Guidance for Industry 

Q10 Pharmaceutical 

Quality System 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

April 2009 

ICH 
 

 

Guidance for Industry 

Q10 Pharmaceutical 

Quality System 

Additional copies are available from: 

Office of Communication
 

Division of Drug Information
 

Center for Drug Evaluation and Research
 

Food and Drug Administration 

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(Tel) 301-796-3400

 http://www.fda.gov/cder/guidance/index.htm 

Office of Communication, Outreach and 

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Center for Biologics Evaluation and Research 

Food and Drug Administration 

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(Tel) 1-800-835-4709 or 301-827-1800 

 http://www.fda.gov/cber/guidelines.htm. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

April 2009 

ICH 
TABLE OF CONTENTS 

I.	 INTRODUCTION (1, 1.1)................................................................................................ 1
 

II.	 PHARMACEUTICAL QUALITY MANAGEMENT SYSTEM ................................. 2
 

A.	 Scope (1.2).......................................................................................................................................2
 

B. Relationship of ICH Q10 to Regional GMP Requirements, ISO Standards, 

and ICH Q7 (1.3)............................................................................................................................3
 

C.	 Relationship of ICH Q10 to Regulatory Approaches (1.4).........................................................3
 

D.	 ICH Q10 Objectives (1.5) ..............................................................................................................3
 

E. Enablers: Knowledge Management and Quality Risk Management (1.6) ............................... 4
 

F.	 Design and Content Considerations (1.7) ....................................................................................4
 

G.	 Quality Manual (1.8)......................................................................................................................5
 

III. MANAGEMENT RESPONSIBILITY (2)...................................................................... 5
 

A.	 Management Commitment (2.1)...................................................................................................5
 

B.	 Quality Policy (2.2).........................................................................................................................6
 

C.	 Quality Planning (2.3)....................................................................................................................6
 

D.	 Resource Management (2.4)..........................................................................................................7
 

E. Internal Communication (2.5) ......................................................................................................7
 

F. Management Review (2.6)............................................................................................................7
 

G. Management of Outsourced Activities and Purchased Materials (2.7)....................................7
 

H. Management of Change in Product Ownership (2.8).................................................................8
 

IV.	 CONTINUAL IMPROVEMENT OF PROCESS PERFORMANCE AND 

PRODUCT QUALITY (3) ............................................................................................... 8
 

A. Lifecycle Stage Goals (3.1) ............................................................................................................8
 

B.	 Pharmaceutical Quality System Elements (3.2) ..........................................................................9
 

V.	 CONTINUAL IMPROVEMENT OF THE PHARMACEUTICAL QUALITY 

SYSTEM (4) .................................................................................................................... 13
 

A.	 Management Review of the Pharmaceutical Quality System (4.1)..........................................13
 

B.	 Monitoring of Internal and External Factors That Can Have an Impacton the 

Pharmaceutical Quality System (4.2).........................................................................................13
 

C.	 Outcomes of Management Review and Monitoring (4.3).........................................................14
 

VI. GLOSSARY (5)............................................................................................................... 15
 

Annex I: Potential Opportunities To Enhance Science- and Risk-Based Regulatory 

Approaches *............................................................................................................... 18
 

Annex 2: Diagram of the ICH Q10 Pharmaceutical Quality System Model....................19
 

i 
 

 

 

 

Guidance for Industry1
 

Q10 Pharmaceutical Quality System 

This guidance represents the Food and Drug Administration's (FDA’s) current thinking on this topic. It 

does not create or confer any rights for or on any person and does not operate to bind FDA or the public. 

You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 

and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 

implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate 

number listed on the title page of this guidance. 

I. INTRODUCTION (1, 1.1)2 

This internationally harmonized guidance is intended to assist pharmaceutical manufacturers by 

describing a model for an effective quality management system for the pharmaceutical industry, 

referred to as the pharmaceutical quality system. Throughout this guidance, the term 

pharmaceutical quality system refers to the ICH Q10 model. 

ICH Q10 describes one comprehensive model for an effective pharmaceutical quality system that 

is based on International Organization for Standardization (ISO) quality concepts, includes 

applicable good manufacturing practice (GMP) regulations, and complements ICH “Q8 

Pharmaceutical Development” and ICH “Q9 Quality Risk Management.”3 ICH Q10 is a model 

for a pharmaceutical quality system that can be implemented throughout the different stages of a 

product lifecycle. Much of the content of ICH Q10 applicable to manufacturing sites is currently 

specified by regional GMP requirements. ICH Q10 is not intended to create any new 

expectations beyond current regulatory requirements. Consequently, the content of ICH Q10 that 

is additional to current regional GMP requirements is optional. 

