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Siegfried Schmitt, vice president Technical at Parexel, discusses the difficulty of operating non-GMP and GMP quality systems in the same facility.
Q: We have been manufacturing specialty chemicals for many years. Some clients have asked us to manufacture intermediates and drug substances for them in compliance with good manufacturing practices (GMPs). We are very interested to do so, but how do we manage two quality systems (GMP and non-GMP) within the same facility?
A: It is understandable that you wish to have a non-GMP quality system for your specialty chemicals business and a GMP system for pharmaceutical intermediates and drug substances, as these have a direct bearing on the cost of goods. Companies can certainly operate more than one quality system; the difficulty however is to operate them within one and the same facility. In short, I have never seen it work. Let us look at some of the reasons for this.
Your personnel will need to be trained in the respective quality system. Following a particular system requires more than training; it needs repeat experience (i.e., learning on the job). Having to switch between two rather different systems would be like having to cook over a campfire today and to prepare the same meal in a professional kitchen tomorrow. This is confusing, to say the least. Where GMP-trained and untrained staff work in close proximity, there is always a chance that untrained operators are called for help, thus creating a risk to product quality and compliance.
Your equipment must be suitably qualified, calibrated, and maintained to meet GMP requirements. Especially during times of high demand, the temptation is all too real to use unqualified equipment due to production pressure and looming deadlines. Or, if there is no clear physical segregation between non-GMP and GMP equipment, the probability to erroneously use unqualified equipment (in manufacturing or the laboratory) is unacceptably high.
You may require the same raw materials for pharmaceutical product manufacture and for other goods, yet in differing qualities (i.e., different specifications). It requires a very robust dispensing and documentation system to prevent any accidental use of raw materials with the incorrect specification. It is, however, not merely the use of the correct material that is of concern. You also need to consider the risk from accidental cross-contamination from non-GMP materials. Such materials may have unknown impurities, which may be difficult to detect and remove during cleaning. Unless you have dedicated GMP and non-GMP equipment, there is a real risk of accidental cross-contamination.
Where things go wrong most often where more than one system is in operation is with documentation. GMP requires not only good documentation practice, but also must meet the strict requirements for data integrity. It matters for GMP products who performed the task, documented the task, and documented it contemporaneously. Yes, mistakes happen with GMP documentation too, but these errors need to be corrected in a controlled manner. GMP processes need to follow documented, controlled procedures and instructions, whereas non-GMP activities don’t. It is human nature to follow the path of least resistance. Thus, there is a real likelihood that staff may not want to bother with onerous procedures, particularly when there is a high workload and pressure to meet deadlines.
In summary, it is conceivable to have more than one quality system, but it is nigh impossible to operate them alternating or in parallel within one and the same facility. Physical and organizational segregation is a necessity, or deviations and costly mistakes will be encountered almost inevitably.
Siegfried Schmitt is vice president Technical at Parexel.
Vol. 35, No. 1
When referring to this article, please cite it as S. Schmitt, “Good Manufacturing Practice on Demand?” BioPharm International 35 (1) 46 (2022).