities of the Quality Unit(s) (2.21).
  • Chapter 5 Process Equipment
    • additions and innovations have been made in subsections: 5.2 Equipment Maintenance and Cleaning, 5.3 Calibration, and 5.4 Computerized Systems
  • Chapter 13 Change Control
    • updates concern items 10, 13.11, 13.12, 13.13, 13.14, 13.15.
  • Chapter 21 ICH Q7 Q&A “how to do” attachment (Questions and Answers linked to the respective sections of ICH Q7)
    • some Questions & Answers in Chapter 5 “Process Equipment – Cleaning” have been more clearly interpreted and aligned with the newly published guidelines.

SOURCE:

https://apic.cefic.org/wp-content/uploads/2025/01/ICH-Q7-How-To-Do-version17_cleandocument_241122.pdf

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08 Apr

Posted at 16:41h in Blog

In January 2025, the US FDA has published in the newsroom of the CDER website the article titled “Determining Recommended Acceptable Intake Limits for N-nitrosamine Impurities in Pharmaceuticals: Development and Application of the Carcinogenic Potency Categorization Approach”.

The article recaps the historical context of the development of the Carcinogenic Potency Categorization Approach (CPCA) methodology, that uses the chemical structure of a nitrosamine impurity to recommend acceptable intake (AI) limits, assigning them to one of five predicted potency categories reflecting carcinogenic risk, and provides an analysis of the the number and distribution of α-hydrogens combined with other activating and deactivating features of nitrosamines.

The complete article can be checked in the newsroom of CDER’s website.

 

SOURCES:

Determining Recommended Acceptable Intake Limits for N-nitrosamine Impurities in Pharmaceuticals: Development and Application of the Carcinogenic Potency Categorization Approach | FDA

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08 Apr

Posted at 16:38h in Blog

In January 2025, the U.S. Food and Drug Administration (FDA) published a draft Guidance for Industry and Other Interested Parties entitled “Considerations for the Use of Artificial Intelligence to Support Regulatory Decision-Making for Drug and Biological Products”.

Public comments on this draft document can be submitted until 7 April 2025 to ensure they are considered in the final development of the Guidance.

This Guidance provides recommendations to sponsors and other interested parties on the use of artificial intelligence (AI) to produce information or data intended to support regulatory decisions regarding the safety, effectiveness or quality for drugs or combination products that include a drug.

The recommendations also may be relevant  across all medical products, including medical devices intended to be used with drugs.

A key element of this guidance is the introduction of a risk-based approach to establish and assess the credibility of AI models for a specific context of use (COU).

The COU defines the specific role and scope of the AI model used to address a question of interest.

The guideline highlights the importance of clarity in defining the context of use through the collection of credibility evidence for each AI model, as this provides the basis for the evaluation of the AI model outputs.

 

A Risk-Based Credibility Assessment Framework

The risk-based credibility assessment framework described in the Guidance  comprises seven step process to establish and assess the credibility of an AI model output for a specific COU:

  • Step 1: Define the question of interest that will be addressed by the AI model.
  • Step 2: Define the COU for the AI model.
  • Step 3: Assess the AI model risk.
  • Step 4: Develop a plan to establish the credibility of AI model output within the COU.
  • Step 5: Execute the plan.
  • Step 6: Document the results of the credibility assessment plan and discuss deviations from the plan.
  • Step 7: Determine the adequacy of the AI model for the COU.

 

Special Consideration: Life Cycle Maintenance of the Credibility of AI Model Outputs in Certain Contexts of Use

The Guide underlines the importance of ongoing monitoring and maintenance of AI models to ensure that they remain suitable for use over the life cycle of the medical product for its Contexts of Use. This includes regular monitoring of model performance and documenting of any changes that could affect model outputs.

 

SOURCE:

Guidance for Industry and Other Interested Parties ‘Considerations for the Use of Artificial Intelligence to Support Regulatory Decision-Making for Drug and Biological Products’

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08 Apr

Posted at 16:35h in Blog

The Directive I-SMI.RL.01, “Conduct of inspections of establishments manufacturing or distributing medicinal products or collecting blood.” Version 4.0 was approved on 21 October 2024 and has thus entered into force.