1 This guidance was developed within the Expert Working Group (Quality) of the International Conference on 

Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has been 

subject to consultation by the regulatory parties, in accordance with the ICH process. This document has been 

endorsed by the ICH Steering Committee at Step 4 of the ICH process, June 2008. At Step 4 of the process, the final 

draft is recommended for adoption to the regulatory bodies of the European Union, Japan, and the United States. 

2

 Arabic numbers reflect the organizational breakdown of the document endorsed by the ICH Steering Committee at 

Step 4 of the ICH process, June 2008. 

3 These guidances are available on the Internet at http://www.fda.gov/cder/guidance/index.htm. We update 

guidances periodically. To make sure you have the most recent version of a guidance, check the CDER guidance 

page at http://www.fda.gov/cder/guidance/index.htm 

1
 
ICH Q10 demonstrates industry and regulatory authorities’ support of an effective 

pharmaceutical quality system to enhance the quality and availability of medicines around the 

world in the interest of public health. Implementation of ICH Q10 throughout the product 

lifecycle should facilitate innovation and continual improvement and strengthen the link between 

pharmaceutical development and manufacturing activities. 

FDA's guidance documents, including this guidance, do not establish legally enforceable 

responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should 

be viewed only as recommendations, unless specific regulatory or statutory requirements are 

cited. The use of the word should in Agency guidances means that something is suggested or 

recommended, but not required. 

II. PHARMACEUTICAL QUALITY MANAGEMENT SYSTEM 

A. Scope (1.2) 

This guidance applies to the systems supporting the development and manufacture of 

pharmaceutical drug substances (i.e., active pharmaceutical ingredients (APIs)) and drug 

products, including biotechnology and biological products, throughout the product lifecycle. 

The elements of ICH Q10 should be applied in a manner that is appropriate and proportionate to 

each of the product lifecycle stages, recognizing the differences among, and the different goals 

of, each stage (see section IV (3)). 

For the purposes of this guidance, the product lifecycle includes the following technical activities 

for new and existing products: 

• Pharmaceutical Development 

o Drug substance development 

o Formulation development (including container/closure system) 

o Manufacture of investigational products 

o Delivery system development (where relevant) 

o Manufacturing process development and scale-up 

o Analytical method development 

• Technology Transfer 

o New product transfers during development through manufacturing 

o Transfers within or between manufacturing and testing sites for marketed products 

• Commercial Manufacturing 

o Acquisition and control of materials 

o Provision of facilities, utilities, and equipment 

o Production (including packaging and labeling) 

o Quality control and assurance 

o Release 

o Storage 

2
 
o Distribution (excluding wholesaler activities) 

• Product Discontinuation 

o Retention of documentation 

o Sample retention 

o Continued product assessment and reporting 

B. Relationship of ICH Q10 to Regional GMP Requirements, ISO Standards, 

and ICH Q7 (1.3) 

Regional GMP requirements, the ICH guidance “Q7 Good Manufacturing Practice Guidance for 

Active Pharmaceutical Ingredients,” and ISO quality management system guidelines form the 

foundation for ICH Q10. To meet the objectives described below, ICH Q10 augments GMPs by 

describing specific quality system elements and management responsibilities. ICH Q10 provides 

a harmonized model for a pharmaceutical quality system throughout the lifecycle of a product 

and is intended to be used together with regional GMP requirements. 

The regional GMPs do not explicitly address all stages of the product lifecycle (e.g., 

development). The quality system elements and management responsibilities described in this 

guidance are intended to encourage the use of science- and risk-based approaches at each 

lifecycle stage, thereby promoting continual improvement across the entire product lifecycle. 

C. Relationship of ICH Q10 to Regulatory Approaches (1.4) 

Regulatory approaches for a specific product or manufacturing facility should be commensurate 

with the level of product and process understanding, the results of quality risk management, and 

the effectiveness of the pharmaceutical quality system. When implemented, the effectiveness of 

the pharmaceutical quality system can normally be evaluated during a regulatory inspection at 

the manufacturing site. Potential opportunities to enhance science- and risk-based regulatory 

approaches are identified in Annex 1. Regulatory processes will be determined by region. 

