The Quality Calibration Handbook: Developing and Managing a Calibration Program

Part I

Why Calibration Is Critical

1

Preventing the Next Great Train Wreck

On January 21, 2005, during the annual Measurement Science Conference (MSC), held at the Disneyland Convention Center in Anaheim, California, the Measurement Quality Division (MQD) sponsored a seminar on metrology education. During that seminar, one of the audience participants was Dr. Klaus-Dieter Sommer of Germany.

Dr. Sommer explained that he was a guest professor at a university in China. He told how the university had an input of 8,000 students every year, and they were all studying measurement techniques within a metrology system. He said the Chinese government has increased their attendance to around 12,000 students in metrology and measurement techniques. His question then was, Why doesn’t the United States and/or Germany train and educate in the field of metrology and calibration they way the Chinese are doing?

After one person gave their ideas, I had an epiphany. I raised my hand and answered, Because we haven’t had the great train wreck yet. We haven’t had a train wreck where someone says, Calibration was the problem. We haven’t had the train wreck where there is a great loss of life or limb, or many businesses go bankrupt, or a great many people lose their livelihood or retirement funds.

The automotive industry has had many train wrecks. We all remember the problems that Ford Motor Company and Firestone had a few years ago. The airline industry has had many instances of tragedy and loss of life over the years. The nuclear industry has had its fair share of problems, too.

Without calibration, or by using incorrect calibrations, all of us pay more at the gas station, for food weighed incorrectly at the checkout counter, and for speeding tickets. Incorrect amounts of ingredients in your prescription and over-the-counter (OTC) drugs can cost more, or even cause illness or death. Because of poor or incorrect calibration, killers and rapists are either not convicted or are released on bad evidence. Crime labs cannot identify the remains of victims or wrongly identify victims in the case of mass graves. Airliners fly into mountaintops and off the ends of runways because they don’t know their altitude and/or speed. Babies are not correctly weighed at birth. The amount of drugs confiscated in a raid determines whether the offense is a misdemeanor or a felony; which weight is correct?

Errors in calibration can effect the automotive, nuclear, or space industries. They can also have an impact on how long or wide a 2 × 4 is, not to mention the thickness of dry-wall, how much radiation is emitted by a microwave oven, how much money you are overcharged each month because your gas meter is turning at the wrong speed, or how much extra a company pays for their stamps because the scale at the post office adds 5 percent to package weight. No more watching your favorite television shows or listening to your favorite songs or talk radio, because due to calibration errors, the frequency would be off enough that TVs and radios would be useless. Satellites and everything they affect would be a thing of the past, as would be the manufacturing and production of almost everything made in the world today.

The United States Food and Drug Administration (FDA), an agency that protects the health of the American people, is one of the most successful and proudest creations of the American democracy. The FDA was created in the early 20th century amid revelations about filth in the Chicago stockyards that shocked the nation into the awareness that in an industrial economy, protection against unsafe products is beyond any individual’s means. The U.S. Congress responded to Upton Sinclair’s best-selling The Jungle by passing the Food and Drugs Act of 1906, which prohibited interstate commerce in misbranded and adulterated food and drugs. Enforcement of the law was entrusted to the U.S. Department of Agriculture’s Bureau of Chemistry, which later became the FDA.

The act was the first of more than 200 laws that constitute one of the world’s most comprehensive and effective networks of public health and consumer protections. Here are a few of the congressional milestones:

The Federal Food, Drug, and Cosmetic (FD&C) Act of 1938 was passed following the death of 107 people, mostly children, who took a legally marketed poisonous elixir of sulfanilamide. The FD&C Act completely overhauled the public health system. Among other provisions, the law authorized the FDA to demand evidence of safety for new drugs, issue standards for food, and conduct factory inspections.

The Kefauver-Harris Amendments of 1962, spurred by the thalidomide tragedy in Europe (and the FDA’s vigilance that prevented the drug from being marketed in the United States), strengthened the rules for drug safety and required manufacturers to prove their drugs’ effectiveness.

The Medical Device Amendments of 1976 followed a U.S. Senate finding that faulty medical devices had caused 10,000 injuries, including 731 deaths. The law applied safety and effectiveness safeguards to new devices.

