LII:LIMS Selection Guide for Manufacturing Quality Control/Introduction to manufacturing laboratories

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1. Introduction to manufacturing laboratories

According to McKinsey & Company, the U.S. manufacturing industry represents only 11 percent of U.S. gross domestic product (GDP) and eight percent of direct employment, yet it "makes a disproportionate economic contribution, including 20 percent of the nation’s capital investment, 35 percent of productivity growth, 60 percent of exports, and 70 percent of business R&D spending." These categories of economic contribution are important as many of them indirectly point to how the work of laboratories is interwoven within the manufacturing industry. As we'll discuss later in this chapter, manufacturing-based laboratories primarily serve three roles: research and development (R&D), pre-manufacturing and manufacturing, and post-production regulation and security (e.g., through exports and trade). We can be sure that if U.S. manufacturers' efforts represent huge chunks of total business R&D spending, trade, and capital expenditure (capex), a non-trivial amount of laboratory effort is associated with that spending. Why? Because R&D, trade, and manufacturing quality control (QC) activities rarely can occur without laboratories backing up their work.

Labs in the manufacturing sector provide vital services, including but not limited to quality assurance (QA), QC, production control, regulatory trade control (e.g., authenticity and adulteration), safety management, label claim testing, and packaging analysis. These activities occur in a wide array of manufacturing industries. Looking to the North American Industry Classification System (NAICS), employed by the U.S. Bureau of Labor Statistics (BLS), manufacturing industries and sub-industries include:

• apparel (e.g., knitted goods, cut-and-sew clothing, buttons and clasps)
• chemical (e.g., pesticides, fertilizers, paints, cleaning products, adhesives, electroplating solutions)
• electric power (e.g., light bulbs, household appliances, energy storage cells, transformers)
• electronics (e.g., sensors, semiconductors, electrodes, mobile phones, computers)
• food and beverage (e.g., baked goods, probiotics, preservatives, wine)
• furniture (e.g., mattresses, sofas, window blinds, light fixtures)
• leather (e.g., purses, saddles, footwear, bookbinding hides)
• machinery (e.g., mining augers, air conditioning units, turbines, lathes)
• materials (e.g., ceramics, cements, glass, nanomaterials)
• medical equipment and supplies (e.g., ventilators, implants, lab equipment, prosthetics, surgical equipment)
• metal forming and casting (e.g., steel beams, aluminum ingots, shipping containers, hand tools, wire)
• paper and printing (e.g., cardboard, sanitary items, stationery, books, bookbinding papers)
• petrochemical (e.g., solvents, fuel additives, biofuels, lubricants)
• pharmaceutical and medicine (e.g., antivenom, vaccines, lab-on-a-chip diagnostic tests, cannabis products, nutraceuticals)
• plastics and rubbers (e.g., dinnerware, tires, storage and shelving, outdoor furniture)
• textiles (e.g., carpeting, upholstery, bulk fabric, yarn)
• vehicular and aerospace (e.g., electric vehicles, reusable rocketry, railroad rolling stock, OEM auto parts)
• wood (e.g., plywood, flooring, lumber, handrails)

If you've ever used a sophisticated two-part epoxy adhesive to repair a pipe crack, used an indoor sun lamp, gotten a lot of mileage out of a pair of leather gloves, received a medical implant, taken a medication, eaten a Twinkie, or ridden on Amtrak, one or more laboratories were involved somewhere in the manufacturing process before using that item. From endless research and testing of prototypes to various phases of quality and safety testing, laboratory science was involved. The importance of the laboratory in manufacturing processes can't be understated.

But what of the history of the manufacturing-focused lab? What of the roles played and testing conducted in them? What do they owe to safety and quality? This chapter more closely examines these questions and more.

1.1 Manufacturing labs, then and now

In 1852, the Putnam's Home Cyclopedia: Hand-Book of the Useful Arts was published as a dictionary-like source of scientific terms. Its definition of a laboratory at that time in U.S. history is revealing (for more on the equipment typically described with a laboratory of that time period, see the full definition):

Laboratory. The workshop of a chemist. Some laboratories are intended for private research, and some for the manufacture of chemicals on the large scale. Hence it is almost impossible to give a description of the apparatus and disposition of a laboratory which would be generally true of all. A manufacturing laboratory necessarily occupies a large space, while that of the scientific man is necessarily limited to a peculiar line of research. Those who study in organic chemistry have different arrangements than that of the mineral analyst.