D. ICH Q10 Objectives (1.5) 

Implementation of the Q10 model should result in achievement of three main objectives that 

complement or enhance regional GMP requirements. 

1. Achieve Product Realization (1.5.1) 

To establish, implement, and maintain a system that allows the delivery of products with the 

quality attributes appropriate to meet the needs of patients, health care professionals, regulatory 

authorities (including compliance with approved regulatory filings) and other internal and 

external customers. 

2 Establish and Maintain a State of Control (1.5.2) 

3
 
 

To develop and use effective monitoring and control systems for process performance and 

product quality, thereby providing assurance of continued suitability and capability of processes. 

Quality risk management can be useful in identifying the monitoring and control systems. 

3 Facilitate Continual Improvement (1.5.3) 

To identify and implement appropriate product quality improvements, process improvements, 

variability reduction, innovations, and pharmaceutical quality system enhancements, thereby 

increasing the ability to fulfill a pharmaceutical manufacturer’s own quality needs consistently. 

Quality risk management can be useful for identifying and prioritizing areas for continual 

improvement. 

E. Enablers: Knowledge Management and Quality Risk Management (1.6) 

Use of knowledge management and quality risk management will enable a company to 

implement ICH Q10 effectively and successfully. These enablers will facilitate achievement of 

the objectives described in section II.D (1.5) above by providing the means for science- and riskbased decisions related to product quality. 

1. Knowledge Management (1.6.1) 

Product and process knowledge should be managed from development through the commercial 

life of the product up to and including product discontinuation. For example, development 

activities using scientific approaches provide knowledge for product and process understanding. 

Knowledge management is a systematic approach to acquiring, analyzing, storing, and 

disseminating information related to products, manufacturing processes, and components. 

Sources of knowledge include, but are not limited to, prior knowledge (public domain or 

internally documented); pharmaceutical development studies; technology transfer activities; 

process validation studies over the product lifecycle; manufacturing experience; innovation; 

continual improvement; and change management activities. 

2. Quality Risk Management (1.6.2) 

Quality risk management is integral to an effective pharmaceutical quality system. It can 

provide a proactive approach to identifying, scientifically evaluating, and controlling potential 

risks to quality. It facilitates continual improvement of process performance and product quality 

throughout the product lifecycle. ICH Q9 provides principles and examples of tools for quality 

risk management that can be applied to different aspects of pharmaceutical quality. 

F. Design and Content Considerations (1.7) 

(a) The design, organization, and documentation of the pharmaceutical quality system 

should be well structured and clear to facilitate common understanding and consistent 

application. 

(b) The elements of ICH Q10 should be applied in a manner that is appropriate and 

proportionate to each of the product lifecycle stages, recognizing the different goals 

4
 
 

and knowledge available for each stage. 

(c) The size and complexity of the company’s activities should be taken into consideration 

when developing a new pharmaceutical quality system or modifying an existing one. 

The design of the pharmaceutical quality system should incorporate appropriate risk 

management principles. While some aspects of the pharmaceutical quality system can 

be company wide and others site specific, the effectiveness of the pharmaceutical 

quality system is normally demonstrated at the site level. 

(d) The pharmaceutical quality system should include appropriate processes, resources, 

and responsibilities to provide assurance of the quality of outsourced activities and 

purchased materials as described in section III.G (2.7). 

(e) Management responsibilities, as described in section III (2), should be identified 

within the pharmaceutical quality system. 

(f) The pharmaceutical quality system should include the following elements, as 

described in section IV (3): process performance and product quality monitoring, 

corrective and preventive action, change management, and management review. 

(g) Performance indicators, as described in section V (4), should be identified and used to 

monitor the effectiveness of processes within the pharmaceutical quality system. 

G. Quality Manual (1.8) 

A Quality Manual or equivalent documentation approach should be established and should 

contain the description of the pharmaceutical quality system. The description should include: 

(a) The quality policy (see section III (2)). 

(b) The scope of the pharmaceutical quality system. 

(c) Identification of the pharmaceutical quality system processes, as well as their 

sequences, linkages, and interdependencies. Process maps and flow charts can be 

useful tools to facilitate depicting pharmaceutical quality system processes in a visual 

manner. 

(d) Management responsibilities within the pharmaceutical quality system (see 

section III (2)). 

III. MANAGEMENT RESPONSIBILITY (2) 

Leadership is essential to establish and maintain a company-wide commitment to quality and for 

the performance of the pharmaceutical quality system. 

