The Impact of OOS Investigations
The cost of your QC solution is not only about the instruments and reagents on your invoice. Choosing based on money alone can have serious long-term effects on your bottom line, including:
- Production Interruptions for Investigations: Time and money is diverted from production to looking into what went wrong
- Risks to Patient Safety: Delivering unsafe medication that may cause adverse effects, injury, or worse
- Damage to Brand Reputation: The public’s reaction, and that of your investors, to poor quality control, negatively affecting value and consumer confidence in your company’s brand
- Loss of Market Share: The potential millions in revenue and sales if your drug is recalled from the market
- Increase in Market Competition: A competing product can quickly take advantage of negative publicity, using it to create a market opportunity for themselves
- Regulatory Scrutiny: The FDA can put a hold on any new drug or therapy approvals
Investigations are important because they support:
Product Quality and Robustness
Events that lead to batch destruction or reprocessing also lead to your company having to invest more into producing one more batch of drug than it would have if no deviation had occurred. Investigations are important because identifying root cause allows organizations to assess risk and get back to a state of producing drugs error- and deviation-free.
Patient Safety and Company Reputation
Investigations allow companies to remediate and correct product quality concerns and deviations before the product is released to the marketplace. This function protects patients from potentially contaminated or unsafe drugs and, in turn, protects a company’s reputation with its patient population. Learn more about What's at Risk.
Investigating to root cause and solving problems means that a lower number of batches get destroyed over the course of a year. The result is a more reliable supply of life-saving medication to the marketplace.
Investigations are recommended when these types of results are observed:
Unexpected or Aberrant Results
Most laboratory and manufacturing processes are validated to produce predictable and reliable results. Electronic systems and tracking and trending strategies have made it easier than ever to identify results that are unexpected or not out of specification.
Out of Trend (OOT) Results
As electronic testing and data capture systems have become more prevalent, so has the trending of data collected in the manufacturing and laboratory work environments. Data no longer sits idle on paper or even in Laboratory Information Management Systems (LIMS) and Manufacturing Execution Systems (MES). Because of this, organizations are now expected to react swiftly to unusual trends in the data sets. Trends can indicate that either the testing or manufacturing process has changed and is potentially out of a state of control. Laboratory assays are sensitive to a variety of fluctuations in the process, such as dilution variability, analyst variability, product and process formulation and processing, and variability in purification and filtering techniques.
Out of Specification (OOS) Results
Out of specification results happen when an assay is run, all assay acceptance criteria are met, and the observed assay results are outside of the limits or specifications set by the process controls or validation.
OOS results could be a potential contamination event; and can result in batch rejection destruction (scrap), manufacturing down time (financial impact), and shorting the marketplace on a potentially life-saving drug or therapy (reputation and regulatory). It’s important to investigate these events with a focus on driving to root cause, as corrective actions, mitigation strategies, along with batch assessment can only be made by knowing the true root cause of the problem.
DMAIC: Define, Measure, Analyze, Improve, and Control
DMAIC is a Six Sigma tool that provides an organized and simple way to tell a story about the problem, how it was solved, and what data was used in the decision-making process. It also creates a sense of ownership over the process by involving the people who know the process best.
D = Define
Part of defining your problem is physically walking your process. Use the Gemba process map.
See the Process
The only way to walk through a process is to physically go see it. Take pictures and ask questions where the work takes place.
Ask Questions, Especially Why
Attempt to view the process via different lenses such as potential solutions, waste, and the problem. Focus on the process and its purpose, and the people.
Give Thanks and Show Respect
Focus on safety, stress, the working environment, and product quality. Award people for teaching you something valuable.
M = Measure
View the historical baseline data visually with time series plots or control charts. Look for trends or data that is out of the ordinary and that can be attributed to process-related activities.
A = Analyze
The fishbone diagram, often called a cause and effect diagram, provides problem-solving teams with a visual way of brainstorming potential root causes. By performing this function visually, more structured brainstorming takes place, with little scope creep.
Applying 5 Whys: Ask yourself why until you can't ask why any longer, then you have found the true root cause. This is what your team should focus on when correcting in the next phase.
I = Improve
Implement improvements in a strategic fashion using sound theory and data to support conclusions.
Phase 1: DUPLICATION
Repeating the same task or effort to identify or avoid error
Phase 2: DEFECT DETECTION AND RECOVERY
Finding errors and getting back to original state or minimizing impact
Phase 3: DEFECT PREVENTION
Using signals or devices to avoid error
Phase 4: ERROR PROOF
Eliminating the possibility of making an error
C = Control
The creation of visual tools requires practitioners to physically walk the process. After an improvement has been identified that will eliminate the root cause of the problem being investigated, it is important for organizations to create a plan for implementation of the identified improvement. Often this is tracked with use of a corrective and/or preventative action (CAPA) plan, where key milestones, data, and personnel are tracked and held accountable.
See how Rapid QC Solutions can streamline your investigations
Charles River offers rapid QC solutions to help streamline your investigations. Click on the investigation flow to view a comparison of an investigation using rapid methods and an investigation using traditional methods to see how Charles River can help you reduce time and resources in your investigations.