GxP/GMP and Document Control

In the regulated environment, the document control is the cornerstone of the quality system. It is so important that if an external audit identifies deficiencies in the document control system, the entire organization can be shut down.

In my last post, I talked about the connection between ISO 9001 and document control. ISO 9001 is one example of the regulated environment. It is usually used in engineering types of companies. In food, drugs, medical devices, and cosmetics industries, GxP/GMP regulations are used. Today, I am going to talk about the connection between GxP/GMP and document control.

GxP is a general term for Good Practice quality guidelines and regulations. The titles of these good practice guidelines usually begin with "Good" and end in "Practice", with the specific practice descriptor in between. GxP represents the abbreviations of these titles, where x (a common symbol for a variable) represents the specific descriptor.

For example: Good Clinical Practice (GCP), Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP), Good Safety Practice (GSP), and many others.

A "c" or "C" is sometimes added to the front of the acronym. The preceding "c" stands for "current." For example, cGMP is an acronym for "current Good Manufacturing Practice." The term GxP is only used in a casual manner, to refer in a general way to a collection of quality guidelines.

The purpose of the GxP quality guidelines is to ensure that a product is safe and meets its intended use. GxP guides quality manufacture in regulated industries such as food, drugs, medical devices, and cosmetics.

The most central aspects of GxP are traceability - the ability to reconstruct the development history of a drug or medical device and accountability - the ability to resolve who has contributed what to the development and when.

GMP is the most well known example of a GxP.

Good Manufacturing Practice (GMP) are practices and the systems required to be adapted in pharmaceutical and medical devices companies. GMP is the guidance that outlines the aspects of production and testing that can impact the quality of a product.

Many countries have legislated that pharmaceutical and medical device companies must follow GMP procedures, and have created their own GMP guidelines that correspond with their legislation. Basic concepts of all of these guidelines remain more or less similar to the ultimate goals of safeguarding the health of the patient as well as producing good quality medicine, medical devices, or active pharmaceutical products.

In the U.S. a drug may be deemed adulterated if it passes all of the specifications tests but is found to be manufactured in a condition which violates current good manufacturing guidelines. Therefore, complying with GMP is a mandatory aspect in pharmaceutical and medical devices manufacturing.

Documentation is a critical tool for ensuring GxP/GMP compliance.

This is what GMP states about document control:

Each manufacturer shall establish and maintain procedures to control all documents that are required. The procedures shall provide for the following:

1. Document approval and distribution. Each manufacturer shall designate an individual(s) to review for adequacy and approve prior to issuance all documents. The approval, including the date and signature of the individual(s) approving the document, shall be documented. Documents shall be available at all locations for which they are designated, used, or otherwise necessary, and all obsolete documents shall be promptly removed from all points of use or otherwise prevented from unintended use.

2. Document changes. Changes to documents shall be reviewed and approved by an individual(s) in the same function or organization that performed the review and approval of original documents, unless specifically designated otherwise. Approved changes shall be communicated to the appropriate personnel in a timely manner. Each manufacturer shall maintain records of changes to documents. Change records shall include a description of the change, identification of the affected documents, the signature of the approving individual(s), the approval date, and when the change becomes effective.

These requirements are consistent with document control requirements stated in ISO 9001 which I described in my previous post.

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 and that all procedures are 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 in Quality Assurance.

These are the steps of the document control procedure:

Creation

Any knowledgeable employee should be able to write or revise documents as needed.

Revising

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. 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.

Good manufacturing practice (GMP) regulations require that all documentation be issued, managed and controlled using a document management system.

In my future posts, I will further describe GMP regulations pertaining to documentation and documentation management systems.