Betting on a winning horse!

Horse race betting is a game of skill. Horse race betting requires you to learn about the players, horses involved, their form, the racetrack, among multiple other things. Placing a wager / bet on this sport necessitates research and a thorough understanding. You must look at various horse racing betting study before setting out to place a wager / bet.

In a straight wager / bet, one can bet on only one horse whereas in exotic wager / bet, one can bet on multiple horses in a single bet. Exotic bets are much harder to win than straight bets and require much more skill and study. After studying the horses involved in the race, their form, the track, one can identify the best bet to win the prize money. It needs extensive study and after a careful study, the betting becomes easier and one can reap huge money. Everyone wants to bet on the winning horse knowing its full capability and potential.

Similarly increasing or reducing instrument calibration frequency requires in-depth study. Any change of calibration frequency should be fully supported by the historical evidence. The ongoing review of the historical evidence should be logged and evaluated for the new calibration frequency. Prior to increase or decrease the calibration frequency, the steps to be followed as a part of risk-based approach for the calibration program will serve as a guide.

Calibration Program

Calibration is an essential element in ensuring compliance in the pharmaceutical industries. To ensure success, calibration should be managed effectively, by appropriately qualified and competent personnel. If neglected, calibration is capable of compromising product and process quality, facility, safety, environmental and patient safety, and dramatically increasing costs. The GAMP® Good Practice Guide: A Risk-Based Approach to Calibration Management provides guidance in setting up a calibration management system, which will give a structured approach to instrument risk assessment, calibration program management, documentation, and corrective actions, essential to regulatory compliance. It is intended to cover both process and laboratory instrumentation.

The FDA has been actively promoting a risk-based approach to GMP as part of the 21st Century Initiative. The change in approach to validation and compliance now puts more focus on the integrity, security, and reliability of process control systems and the instrumentation supporting them. The benefit will be a focused calibration effort that concentrates on risks to product quality and public safety.

The calibration of process control instruments may drift, due to the complexity of their construction and the environmental conditions in which they operate. This drift may be significant within a short period of time and accounts for the requirement for periodic recalibration. The process of risk assessment will help in achieving this and in reducing costs.

The performance of an instrument should be such that there is high confidence that the process has remained within the desired range, i.e., indicated value and associated measurement uncertainty will remain within desired limits. Instruments should be assessed for potential impact on product quality and patient safety, as well as their accuracy and their stability. Effective calibration is essential in achieving a high degree of confidence that a manufacturing process remains within the defined operating limits.

Software system should include the provision of historical data to assist in calibration optimization, e.g., Historical Analysis Graphs, Failure Alarms, Drift Analysis to predict failures. The focus of activities shall be based on risk, impact, and criticality. The required expertise particularly when performing risk assessments should be minimally with Process owner, Quality Assurance and Engineering.

Steps of Risk based calibration program.

Step-1 Criticality Risk Assessment

The Criticality Risk Assessment [CRA] acts as the key to calibration activities. It helps to define the limits and frequency of subsequent calibration. The CRA is part of the Project Phase of introduction of new equipment and should be completed prior to handover of the equipment to routine operations.

Step-2 Determination of Process Limits and Tolerances

Process tolerances should be correctly defined, relating to the process or task in which the equipment or instrument will perform in accordance with registered values associated with GxP requirements. Suitable test points across the process range must be defined to ensure that instrument accuracy and precision is clearly demonstrated.

Step-3 Determination of Instrument Categorization

A product critical instrument is an instrument whose accuracy or failure has a high potential impact on product quality or patient safety. All other instruments may be regarded as non-critical instruments. For such instruments, their specification, design, and verification may proceed following Good Engineering Practices.

Step-4 Defining Required Instrument Calibration Ranges and Limit

When deciding on calibration ranges and limits, the instrument ranges, the manufacturer’s accuracy, and the process requirements should be taken into account. The full range of an instrument may prove most appropriate for the calibration range. Conversely, for instruments that have a full calibrating range much greater than the actual operating values, it may be appropriate to reduce the maximum and minimum calibration range closer to that of the standard operating values. Suitable test points across the process range should be defined to ensure that instrument accuracy and precision is clearly demonstrated.

Step-5 Instrument Calibration Frequency

Where the probability of error detection is low and the consequences high, a high calibration frequency should be adopted. Where error detection and consequences are considered to be moderate, a lower calibration frequency may be adopted.

Step-6 Selection of Instrumentation and Closure of Criticality Risk Assessment

Once the above processes have been completed and the required ranges, tolerances, and calibration frequencies have been defined, the instrumentation required for the process can be selected. The findings of the risk assessment, the calibration ranges, tolerances, and frequencies defined should be agreed. Closure of the CRA should include approval by all members of the team.

Step-7 Increasing or Reducing Instrument Calibration Frequency

Instrument manufacturers may provide information on suitable periods between calibrations; however, the environment and operation of the instrument should be considered and an assessment of the implications of uncertainty should be performed. When data has been obtained to show the stability of operation of an instrument in a particular environment, it may be feasible to review the periods between calibrations.

Statistically acceptable data should be available to justify decreasing the instrument calibration frequency. For example, data of at least three successive calibration periods without instrument adjustment under normal operating conditions may be deemed sufficient based on the instrumentation specification and related process requirements and criticality. The exact amount of data points necessary should be determined by the CRA team on a case-by-case basis. Any change of calibration frequency should be fully supported by the historical evidence. The ongoing review of the historical evidence should be logged and evaluated for the new calibration frequency.

In cases when instrumentation has behaved in an unpredictable manner it may be more appropriate to remove or replace instruments with new instruments, rather than increasing the calibration frequency.

Step-8 Calibration Management Software

The advent of electronic calibration management provides the opportunity to have a highly compliant and controlled calibration procedures, systems, and data archives and shall be validated as per the requirements defined in GAMP-5.

Flow chart for the overall calibration program

Note-The images given for representation in this blog are taken from Google Images. Many thanks for Google.