Business Biotics Group has designed a generic investigative procedure specifically tailored for bioburden detection involving:

• a product sterility failure
• media fill contamination
• routine environmental monitoring program
• product sterility testing process

Our investigative methodology is based on a root/cause analysis which is coupled with a risk assessment whereby risks are graded against predetermined impacts. The impact is graded against its potential severity which may directly impact on the company’s business operations.

Once the cause and effect of the contamination has been established, it can be controlled and eliminated. This process is in line with the FDA preference of Risk Based Management with an integrated quality system approach.

A Risk associated with contamination can be defined as a characteristic of a specific aseptic manufacturing process that has a potentially adverse effect on the quality of the product or media fill.

The Risk is the potential “cause” of the contamination which has an effect (Impact) on the process viability. A Risk/ Impact Assessment should be performed for every bioburden incident effecting product or media fill.

The flow chart below shows the main steps involved in this process:

The main areas of our investigation are shown in the following Table:

	Area of Investigation	Description
1	Environmental monitoring results and trends	All environmental monitoring results and trends from the process are systematically reviewed to establish the presence of or increasing levels of bioburden
2	Environmental cleaning	Environmental cleaning documentation is reviewed to ensure conformance to procedures
3	Operator behaviour	Operators are observed and appraised for conformance to “correct” clean room behavioural standards
4	HVAC operations	The operational data from the HVAC is analysed to ensure conformance to validated limits
5	Sterilization processes	The operational data from autoclaves, hot air sterilizers, ethylene oxide and gamma irradiation etc are reviewed to ensure conformance with validated limits
6	Process deviations/observations	The batch/lot manufacturing records are reviewed for the documentation of process deviations/observations.
7	Process validation	The Process Validation procedures and results are examined to determine whether the process was carried out within validated limits
8	Test Methods	Quality Control product sterility and microbial test methods are investigated to ensure they were performed correctly and are appropriately validated.
9	Change Control	An investigation is carried out to establish whether approved or non approved changes were introduced into the process and if so, what impact the change may have had on the aseptic process.

Business Biotics Group has more than 40 years experience in the design, operation and investigation of aseptic pharmaceutical processes.

Our aseptic design, operation and investigative expertise ranges from pilot scale plants for the production of Phase I/II clinical trial product, through to large scale pharmaceutical manufacturing plants.

Our aim is to reduce the risks of aseptic manufacturing for the client. An essential element of this risk is contamination control and elimination.

Our strategy is designed to assist the Quality Director enhance the company’s Quality Management Plan with the inclusion of a contamination investigation and control procedure.

This approach will strengthen the client’s regulatory compliance and safeguard the company’s manufacturing license, revenue and reputation.