1-4 ChangeControl

Change Control
Luisa Stoppa
Manufacture of sterile medicines Advanced workshop for SFDA GMP inspectors Nanjing, the Peoples Republic of China 16-20 November 2009
Objectives of the presentation

To answer to the following questions:
What is the purpose of change control? What must be taken into consideration when introducing change control programs? How can changes be graded? What should be regulated in a change control operating instruction? What is the function of the change control committee? How shall the implementation of changes be recorded? What has an inspector to inspect and to check?
Manufacture of sterile medicines Advanced workshop for SFDA GMP inspectors 2 | Nanjing, the Peoples Republic of China, 16-20 November 2009
Programme
To introduce the general elements on change control
To train you in the guidelines (WHO-GMP, PIC/S guidelines, EU-GMP)
To become confident with SOP, forms and records of Change Control System To develop your inspection plan on change control
Principles of change control

Before a medicinal product can be released, we need:
the manufacture and quality control procedure should be documented in the form of instructions;
The materials to be used must be specified;

The basic conditions required for a reproducible quality, efficacy and safety must be defined (i.e. suitable rooms, qualified facilities, trained personnel, validated procedures, established specifications)

Before the requirements can be implemented, the suitability of equipments/facilities and procedures must be proven with qualification / validation This principle is not only valid the first time a medicinal product is manufactured or the first time a facility is used or a procedure comes into effect The principle applies to the whole history of a medicinal product, a procedure or a facility and it is to be guaranteed As each requirement is stated in a document, it is clear that each change control for the requirements must also always involve a documentation control

Each change to previously approved requirements requires a review and authorization to keep the system in its original state of proven suitability Formal change control guarantees that all changes are evaluated for their effect on product quality or validation status Change control minimizes the risk that changes can have on the quality or process characteristics Change control programs have become recognized as essential element of the pharmaceutical quality assurance system
The task of change control

In the WHO-GMP guideline glossary there is definition of the term change control
However, the GMP guideline basically contains only few notes about the handling of changes

In the American Code of Federal Regulation CFR, the responsibility for the verification and authorization of changes is task of the quality control unit In the EU regulations, the responsibility is assigned to Quality Unit
As the change control is considered an essential element of the pharmaceutical quality assurance system, it is logical the person responsible is quality assurance (QA representative, QA head)

Change control is not department-specific, rather the task of the whole company
The change control monitors all types of changes which can influence the process or product quality and states the measures necessary for implementing the change or decides that a change should not be implemented
Change control programs

Change control program is a managerial task
We expect a quality structure of change control
QM statement standard operating procedure / instructions records / forms and other relevant documents
change policy operating instruction for change control change requests and other relevant documents

Many types of changes affect several areas at the same time:
GMP requirements Process security (validation) Product quality (specifications, approval) Regulatory requirements
Effectiveness / safety (approval)
Suitable rooms and equipment (qualification) Suitable personnel (training, experience)

A central processing of change procedures, coordinated by the quality assurance department, has several advantages:
there is a common understanding of what a change represents; the classification schemes used by the staff involved to rate changes are congruent; the risk connected with the change can be evaluated in a multidisciplinary manner; there is uniform documentation and authorization procedure

The type and scope of a change control program must comply with the requirements:
1. In the classical GMP-relevant areas the change control helps to maintain the validated and established status. Validated processes, qualified facilities, material specifications can be influenced by changes and medicinal products no longer comply with specifications

2. Holder of marketing authorization must guarantee that necessary regulatory pre-requisites are met. Contract manufacturers that do not have their own authorization must guarantee that the contract giver is informed of internal changes that could have an influence on their application documentation (this requires that the contract giver is included in the change control program of the contract manufacturer)

3. In areas where medicinal products are developed, processes are optimized or clinical research takes place, changes should also evaluated and documented so that the development of medicinal product or process must be consistently proved

