Document Control Deficiencies – USFDA 483 to UCB

Inadequate control of forms used for recording GMP activities.

• Uncontrolled blank forms for in process sample logs.
• Uncontrolled facility cleaning logs.
• Uncontrolled Batch Release Checklist.
• Shredded documents observed in office area; No assurance that the shredded material did not have Quality documents.

The issue and concern with documenting GMP and Quality data in uncontrolled forms, Log Books, loose papers etc. is that such documents can be replaced, discarded without any traceability, which means integrity of the data is not reliable. Uncontrolled document are those whose source, version, history cannot be traced. All documents in GMP operations – Formats, Log sheets / log books, Records (Batch record, Analytical record and so on..), Work instructions including displays, Procedures, Reports (investigation reports, Trend reports, reviews..) all should be controlled. There shall be no piece of uncontrolled paper in GMP areas. This is to ensure that any replacements / destructions can be traced, authenticity of the data and document can be verified.

A Document control system should ensure:

• All documents used in the GMP operations (including Forms, Formats, Log books or any piece of paper that is used in GMP area) are described in an associated, parent procedure.
• Identification & Traceability: All such documents have Identity (a document number, title), Procedure for Issuance, retrieval, archival of the documents are defined. When working documents are issued such as raw data sheets, sampling log sheets etc. from a master document, these working documents have specific issue numbers and date; and issuance and retrieval of all such documents is controlled.
• Version and Revision controls for documents shall be defined, revision history is available. Validity period of the documents is defined.
• Authenticity –Define who prepare, review, and approve each and every master document – Forms, Formats, Templates, Work instructions, Procedures, Specifications, Test Methods, Reports and so on. Similarly, procedures shall define who update the different forms, formats, records with data, who review and who authorises & the documents carry evidence of the same.
• Retention – Retention periods of all documents is defined and documents are retained till the end of the defined retention period.
• All entries in the GMP documents are made indelibly.

(ICH Q7A, Section 6, guideline defines requirements for control of documents and records in detail; please refer and ensure compliance).

Procedures should also be established for shredding, destruction and scrapping of GMP documents.  It should be a controlled activity with authorisation by Quality unit and usage logbooks for paper shredders. Various citing on finding of GMP documents in scrap, reinforce the point that if an auditor picks up such a piece of document from anywhere in the site and challenge, the Quality unit and the Firm should be able to trace and explain the shredded / scrapped piece of document and why it was scrapped.

Document Control and documentation management is fundamental to GMP. Gaps in the document control procedures and practices lead to citing for lapses in Data Integrity.

Firms and sites may well review and make an assessment whether there are practices of uncontrolled documents in GMP areas (for e.g.  as cited in these observations or other similar issues) In their sites. If so, address the same by establishing comprehensive Document Control procedures, as discussed above.

But if lapses were observed during the assessment, enhancing the Document Control procedures alone is not sufficient. In areas of operations and activities where uncontrolled GMP documentations were practiced, review whether there are alternate checks and balances which can support the integrity of activities performed. For example, If in process samples were documented in uncontrolled sheets, whether the corresponding intermediate and finished product samples are handled with appropriate controls. And if there are no discrepancies, this can support the integrity of activity performed and there was no quality impact. Such comprehensive assessment, and enhancement of the Document Control procedures, can help give confidence to the auditors / agency that the Firm evaluated assessed the gaps in Document Control procedures and practices and their impact, implemented appropriate corrective measures (CAPAs) and the Firm Is in control.