Management strategies for risk assessment

A safe, effective and state-of-the-art cleanroom requires significant investment and manpower. To sustain long-term development and meet objectives, as well as maintain a contamination-free environment, it is essential that sound procedures are in place from day one, as part of a dedicated management program.

There are five steps that support effective cleanroom management: Containment of an immediate threat; Documentation of an incident; Investigation of an incident and verification of product quality; Documenting action to prevent a future reoccurrence; Demonstration of product and procedural confidence to regulators.

Containing the immediate threat

When it comes to pre-empting a threat, time and resources are well invested, even if the exercise appears laborious at the time. It is essential to perform a risk assessment in order to understand the threats specific to your operations. The key is to be pro-active, not simply reactive – by which time any actions could be too late. Follow a simple four-stage checklist to containing a potential threat:

1. Comprehend (understand the incoming ‘threat’ i.e. primary packaging materials)
2. Control (environmental effects within the facility; utilities)
3. Check (delegate responsibilities; ensure every action is managed)
4. Correct (report, train, learn from experiences)

It is important to control incoming goods such as raw materials, lubricants and in turn understand a supplier’s operation and distribution. Utilities such as water, gasses and HVAC are, of course, control elements, as well as storage conditions. These conditions include temperature, humidity, packaging and segregation. A cleanroom manager is at a distinct advantage when the facility itself has benefited from appropriate design considerations. Easy-to-clean design features, adequate airlocks and appropriate equipment design are key. The working environment deserves equal attention: consider personnel (the number, as well as their behaviour and training) and air (temperature, humidity, particles and viable organisms). Containing the process threat demands robust systems and processes that minimise holding times and changes, coupled with good documentation. This provides a framework from which to work. Documentation should be clearly written; in the local language; sufficiently detailed and with useful illustrations e.g. flowcharts. In addition it is important to eliminate potential conditions that might promote growth such as moisture and agar residues. Segregation is part of this process too; separating dirty and clean areas and individual production steps (e.g. filling and capping). It is also necessary to remove unnecessary equipment. Communication is an integral part of cleanroom management and is a discipline best instigated through proper training. A qualification process should be followed through with continuous monitoring and further training. Staff should be encouraged to report incidences thereby keeping operations transparent and accountable.

Documenting the incident

In order to be able to document anything it is imperative that parameters – appropriate limits – are in place. ‘Alert’ and ‘action’ limits should be based on historical data. As stated before, communication is key. Alert limits constitute out-of-trend results or ‘outliers’. Through a formal, but simple, communication process steps should be taken to avoid exceeding the limit. In the case of an alert limit being exceeded, a documented investigation must be instigated. Subsequent action should be meaningful (i.e. more than just a documentary record), offer satisfactory corrections to existing procedures and also take preventative steps to avoid future repetition. Incident documents should be included in the Event Reporting System and the facts communicated to all concerned. The document should include a detailed description of the incident and all related data should be recorded, whether it is deemed important or not. The action taken immediately after the incident should also be recorded.

Investigating the incident

Speed and clarity are essential to any investigation. The investigation should commence immediately after communication of the event and within a 30 day timescale. Experts should be consulted and it is crucial to remain focused on discovering the root cause. Also bear in mind any ‘knock-on’ effect on other operations and products, for example batches, areas or systems. Understanding of the incident centres on the following: the origin of the problem; the reason it occurred and the consequent impact on product quality and safety. Where applicable, an understanding of the organism concerned will also be necessary. Remember to review existing data before creating additional data relating to the incident. Data should include:

• Operations leading to the result
• All related QC results for the batch
• Batch documentation
• Quality of utilities such as water and gas
• Quality of materials such as containers

When additional testing is necessary, it must be justified and pre-defined – should it include personnel and equipment, for example. Documenting action to prevent a future reoccurrence When deciding on appropriate future steps, criteria should be meaningful, corrective, preventative and documented. New procedures should be included in the CAPA (Corrective And Preventative Action) program with defined responsibilities and timelines.

Demonstrating confidence to regulators

Even the very best facilities will experience an incident at some stage and, as the saying goes, “prevention is better than cure”. It is important to understand the risks, document the incidents and investigate immediately. Investigations should prove themselves to be effective by resulting in corrective actions. These lessons can be integrated into future procedures to prevent reoccurrence. Confidence amongst staff and regulators is a by-product of the steps outlined above. By demonstrating control of these process steps you are also showing that you understand their purpose and inherent efficiency.