A. Management Commitment (2.1) 

(a) Senior management has the ultimate responsibility to ensure an effective 

pharmaceutical quality system is in place to achieve the quality objectives, and that 

5
 
roles, responsibilities, and authorities are defined, communicated, and implemented 

throughout the company. 

(b) Management should: 

(1) Participate in the design, implementation, monitoring, and maintenance of an 

effective pharmaceutical quality system. 

(2) Demonstrate strong and visible support for the pharmaceutical quality system 

and ensure its implementation throughout their organization. 

(3) Ensure a timely and effective communication and escalation process exists to 

raise quality issues to the appropriate levels of management. 

(4) Define individual and collective roles, responsibilities, authorities, and interrelationships of all organizational units related to the pharmaceutical quality 

system. Ensure these interactions are communicated and understood at all 

levels of the organization. An independent quality unit/structure with authority 

to fulfill certain pharmaceutical quality system responsibilities is required by 

regional regulations. 

(5) Conduct management reviews of process performance and product quality and 

of the pharmaceutical quality system. 

(6) Advocate continual improvement. 

(7) Commit appropriate resources. 

B. Quality Policy (2.2) 

(a) Senior management should establish a quality policy that describes the overall 

intentions and direction of the company related to quality. 

(b) The quality policy should include an expectation to comply with applicable regulatory 

requirements and should facilitate continual improvement of the pharmaceutical 

quality system. 

(c) The quality policy should be communicated to and understood by personnel at all 

levels in the company. 

(d) The quality policy should be reviewed periodically for continuing effectiveness. 

C. Quality Planning (2.3) 

(a) Senior management should ensure the quality objectives to implement the quality 

policy are defined and communicated. 

(b) Quality objectives should be supported by all relevant levels of the company. 

(c) Quality objectives should align with the company’s strategies and be consistent with 

the quality policy. 

(d) Management should provide the appropriate resources and training to achieve the 

6
 
 

 

quality objectives. 

(e) Performance indicators that measure progress against quality objectives should be 

established, monitored, communicated regularly, and acted upon as appropriate as 

described in section V.A (4.1) of this document. 

D. Resource Management (2.4) 

(a) Management should determine and provide adequate and appropriate resources 

(human, financial, materials, facilities, and equipment) to implement and maintain the 

pharmaceutical quality system and continually improve its effectiveness. 

(b) Management should ensure that resources are appropriately applied to a specific 

product, process, or site. 

E. Internal Communication (2.5) 

(a) Management should ensure appropriate communication processes are established and 

implemented within the organization. 

(b) Communications processes should ensure the flow of appropriate information between 

all levels of the company. 

(c) Communication processes should ensure the appropriate and timely escalation of 

certain product quality and pharmaceutical quality system issues. 

F. Management Review (2.6) 

(a) Senior management should be responsible for pharmaceutical quality system 

governance through management review to ensure its continuing suitability and 

effectiveness. 

(b) Management should assess the conclusions of periodic reviews of process 

performance and product quality and of the pharmaceutical quality system, as 

described in sections IV (3) and V (4). 

G. Management of Outsourced Activities and Purchased Materials (2.7) 

The pharmaceutical quality system, including the management responsibilities described in this 

section, extends to the control and review of any outsourced activities and quality of purchased 

materials. The pharmaceutical company is ultimately responsible to ensure processes are in place 

to assure the control of outsourced activities and quality of purchased materials. These processes 

should incorporate quality risk management and include: 

(a) Assessing prior to outsourcing operations or selecting material suppliers, the suitability 

and competence of the other party to carry out the activity or provide the material 

7
 
using a defined supply chain (e.g., audits, material evaluations, qualification). 

(b) Defining the responsibilities and communication processes for quality-related 

activities of the involved parties. For outsourced activities, this should be included in a 

written agreement between the contract giver and contract acceptor. 

(c) Monitoring and review of the performance of the contract acceptor or the quality of 

the material from the provider, and the identification and implementation of any 

essential improvements. 

(d) Monitoring incoming ingredients and materials to ensure they are from approved 

sources using the agreed supply chain. 

H. Management of Change in Product Ownership (2.8) 

When product ownership changes (e.g., through acquisitions), management should consider the 

complexity of this and ensure: 

(a) The ongoing responsibilities are defined for each company involved 

(b) The essential information is transferred 

IV. CONTINUAL IMPROVEMENT OF PROCESS PERFORMANCE AND 

PRODUCT QUALITY (3) 

This section describes the lifecycle stage goals and the four specific pharmaceutical quality 

system elements that augment regional requirements to achieve the ICH Q10 objectives, as 

defined in section II.D (1.5). It does not restate all regional GMP requirements. 