This definition highlights the state of laboratories at the time: typically you either had a small private laboratory for experiments in the name of research and development (R&D) and producing prototype solutions, or you had a slightly larger "manufacturing laboratory" that was responsible for the creation of chemicals, reagents, or other substances for a wider customer base. These laboratory types date back further than the mid-1800s, to be sure, though they also saw great change leading up to and after this time period. This is best characterized by the transition from the humble apothecary lab to the small-scale manufacturing laboratory before the mid-1800s, to the full-scale pharmaceutical manufacturing lab and facility well beyond the mid-1800s.

1.1.1 From apothecary to small-scale manufacturing laboratory

A critical area to examine in relation to the evolution of manufacturing laboratories involves pharmaceuticals and the apothecary, which is steeped in the tradition of making pharmaceutical preparations, as well as prescribing and dispensing them to customers. The idea of an individual who attempted to make medical treatments dates back to at least 2000 BC, from which Sumerian documents reveal compounding formulas for various medicinal dosage types. By 1540, Swiss physician and chemist Paracelsus made a significant contribution to the early apothecary, influencing "the transformation of pharmacy from a profession based primarily on botanic science to one based on chemical science." Thanks to Paracelsus and other sixteenth century practitioners, the concept of the apothecary became more formalized and chemistry-based in the early seventeenth century. With this formalization came the need for the regulation of apothecaries to better ensure the integrity of the profession. For example, the Master, Wardens and Society of the Art and Mystery of Pharmacopolites of the City of London was founded in 1617 through the Royal Charter of James the First, requiring an aspiring apothecary to conduct an apprenticeship or pay a fee, followed by taking an examination proving the individual's knowledge, skill, and science in the art.

However, despite this sort of early regulation, medical practitioners took exception to apothecaries encroaching upon the medical practitioners' own services, and apothecaries took exception to the untrained and uncertified druggists who were still performing the work of pharmacists. (As it turns out, these sorts of recriminations would continue on in some form or another into the beginning of the twenty-first century, discussed later.) But as an 1897 article from The Pharmaceutical Journal portrayed, the apothecaries likely wanted to have their cake and eat it too. "[W]hile the apothecaries urged, in the interest of the public, the desirability of a guarantee for the the competences of every person authorised to practise pharmacy," the journal noted, "they also sought, in their own interest, to extend the scope of their medical practice." This led to further debate and changes over time, including British Parliament declaring medicinal preparations as "very proper objects for taxation" in 1783, while at the same time requiring non-apprenticed apothecaries to apply annually for a license. By this time, most apprenticed apothecaries ceased being perceived as mere pharmacists and more as medical practitioners, though the Society's power of conferring medical qualifications, given to them in 1617, were by this point largely lost.

By the end of the eighteenth century, apothecaries and druggists were setting up their own manufacturing laboratories to make chemical and pharmaceutical products. However, these labs were likely still limited in scope. In 1897, The Pharmaceutical Journal portrayed manufacturing labs as such, in the scope of the growing Plough Court Pharmacy run by William Allen and Luke Howard:

It is, however, difficult to at the present time to realise what must have been the position of a manufacturing chemist in 1797, or to comprehend, without some reflection, how limited was the range of his operations and how much his work was beset with difficulties which are now scarcely conceivable. At that time chemical industry was confined to the production of soap, the mineral acids, and some saline compounds then used in medicine. Among the latter, mercurial preparations held an important place, and some of these appear to have first received attention by the firm of Allen and Howard. The early laboratory account books of the firm mention ammoniacals, caustic potash, borax, argentic nitrate, and cream of tartar, as well as ether, benzoic acid, and refine camphor, which were then articles of the materia medics, citric, tartatic and oxalic acids, etc.

To be sure, other types of manufacturing were occurring during the rise and dominance of the apothecary, not just pharmaceutical manufacture. But, retrospectively, the pharmaceutical manufacturing lab in general was likely not in the best of shape as the nineteenth century approached. With several changes in Europe and United States in the early 1800s, the apothecary's manufacturing lab arguably saw more formalized and regulated activity, through various releases of pharmacopoeias, openings of new pharmacy schools (though still limited in scope), publishing of books, and additional formalization of regulating legislation (such as Britain's Apothecaries Act of 1815). By the time the United States Pharmacopeia came upon the scene in 1820, the apothecary was viewed as "competent at collecting and identifying botanic drugs and preparing from them the mixtures and preparations required by the physician." Pharmaceutical historian Loyd Allen, Jr. refers to this time period as "a time that would never be seen again," a sort of Golden Age of the apothecary, given the increasingly rapid rate that scientific and technological discoveries were being made soon after, particularly in synthetic organic chemistry.

