[Stability Testing related News – vol.65]

◆  11th Edition of The International Pharmacopoeia (29-Mar-23 ECA)

The International Pharmacopoeia (Ph. Int.) contains recommended procedures for analysis and specifications for pharmaceutical substances and dosage forms. According to the WHO (World Health Organization) it is intended to serve as source for reference or adaptation by any WHO Member State. The Ph. Int. is available online. It has legal status, whenever a national or regional authority refers to it in appropriate legislation.

11th Edition of the Ph. Int.
New and revised texts are introduced for

  • 16 monographs on pharmaceutical substances,
  • 10 monographs on dosage forms (pharmaceutical preparations),
  • 3 methods of analysis,
  • 3 general monographs on dosage forms.

A list of new, revised and omitted texts is provided as an annex to the preface of the 11th Edition.

Contribution to Quality Assurance
It is emphasized that pharmacopoeial specifications represent only one element of quality assurance. Pharmaceutical substances and dosage forms should be manufactured according to the current GMP requirements (GMP = Good Manufacturing Practices). In many cases, this compliance cannot be verified by only analyzing a sample of the final product against a pharmacopoeial monograph. The national, regional or other competent authority will need to ensure that all relevant provisions have been met (e.g. by GMP inspection of the manufacturing sites or testing of samples beyond specifications).

In addition, there is a distinction between pharmacopoeial standards and the manufacturers’ release specifications:

  • Pharmacopoeial standards are publicly-available compliance specifications and provide the means for an independent check of the quality of a product at any time during its shelf life.
  • Release specifications should generally be aligned to pharmacopoeial specifications; they may, however, include additional tests or limits to meet regulatory requirements (e.g. for other possible impurities).

For more information please see The International Pharmacopoeia, Eleventh Edition.

◆  ICH Information Material on the ICH Q9 revision Quality Risk Management (05-Apr-23 ECA)

Since 2005, the ICH Q9 Guideline on Quality Risk Management has represented the state of the art. A revision was announced at the end of 2020.  In January, this revision has reached stage 4 and is now moving into implementation.

ICH now provided slides that give a deeper insight into the revision. Spanning 29 pages, the set of slides describes the background of the revised guideline, its objectives through to its implementation. The table of contents includes:

  • Disclaimer
  • Background
  • Key Principles
  • Objectives of the Guideline (subjectivity in quality risk management, risks related to product availability, formalities in quality risk management, risk-based decision making, the objective itself)
  • Table of Contents
  • Overview of Guideline Content (including cross-references to ICH Q10)
  • Results of the Public Consultation
  • Considerations
  • Guideline for Implementation
  • Conclusion
  • Contact

Key principles identified are:

  • Subjectivity in risk assessments and QRM results
  • Inadequate management of supply and product availability risks
  • Lack of understanding about QRM formalities
  • Lack of clarity about risk-based decision making

There is one more interesting note in the Key Principles chapter. It is noted that the topic of “Risk-Review” needs additional clarification. However, no changes were made to this topic in the guideline itself. Clarification will be provided via the training material that is currently being prepared.

Slides 14-20 clarify the six requirements that were targeted for change.

Slides 21-22 explain the references to the ICH Q10 document. Explicitly mentioned are references to knowledge management in ICH Q10 and to points 1.6.1 and 2.7 of the Q10 guideline.

The information on the results of the public consultation is also interesting. Approximately 775 comments were submitted and evaluated at Stage 3 of the ICH process. Some comments were also incorporated into the revision, such as the introduction of a separate subchapter on subjectivity to emphasize the importance of this topic. The importance of root cause analysis was also emphasized more in the revision as a result of the comments. References to ICH Q11 and Q12, as well as updating ISO standards, are also results of the comments.

Also of interest is the comment in the Guideline for Implementation chapter that the ICH Q9 guideline in the revision is a fundamental guideline and supports the implementation of the other ICH guidelines Q7, Q8, Q10, Q11, Q12, Q13, as well as other quality guidelines. The target audience is addressed as industry and authorities. Explicitly addressed is the change in terminology from risk identification to hazard identification. It is not expected that already existing risk assessments will have to be adapted accordingly. Future risk assessments should naturally consider the change. It is important to note again that the ICH Q9 revision should be read in conjunction with the training material yet to be produced.

The conclusion again refers to the four key principles mentioned above and the change in terminology from risk identification to hazard identification. It also mentions the training material to be prepared, which is considered as support, especially also with regard to the “Risk-Rewiew”. Finally, the integration of industry comments is discussed.

Conclusion: The slides give a great overview of the background and objectives of the ICH Q9 revision. It will be exciting to see how the training material mentioned several times will “support” the revised ICH Q9 guidelines.

The entire slide set is available on the ICH website.

◆  USP Draft Chapters for Glass and Plastic Packaging Systems (26-Apr-23 ECA)

The two proposed USP General Chapters <660> and <661.2> have been published for comment in the current issue of Pharmacopeial Forum PF 49(2). The deadline for comments is May 31, 2023.

<660> Containers – Glass
As previously announced in USP´s Notice of Intent to Revise, the General Chapters—Packaging and Distribution Expert Committee (PDEC) is proposing to revise its general chapter <660> to address a recent FDA request to update the Type I definition from one that is composition-based to performance-based (e.g. hydrolytic resistance). The request highlighted the FDA’s concern about global issues regarding glass production and resulting drug shortages. The agency is supportive of the use of new glass compositions that are not currently outlined in the USP if they demonstrate equivalency or superior performance to Type I borosilicate glass. According to the proposal´s briefing, “the current USP definition is impeding the adoption of new glass compositions and delaying drug approvals”.

<661.2> Plastic Packaging Systems for Pharmaceutical Use
The General Chapters—PDEC is proposing the following changes:

  • Physicochemical Tests: Revision of the extraction time and temperature to address the concern that some plastic packaging materials start to melt and deform at the temperatures currently outlined in the chapter. Thus, the revision includes an additional extraction time and temperature of 50 ± 2° for 72 h.
  • Total Organic Carbon (TOC): Revision of the acceptance criteria to align with that in USP´s TOC Chapter <643>, which was revised in 2021.

The proposed USP General Chapters <660> and <661.2> are available after registration to the Pharmacopeial Forum.

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