A. Lifecycle Stage Goals (3.1) 

The goals of each product lifecycle stage are described below. 

1. Pharmaceutical Development (3.1.1) 

The goal of pharmaceutical development activities is to design a product and its manufacturing 

process to consistently deliver the intended performance and meet the needs of patients and 

healthcare professionals, and regulatory authorities and internal customers’ requirements. 

Approaches to pharmaceutical development are described in ICH Q8. The results of exploratory 

and clinical development studies, while outside the scope of this guidance, are inputs to 

pharmaceutical development. 

2. Technology Transfer (3.1.2) 

The goal of technology transfer activities is to transfer product and process knowledge between 

development and manufacturing, and within or between manufacturing sites to achieve product 

8
 
 

realization. This knowledge forms the basis for the manufacturing process, control strategy, 

process validation approach, and ongoing continual improvement. 

3. Commercial Manufacturing (3.1.3) 

The goals of manufacturing activities include achieving product realization, establishing and 

maintaining a state of control, and facilitating continual improvement. The pharmaceutical 

quality system should assure that the desired product quality is routinely met, suitable process 

performance is achieved, the set of controls are appropriate, improvement opportunities are 

identified and evaluated, and the body of knowledge is continually expanded. 

4. Product Discontinuation (3.1.4) 

The goal of product discontinuation activities is to manage the terminal stage of the product 

lifecycle effectively. For product discontinuation, a predefined approach should be used to 

manage activities such as retention of documentation and samples and continued product 

assessment (e.g., complaint handling and stability) and reporting in accordance with regulatory 

requirements. 

B. Pharmaceutical Quality System Elements (3.2) 

The elements described below might be required in part under regional GMP regulations. 

However, the Q10 model’s intent is to enhance these elements to promote the lifecycle approach 

to product quality. These four elements are: 

• Process performance and product quality monitoring system 

• Corrective action and preventive action (CAPA) system 

• Change management system 

• Management review of process performance and product quality 

These elements should be applied in a manner that is appropriate and proportionate to each of the 

product lifecycle stages, recognizing the differences among the stages and the different goals of 

each stage. Throughout the product lifecycle, companies are encouraged to evaluate 

opportunities for innovative approaches to improve product quality. 

Each element is followed by a table of example applications of the element to the stages of the 

pharmaceutical lifecycle. 

1. Process Performance and Product Quality Monitoring System 3.2.1 

Pharmaceutical companies should plan and execute a system for the monitoring of process 

performance and product quality to ensure a state of control is maintained. An effective 

monitoring system provides assurance of the continued capability of processes and controls to 

produce a product of desired quality and to identify areas for continual improvement. The 

process performance and product quality monitoring system should: 

9
 
(a) Use quality risk management to establish the control strategy. This can include 

parameters and attributes related to drug substance and drug product materials and 

components, facility and equipment operating conditions, in-process controls, finished 

product specifications, and the associated methods and frequency of monitoring and 

control. The control strategy should facilitate timely feedback/feedforward and 

appropriate corrective action and preventive action. 

(b) Provide the tools for measurement and analysis of parameters and attributes identified 

in the control strategy (e.g., data management and statistical tools). 

(c) Analyze parameters and attributes identified in the control strategy to verify continued 

operation within a state of control. 

(d) Identify sources of variation affecting process performance and product quality for 

potential continual improvement activities to reduce or control variation. 

(e) Include feedback on product quality from both internal and external sources (e.g., 

complaints, product rejections, nonconformances, recalls, deviations, audits and 

regulatory inspections, and findings). 

(f) Provide knowledge to enhance process understanding, enrich the design space (where 

established), and enable innovative approaches to process validation. 

Table I: Application of Process Performance and Product Quality Monitoring System 

Throughout the Product Lifecycle 

Pharmaceutical 

Development 

Technology 

Transfer 

Commercial 

Manufacturing 

Product 

Discontinuation 

Process and product Monitoring during A well-defined system Once manufacturing 

knowledge generated scale-up activities can for process ceases, monitoring 

and process and provide a preliminary performance and such as stability testing 

product monitoring indication of process product quality should continue to 

conducted throughout performance and the monitoring should be completion of the 

development can be successful integration applied to assure studies. Appropriate 

used to establish a into manufacturing. performance within a action on marketed 

control strategy for Knowledge obtained state of control and to product should 

manufacturing. during transfer and 

scale-up activities can 

be useful in further 

developing the control 

strategy. 

identify improvement 

areas. 

continue to be executed 

according to regional 

regulations. 