Of course, the manufacturing lab—pharmaceutical and otherwise—had other issues as well. For example, just because a small-scale experimental R&D process yielded a positive result didn't mean that process was scalable to large-scale manufacturing. "Frequently, things work well on a small scale, and failure results when mass action comes into effect," noted Armour Fertilizer Company's president Charles McDowell in April 1917, while discussing American research methods. Sometimes a process was sufficiently simple that switching to more robust and appropriate apparatuses was all that was needed to scale up from experiment to full production. In other cases, a full-scale manufacturing laboratory process had yet to be developed, let alone the experiments conducted to develop a proof-of-concept solution in the experimental lab.

Another challenge the manufacturing lab had was in ensuring the stability of any laboratory manufactured solution. Discussing the British Pharmacopoeia-introduced substance of sulphurous acid for afflictions of the throat, Fellow of the Chemical Society Charles Umney noted the stability considerations of the substance when made in the manufacturing laboratory:

Now the Pharmacopoeia solution (which is about 37 volumes) was designedly made nearly one of saturation at the average summer temperature of this country, and, if one may be excused for making a guess, we described from calculations made from the above data of Bunsen's, and not practically worked out to see whether such a solution could be ordinarily obtained in the manufacturing laboratory without chance of failure, and, when made, be kept without great alteration in the various stages it would have to pass through, even if only from the manufacturer to the wholesale druggist, then to the pharmacists, in whose store it might retain for a year or more, being perhaps placed in a temperature many degrees above the point at which it was saturated, thereby causing expansion, liberation of gas, and inconvenience.

Difficulties aside, as the 1800s progressed, the resources of a collaboratory manufacturing laboratory were often greater than those of the individual private laboratory, with enterprising businesses increasingly turning to larger labs for greater and more high-quality quantities of materials. For example, in a letter from the Royal Institution of Great Britain, editor William Crookes discussed the discovery of thallium, noting that the manufacturing lab of noted manufacturing chemists Hopkin and Williams were able to prepare chloride of thallium for him from two hundredweight (cwt) in less time than it took Crookes to make 10 pounds of sulfur in his private laboratory. This trend would continue into the late 1800s, for pharmaceutical and other manufactured goods.

1.1.2 From small-scale private manufacturing lab to larger-scale industrial manufacturing lab

By the 1860s, numerous changes to the paradigm of the manufacturing lab were beginning to take shape, with noticeable momentum away from the small-scale private manufacturing labs to those larger in scope and output, putting competitive pressures on the smaller manufacturing labs. Take, for example, one of the largest U.S.-based enameled brick factories for its time, in 1896, which "[i]n addition to their manufacturing laboratory for slips, enamels and glazes, they maintain an analytical chemical laboratory, and have two chemists in their employ." Ten years prior, a report on the visit to the experimental and manufacturing laboratories of Louis Pasteur highlights the need for a more sizeable facility for meeting demand for the anthrax vaccine:

To meet the demands upon the laboratory work for the supply of anthrax vaccine, the preparation of this is now carried out in an establishment apart from the experimental laboratory in connection with the Ecole Normale, where it was originally started. In the Rue Vaquelin, under the charge of educated assistants, M. Chamberland carries out the preparation on a large scale—the necessity for this being apparent when regard is had to the statement of the quantity demanded for France and other countries.

The author, William Robertson, then goes into greater detail of the many rooms and floors of the building housing the manufacturing laboratory and its apparatuses, highlighting the grandness of the lab's efforts.

The change from small-scale private to larger-scale industrial manufacturing labs—in turn seemingly being supplanted by analytical laboratories—is arguably best seen in the transition from the apothecary and pharmacist to the large-scale pharmaceutical manufacturer. During this time of change in the late 1800s, laws dictating higher manufacturing quality, educational requirements, and restrictions on who can sell medicines were derided, debated, or cheered, depending on who was involved.

