For life science and other regulated manufacturers, cleanroom maintenance is an important part of compliance. It’s not enough that you have written meticulous quality protocols and procedures for maintenance of your equipment and facilities — it’s equally important to control and manage all accompanying documentation that will show regulators that your cleanroom is compliant.
For companies regulated by the FDA, requirements pertaining to cleanroom and controlled environment procedures can be found in predicate rules such as 21 CFR Part 211 for pharmaceutical companies and 21 CFR Part 820 for medical device manufacturers.1 These require documentation of standard operating procedures and instructions as well as documented procedures for process changes related to equipment, buildings, and facilities.
A recent warning letter to a medical device firm shows the importance of proper documentation and corresponding control of those documents. The FDA noted the company’s failure to establish and maintain written procedures for avoiding contamination of equipment, as well as the incongruity between some of its cleanroom procedures and records of actual practice.2
Long document cycle times
To maintain a cleanroom and train its personnel, organizations generate numerous records and documents that need to be controlled and managed. Whether it’s the SOP for sanitizing a cleanroom against particulates and pathogen contamination or written materials for training technicians on sterile gowning procedure, you need to be able to create, approve, and revise documents efficiently.
The biggest problem for companies that use paper or hybrid (part electronic and part paper) processes lies in administration itself. When the cleanroom and quality departments create documents, they must route those files for review and approval either in person or through email. Follow up is also conducted by email, phone, or in person. Once approved, those documents are typically stored in electronic servers, printed in hard copy, compiled in binders, and stored in filing cabinets in a document room. It is difficult to manage hundreds or thousands of documents, especially if they undergo multiple revisions and regular updates.
Companies typically cut down their review and approval turnaround time significantly after automating their document control process. A manufacturer of nutritional supplements noted that its document-approval cycle time improved from months to days after it switched to an electronic document management system. This company automated 46,000 documents during the switch.3
With an electronic system in place, routing, follow up, escalation, and distribution are all automatic, saving time and effort. Obtaining approval and signatures of stakeholders who are out in the field or are scattered in various facilities is also easier, especially users can participate in quality processes with mobile devices. An electronic document control system that allows cleanroom personnel to use a smartphone or a tablet instead of paper documents is more convenient and efficient for them, which in turn could help reduce document cycle times.
Lack of control in the change control process
Where companies usually run into trouble in the distribution of new revisions is not knowing where all the copies of the old revision are. It helps to have a system that allows the lock down uncontrolled copies and facilitates tracking of controlled copies.
Make document review a part of your change control process. Most regulated companies have a document review policy to ensure that important quality documents are still applicable and accurate. A regular review process can help ensure necessary changes have been documented and that the actual process and the documented process are in sync.
Training falls through the cracks
Once a quality document is approved (either for the first time or after an update), affected personnel should be notified and provided access to the document so they can be trained on the document prior to its effective date.
For example, if your organization has implemented an extra wipe-down of the cleanroom at the end of every work day as a result of an audit observation, you have to make sure all cleanroom operators understand the change and are given enough time and appropriate tools to perform the new task. Not only that, you have to make sure your GMP records reflect this additional wipe-down for the benefit of your next audit.
In a paper or hybrid quality system, it’s easy for training to fall through the cracks because the document approval process is not connected to the training process. Someone has to make sure that when a quality document is approved and released, the corresponding training will be conducted. Automatic quality systems integrate document control with a learning management system to ensure that training related to important documents will be implemented.
Going back to our example above, once the SOP explaining the additional wipe-down is approved, the system will automatically notify all affected personnel of the change. It will seamlessly trigger the training of cleanroom technicians on the updated SOP.
In regulated environments, document control is the foundation of quality. All procedures and processes that directly affect product quality and safety must be documented. In turn, all important documents (and the process for changing those documents) must be controlled. It is no different for cleanrooms and controlled environments of organizations that want to ensure regulatory compliance.
1. For medical device companies, see 21 CFR 820.70 (Production and Process Controls): http://1.usa.gov/24YUmQ4. For pharmaceutical companies, see 21 CFR 211.67 (Equipment cleaning and maintenance) and 21 CFR 211 Subpart C (Building and Facilities), Subpart D (Equipment) and Subpart J (Records and Reports): http://1.usa.gov/1YOQ35I
2. FDA warning letter to Excelsior Medical Corp., issued on Nov. 7, 2014: http://1.usa.gov/1QWBS9k.
3. MasterControl Helps Weider Nutrition International Stay on Top of its Document Control and Change Management Processes: http://bit.ly/1TGFNx1
Dave Hunter is product management director at MasterControl Inc. His extensive technology experience includes working for Microsoft, EDS, Intel, and TenFold for over 20 years. firstname.lastname@example.org
This article appeared in the March/April 2016 issue of Controlled Environments.