2. Corrective Action and Preventive Action (CAPA) System (3.2.2) 

The pharmaceutical company should have a system for implementing corrective actions and 

preventive actions resulting from the investigation of complaints, product rejections, 

nonconformances, recalls, deviations, audits, regulatory inspections and findings, and trends 

from process performance and product quality monitoring. A structured approach to the 

10
 
investigation process should be used with the objective of determining the root cause. The level 

of effort, formality, and documentation of the investigation should be commensurate with the 

level of risk, in line with ICH Q9. CAPA methodology should result in product and process 

improvements and enhanced product and process understanding. 

Table II: Application of Corrective Action and Preventive Action System Throughout the 

Product Lifecycle 

Pharmaceutical 

Development 

Technology 

Transfer 

Commercial 

Manufacturing 

Product 

Discontinuation 

Product or process 

variability is explored. 

CAPA methodology is 

useful where corrective 

actions and preventive 

actions are incorporated 

into the iterative design 

and development 

process. 

CAPA can be used as 

an effective system for 

feedback, feedforward, 

and continual 

improvement. 

CAPA should be used, 

and the effectiveness of 

the actions should be 

evaluated. 

CAPA should continue 

after the product is 

discontinued. The 

impact on product 

remaining on the 

market should be 

considered, as well as 

other products that 

might be affected. 

3. Change Management System (3.2.3) 

Innovation, continual improvement, the outputs of process performance and product quality 

monitoring, and CAPA drive change. To evaluate, approve, and implement these changes 

properly, 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. It should provide 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: 

(a) Quality risk management should be utilized to evaluate proposed changes. The level of 

effort and formality of the evaluation should be commensurate with the level of risk. 

(b) Proposed changes should be evaluated relative to the marketing authorization, 

including design space, where established, and/or current product and process 

understanding. There should be an assessment to determine whether a change to the 

regulatory filing is required under regional requirements. As stated in ICH Q8, 

working 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. 

(c) Proposed changes should be evaluated by expert teams contributing the appropriate 

11
 
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. 

(d) 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. 

Table III: Application of Change Management System Throughout the Product Lifecycle 

Pharmaceutical 

Development 

Technology 

Transfer 

Commercial 

Manufacturing 

Product 

Discontinuation 

Change is an inherent 

part of the development 

process and should be 

documented; the 

formality of the change 

management process 

should be consistent 

with the stage of 

pharmaceutical 

development. 

The change 

management system 

should provide 

management and 

documentation of 

adjustments made to 

the process during 

technology transfer 

activities. 

A formal change 

management system 

should be in place for 

commercial 

manufacturing. 

Oversight by the 

quality unit should 

provide assurance of 

appropriate scienceand risk-based 

assessments. 

Any changes after 

product discontinuation 

should go through an 

appropriate change 

management system. 

4. Management Review of Process Performance and Product Quality (3.2.4) 

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. 

(a) The management review system should include: 

(1) The results of regulatory inspections and findings, audits and other 

assessments, and commitments made to regulatory authorities 

(2) Periodic quality reviews, that can include: 

(i)	 Measures of customer satisfaction such as product quality 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 

(3) Any follow-up actions from previous management reviews 

(b) The management review system should identify appropriate actions, such as: 

(1) Improvements to manufacturing processes and products 

(2) Provision, training, and/or realignment of resources 

12
 
 

 

(3) Capture and dissemination of knowledge 

Table IV: Application of Management Review of Process Performance and Product 

Quality Throughout the Product Lifecycle 

Pharmaceutical 

Development 

Technology 

Transfer 

Commercial 

Manufacturing 

Product 

Discontinuation 

Aspects of management 

review can be 

performed to ensure 

adequacy of the product 

and process design. 

Aspects of 

management review 

should be performed to 

ensure the developed 

product and process 

can be manufactured at 

commercial scale. 

Management review 

should be a structured 

system, as described 

above, and should 

support continual 

improvement. 

Management review 

should include such 

items as product 

stability and product 

quality complaints. 