Reading for a meeting at the Kings County Pharmaceutical Society of Ohio, Charles E. Parker had the following to say about the state of the apothecary-turned-pharmacist in 1896, which fully highlights the transition from small-scale private to larger-scale industrial manufacturing of pharmaceuticals:

The modern pharmacist succeeds to all the responsibilities and obligations of the ancient apothecary without opposition, but his utmost efforts have not preserved to him his inheritance of former privileges and emoluments ... Technical skill is of no use to the professional side of pharmacy unless it is used, and used for the public welfare as well as that of its possessor. The dispenser is the typical pharmacist. But where in former years his sphere included many activities and much manipulative expertness in the preparation of drugs, and even the production of many of them, the modern tendency is for him to become a mere compounder and dispenser. Of course he is expected to know how, but actually is seldom required to perform the operations once a matter of constant routine. Step by step the productive processes of his little laboratory have been transferred to the works of large manufacturers. Year by year the pharmaceutical improvements and useful inventions which would once have conferred reputation and profit upon the dispensing pharmacies where they originated, have found a better market through these same manufacturers ... In addition, it is to be considered that some of the requisites of modern pharmacy are of a nature involving the use of expensive machinery and large plant, which places their production quite beyond the reach of the pharmacy.

Writing for the Pharmaceutical Review in 1897, editor Dr. Edward Kremers penned an editorial on the role of the manufacturing laboratory in the growing pharmaceutical industry, noting that "[d]uring the past hundred years a most remarkable industrial revolution has taken place," and that pharmacy was also victim to that, lamenting that the apothecaries of the beginning of the century—along with the druggists of 1897—had largely become "relics of the past." Kremers also touched upon another complaint popular at the time: that of pharmacy as a money-making venture. In his editorial, Kremers said:

It is a hope cherished by some that higher education will revolutionize pharmacy of today and lift her out of her present unenviable situation. The manufacturing industries, however, have revolutionized pharmacy of fifty years ago and are to no small extent coresponsible for the present state of affairs. The pharmaceutical profession as a whole is justified in asking what a particular branch is doing for the general good. Is the pharmaceutical manufacturer in the erection of his buildings, in the equipment of his laboratories and in the selection of his working force simply bent upon making so many thousands of dollars a paying investment, viewed from a merely commercial standpoint, or are his doings influenced to some extent to at least by higher than purely necessary motives.

By the early years of 1900, recognition of the sea-level change to the apothecary, pharmacist, and manufacturing laboratory had arguably gained traction, and by 1920 it was largely accepted. Writing for The Rocky Mountain Druggist in 1908, pharmaceutical doctor Geo H. Meeker laid it out in no uncertain terms:

Large manufacturing establishments can, for the most part, furnish the druggist at lower prices, with better authentic goods than he himself could produce, assay and guarantee. The inevitable result is that the druggist of today purchases finished products rather than raw materials as did the apothecary of yesterday. It is obvious that a large manufacturing establishment, conducted on ethical lines, employing a complete corps of specialists, buying raw materials to the best advantage and by assay only, making preparations on a large and intelligent technical scale and testing and assaying the finished products, does a work that is too immense in its scope for the individual apothecary ... Our present remnant of the drug store laboratory is, as in the past, essentially a manufacturing laboratory. It is of limited and rapidly vanishing scope because the small local laboratory man cannot successfully compete with his rivals, the great and highly-organized factories.

Similar comments were being made by Pearson in 1911, Thiesing in 1915, and Beal in 1919. Beal in particular spoke solemnly of the transition, largely complete by the time of his acceptance of the Joseph P. Remington Honor Medal in 1919. Speaking of Remington and his experiences in pharmacy, until his death in 1918, Beal said:

Professor Remington's professional experience bridged the space between two distinct periods of pharmaceutical development. When he began his apprenticeship the apothecary, as he was then commonly called, was the principal manufacturer as well as the purveyor of medical supplies ... He lived to see the period when the apothecary ceased to be the principal producer of medicinal compounds and became mainly the purveyor of preparations manufactured by others, and when the medicinal agents in most common use assumed a character that required for the successful production the resources of establishments maintained by large aggregations of capital and employing large numbers of specially trained workers.
 
To those who knew him intimately it was evident that although Professor Remington did not welcome the passing of the manufacturing functions of the apothecary to the large laboratory, he at length came to realize that such a change was inevitable, that it was but a natural step in the process of social evolution, and that the logical action of the apothecary was not to resist that which he could neither prevent nor change, but to readjust himself to the new conditions.

Of course, by then, the rise of the industrial research lab within large-scale manufacturing enterprises was in full swing.