Today, the FDA regulates an estimated $1 trillion worth of products a year. It ensures the safety of all food except for meat, poultry, and some egg products; ensures the safety and effectiveness of all drugs, biological products (including blood, vaccines, and tissues for transplantation), medical devices, and animal drugs and feed; and makes sure that cosmetics and medical and consumer products that emit radiation do no harm.¹

But there has not been a calibration train wreck . . . yet. Until there is, people will not realize that they need a quality calibration system.

Today, it is even more important that we be proactive in our application of quality calibration programs. If industry waits for the great train wreck, it will be too late. The pendulum will swing too far and we will have to abide far more government control than is needed. Recent history provides myriad examples of the need.

Hurricanes were killing hundreds of people along the gulf coast. Area residents needed more advance notice to help with timely evacuations. Hurricane hunters, satellites, and advanced radar have greatly increased the time we have to see and try to predict hurricane paths.

As mentioned previously, the FDA came about because of the pain and suffering of many people. Their system has evolved into one of the toughest to pass among any of our auditing agencies, and for good reason. The FDA makes decisions that affect public safety.

Generally speaking, one should know where they are going before they start any journey. One should know what a building is going to be used for before actually constructing it. For example, a high-tech warehouse would not do a dairy farmer much good, and likewise, a state-of-the-art dairy barn would not do a distribution facility any good. The same can be said about a quality calibration system. Is there a need? What does a company gain by implementing a quality calibration system? Is it worth the time, effort, and expense? Yes, it is! Most governments, industries, and private companies worldwide would agree. The U.S. government regulates to the extent that about 22 percent of all industry in the United States falls under FDA guidelines, which are very specific about the requirements for documented, traceable calibrations (see Chapter 2 for details). All ISO standards have a requirement for calibration when test equipment is involved. The requirements for calibration in other industries such as automotive, airline, nuclear, chemical, and manufacturing are well known throughout their industries. In other words, humankind’s need to measure has been around for generations; that need has been and continues to be addressed in a variety of ways.

Humankind understandably turned first to parts of its body and natural surroundings for measuring instruments. Early Babylonian and Egyptian records and the Bible indicate that length was first measured with the forearm, hand, or finger and that time was measured by the periods of the sun, moon, and other heavenly bodies. When it was necessary to compare the capacities of containers such as gourds or clay or metal vessels, they were filled with plant seeds, which were then counted to measure the volume. When means for weighing were invented, seeds and stones served as standards. For instance, the carat, still used as a mass unit for gems, was derived from the carob seed.

As societies evolved, measurement units became more complex. The invention of numbering systems and the science of mathematics made it possible to create whole systems of measurement units suited to trade and commerce, land division, taxation, or scientific research. For these more sophisticated uses it was necessary not only to weigh and measure more complex things, it was also necessary to do it accurately time after time and in different places. However, with limited international exchange of goods and communication of ideas, it is not surprising that different systems for the same purpose developed and became established in different parts of the world—even in different parts of a single continent.

The measurement system commonly used in the United States today is nearly the same as that brought by the colonists from England. These measures had their origins in a variety of cultures—Babylonian, Egyptian, Roman, Anglo-Saxon, and Norman-French. The ancient digit, palm, span, and cubit units evolved into the inch, foot, and yard through a complicated transformation not yet fully understood.

Roman contributions include the use of the number 12 as a base (our foot is divided into 12 inches) and words from which we derive many of our present measurement unit names. For example, the 12 divisions of the Roman pes, or foot, were called unciae. Our words inch and ounce are both derived from that Latin word.

The yard as a measure of length can be traced back to the early Saxon kings. They wore a sash or girdle around the waist that could be removed and used as a convenient measuring device. Thus the word yard comes from the Saxon word gird, meaning the circumference of a person’s waist.

Standardization of the various units and their combinations into a loosely related system of measurement units sometimes occurred in fascinating ways. Tradition holds that King Henry I decreed that the yard should be the distance from the tip of his nose to the end of his thumb. The length of a furlong (or furrow-long) was established by early Tudor rulers as 220 yards. This led Queen Elizabeth I to declare, in the 16th century, that henceforth the traditional Roman mile of 5,000 feet would be replaced by one of 5,280 feet, making the mile exactly eight furlongs and providing a convenient relationship between two previously ill-related measures.

