Change Control Process
Purpose and Scope
The purpose of this document is to describe the process to be undertaken when a change that could affect product quality or regulatory compliance needs to be made, to ensure that the change is suitably documented and reviewed / approved by competent personnel, and to follow-up the complementary actions related to the change.
Formal change control is an essential feature of any Quality Assurance system, to ensure that all changes are fully evaluated for their effect on product quality or validated status, and authorised before their implementation.
Change Control systems under GMP also ensure coordination of changes with all parts of the organisation and where relevant, with Regulatory Authorities.
The types of changes covered (but not limited to) are detailed below.
This list may not be exhaustive.
> product formulation
> process
> batch size
> processing equipment
> in-process control
> starting material / excipient / intermediate
> primary packaging
> secondary packaging (e.g. labels, leaflets, cartons, other printed items, etc)
> analytical testing methods
> analytical testing specifications
> water systems
> cleaning and sanitization procedures
> suppliers
> active pharmaceutical ingredient (API) process
> production site
> expiry date
> Quality and GMP related documentation
Changes in Computer Systems and Software which may have an impact on product quality or GMP are also the subject of change control
Responsibilities
It is the responsibility of the site QA manager to ensure that a suitable procedure is established to cover the requirements of change control. This could be achieved by a change control committee or a co-ordinator for all changes.
It is the responsibility of the site QA manager and the committee or the co-ordinator to ensure that all changes proposed are suitably reviewed and approved such that all of the implications of the change are evaluated, any additional testing / revalidation undertaken, and the required regulatory approval obtained before implementation.
In liaison with the change control committee or the co-ordinator, it is the responsibility of Regulatory Affairs Department or the compliance group to ensure that all appropriate amendments are made to the product and/or manufacturer’s licence. A particular change may not be significant enough for notification to the authorities; however consideration must be given to the cumulative impact of a number of small changes which together might justify notification to the authorities.
It is the responsibility of the site QA manager to audit the effectiveness of the change control procedure, and to initiate corrective action if required.
Requirements
When a requirement for change has been identified, the originator of that change is required to fill in the details on an appropriate form. Whilst filling in this form the originator should consider and record, if appropriate, the implications for:
> impurity profile
> conformation of drug substance
> interactions
> ability to scale-up
> stability
> bioequivalence / bioavailability
> critical steps of the process
> safety
> specifications
> integrity of qualification
> integrity of validation
> need for re-validation / re-qualification / re-calibration
> integrity of regulatory status
> need to inform regulatory authorities or submit a new file
> GMP compliance
(This list may not be exhaustive)
For certain documentation changes, a separate application form may not be necessary, at the document itself may include the approval signatures etc.
After completion, this form is passed to the change control committee or to the coordinator for further action.
The appropriate technical experts should be contacted for their comments (including any additional release and stability testing and any re-validation or qualification requirements etc.), which should be appended, the experts’ approval should be given to implement the change
The approved form with signatures of at least QA/QC, the implementing department and DRA, when relevant, is then returned to those departments involved, so that the change can be implemented.
Changes must not be implemented without completion of the formal approval process.