1.1.3 The rise of the industrial research lab within large-scale manufacturing, and today's manufacturing landscape

Like the small, privately owned manufacturing labs evolving to large-scale company-run manufacturing labs, so did the research processes of prior days. The individual tinkering with research in their private laboratory and making small batches of product gave way to a collective of individuals with more specialized talents cooperatively working in a large industrial manufacturing center towards a common, often complex research goal, i.e., within the industrial research laboratory. Those larger manufacturing entities that didn't have an industrial research lab were beginning to assess the value of adding one, while smaller enterprises that didn't have the resources to support an extensive collection of manufacturing and research labs were increasingly joining forces "to maintain laboratories doing work for the whole industry."

But what drove the advance of the industrial research lab? As the National Research Council pointed out in 1940, "individuals working independently could not, for very long, provide the technical and scientific knowledge essential to a rapidly developing industrial nation." Newly emerging industries had a need for new knowledge to feed their growth, and they proved to be the early adopters of establishing separate research departments or divisions in their businesses, unlike businesses in long-established industries. The First World War was also responsible for driving organized research efforts in various industries to solve not only wartime problems but also plant the seed of development in peacetime industries. By 1920, two-thirds of all research workers surveyed by the National Research Council were employed in the emerging electrical, chemical, and rubber industries, though the overall adoption of industrial research approaches was still limited across all companies.

In 1917, the previously mentioned Charles McDowell presented his view of American research and manufacturing methods of his time, referring to research as "diligent inquiry." In his work, McDowell stated three types of research that leads up to the manufacturing process: pure scientific inquiry, industrial research, and factory research. He noted that of pure scientific inquiry, little thought is typically given to whether the research—often conducted by university professors—will have any real commercial value, though such value is able to emerge from this fundamental research. As for factory research, McDowell characterized it as full-scale factory-level operations that range from haphazard approaches to well-calculated contingency planning, all of which could make or break the manufacturing business.

In regards to the middle category of industrial research, McDowell made several observations that aptly described the state of manufacturing research in the early 1900s. He noted that unlike pure scientific inquiry, industrial research had commercial practicality as a goal, often beginning with small-scale experiments while later seeking how to reproduce those theoretical results into large-scale manufacturing. He also reiterated his point about needing to "have good backing" financially. "The larger manufacturer maintains his own staff and equipment to carry out investigations along any line that may seem desirable," he said, "but the smaller industries are not able to support an establishment and must rely on either consulting engineers or turn their problems over to some equipped public or private laboratory to solve."

In his 1920 book The Organization of Industrial Scientific Research, Mees presented these three types of research somewhat similarly, though in the context of the industrial laboratory and its operations. Mees argued that industrial laboratories could be classified into three divisions:

• Laboratories "working on pure theory and the fundamental sciences associated with the industry," aligning in part with McDowell's "pure scientific inquiry";
• Work laboratories "exerting analytical control over materials, processes and product," aligning slightly with McDowell's "factory research" but more akin to the modern quality control lab; and
• Industrial laboratories "working on improvements in product and in processes," aligning with McDowell's "industrial research."

Mees argued in particular that those industrial research laboratories that simply improve products and processes were not doing enough; they should, necessarily, also direct some of their goals towards more fully understanding the fundamental and underlying theory of the topic of research. In other words, Mees suggested that those labs simply working on theoretical and fundamental science research, as well as those labs conducting industrial research to improve products and processes, shouldn't necessarily function in separate vacuums. "Research work of this fundamental kind involves a laboratory very different from the usual works laboratory and also investigators of a different type from those employed in a purely industrial laboratory," he noted. Of course, this hybrid approach to fundamental and industrial research was largely reserved for the largest of manufacturers, and solutions were needed for smaller manufacturing endeavors. Here, like McDowell in 1917, Mees argued for smaller businesses with limited resources to adopt both cooperative laboratory (those businesses that pool resources together for a fully supported research laboratory) and consulting laboratory (a third-party lab with the resources to fully study a problem, undertake investigations, model a manufacturing process, and implement that process into its client's factory, all for a fee) approaches. With such solutions, the industrial research laboratory continued to take on a new level of complexity to address emerging industry needs, far from the humble origins of an early nineteenth-century manufacturing laboratory.

This growth or industrial research would continue onward from the twentieth century into the twenty-first century. In 1921, some 15 companies maintained research groups of more than 50 people; by 1938, there were 120 such businesses. By the 1990s, "the share of funding for basic research provided by industry actually grew from 10 percent to 25 percent of the national total, even though basic research accounted for just 5-7 percent of total R&D expenditures by industry." This trend of large research groups continues today, though with the recognition that smaller teams may still have advantages. In a 2019 article in the Harvard Business Review, Wang and Evans recognize "large teams as optimal engines for tomorrow’s largest advances," while smaller research teams are better poised to ask disruptive questions and make innovative discoveries.

