You’ve Found The Cure For Cancer… But Can’t Reproduce Your Results! Could Your Test Equipment Be The Weakest Link?

Did you know? In the year 2000, the FDA approved only 27 new drugs, or one per every $950,000, in R&D spending by pharmaceutical companies From a compliance guide covering GMP: “Manufacturers are responsible for ensuring the establishment of routine calibration on their test equipment so it will be suitable for its intended use” The FDA regulates 25% of the Gross National Product

Why we need to calibrate equipment

What is Metrology? Where did it come from? Why do we need it? What does it do for me? Questions (?) Questions (?) Questions It all started a long time ago… In a land far, far away!

The weapon of choice was... A Canon!

OOPS...Sorry. As I was saying, the weapon of choice was... The Cannon!

It wasn’t a very accurate weapon for a couple of reasons... First, the amount of powder used in the cannon usually varied every time it was fired.

Another reason? The cannon balls were always of a different size and weight...you never knew what to expect when you fired the cannon!

They were not weighing the gunpowder or standardizing the size of the cannonballs! So what did they do?

They started weighing the gunpowder... And measuring the cannonballs...

And they started to hit what they were shooting at...

They decided the exact size of the cannon ball they needed, and made it their “Gold Standard”. Then they used a tool to accurately measure the “Gold Standard”... And now they had a traceable measurement!

Please ask yourself this question… How can you ensure that test equipment isn’t the weakest link in your production, manufacturing or research programs?

Metrology Management

"Say what you do” "Do what you say” "Record what you did” "Check the results” "Act on the difference” Metrology Management

A quality management system Steady and even operations Stable processes Consistent output Metrology Management Process improvement

Technical education and experience Basic knowledge of metrology/calibration concepts Understand basic principles of measurement disciplines…and acceptance requirements Knowledge of the overall calibration program Ability to follow instructions regarding the maintenance and use of measurement equipment and standards Metrology Management

Calibration Procedures

Say what you do:  Step by step instructions for performing calibration  Following the SOP ensures consistent, repeatable calibrations Do what you say: Calibration Procedures

Specific Instructions The specifications and ranges of the test instrument The required standards, with their tolerances SOP #, with revision and effective date

Examples and diagrams as needed List the changes that have been made to SOP Specified test points for each balance or scale Detailed instructions every step of the way

Calibration Records

 Standard(s) & ‘As Found’ values  Identify standard(s) used (w/DDC)  Indicate if readings pass or fail Record what you did: Check the results:  If failed, adjust and obtain ‘As Left’ data Calibration Records

Electronic Records... Benefits of Paperless System Workload increased 33.5% No increase in manpower Saved $100,000 in labor costs Increased productivity… eliminated all storage cabinets!

Record/Form Requirements Identification of the test equipment The location of the test equipment A history of each calibration Traceability documentation

Traceability Documentation Each individual record contains a traceability statement identifying an unbroken chain of comparisons back to NIST Measurement uncertainty budgets or ratios should support traceability

ID #, Part #, last, today’s & next Cal. Dates, etc. The specifications and ranges of the test instrument SOP #, with revision # The specifications and ranges of the standard used

Calibration Records 21 CFR Part 11 – Electronic Records and Electronic Signatures…It is all about DATA INTEGRITY and ACCOUNTABILITY! …“A ‘bullet-proof’ solution isn’t required for compliance, but must leverage current technologies, procedures, and methods as to make it very difficult to alter, obscure or delete applicable electronic records without detection.”

We must Act on the Difference by:  Adjusting the equipment to meet specifications and document ‘As Left’ data  Giving the equipment a ‘Limited Calibration’  Remove the equipment from service Calibration Records

It’s out of tolerance, now what? Alert/Action procedures Alert:  2X tolerance Action: > 2X tolerance Your needs dictate your limits Calibration Records

Scheduling Your Equipment

Measuring instruments should be calibrated at periodic intervals established on the basis of stability, purpose, and degree of usage of the equipment… A manufacturer should use a suitable method to remind employees that calibration is due.

Scheduling Your Equipment Overdues/coming due Standards due for calibration Calibration Management Software Sort by type and location Optimize use of standards

Traceability of Equipment and Standards

Traceability of Standards The QS regulation requires that standards used to calibrate equipment be traceable to the National Institute of Standards and Technology (NIST), or other recognized national or international standards. Traceability also can be achieved through a contract calibration laboratory which in turn uses NIST services.

Uncertainty Ratio The collective uncertainty of the measurement standards shall not exceed 25% of the acceptable tolerance … ANSI/NCSL Z states... 4:1 ratio

A pyramid of traceability looks something like this... Primary Standard Secondary Standards Reference Standards Gold Standard Working Standards

An example of traceability at Promega... NIST Standard Hart Scientific Std. SPRT & Black Stack 4600 & 480 Cal. Kit Waterbaths, Incubators, & Thermal Cyclers

Calibration Environment

…environmental controls should be established and monitored to assure that measuring instruments are calibrated and used in an environment that will not adversely effect the accuracy required. The calibration environment need be controlled only to the extent required by the most environmentally sensitive measurement performed in the area.

Lessons Learned

Of the things you must remember… metrology management, writing calibration procedures, maintaining records, effectively scheduling your workload, traceability issues from your test equipment back to NIST, and ensuring your system is functioning on the cutting edge… Here’s the one thing to never forget… Lessons Learned Train – Train – Train!

Limited Calibrations... Lessons Learned Increase usability by the customer Reduce down-time of equipment Limited Cal Label informs user Use for “charting” of measurements