Many companies rate the changes requiring control
EU-GMP

Major change Minor change Influences a unit requiring control
The example is one way to rate them:
Not requiring control No relevance to GMP or authorization No relevance to GMP or authorization
Significance of change Possible measures (selection)
Influences product quality or process reliability
Official license New approval revalidation
Amendment Review documentation
examples
Change of manufacturer: other synthesis route of a starting material (other impurities)
Replacement of apparatus part of the same design Change of cleaning agent for floors
Change to working times
Removal of processes to another site
Installation of air conditioner in administrative area
Change in the product composition
Change of laundry for work clothes (nonsterile or antibiotics area)
Change in purchase procedure
Change to the process parameters

Other classifications are possible

It is not decisive which and how many changeclasses a company has rated, but how it is guaranteed that changes requiring control are recognized as such and implemented according to a defined procedure

Not all changes require a revalidation
WHO-GMP

In the PIC/S document PI 006 (chapter 6.7.4) there is a list of changes that may require a re-validation:

Also in the WHO-GMP guidelines there is a list of changes that may require a re-validation

WHO-GMP guidelines

PIC/S document PI006

The so called trials cause a problem in change control program. Trials are preliminary, temporary changes which can permanently established or revoked after a trial period
With trials, there is a risk that these intended temporary changes gradually become permanent changes without a formal change control procedure being carried out How long a trial is retained and whether it is withdrawn after a trial phase or be introduce permanently, should be included in the same procedure change control as all other changes

Deviations should not be treated as changes, not even when deviations become changes after a failure has been clarified
Deviation is an unplanned and undesirable deviation from a requirement; it occurs spontaneously Deviations should be dealt with according a procedure about handling deviations All variations implemented in emergency (no planned, no controlled, no permanent) are included in deviations

Changes (planned changes) Deviations (unplanned changes)
Submission of request - description of change - rationale Evaluation
Notification - description of deviation Evaluation - effect on product quality - definition of corrective actions - effect on validation status - definition of revalidation measures Implementation of deviation Closing
- effect on validation status - definition of revalidation measures Approval Implementation of change Closing

An important function as part of the change control program is fulfilled by the change control committee CCC (also known as change control team or change control board) This committee consists of the head of Quality assurance, the heads of manufacturing, quality control, regulatory affairs, IT department, engineering, sales
The task of the committee is to evaluate the changes, establish and coordinate measures to put in place and authorize the changes
PIC/S guideline

A problem is the issue of which changes the change control team should dealt with
It is obvious that this team cannot deal with all changes in the company As matter of fact, only changes requiring control should be processed by this team

Firstly, these are changes relevant for the regulatory status
Secondly, they are changes which could have an influences on the attributes of a GMP-relevant system, facility, equipment, material/product, procedure/process The team should also deal with all changes whose grade or implementation is unclear or questionable

How the team members communicate with each other?
Not all changes require a meeting In cases which are easy to make a decision about, it can be useful traditional paper-based circulation procedures, e-mail agreement or access to Intranet-based forms