1.2 Laboratory roles and activities in the industry

Today, the "manufacturing laboratory" is a complex entity that goes beyond the general idea of a lab making or researching things. Many of the historical aspects discussed prior still hold today, but other aspects have changed. As indicated in the introduction, the world of manufacturing encompasses a wide swath of industries and sub-industries, each with their own nuances. Given the nuances of pharmaceutical manufacturing, food and beverage development, petrochemical extraction and use, and other industries, it's difficult to make broad statements about manufacturing laboratories in general. However, the rest of this guide will attempt to do just that, while at times pointing out a few of those nuances found in specific industries.

The biggest area of commonality is found, unsurprisingly, in the roles manufacturing-based labs play today, as well as the types of lab activities they're conducting within those roles. These roles prove to be important in the greater scheme of industry activities, in turn providing a number of benefits to society. As gleaned from prior discussion, as well as other sources, these laboratory roles can be broadly broken into three categories: research and development (R&D), pre-manufacturing and manufacturing, and post-production regulation and security. Additionally, each of these categories has its own types of laboratory activities.

The scientific disciplines that go into these laboratory roles and activities is as diverse as the manufacturing industries and sub-industries that make up the manufacturing world. For example, the food and beverage laboratory taps into disciplines such as biochemistry, biotechnology, chemical engineering, chemistry, fermentation science, materials science, microbiology, molecular gastronomy, and nutrition. However, the paper and printing industry taps into disciplines such as biochemistry, biology, chemistry, environmental science, engineering, forestry, and physics. By extension, the reader can imagine that these and other industries also have a wide variety of laboratory techniques associated with their R&D, manufacturing, and post-production activities.

The following subsections more closely examine the three roles manufacturing-based labs can play, as well as a few examples of lab-related activities found within those roles.

1.2.1 R&D roles and activities

The National Institute of Standards and Technology (NIST) and its Technology Partnerships Office offer a detailed definition of manufacturing-related R&D as an activity "aimed at increasing the competitive capability of manufacturing concerns," and that "encompasses improvements in existing methods or processes, or wholly new processes, machines or system." They break this down into four different technology levels:

• Unit process-level technologies that create or improve manufacturing processes,
• Machine-level technologies that create or improve manufacturing equipment,
• Systems-level technologies for innovation in the manufacturing enterprise, and
• Environment- or societal-level technologies that improve workforce abilities and manufacturing competitiveness.

Obviously, this definition applies to actual development of and innovation towards methods of improving and streamlining manufacturing processes. However, this same concept can, in part, can be applied to the actual products made in a manufacturing plant. Not only does product-based R&D focus on improving "existing methods and processes," but it also focuses on "manufacturing competitiveness" by developing new and innovating existing products that meet end users' needs. Manufacturing-based R&D laboratories play an important role in this regard.

The laboratory participating in this role is performing one or more tasks that relate to the development or improvement of a manufactured good. This often leads to a commercial formulation, process, or promising insight into a product. The R&D lab may appear outside the manufacturing facility proper, but not necessarily always. Some manufacturing companies may have an entire research complex dedicated to creating and improving some aspect of their products. Other companies may take their R&D to a third-party consulting lab dedicated to conducting development and formulation activities for manufacturers. Industrial research activities aren't confined to manufacturers, however. Some higher education institutions provide laboratory-based research and development opportunities to students engaging in work-study programs, often in partnership with some other commercial enterprise.

The following types of lab-related activities may be associated with the R&D role:

Overall product development and innovation: Jain et al. note in their book on managing R&D activities that in 2010, 60 percent of U.S. R&D was focused on product development, while 22 percent focused on applied research and 18 percent on basic research. However, they also argue that any R&D lab worth its weight should have a mix of these activities, while also including customer participation in the needs assessment and innovation activities that take place in product development and other research activities. Jain et al. define a manufacturer's innovation activities as "combining understanding and invention in the form of socially useful and affordable products and processes." As the definition denotes, newly developed products ("offerings") and processes (usually which improve some level of efficiency and effectiveness) come out of innovation activities. Additionally, platforms that turn existing components or building blocks into a new derivative offering (e.g., a new model or "generation" of product), as well as "solutions that solve end-to-end customer problems," can be derived from innovation. Those activities can focus on more risky radical innovation to a new product or take a more cautious incremental approach to improvements on existing products.