By the 18th century, England had achieved a greater degree of standardization than the continental countries. English units were well-suited to commerce and trade because they had been developed and refined to meet commercial needs. Through colonization and dominance of world commerce during the 17th, 18th, and 19th centuries, the English system of measurement units was spread to and established in many parts of the world, including the American colonies.

However, standards still differed to the extent that they were undesirable for commerce among the 13 colonies. The need for greater uniformity led to clauses in the Articles of Confederation (ratified by the original colonies in 1781) and the Constitution of the United States (ratified in 1790) giving power to the Congress to fix uniform standards for weights and measures. Today, standards supplied to all the states by the National Institute of Standards and Technology (NIST) ensure uniformity throughout the country.²

This book is about how to design, implement, maintain, and/or continuously improve a quality calibration system, with all the required documentation, traceability, and known uncertainty for each and every item of test equipment owned and used by any company, large or small. If a business expects to be a player in their market segment, their product must have the quality expected by their customers. This can be accomplished only with test equipment that produces repeatable, accurate, and traceable measurements and/or outputs. Without a quality calibration system in place, this cannot and will not happen. This book will benefit companies that want to implement a program and companies that already have an established program in place.

Some industries have tighter requirements than others on how they treat calibration. Some are more specific about how their standards are read, while being vague about what is needed to meet calibration. Keeping this in mind, this book has been written to meet or exceed these requirements. It does not cost any more to put together a first-class program than it does to put together a ragged-edge one. Both need documentation, records, uncertainty budgets, and written procedures, to name a just a few requirements. And every program needs to continually improve whatever process they have in place on a regular basis.

How can the average calibration technician make an impact within an organization? Are they just another cog in the wheel of industry? No, I believe calibration technicians can have a significant impact on the bottom line of any company and be instrumental in product development, production processes, and customer satisfaction, all through their knowledge of the test equipment that is used in their company. They have a perspective of what works and what doesn’t at the ground floor where decisions are made. Their inputs and analysis can make the difference between success and failure of product, process, or manufacturing functions.

NOTES

1  FDA Protects the Public Health; Ranks High in Public Trust, February 2002. http://www.fda.gov (18 August 2006).

2  A Brief History of Measurement Systems, 15 September 1999. http://www.slcc.edu (18 August 2006).

2

Requirements and Standards—

What They Really Say

Before going into what the current standards and regulations actually state, here is a reminder from times past about measurement practices and how important they really are.

Immersion in water makes the straight seem bent; but reason, thus confused by false appearance, is beautifully restored by measuring, numbering and weighing; these drive vague notions of greater or less or more or heavier right out of the minds of the surveyor, the computer, and the clerk of the scales. Surely it is the better part of thought that relies on measurement and calculation. (Plato, The Republic, 360 B.C.E.)

¹

There shall be standard measures of wine, beer, and corn . . . throughout the whole of our kingdom, and a standard width of dyed russet and cloth; and there shall be standard weights also. (Clause 35, Magna Carta, 1215)¹

When you can measure what you are speaking about and express it in numbers, you know something about it; but when you cannot express it in numbers, your knowledge is of a meager and unsatisfactory kind. It may be the beginning of knowledge, but you have scarcely, in your thoughts, advanced to the stage of science. (William Thomson, First Baron Kelvin, GCVO, OM, PC, PRS 26 June 1824-17 December 1907; also known as Lord Kelvin)¹

All of the following Code of Federal Regulations (CFR) can be located at https://www.ecfr.gov/ .² Underscore emphasis has been added.

FDA Regulations

The FDA is the federal agency responsible for ensuring that foods are safe, wholesome and sanitary; human and veterinary drugs, biological products, and medical devices are safe and effective; cosmetics are safe; and electronic products that emit radiation are safe. FDA also ensures that these products are honestly, accurately and informatively represented to the public.

21 CFR Part 211

Current Good Manufacturing Practice for Finished Pharmaceuticals—specifies FDA regulations concerning the minimum current good manufacturing practice (cGMP) for preparation of drug products for administration to humans or animals.

TITLE 21—FOOD AND DRUGS

CHAPTER I—FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES

Calibration equipment requirements are specified in Section 211.68.