In February 2025, the “Questions and Answers (Q&A)” document related to centralized procedures was updated and published on the website of the European Medicines Agency (EMA).

The new edition of the Q&A document “European Medicines Agency post-authorization procedural advice for users of the centralised procedure” includes some additions and revisions and addresses relevant issues in the post-grant phase of marketing authorization.

Below are references to the chapters and questions that have been changed:

 

Chapter 1 Type IA Variations

Questions:

  • 4. How shall I present and submit my Type IA/ IAIN Variation(s)?
  • 12. When do I have to submit revised product information? In all languages?

 

Chapter 2 Type IB variations

Questions:

  • 4. How shall I present and submit my Type IB Variation?

In the related answer, the paragraph “Variations to implement changes for generic/hybrid/biosimilar products” was added.

  • 5. When shall I submit my Type IB Variation?
  • 10. How should I submit revised product information? In all languages?

 

Chapter 3 Type II variations

Questions:

  • 16. When do I have to submit revised product information? In all languages?

 

Chapter 6 Worksharing of variations

Questions:

  • 10. When do I have to submit revised product information? In all languages?

 

Chapter 19 Transfer of Marketing Authorisation

Questions:

  • 2. How shall I present my application for the Transfer of Marketing Authorisation?

 

Chapter 22 Article 61(3) Notifications

Questions:

  • 4. How shall I present my 61(3) Notification?

 

SOURCES:

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure

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23 Dec

Posted at 09:47h in Blog

The Directive I-SMI.RL.01, “Conduct of inspections of establishments manufacturing or distributing medicinal products or collecting blood.” Version 4.0 was approved on 21 October 2024 and has thus entered into force.

The purpose and scope of the document is defined as “to provide guidance on the conduct of inspection of an establishment collecting blood, manufacturing or distributing medicinal products and holding or seeking an establishment licence […] The Directive shall harmonise inspection procedures, frequency of inspections and follow-up procedures thus ensuring a consistent approach to assessment and decision-making by the competent Swiss inspectorates and Swissmedic as the competent Establishment authority.”

The new document replaces the previous version I-SMI.RL.01_03 dated 26.05.2020, the changes concern the following chapters:

  • Chapter 5.6: Handling of urgent follow up actions during the closing meeting including submission of information prior to completing the inspection report and its description in the inspection report
  • Chapter 5.9: Clarification on expectations regarding critical and major deficiencies

 

SOURCES:

https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/bewilligungen_zertifikate/authorisations/inspectorates.html

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23 Dec

Posted at 09:44h in Blog

The European Medicines Agency (EMA) has updated the question and answer session good manufacturing practice (GMP) and distribution (GDP) on on its website “Guidance on good manufacturing practice and good distribution practice: Questions and answers”, regarding section “EU GMP guide annexes: Supplementary requirements: Annex 16”.

The question focuses on the method to be adopted to create and maintain a reliable documentation system to ensure the traceability of an active substance and a medicinal product useful to support the QP in fulfilling their legal obligations during batch certification and release.

Recommendations

  • Supply chain records should provide adequate traceability and be available in a timely manner, to facilitate quality defect investigations and product recalls, or requests of competent authorities.
  • Records should make it possible to identify, for active substances and medicinal products, all the entities, including suppliers and outsourced activities, involved in the manufacture of a specific batch of the drug product, in line with the registered supply chain.
  • Associated risks should be formally assessed and periodically reviewed with appropriate risk-mitigation measures determined to mitigate any risks identified.

 

SOURCES:

Guidance on good manufacturing practice and good distribution practice: Questions and answers | European Medicines Agency (EMA)

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16 Dec

Posted at 16:56h in Blog

The European Directorate for the Quality of Medicines & HealthCare (EDQM) has published a draft version of General Chapter 5.38 “Quality of Data,” which is now open for public review and can be commented on until 31 December 2024.

Impact of Technological Advancements

The draft of the new chapter refers to data generated, collected, stored, or used in the context of experimental analyses performed by quality control (QC) laboratories and highlights their increasing importance in relation to the quality assessment of medicines, particularly when these data are fed into numerical models based on chemometrics, machine learning (ML), or other forms of artificial intelligence (AI) in order to make inferences, make decisions and take action.