Reformulation: Reformulation involves the material substitution of one or more raw materials used in the production of a product to accomplish some stated goal. That goal may be anything from reducing the toxicity or volume of wastes generated and improving the overall healthiness of the product, to transitioning from traditional holistic medicine approaches to more modern biomedical approaches. Examples of products that have seen reformulation by manufacturers include:

• Paints and other coatings,
• Fuels such as gasoline,
• Foods and beverages, and
• Pharmaceuticals and cosmetics.

In the end, reformulation is a means for improving impacts on the end user, the environment, or even the long-term budget of the manufacturer. The type of lab activities associated with reformulation largely varies by product; the laboratory methods used to reformulate gasoline may be quite different from those in a food and beverage lab. Reformulation can also be a complicated process, as found with pharmaceutical products. The reformulated product "must have the same therapeutic effect, stability, and purity profile" as the original, while maintaining pleasing aesthetic qualities to the end user. Adding to the problem is regulatory approval times of such pharmaceutical reformulations.

Nondestructive testing and materials characterization: Raj et al. describe nondestructive testing (NDT) as "techniques that are based on the application of physical principles employed for the purpose of determining the characteristics of materials or components or systems and for detecting and assessing the inhomogeneities and harmful defects without impairing the usefulness of such materials or components or systems." NDT has many applications, including with food, steel, petroleum, medical devices, transportation, and utilities manufacturing, as well as electronics manufacturing. It also plays an important role in materials testing and characterization. NDT and materials testing is often used as a quality control mechanism during manufacturing (see the next subsection), but it can also be used during the initial R&D process to determine if a prototype is functioning as intended or a material is satisfactory for a given application.

Stability, cycle, and challenge testing: Multiple deteriorative catalysts can influence the shelf life of a manufactured product, from microbiological contaminants and chemical deterioration to storage conditions and the packaging itself. As such, there are multiple approaches to taming the effects of those catalysts, from introducing additives to improving the packaging. However, stability, cycle, and challenge testing must be conducted on many products to determine what deleterious factors are in play. The analytical techniques applied in stability, cycle, and challenge testing will vary based on, to a large degree, the product matrix and its chemical composition. Microbiological testing is sure to be involved, particularly in challenge testing, which simulates what could happen to a product if contaminated by a microorganism and placed in a representative storage condition. Calorimetry, spectrophotometry, spectroscopy, and hyperspectral imaging may be used to properly assess color, particularly when gauging food quality. Other test types that may be used include water content, texture, viscosity, dispersibility, glass transition, and gas chromatography. In the end, the substrate being examined will be a major determiner of what kind of lab methods are used. The lab method chosen for stability, cycle, and challenge testing should optimally be one that errs on the side of caution and is appropriate to the test, even if it takes longer. As Chen notes: "A longer test cycle is less a concern for stability protocol as the study typically has a limited number of samples. Applying a less reliable method to the limited number of samples in a stability study can be problematic."

Packaging analysis and extractable and leachable testing: Materials that contact pharmaceuticals, foods and beverages, cosmetics, and more receive special regulatory consideration in various parts of the world. This includes alloys, bioplastics, can coatings, glass, metals, regenerated cellulose materials, paper, paperboard, plastics, printing inks, rubber, textiles, waxes, and woods. As such, meeting regulatory requirements and making inroads with packaging development can be a complicated process. Concerns of chemicals and elements that can be extracted or leach into sensitive products add another layer of complexity to developing and choosing packaging materials for many manufactured goods. This requires extractable and leachable testing at various phases of product development to ensure the packaging selected during formulation is safe and effective. Extractable and leachable testing for packaging could involve a number of techniques ranging from gas and liquid chromatography to ion chromatography and inductively coupled plasma mass spectrometry.

1.2.2 Pre-manufacturing and manufacturing roles and activities

The laboratory participating in these roles is performing one or more tasks that relate to the preparative (i.e., pre-manufacturing) or quality control (QC; i.e., manufacturing) activities of production. An example of preparative work is conducting allergen, calorie, and nutrition testing for a formulated food and beverage product. Calorie and nutrition testing—conducted in part as a means of meeting regulation-driven labeling requirements—lands firmly in the role of pre-manufacturing activity, most certainly after commercial formulation and packing requirements have been finalized but before the formal manufacturing process has begun. Allergen testing works in a similar fashion, though the manufacturer ideally uses a full set of best practices for food allergen management and testing, from confirming allergens (and correct labeling) from ingredients ordered to performing final production line cleanup (e.g., when a new allergen-free commercial formulation is being made or an unintended contamination has occurred). These types of pre-production analyses aren't uncommon to other types of manufacturing, discussed below.

