31.03.2014 |

LOGFILE No. 14/2013 - GMP Validation Documentation

Documenting Process Validation: Introduction

Extract from “Documenting Process Validation: A Drugmaker’s Guide”

The general principle of the GMP validation documentation (e.g., for manufacture, cleaning, analysis, qualification, maintenance, etc.) is that a plan or protocol containing all the work stages and procedures to be carried out and the specific acceptance criteria is established in written documentation and authorized by the responsible person. While the work is being carried out, the actual data is gathered and entered into a record. The data is then compared with the requirements, and conclusions are drawn. This is all reviewed and authorized by the responsible person. This may either take place as part of the record or as a separate outline report. It is important to note, for the U.S., all validation plans, protocols, etc., must be reviewed and approved specifically by the quality unit of the firm.

The documentation for validation projects is structured accordingly. Each validation project mentioned in the validation matrix is described in detail in its own validation protocol. As several checks, which are frequently performed by different people, generally need to be conducted for each validation protocol, it is usual to describe each of these checks in separate test or inspection plans. These test plans must, like the validation protocol, also be approved – either as annexes to the validation protocol or as separate documents.

Requirements for the format and structure of the validation protocol and report should be set out in the validation master plan.

Chronology of Document Creation

As soon as the validation protocol and test plans have been approved, practical implementation of process validation can begin. Great care should be taken to ensure that the start of batch production (i.e., the date of weighing the components) of the first validation batch takes place only after the validation protocol has been approved.

While the validation batches are being manufactured, the usual production records are created and, in addition, the as-is data which is required for validation purposes is logged in the test plans.

After the validation batches have been produced, the completed test plans are evaluated together with the production records and analysis results and compared with the specifications in the validation protocol. This evaluation is documented in a validation report, which can be created either for each individual validation batch (in the case of continuous validation) or as a summary for more than one validation batch (prospective and retrospective validation).

Occasionally it occurs that, for certain aspects, no final statement can be made regarding the validity of the process. In this case, follow-up measures must be defined, such as collecting further data while the next production batches are manufactured. This data is then assessed and evaluated in a final validation report. A summary report is also required if individual reports were created earlier for each validation batch.

Each company should define its own specifications for the formats and structures of validation protocols, test and inspection plans, and reports in its validation master plan.

Archiving of the Validation Documents

The documentation drawn up as part of the process validation (plans, raw data and reports) should be available at the manufacturing site (for packaging validation, at the packaging site) so that it is accessible for any inspections by authorities

As the validation documentation generally comprises extremely extensive data pools, before importing it to an archive it is particularly important to ensure that everything is complete and structured in such a manner that all the information can still be found quickly, even years later. In recent years, the socalled Traceability Matrix has established itself as a useful overview document for more complex validation projects that frequently result in a veritable flood of plans and reports. This matrix provides a tabular overview of the document names and archiving locations of all validation protocols, test plans, interim and final reports, follow-up measures, raw data, etc., which were created in conjunction with a validation project. For data recorded electronically, it must be ensured that this data is available for the duration of the retention period and can be made readable within an appropriate period of time. The stored data must be protected against loss and damage.

The length of time that the validation documentation is to be archived depends on how long the corresponding product is in circulation. Validation documents must be kept for at least as long as the batch documentation for the final batch ever produced. In Europe, this is at least one year after the expiration date or five years after batch certification by the Qualified Person, whichever is the longer period. If clinical studies are still being carried out with the product at that time, the documentation must be archived for at least five years after the completion or formal discontinuation of the last clinical trial in which the batch was used. For the U.S., see applicable regulations and guidelines for specific retention requirements.

Retention periods for all validation reports, documents and records should always comply with local regulatory requirements for the country where the product is made or will be distributed, whether it is the EU, the U.S., or any other country.

Extract from “Documenting Process Validation: A Drugmaker’s Guide”