In this context, a defined quality standard must be applied and ensured.

Scope 

The purpose of this chapter is to focus on the “raw material” of data analysis, providing an overview of applicable data quality concepts, describing best practices for achieving a sufficiently high data quality, and reporting a summary of data governance procedures.

Quality of Data 

The text defines data as a collection of values, as “data elements” or “unit of data” with specific meaning derived from its context, including the source and generation processes.

Data elements can be classified into:

  • Primitive types (e.g., Boolean, , integers, real values, characters)
  • Composite, structured types (e.g., arrays, tables)
  • Unstructured types, not following a predefined format (e.g., text documents, natural language)

You can view and comment on the draft of chapter “5.38. QUALITY OF DATA” at: https://pharmeuropa.edqm.eu/home.

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01 Oct

Posted at 09:45h in Blog

The European Directorate for the Quality of Medicines & HealthCare (EDQM) has recently published updated versions of three water monographs in the European Pharmacopoeia (Ph.Eur.):

  • Water for injections (0169)
  • Purified water (0008)
  • Total organic carbon (TOC) in water for pharmaceutical use (2.2.44)

The updates include some key clarifications:

 

Water for Injection (0169)

TOC Limit Adjustment: to reduce ambiguity, the upper limit for Total Organic Carbon (TOC) has been restricted from 0.5 mg/L to 0.50 mg/L.

Testing Requirements: the requirement to test oxidisable substances (OS) in “Sterilized Water for Injection” (SWFI) has been superseded by the introduction of the mandatory use of the total organic carbon (TOC) method B. This change simplifies the testing procedure by focusing solely on TOC measurements.

The TOC test is a state-of-the-art quantitative method that is more sensitive and non-selective than the OS test for the control of organic impurities present in pharmaceutical waters.

Residue on Evaporation: the “Residue on Evaporation” test, which measures non-volatile residue, has been changed from percentage to parts per million (ppm), offering a more standardized expression of the results.

 

Purified Water (0008)

Harmonization with WFI Standards: the TOC limit for Purified Water has also been aligned with the update to Water for Injection, now set at a 0.50 mg/L.

Standardized Units: for “Purified Water in Containers,” the measurement unit for “Residue on Evaporation” has changed from percentage to ppm, standardizing the way results are reported.

 

Total Organic Carbon in Water for Pharmaceutical Use (2.2.44)

Clarification of Water Specifications: the term “highly purified water” has been replaced with “water,” which corresponds to the specifications conductivity LF of ≤ 1.0 µS/cm at 25 °C and a TOC level of ≤ 0.1 mg/L.

Moreover, in the proposed revision of chapter 2.2.44, the reagents sucrose R and 1,4-benzoquinone R have been replaced by chemical reference substances (CRSs) to streamline the application of the TOC test.

The commenting period runs until 30 September 2024.

 

SOURCES:

The monographs can be found in draft status on the website of the European Pharmacopoeia.

More information on how to comment is available at: “Comment on drafts (Pharmeuropa)”.

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01 Oct

Posted at 09:39h in Blog

The updated guideline will replace the “Note for guidance on chemistry of new active substances – (CPMP/QWP/130/96, Rev 1)” and the “Chemistry of active substances – (3AQ5a)”, it has been revised to cover new and existing active substances in one guideline.

As reported, the Concept paper on the revision of the guideline on the chemistry of active substances” of the Quality Working Party (QWP) was published for comments in June 2022. This document aimed to explain and clarify the need to revise and update the “Guideline on the chemistry of active substances (EMA/454576/2016)” and to outline the procedure for the revision.

The results obtained and insights gained were incorporated into the draft of revision 1 of the “Guideline on the chemistry of active substances,” which was published in July 2024. The draft is now open for public comments until the end of January 2025.

 

As already contemplated in the concept paper, the topic of N-nitrosamine was considered and integrated throughout the text of the guideline

 

SOURCES:

https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-chemistry-active-substances-revision-1_en.pdf

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