V. CONTINUAL IMPROVEMENT OF THE PHARMACEUTICAL QUALITY 

SYSTEM (4) 

This section describes activities that should be conducted to manage and continually improve the 

pharmaceutical quality system. 

A. Management Review of the Pharmaceutical Quality System (4.1) 

Management should have a formal process for reviewing the pharmaceutical quality system on a 

periodic basis. The review should include: 

(a) Measurement of achievement of pharmaceutical quality system objectives 

(b) Assessment of performance indicators that can be used to monitor the effectiveness of 

processes within the pharmaceutical quality system, such as: 

(1) Complaint, deviation, CAPA and change management processes 

(2) Feedback on outsourced activities 

(3) Self-assessment processes including risk assessments, trending, and audits 

(4) External assessments such as regulatory inspections and findings and customer 

audits 

B. Monitoring of Internal and External Factors That Can Have an Impacton 

the Pharmaceutical Quality System (4.2) 

Factors monitored by management can include: 

(a) Emerging regulations, guidance, and quality issues that can have an impact on the 

Pharmaceutical Quality System 

(b) Innovations that might enhance the pharmaceutical quality system 

(c) Changes in business environment and objectives 

13
 
 

 

(d) Changes in product ownership 

C. Outcomes of Management Review and Monitoring (4.3) 

The outcome of management review of the pharmaceutical quality system and monitoring of 

internal and external factors can include: 

(a) Improvements to the pharmaceutical quality system and related processes 

(b) Allocation or reallocation of resources and/or personnel training 

(c) Revisions to quality policy and quality objectives 

(d) Documentation and timely and effective communication of the results of the 

management review and actions, including escalation of appropriate issues to senior 

management 

14
 
 

VI. GLOSSARY (5) 

ICH and ISO definitions are used in ICH Q10 where they exist. For the purpose of ICH Q10, 

where the words “requirement”, “requirements,” or “necessary” appear in an ISO definition, they 

do not necessarily reflect a regulatory requirement. The source of the definition is identified in 

parentheses after the definition. Where no appropriate ICH or ISO definition was available, an 

ICH Q10 definition was developed. 

Capability of a Process: Ability of a process to realize a product that will fulfill the 

requirements of that product. The concept of process capability can also be defined in statistical 

terms. (ISO 9000:2005) 

Change Management: A systematic approach to proposing, evaluating, approving, 

implementing, and reviewing changes. (ICH Q10) 

Continual Improvement: Recurring activity to increase the ability to fulfill requirements. (ISO 

9000:2005) 

Control Strategy: A planned set of controls, derived from current product and process 

understanding, that assures process performance and product quality. The controls can include 

parameters and attributes related to drug substance and drug product materials and components, 

facility and equipment operating conditions, in-process controls, finished product specifications, 

and the associated methods and frequency of monitoring and control. (ICH Q10) 

Corrective Action: Action to eliminate the cause of a detected nonconformity or other 

undesirable situation. NOTE: Corrective action is taken to prevent recurrence whereas preventive 

action is taken to prevent occurrence. (ISO 9000:2005) 

Design Space: The multidimensional combination and interaction of input variables (e.g., 

material attributes) and process parameters that have been demonstrated to provide assurance of 

quality. (ICH Q8) 

Enabler: A tool or process that provides the means to achieve an objective. (ICH Q10) 

Feedback/Feedforward: 

Feedback: The modification or control of a process or system by its results or effects. 

Feedforward: The modification or control of a process using its anticipated results or 

effects. (Oxford Dictionary of English by Oxford University Press, 2003) 

Feedback/feedforward can be applied technically in process control strategies and conceptually 

in quality management. (ICH Q10) 

Innovation: The introduction of new technologies or methodologies. (ICH Q10) 

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Knowledge Management: Systematic approach to acquiring, analyzing, storing, and 

disseminating information related to products, manufacturing processes, and components. (ICH 

Q10) 

Outsourced Activities: Activities conducted by a contract acceptor under a written agreement 

with a contract giver. (ICH Q10) 

Performance Indicators: Measurable values used to quantify quality objectives to reflect the 

performance of an organization, process, or system, also known as performance metrics in some 

regions. (ICH Q10) 

Pharmaceutical Quality System (PQS): Management system to direct and control a 

pharmaceutical company with regard to quality. (ICH Q10 based upon ISO 9000:2005) 

Preventive Action: Action to eliminate the cause of a potential nonconformity or other 

undesirable potential situation. NOTE: Preventive action is taken to prevent occurrence whereas 

corrective action is taken to prevent recurrence. (ISO 9000:2005) 

Product Realization: Achievement of a product with the quality attributes appropriate to meet 

the needs of patients, health care professionals, and regulatory authorities (including compliance 

with marketing authorization) and internal customers requirements. (ICH Q10) 

Quality: The degree to which a set of inherent properties of a product, system, or process fulfils 

requirements. (ICH Q9) 

Quality Manual: Document specifying the quality management system of an organization. 

