1. Purpose
The purpose of this Guideline is to provide the regulatory requirements for the management of master GMP documents; issued, controlled and used to verify compliance with required codes of GMP and/or other relevant Quality and Compliance Standards. Recommendations are also included on how to achieve compliance.
2. Scope and Applicability
Master GMP documents issued and used by manufacturing functions, departments or sites to verify compliance with Good Manufacturing Practice (GMP) and/or other relevant Quality and Compliance Standards.
3. Definitions
3.1 GMP Master Document
An approved, version controlled GMP document is any policy, procedure, guideline, protocol, report, controlled form or template in paper or electronic form that is required for compliance with the GMP codes of practice and/or company Standards.
Notes:
(I) These documents are considered to be “records”.
(ii) Where a record, outlined above, contains raw data, these should be managed in accordance with the Quality and Compliance Manual guideline.
4. Responsibilities
Management is responsible for:
* Establishing procedures, guidelines and instructions within its function, department or site, to ensure compliance with document management practices as outlined in this guideline.
* Ensuring the preparation, review, approval and availability of master GMP documents required within its area of responsibility and provision of training where necessary.
4.2 Quality Assurance (QA)
QA within the functions, departments or sites is responsible for:
* Providing advice and support to management in the preparation of master GMP documents, ensuring that company standards and GMP regulatory requirements have been met.
* Reviewing and formally approving master GMP documents, as required by regulatory requirements.
* Establishing monitoring programs to assure management that the documentation procedures are being followed.
Note: where some activities are delegated to the QA function, for example, the management of the SOP system or archive for the function, department or site, then monitoring programs to verify adherence to the procedures, guidelines and instructions should be independently assessed by a third party.
5. Guideline
5.1 General Principles
Each function, department or site must establish, maintain and monitor master Medicament management practices to ensure compliance with the GMP codes of practice and/or Standards. Examples of documents that are subject to the requirements of this guideline are given in Appendix 1. It is not intended to be an exhaustive or all-inclusive list and advice should be sought from QA supporting the function, department or site. All staff must verify the validity of a document prior to its use.
5.2 Document Preparation
The need for a new (or revised) master GMP document should be determined in consultation between line management and operational units and, where relevant, in conjunction with QA. These may be as a result of new or modified working practices, deficiencies in existing practices and/or documentation assessed by internal monitoring programs (audits), external inspections and/or changing regulatory requirements.
The document must be prepared by technically competent staff within the specific work area and be clearly and concisely written. The document must have a unique identifier and be version controlled. Where a checklist or template is associated with the document, for example, a checklist associated with a Standard Operating Procedure (SOP), it may be prepared, approved and controlled separately from the SOP, as long as a traceable link is maintained. Other documents, including checklists or templates should have as a minimum, an identifier to differentiate versions, for example, by approval date or used from date.
Guidance on the level of detail to be included in a specific document, for example, asp on SOPs should be available within the specific function, department or site.
5.3 Document Review and Approval
Relevant staff and line management/process managers must review the document to ensure that it is technically sound, scientifically valid and can be implemented. Approval of the document must be by appropriate and authorized personnel. Additionally, QA must review the document to ensure that the GMP requirements have been met.
5.4 Effective Date
The document must contain an effective date, taking into account any implementation and/or training requirements, which must be completed prior to its use.
5.5 Control and Access to Master
GMP Document Once approved, the master GMP document must be returned to and retained by authorized personnel. Access to the master must be restricted. Where appropriate, the master GMP document must be retained in a secure archive. A copy of the master GMP document may be taken and made available for use.
For example, a master SOP and master batch manufacturing record may be copied and distributed for use. In some cases, however, the master document may be the working copy for a given GMP activity, for example, protocols for validations and/or qualification.
Procedures for the control of these documents, for example, documenting the location of and accountability for the document may be required. This is of particularly importance during the final review/approval of completed documents, as this may involve staff outside of the immediate location of the GMP activity.
Where the master document is used to generate the working copies, there production process must not allow any errors to be introduced or any reduction in clarity or legibility from the original. The master and copies taken from it must be distinguishable.
Where work is undertaken by a third party on behalf of the GMP function, department or site, clear responsibilities for the preparation, issue, use and archiving of the master must be defined in a Quality Agreement (contract).
5.6 Documents Available Electronically
Where documents are prepared and approved electronically, the above requirements in 5.2- 5.5 apply, and the systems must be validated. In particular, system safeguards and procedures must be in place to ensure that the master file is protected and not accessible to change and/or deletion by the user.
A business continuity plan must be in place, in the event of electronic documents not being available to staff. Documents held electronically may be printed for use in the local work environment, for example, SOPs. The printed document should indicate a “validate” or display other suitable warning, where this is considered necessary. Documents held electronically may also be required to be displayed or provided to third parties.
5.7 Distribution of Documents and Retrieval/Disposal of Superseded Documents
Concurrent with the issue of a revised document, the master of the superseded version must be made unavailable for use and formally archived.
Procedures must be defined to ensure that superseded copies of the revised master GMP document, which are available in the work place, are retrieved and/or destroyed.
Full accountability and traceability of documents should be considered and procedures established to verify this activity.
For paper copies, the authorized person(s) or delegate should circulate copies to relevant staff.
For a document that is available electronically, the authorized person(s) or delegate should inform relevant staff that the new or revised document is available for use. Alternatively, the person may be authorized to make the copy available for use. Confirmation of receipt of an electronic document may be required to indicate receipt and/or that training has been completed.
Training may be required for new or revised documents prior to their use and this should be documented, where applicable.
Superseded master GMP documents may need to be used for reference purposes and/or retrace previous GMP activities. In these cases, procedures for them use/retrieval must be implemented to prevent unauthorized use for current activities.
5.8 Unofficial Copies
Unofficial copies of GMP master documents may only be used for review, training or audit purposes. They must be marked as such to avoid unauthorized use.
5.9 Archiving of Master GMP Documents
Superseded master GMP documents must be archived in secure, access restricted and, where possible, purpose-built archives. Retention periods for master GMP documents must be defined to meet specific codes of practice and business needs.
Appendix 1
Examples of Master GMP Documents
* Policy Documents
* Standard Operating Procedures, Guidelines, Working Instructions
* Product Specifications
* Analytical and Manufacturing Methods
* Manufacturing Formulae
* Qualification and Validation Documents
* Protocols and Reports
* Technology Transfer Documents
* Checklists or Templates to record standardized tasks and procedures
It is not intended to be an exhaustive or all-inclusive list and advice should be sought from Quality Assurance supporting the function, department or site, for control practices for other documents not defined here.