GxP-Blog

Efficient and well-organized manufacturing documents are essential to success in production. The problem is familiar: every year, the time comes to prepare your tax returns. Do you still do it yourself, or have you decided to hire a tax consultant? These days, some employees find the preparation of manufacturing documentation at work similar to doing one’s tax returns. Manufacturing instructions have often been changed, adapted and/or bloated over many years. They contain revisions from audits, are subject to specific and local wishes from plant managers or compliance officers, contain references to change documents or are linked by cross-references. There must be a better way to do this.

In pharmaceutical manufacturing, the manufacturing instructions as well as processing instructions and protocols are integral parts of batch documentation. The batch documentation can be used to prove that the production complies with the approval documentation. It likewise shows that the manufacturing was executed in accordance with the laws and regulations. Via the manufacturing instructions, all of the work done in conjunction with production, such as processing steps, packaging steps, sampling, in-process checks, etc., can be traced. In addition to its role in the approval of batches, the batch documentation plays a particularly important role if quality problems appear at a later point in the process. These problems may not have existed at the time of approval and may have occurred only later. This is why the documentation serves as substantive evidence in legal disputes. In short, the manufacturing documentation is an essential element of quality assurance.

Even if today’s statutory guidelines and regulations merely provide a framework, a continuous increase in documentation is to be expected. While a manufacturing instruction consisted of 20–30 pages in the 1990s, the dimensions soared in 2015 to over 100 pages. The number of entries (raw data, dates and times, checkboxes, etc.) rose from 100 (1990) to 500 (2015), while the number of signatures per manufacturing instruction rose from 100 (1990) to 500 (2015)1 and more. Manufacturing instructions consisting of more than 200 pages are no longer rarities today. The requirements for documentation will continue to increase in the future. In the context of globalization, in addition to the German Ordinance on the Manufacture of Medicinal Products and Active Pharmaceutical Ingredients (AMWHV), the EU directives (EU GMP Guideline) and FDA regulations (21 CFR 211) as well as ICH and WHO guidelines, other (regional) laws and regulations may have a significant impact.

Based on the aforementioned points, a concept must be prepared for the content in order to guide the employees easily and intuitively through the manufacturing instructions. Content requirements for efficient manufacturing instructions should include the following points:

The content of manufacturing instructions should not be a detailed description of individual work steps. In this regard, reference may be made to the relevant SOPs at the relevant points. The manufacturing instructions function as a protocol, and represent only a query that must be answered by the employees during execution.

The manufacturing protocols are subject to mandatory review and approval by the quality control department. Accordingly, the documents must be designed so that they can be reviewed quickly, easily and in a well-organized manner.

The style and language of the document must be appropriately adapted to the purpose. Every user who works with the document must be able to understand the document. This can be ensured in that technical terminology is avoided whenever possible and that short sentences in the active voice are used.

Always formulate your instructions so that the employee knows exactly what he’s supposed to do. Ambiguous formulations such as «properly», «n/a», «reviewed», etc. should not be used. Instead of writing «properly transferred», a more precise formulation should be used, e.g. «One day before the initial weighing, the product was transferred from a –20°C freezer to a 5°C refrigerator.»

In addition to the aforementioned points regarding content design, visual representation options should also be taken into account. A visual structure and orientation can be implemented via the definition of a color code, e.g. by department (initial weighing, filling, packaging, etc.), and by persons (inspector, technician, batch record reviewer, etc.). The advantage of this method is that the employee immediately sees whether the current document belongs to his area of responsibility.

Another tool that can be used for employee guidance is the insertion of pictograms. Symbols indicate special situations to the employees, e.g. GHS hazard symbols, PAS symbols, symbols for sampling points or signatures, symbols for electronic documents, etc.

Many pharmaceutical companies balk at subjecting their manufacturing instructions to review, as this involves a lot of time and effort on the part of the employees and high financial costs as well. However, when you compare the effort and expense involved to the benefits resulting from successful batches, faster approvals, lower storage costs and successful audits, the investment is well worth it. Should you wish to revise and optimize your manufacturing instructions, Chemgineering will be happy to provide you with competent support.