This article is part of a special feature on cleanrooms that was published in the December issue of PTE Digital, available at http://www.pharmtech.com/ptedigital1210.
A review of warning letters from the last 10 years relating specifically to cleanrooms has indicated several concerns with the appropriateness of cleanroom design — primarily regarding air flow and laminarity. Additional citations have been made about area maintenance, e.g., in need of repair, presence of "rust", peeling or damaged surfaces, and so forth. Meanwhile, additional observations have related to monitoring plan inappropriateness/insufficience and the poor aseptic behaviour observed within the cleanroom.
To reduce the chance of receiving a warning letter, companies must review the design features of a cleanroom on a regular basis and take appropriate corrective actions to ensure that both airflow and laminarity are maintained, especially when personnel are operating in the area. Maintenance issues could be mitigated by conducting routine and frequent checks of both the condition of the area and the equipment, ensuring that concerns are quickly repaired. Cleanroom monitoring programmes should also be routinely reviewed to determine whether they reflect current, stateofthe art thinking. If not, the programmes should be updated as appropriate. Finally, poor aseptic behaviour must be mitigated with training and retraining of operators. This should be supplemented with supervisory oversight and coaching, as appropriate.It is important that a group or person within a company is responsible for keeping abreast of current regulatory trends, e.g., by reviewing recent warning letters, benchmarking against other companies, reviewing literature, and assessing the company's performance against current trends and standards.
Best practice for environmental monitoring
It is a little more difficult for companies to meet all of the requirements for environmental monitoring. First, one must understand which regulatory requirements are applicable. There are compendial monographs in the USP, JP and EP; guidance in various regulatory documents; GMP requirements for Europe; GMP requirements in the US FDA's Aseptic Guidance; ISO Documents; and World Health Organisation documents, to name a few of the applicable requirements.
Many traditional companies use programmes that were established more than 10 years ago. While the programme may still evaluate a state of control, it may not appropriately implement the current regulatory expectations.
In order to define an appropriate environmental monitoring programme, it is advisable that companies use risk assessments to determine the appropriateness of sample locations, monitoring equipment and control levels, as well as in determining the types of organisms that should be considered "objectionable" to the process. Once these parameters have been defined, the process of developing an effective environmental monitoring can begin.