ICH Publishes Q10 Guideline as Step 2
In a nutshell the ICH Q10 guideline is structured in five chapters and an annex:
This structure already shows the concentration on a continuous improvement process (KVP), a typical element in the ISO quality standard.
In the introduction to chapter 1 ("Pharmaceutical Quality System") it is also mentioned that ICH Q10 describes an approach to pharmaceutical quality systems based on ISO quality management system concepts. However, it also incorporates GMP regulations and complements ICH Q8 and Q9. Elsewhere the document also refers to ICH Q7A as an element that was also included.
In general, ICH Q10 does not want to set up new requirements beyond those that already exist. That's why the parts that are included in addition to the current GMP regulations are rather options according to the wording in ICH Q10!
The new guideline addresses API manufacturers as well as pharmaceutical companies, and includes the complete product life cycle from API development to phasing out of the product. The pharmaceutical quality system centres on the three issues
These three activities can only be realised through "knowledge management" and "quality risk management". Including specific "quality system elements" and management responsibilities ICH Q10 is supposed to build a bridge to national regulations.
The new guideline now also refers to a "quality manual" (or a similar documentation), another typical ISO element with the following expected content:
Chapter 2, "Management Responsibilities", is structured in seven sub-chapters that are mostly known from ISO standards:
In chapter 3 "Continual Improvement of Process Performance and Product Quality" four elements are repeated supporting the life cycle approach:
Again, this chapter also includes CAPA and management review as typical ISO elements. In addition the following steps are mentioned for a life cycle approach:
Four tables show application areas of a process performance and product
quality monitoring system, of CAPA and change management as well as of the
management review each in the product life cycle. According to the new
guideline there is an advantage in a better process understanding as well as in
a modern approach to a process validation. However, ICH Q10 does not
substantiate this proposition.
Table I: Application of Process Performance and Product Quality Monitoring throughout the Product Lifecycle
ii) Corrective Action and Preventive Action System (CAPA)
The pharmaceutical company should have a system for implementing corrective actions and preventive actions resulting from the investigation of complaints, product rejections, non-conformances, recalls, deviations, audits, regulatory inspections and findings, and trends from process performance and product quality monitoring. A structured approach to the investigation process should be used with the objective of determining root cause. The level of effort and formality of the investigation should be commensurate with the level of risk. CAPA methodology should result in product and process improvements and enhanced product and process understanding.
Table II: Application of Corrective Action/Preventive Action throughout the Product Lifecycle
iii) Change Management System
Innovation, continual improvement, the outputs of process performance and product quality monitoring and CAPA drive change. In order to properly evaluate, approve and implement these changes, a company should have an effective change management system. There is generally a difference in formality of change management processes prior to the initial regulatory submission and after submission, where changes to the regulatory filing might be required under regional requirements.
The change management system ensures continual improvement is undertaken in a timely and effective manner while providing a high degree of assurance there are no unintended consequences of the change.
The change management system should include the following, as appropriate for the stage of the lifecycle:
(1) Quality risk management should be utilised to evaluate proposed changes. The level of effort and formality of the evaluation should be commensurate with the level of risk. There should be an assessment to determine whether a change to the regulatory filing is required under regional requirements;
(2) All changes should be properly evaluated. Proposed changes should be evaluated relative to the marketing authorisation, including design space, where established, and / or current product and process understanding. As stated in ICH Q8, movement within the design space is not considered a change (from a regulatory filing perspective). However, from a pharmaceutical quality system standpoint, all changes should be evaluated by a company's change management system;
(3) Proposed changes should be evaluated by expert teams contributing the appropriate expertise and knowledge from relevant areas, e.g., Pharmaceutical Development, Manufacturing, Quality, Regulatory Affairs and Medical, to ensure the change is technically justified. Prospective evaluation criteria for a proposed change should be set;
(4) After implementation, an evaluation of the change should be undertaken to confirm the change objectives were achieved and that there was no deleterious impact on product quality;
(5) Regional regulatory submission/approval requirements should be assessed for a proposed change to a marketed product.
Table III: Application of Change Management System throughout Product Lifecycle
iv) Management Review of Process Performance and Product Quality
Management review should provide assurance that process performance and product quality are managed over the lifecycle. Depending on the size and complexity of the company, management review can be a series of reviews at various levels of management and should include a timely and effective communication and escalation process to raise appropriate quality issues to senior levels of management for review.
(1) The management review system should include:
(a) The results of regulatory inspections and findings, audits and other assessments;
(b) Periodic quality reviews, that can include:
(i) Measures of customer satisfaction such as customer complaints and recalls;
(ii) Conclusions of process performance and product quality monitoring;
(iii) The effectiveness of process and product changes including those arising from corrective action and preventive actions.
(c) Any follow-up actions from previous management reviews;
(2) The management review system should identify appropriate action, such as:
(d) Improvements to manufacturing processes and products;
(e) Provision, training and/or realignment of resources;
(f) Capture and dissemination of knowledge.
Table IV: Application of Management Review of Process Performance and Product Quality throughout the Product Lifecycle
The repeated integration of ISO quality standards is also shown in the glossary which partly directly refers to ISO 9000-2005 (and to other ICH guidelines as well).
In a table (Annex 1) various scenarios are used to demonstrate the advantages
of implementing ICH Q10 ideally in combination with ICH Q8 and Q9.
Is the new ICH Q10 guideline the start for implementing ISO quality standard elements in GMP? De facto many companies in the GMP environment already integrated ISO elements in their quality management systems. Further, management reviews are absolutely common in the industry. Moreover, CAPA is also increasingly employed. Almost all pharmaceutical companies already established quality manuals or as ICH Q10 specifically approves similar documents as well. Thus many companies are already in the middle of the ICH Q10 process.
It will be interesting to see whether ICH Q10 will really be able to smooth the way between the regions. Possibly, a worldwide harmonisation of "GMP for medicinal products" as an ICH guideline Q7X similar to the very successful ICH Q7A "Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients" would be more helpful. Also, a certain redundancy is noticeable in the entire document. Maybe future ICH steps can help to clean the document.
The complete document is available at: http://www.ich.org/LOB/media/MEDIA3917.pdf
In expectation of the discussion process the European Medicines Agency (EMEA)
published the document with the same content as step 3 at
ICH Q10 Discussion with Representatives from the ICH Q10 Expert Working Group
A member of the ICH Q10 Expert Working Group (Dr. Jacques Morénas from the French authority AFSSAPS) will introduce the document at the 2nd European GMP Conference in Heidelberg, Germany, on 25/26 June. The new developments will be part of a separate session. The conference is organised by the European Compliance Academy (ECA), the European QP Association and the University of Heidelberg. Altogether 24 speakers from EMEA, FDA, other members of the ICH Expert Working Groups and others will provide information on the latest developments.
Quality management systems are also in the centre of the ECA education course GMP and FDA compliant Quality and Documentation Systems in Copenhagen on 22/23 October 2007.