GMP Document Management System - a brief Guide

A key aspect of a GMP facility is well written procedures. Procedures should be clear, concise, unambiguous, and easy for employees to follow.
Well written procedures should not leave any room for misinterpretation. They should be written in such a manner that anyone who is properly
trained and knowledgeable in the field can follow them as they are written.

There are various types of procedures that a GMP facility can have. The following is a list and brief description of the most common types of documents.

Quality Manual

A global company document that describes, in paragraph form, the regulations and/or parts of the regulations that the company is required to follow.

Policies

Documents that describe, in general terms and not with step-by-step instructions, how overall guidelines for how specific GMP aspects
(such as security, documentation, health, and responsibilities) will be implemented.

Standard Operating Procedures (SOPs)

Step-by-step instructions for how to perform operational tasks or activities.

Batch Records

These documents are typically used and completed by the manufacturing department.  
Batch records provide step-by-step instructions for production related tasks and activities as well as include areas on the batch record itself for
documenting such tasks.

Test Methods

These documents are typically used and completed by the Quality Control Department.
Test Methods provide step-by-step instructions for testing supplies, materials, products and other production related tasks and activities such as environmental
monitoring of the GMP facility.
Test Methods typically contain forms at the end of the procedure which are used for documenting the testing and the results of the testing.

Specifications

Documents that list the requirements that a supply, material, or product must meet before being released for use or sale.
The Quality Control Department will compare their test results to specifications to determine if the testing passes.

Logbooks

Bound collection of forms used to document activities.
Typically logbooks are used for documenting the operation, maintenance, and calibration of a piece of equipment Logbooks are also used for such
things are recording the monitoring of clean room activities, solution preparations, deviation and corrective action assignment.

• Controlled Document Management System
• A controlled document template should be created for each document type.
  This template can then be used by all personnel who are writing documents. 
  The following are examples of a document template:

A document number system also needs to be established for the various types of documents that are created.

Document # Examples: GEN-001 (General SOPs), TM-001 (Test Methods), BR-001 (Batch Records), QP-001 (Quality Policy),

Creation

Any knowledgeable employee should be able to write or revise documents as needed.
When revising a document the redline changes along with detailed justification of the changes should be routed.

Routing

The document control function of QA is responsible for routing documents for review and approval.
It is suggested that a pre-route be done to ensure that all affected parties are in agreement with the document before it is submitted to QA.
There should be a documented process detailing how documents are submitted for review and approval.
A controlled form listing all the changes made to the document, justification for the changes, and a list of personnel who need to review
the document needs to be routed along with the document.
At a minimum the author’s manager, all affected department heads, and QA need to review the document. Other Subject Matter Experts can be included.

Approval

Once all affected parties have agreed to the changes, document control will prepare the document for approval.
All changes will be incorporated into the document.
For new documents the version # will be 00. For each revision of a document the version number will increase (01, 02, 03, etc).
A master document will be routed for approval signatures.
Typically the approval signatures are the Author, the Department Head, and QA. QA must be the last signature on all documents.
The approval signatures on Batch Records are typically the Head of Manufacturing and the Head of QA.
Usually the approval signatures only appear on the first page of the document.
Once the master document has been signed, and effective date is stamped onto each page of the document. 
The effective date must be far enough in advance to allow for the document to be trained on before it becomes effective (typically this is 5 days).

Distributing

On the effective day copies of the signed master document are routed to the affected departments.
The departments will remove the old version and replace it the new version (for revised documents).
If the document is new, there will be no replacement document to remove. The old versions must be returned to document control.  
On a periodic basis document control personnel should audit the binders to determine if they contain the correct versions.
Each document binder should contain a table of contents and only those documents that the department is responsible for.
A full set of all approved documents should be in the QA department as well as in a central company location.

Archiving

Old revisions of documents will be stamped as superseded. No document revisions will be discarded or altered.
A file will be maintained within QA that contains all the Superseded documents and the signature approvals of personnel who agreed to the revisions.

Obsolete

If a document will no longer be used by any department in the company it can become obsolete.
The document must be stamped as Obsolete and all copies removed from all document binders.
It is a good idea to place a notice in the document stating that the document has been Obsolete.

The role of QA , in regards to the document system, is one of management and overview.
QA ensures that all documents are maintained in a controlled fashion.
That all procedures being used within a company are approved by the appropriate subject matter experts, are consistent with other documents,
and are the most current version. One way that QA ensures this is by being the last signature on all approved documents.  
All documents; current, obsolete, superseded, as well as all the history on the creation and revision of the document are kept with in Quality Assurance.

Document Hierarchy

A company’s controlled GMP document system should be established in a hierarchical manner starting with the general regulations and working downward
to more specific documents such as batch records.  Refer to Diagram below for an example of a hierarchical document system.

The regulations that a company is responsible for following (e.g. 21CFR210, 21CFR211, 21CFR820, etc) should be at the top of the document pyramid
and should govern the directives of the sub levels.

The level underneath the regulations, Level 1 documents (e.g. Quality Manual), should break the regulations into parts specific to those
that the company is required to follow.
These documents should establish overall principles and guidelines for how the company plans on developing, documenting, and implementing
a CGMP compliant quality system. Top level documents apply to all departments within a CGMP compliant company and are not specific in nature.

The next level, Level 2, of documents on the hierarchy document pyramid should further break down the parts of the regulations into specific subjects or topics.
These documents (e.g. Company Polices) should establish guidelines to which all subordinate level procedures must comply with to ensure consistency across
departments.
Level 2 documents should not provide specific how to directive instructions or forms for documenting data on but rather provide overall intentions
and guidelines governing critical programs or systems as well as explanations for the rationale and program designs.
These documents will apply to all departments within a GMP compliant company.
(Example: Company X Quality Policy: GMP Personnel Responsibility. “To describe the responsibility that personnel have in achieving and maintaining
compliance to Current Good Manufacturing Practices (GMP) and to the Quality System that has been established at Company XXX.”)

Standard Operating Procedures (SOP) should be the next level in the document hierarchy after Company Policy documents.
These types of documents should provide specific step-by-step instructions for how to perform the operational tasks or activities that were generally
talked about in the previous levels.
(Example: SOP titled “Writing, Revising, Numbering, and Distributing Controlled Documents”) Level 3 documents (e.g., SOPs)
should be department specific or function specific.

The last level of documents in a document hierarchical structure is the Level 4 documents.
These documents are the most specific in nature, (e.g. Batch Record, Test Methods, Validation Procedures) they would apply to a specific department,
product, equipment, or process. Level 4 document provide step-by-step instructions for production related tasks and activities as well as providing a
means for documenting such tasks such as data sheets, forms, or batch records. 
The details outlined in these documents may override directions given in other level documents.
(Example: The Company’s documentation SOP states to round numbers to 3 significant figures but the batch record states to record all numbers
calculated in scientific notation. The requirements listed in the batch record are what are followed.)

The document hierarchy pyramid is an example of one way to organize your company’s documents.
More or less levels may be added/subtracted to meet your company’s specific needs.

Regulations (CFR)