When a change control program has been introduced, the effectiveness of the system can be reviewed using data which is easy to determine
Total number of changes request /year
Number of completed change requests / year Change type / department involved Duration of procedure: from application to closing Number of deviations/year Number of internal or external complaints /year Number of OOS /year
EU-GMP
Documentation
Change control requires a written procedure to establish at least the following steps:
What type of changes does change control take into account? What are the requirements for urgent changes? For which areas does this operating procedure apply? Who can suggest changes? How are changes requested (forms, method of communication)? How are changes graded and who is responsible for the rating? How are the measures for carrying out the change established? Who is responsible for the implementation and monitoring of all measures? Who is included in the change control team? What are the duties of the change control team? How is the change documented (format, content, storage)? Who is responsible to authorize changes?
Documentation
Documentation
Documentation
All quality-relevant changes should be documented
All actions to be taken, including the need for and extent of qualification or validation, should be described
The records can be archived in paper form or electronically When storing documents, raw data and other relevant documents for change should be kept accessible
Documentation
Changes requiring control are generally documented in the form of a change request in which the applicant for the change proposes the type of change, suggests the timeframes and measures for carrying out the change
The change control team authorizes or not the change The documentation for the change procedure should show that the change was evaluated (risk analysis)
Documentation
WHO-GMP
Documentation
Change control procedure (example 1)
Documentation
Change control procedure (example 2, 1/2)
Documentation
Change control procedure (example 2, 2/2)
Documentation
Change control procedure includes flow chart of the change control process and the change request form (or change form)
Change request form records a request for change so that each change is documented before it is approved The change request form includes the description of the change, the benefits, costs, urgency of the change, change impact
Documentation
Change control procedure: flow chart (example 1)
Documentation
More information required
Change Request Submission Evaluation of Change Impact Validation Change Request Change Activities
Change Activities
Approval Activities Completion Change Closed Manufacture of sterile medicines Advanced workshop for SFDA GMP inspectors 46 | Nanjing, the Peoples Republic of China, 16-20 November 2009
Approval Activities Completion
Documentation
Documentation
CCB = change control board
Documentation
Change control procedure: flow chart for change master documents (example 1)
Documentation
Change request form (example 1, 1/2)
Documentation
Documentation
Documentation
Documentation
Change request form (example 3)
Documentation
Change database: electronic copy
Documentation
Change control logbook
Page:__ of ____
Change control logbook (year:________)

Nb. Request date Requester / department Item Description Approval date Actions and time limit Closing date
QA Manager signature _________ Date_______

Examples of changes
Changes to the cleaning procedure
- use of a new cleaning agent - change in concentration / volumes of cleaning agent - change in volumes of rinsing water - change of cleaning process parameters
Changes to the production equipment

- changes to the CIP equipment - changes to / replacement of equipment parts (difficult to give detailed examples as these changes are too diverse) - change of process parameters
Examples of changes
Changes to the product - changes to composition (reformulation with different excipients)
- changes to the manufacturing process (i.e. transfer of a product)
Changes to HVAC system / unidirectional flow

Changes in lay-out (i.e. implementation of a pass-box)
Inspection plan
To ask for the Change Control standard operating procedure
To check that all relevant steps for change control implementation are detailed To choose some applications (from the list in the logbook)
To verify the applications and all requested documents (change request form, investigation, request and closing date)
Conclusion
The old adage says: the only thing constant is change!
Reference documents
WHO GMP guidelines Technical Report series n. 937
EU GMP guidelines, Part I annex 15 ICH Q7A or EU GMP Part II chapter 13 PIC/S Recommendations PI 006-3
[email protected]
Workshop on WHO prequalification requirements for reproductive health medicines, Jakarta, October 2009
62 |

1-4 ChangeControl

Uploaded by

Copyright:

Available Formats

1-4 ChangeControl

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

1-4 ChangeControl

Uploaded by

Copyright:

Available Formats

Change Control

Objectives of the presentation

Principles of change control

The materials to be used must be specified;

Principles of change control

Principles of change control

The task of change control

Principles of change control

Principles of change control

Principles of change control

Change control programs

Change control programs

Effectiveness / safety (approval)

Suitable rooms and equipment (qualification) Suitable personnel (training, experience)

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

The example is one way to rate them:

Not requiring control No relevance to GMP or authorization No relevance to GMP or authorization

Significance of change Possible measures (selection)

Influences product quality or process reliability

Official license New approval revalidation

Amendment Review documentation

Change of manufacturer: other synthesis route of a starting material (other impurities)

Change to working times

Removal of processes to another site

Installation of air conditioner in administrative area

Change in the product composition

Change of laundry for work clothes (nonsterile or antibiotics area)

Change in purchase procedure

Change to the process parameters

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Submission of request - description of change - rationale Evaluation

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Change control programs

Approval Activities Completion

CCB = change control board

Change control logbook (year:________)

QA Manager signature _________ Date_______

Changes to the production equipment

Changes to HVAC system / unidirectional flow

QA Manager signature ___ Date_