(ISO 9000:2005) 

Quality Objectives: A means to translate the quality policy and strategies into measurable 

activities. (ICH Q10) 

Quality Planning: Part of quality management focused on setting quality objectives and 

specifying necessary operational processes and related resources to fulfill the quality objectives. 

(ISO 9000:2005) 

Quality Policy: Overall intentions and direction of an organization related to quality as formally 

expressed by senior management. (ISO 9000:2005) 

Quality Risk Management: A systematic process for the assessment, control, communication, 

and review of risks to the quality of the drug (medicinal) product across the product lifecycle. 

(ICH Q9) 

Senior Management: Person(s) who direct and control a company or site at the highest levels 

with the authority and responsibility to mobilize resources within the company or site. (ICH Q10 

based in part on ISO 9000:2005) 

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State of Control: A condition in which the set of controls consistently provides assurance of 

continued process performance and product quality. (ICH Q10) 

17
 
 

Annex I: Potential Opportunities To Enhance Science- and Risk-Based 

Regulatory Approaches * 

*Note: This annex reflects potential opportunities to enhance regulatory approaches. The actual 

regulatory process will be determined by region. 

Scenario Potential Opportunity 

1. Comply with GMPs Compliance – status quo 

2. Demonstrate effective Opportunity to: 

pharmaceutical quality system, • increase use of risk-based 

including effective use of quality approaches for regulatory 

risk management principles (e.g., inspections 

ICH Q9 and ICH Q10). 

3. Demonstrate product and process 

understanding, including effective 

use of quality risk management 

principles (e.g., ICH Q8 and ICH 

Q9). 

Opportunity to: 

• facilitate science-based 

pharmaceutical quality assessment 

• enable innovative approaches to 

process validation 

• establish real-time release 

mechanisms 

4. Demonstrate effective 

pharmaceutical quality system and 

product and process understanding, 

including the use of quality risk 

management principles (e.g., ICH 

Q8, ICH Q9, and ICH Q10). 

Opportunity to: 

• increase use of risk-based 

approaches for regulatory 

inspections; 

• facilitate science-based 

pharmaceutical quality assessment; 

• optimize science- and risk-based 

postapproval change processes to 

maximize benefits from innovation 

and continual improvement; 

• enable innovative approaches to 

process validation; 

• establish real-time release 

mechanisms. 

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Annex 2
 

Diagram of the ICH Q10 Pharmaceutical Quality System Model
 

GMP 

ICH Q10 Pharmaceutical Quality System 

Pharmaceutical 

Development 

Commercial 

Manufacturing 

Product 

Discontinuation 

Technology 

Transfer 

Investigational products 

Management Responsibilities 

Process Performance & Product Quality Monitoring System 

Corrective Action / Preventive Action (CAPA) System 

Change Management System 

Management Review 

PQS 

elements 

Knowledge Management 

Quality Risk Management 

Enablers 

This diagram illustrates the major features of the ICH Q10 Pharmaceutical Quality System 

(PQS) model. The PQS covers the entire lifecycle of a product including pharmaceutical 

development, technology transfer, commercial manufacturing, and product discontinuation as 

illustrated by the upper portion of the diagram. The PQS augments regional GMPs as illustrated 

in the diagram. The diagram also illustrates that regional GMPs apply to the manufacture of 

investigational products. 

The next horizontal bar illustrates the importance of management responsibilities explained in 

section III (2) to all stages of the product lifecycle. The following horizontal bar lists the PQS 

elements that serve as the major pillars under the PQS model. These elements should be applied 

appropriately and proportionally to each lifecycle stage, recognizing opportunities to identify 

areas for continual improvement. 

The bottom set of horizontal bars illustrates the enablers: knowledge management and quality 

risk management, which are applicable throughout the lifecycle stages. These enablers support 

the PQS goals of achieving product realization, establishing and maintaining a state of control, 

and facilitating continual improvement. 

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