PART 211—CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS

Subpart D—Equipment

Sec. 211.68 Automatic, mechanical, and electronic equipment.

(a) Automatic, mechanical, or electronic equipment or other types of equipment, including computers, or related systems that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a drug product. If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a written program designed to assure proper performance. Written records of those calibration checks and inspections shall be maintained.

Laboratory controls procedures are specified in Section 211.160.

PART 211—CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS

Subpart I—Laboratory Controls

Sec. 211.160 General requirements.

(a) The establishment of any specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms required by this subpart, including any change in such specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms, shall be drafted by the appropriate organizational unit and reviewed and approved by the quality control unit. The requirements in this subpart shall be followed and shall be documented at the time of performance. Any deviation from the written specifications, standards, sampling plans, test procedures, or other laboratory control mechanisms shall be recorded and justified.

(b) Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity. Laboratory controls shall include:

(1) Determination of conformance to appropriate written specifications for the acceptance of each lot within each shipment of components, drug product containers, closures, and labeling used in the manufacture, processing, packing, or holding of drug products. The specifications shall include a description of the sampling and testing procedures used. Samples shall be representative and adequately identified. Such procedures shall also require appropriate retesting of any component, drug product container, or closure that is subject to deterioration.

(2) Determination of conformance to written specifications and a description of sampling and testing procedures for in-process materials. Such samples shall be representative and properly identified.

(3) Determination of conformance to written descriptions of sampling procedures and appropriate specifications for drug products. Such samples shall be representative and properly identified.

(4) The calibration of instruments, apparatus, gauges, and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and provisions for remedial action in the event accuracy and/or precision limits are not met. Instruments, apparatus, gauges, and recording devices not meeting established specifications shall not be used.

PART 211—CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS

Subpart J—Records and Reports

Sec. 211.194 Laboratory records.

(a) Laboratory records shall include complete data derived from all tests necessary to assure compliance with established specifications and standards, including examinations and assays, as follows:

(1) A description of the sample received for testing with identification of source (that is, location from where sample was obtained), quantity, lot number or other distinctive code, date sample was taken, and date sample was received for testing.

(2) A statement of each method used in the testing of the sample. The statement shall indicate the location of data that establish that the methods used in the testing of the sample meet proper standards of accuracy and reliability as applied to the product tested. (If the method employed is in the current revision of the United States Pharmacopeia, National Formulary, Association of Official Analytical Chemists, Book of Methods, \1\ or in other recognized standard references, or is detailed in an approved new drug application and the referenced method is not modified, a statement indicating the method and reference will suffice). The suitability of all testing methods used shall be verified under actual conditions of use.

(3) A statement of the weight or measure of sample used for each test, where appropriate.

(4) A complete record of all data secured in the course of each test, including all graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific component, drug product container, closure, in-process material, or drug product, and lot tested.

(5) A record of all calculations performed in connection with the test, including units of measure, conversion factors, and equivalency factors.

(6) A statement of the results of tests and how the results compare with established standards of identity, strength, quality, and purity for the component, drug product container, closure, inprocess material, or drug product tested.

(7) The initials or signature of the person who performs each test and the date(s) the tests were performed.

(8) The initials or signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards.

(b) Complete records shall be maintained of any modification of an established method employed in testing. Such records shall include the reason for the modification and data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method.

(c) Complete records shall be maintained of any testing and standardization of laboratory reference standards, reagents, and standard solutions.

(d) Complete records shall be maintained of the periodic calibration of laboratory instruments, apparatus, gauges, and recording devices required by Sec. 211.160(b)(4).

(e) Complete records shall be maintained of all stability testing performed in accordance with Sec. 211.166.

21 CFR Part 820

Quality System Regulation—specifies FDA requirements that govern the methods used in, and the facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished devices intended for human use. Current good manufacturing practice (cGMP) requirements are set forth in this regulation.

Calibration requirements are specified in Sec. 820.72.

PART 820—QUALITY SYSTEM REGULATION

Subpart G—Production and Process Controls

Sec. 820.72 Inspection, measuring, and test equipment.

(a) Control of inspection, measuring, and test equipment. Each manufacturer shall ensure that all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purposes and is capable of producing valid results. Each manufacturer shall establish and maintain procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained. The procedures shall include