31 August - 3 September 2021
ICH Publishes Q10 Guideline as Step 2
In a nutshell the ICH Q10 guideline is structured in five chapters and anannex:
This structure already shows the concentration on a continuous improvementprocess (KVP), a typical element in the ISO quality standard.
In the introduction to chapter 1 ("Pharmaceutical Quality System") it is alsomentioned that ICH Q10 describes an approach to pharmaceutical quality systemsbased on ISO quality management system concepts. However, it also incorporatesGMP regulations and complements ICH Q8 and Q9. Elsewhere the document alsorefers to ICH Q7A as an element that was also included.
In general, ICH Q10 does not want to set up new requirements beyond thosethat already exist. That's why the parts that are included in addition to thecurrent GMP regulations are rather options – according to the wording in ICHQ10!
The new guideline addresses API manufacturers as well as pharmaceuticalcompanies, and includes the complete product life cycle – from API developmentto phasing out of the product. The pharmaceutical quality system centres on thethree issues
These three activities can only be realised through "knowledge management"and "quality risk management". Including specific "quality system elements" andmanagement responsibilities ICH Q10 is supposed to build a bridge to nationalregulations.
The new guideline now also refers to a "quality manual" (or a similardocumentation), another typical ISO element – with the following expectedcontent:
Chapter 2, "Management Responsibilities", is structured in seven sub-chaptersthat are mostly known from ISO standards:
In chapter 3 – "Continual Improvement of Process Performance and ProductQuality" four elements are repeated supporting the life cycle approach:
Again, this chapter also includes CAPA and management review as typical ISOelements. In addition the following steps are mentioned for a life cycleapproach:
Four tables show application areas of a process performance and productquality monitoring system, of CAPA and change management as well as of themanagement review – each in the product life cycle. According to the newguideline there is an advantage in a better process understanding as well as ina modern approach to a process validation. However, ICH Q10 does notsubstantiate this proposition.
Table I: Application of Process Performance and Product Quality Monitoringthroughout the Product Lifecycle
ii) Corrective Action and Preventive Action System (CAPA)
The pharmaceutical company should have a system for implementing correctiveactions and preventive actions resulting from the investigation of complaints,product rejections, non-conformances, recalls, deviations, audits, regulatoryinspections and findings, and trends from process performance and productquality monitoring. A structured approach to the investigation process should beused with the objective of determining root cause. The level of effort andformality of the investigation should be commensurate with the level of risk.CAPA methodology should result in product and process improvements and enhancedproduct and process understanding.
Table II: Application of Corrective Action/Preventive Action throughout theProduct Lifecycle
iii) Change Management System
Innovation, continual improvement, the outputs of process performance andproduct quality monitoring and CAPA drive change. In order to properly evaluate,approve and implement these changes, a company should have an effective changemanagement system. There is generally a difference in formality of changemanagement processes prior to the initial regulatory submission and aftersubmission, where changes to the regulatory filing might be required underregional requirements.
The change management system ensures continual improvement is undertaken in atimely and effective manner while providing a high degree of assurance there areno unintended consequences of the change.
The change management system should include the following, as appropriate forthe stage of the lifecycle:
(1) Quality risk management should be utilised to evaluate proposed changes. Thelevel of effort and formality of the evaluation should be commensurate with thelevel of risk. There should be an assessment to determine whether a change tothe regulatory filing is required under regional requirements;
(2) All changes should be properly evaluated. Proposed changes should beevaluated relative to the marketing authorisation, including design space, whereestablished, and / or current product and process understanding. As stated inICH Q8, movement within the design space is not considered a change (from aregulatory filing perspective). However, from a pharmaceutical quality systemstandpoint, all changes should be evaluated by a company's change managementsystem;
(3) Proposed changes should be evaluated by expert teams contributing theappropriate expertise and knowledge from relevant areas, e.g., PharmaceuticalDevelopment, Manufacturing, Quality, Regulatory Affairs and Medical, to ensurethe change is technically justified. Prospective evaluation criteria for aproposed change should be set;
(4) After implementation, an evaluation of the change should be undertaken toconfirm the change objectives were achieved and that there was no deleteriousimpact on product quality;
(5) Regional regulatory submission/approval requirements should be assessed for aproposed change to a marketed product.
Table III: Application of Change Management System throughout ProductLifecycle
iv) Management Review of Process Performance and Product Quality
Management review should provide assurance that process performance andproduct quality are managed over the lifecycle. Depending on the size andcomplexity of the company, management review can be a series of reviews atvarious levels of management and should include a timely and effectivecommunication and escalation process to raise appropriate quality issues tosenior levels of management for review.
(1) The management review system should include:
(a) The results of regulatory inspections and findings, audits and otherassessments;
(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 fromcorrective 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 ProductQuality throughout the Product Lifecycle
The repeated integration of ISO quality standards is also shown in theglossary which partly directly refers to ISO 9000-2005 (and to other ICHguidelines as well).
In a table (Annex 1) various scenarios are used to demonstrate the advantagesof implementing ICH Q10 – ideally in combination with ICH Q8 and Q9.
Is the new ICH Q10 guideline the start for implementing ISO quality standardelements in GMP? De facto many companies in the GMP environment alreadyintegrated ISO elements in their quality management systems. Further, managementreviews are absolutely common in the industry. Moreover, CAPA is alsoincreasingly employed. Almost all pharmaceutical companies already establishedquality manuals or – as ICH Q10 specifically approves – similar documents aswell. 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 smooththe way between the regions. Possibly, a worldwide harmonisation of "GMP formedicinal products" as an ICH guideline Q7X – similar to the very successful ICHQ7A "Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients" –would be more helpful. Also, a certain redundancy is noticeable in the entiredocument. Maybe future ICH steps can help to clean the document.
The complete document is available here.
In expectation of the discussion process the European Medicines Agency (EMEA)published the document with the same content as step 3 athttp://www.emea.europa.eu/pdfs/human/ich/21473207en.pdf.
ICH Q10 – Discussion with Representatives from the ICH Q10 Expert WorkingGroup
A member of the ICH Q10 Expert Working Group (Dr. JacquesMorénas from the French authority AFSSAPS) will introduce the document at the 2nd European GMP Conferencein Heidelberg, Germany, on 25/26 June. The new developments will be part of aseparate session. The conference is organised by the European Compliance Academy(ECA), the European QP Association and the University of Heidelberg. Altogether24 speakers – from EMEA, FDA, other members of the ICH Expert Working Groupsand others – will provide information on the latest developments.
Quality management systems are also in the centre of the ECA education courseGMP and FDA compliantQuality and Documentation Systems inCopenhagen on 22/23 October 2007.