As for in-process manufacturing QC, some QC and quality assurance (QA) methods may already be built into the manufacturing process in-line, not requiring a lab. For example, poka-yoke mechanisms that inhibit, correct, or highlight errors as they occur, as close to the source as possible—may be built in-line to a manufacturing process to prevent a process from continuing should a detectable error occur, or until a certain condition has been reached. However, despite the value of inline QC/QA, these activities also happen beyond the production line, in the laboratory (discussed further, below).

The following types of lab-related activities may be associated with the pre-manufacturing and manufacturing role:

Various pre-manufacturing analyses: Also known as pre-production, some level of laboratory activity takes place here. Like the previously mentioned food and beverage industry, the garment manufacturing industry, for example, will have its own laboratory-based pre-production activities, including testing various raw material samples for potential use and quality testing pre-production samples before deciding to go into full production. In another example, a manufacturer intending to produce "a new chemical substance for a non-exempt commercial purpose" in the U.S. must submit a pre-manufacture notice to the Environmental Protection Agency (EPA), which must include "test data on the effect to human health or the environment." Given this regulatory requirement, some final pre-approval testing much occur to ensure the chemical meets regulatory requirements before full manufacturing processes begin.

Quality control testing: While QC testing can appear in multiple manufacturing laboratory roles, it's most noticeable in the pre-manufacturing and manufacturing role. Manufacturers in many industries have set up formal testing laboratories to better ensure that their products conform to a determined set of accepted standards, whether those standards come from a standards-setting organization or are internally derived. QC testing is a multi-pronged approach that includes both non-laboratory and laboratory analyses, whether it is in real-time or periodically during manufacturing activities. The previously mentioned inline poka-yoke mechanisms provide an example of non-laboratory QC activities. However, when rigorous mechanical, chemical, or some other form of testing of a manufactured product is required at different stages of production, a laboratory will be involved. This type of in-process inspection occurs after roughly 10 to 30 percent of products are completed. Manufacturers can take multiple approaches to QC testing, depending on the circumstances of manufacturing. This includes 100 percent inspection methods, Six Sigma approaches, X-bar charting, total quality management, statistical quality control, Taguchi approaches, and more.

The actual types of analyses going on during QC will entirely depend on the material being tested, the functionality of the item, and the intended goal of testing. For example, polymerase chain reaction (PCR) testing of infant formula for the pathogenic bacterium Cronobacter sakazakii during production runs is entirely different from periodic Rockwell, Brinell, or Vickers hardness testing of aerospace fasteners. NDT and materials testing, discussed in the prior subsection about R&D, can also occur during the various phases of manufacturing, as part of an overall quality control effort.

1.2.3 Post-production regulation and security roles and activities

The laboratory participating in these roles is performing one or more tasks that relate to the post-production examination of products for regulatory, security, or accreditation purposes. Labs are often third parties accrediting a producer to a set of standards, ensuring regulatory compliance, conducting authenticity and adulteration testing, conducting security checks at borders, and applying contamination testing as part of an overall effort to track down contamination sources. In addition to ensuring a safer product, society also benefits from these and similar labs by better holding producers legally accountable for their production methods and obligations.

The following types of lab-related activities may be associated with the post-production regulation and security role:

Authenticity and adulteration testing: This type of testing is largely conducted to ensure products ingested, injected, inserted, and/or handled by humans and animals are safe to use and authentic to consumer expectations. Anything from food and pharmaceuticals to children's toys and fishing sinkers may be tested to ensure they contain what the manufacturer claims is contained in them. Foods and beverages, for example, are subject to a variety of food supply chain laws and regulations across national and international borders. As such, scientists have developed a number of analytical techniques "to identify foods or food ingredients that are in breach of labeling requirement and may consequently be adulterated." Among these techniques are DNA fingerprinting; visible, ultraviolet, infrared, fluorescence emission, and nuclear magnetic resonance spectroscopy; mass spectrometry; isotopic analysis; chromatography; polymerase chain reaction; differential scanning calorimetry; chemometric; and "electric nose and tongue" techniques. In the United States, certain toys are subject to being tested and certified to the ASTM F963-17 standard by the U.S. Consumer Product Safety Commission (CPSC), with some toys being tested for heavy metals in surface coatings, nitrosamines in rubber, and contaminates in pastes, putties, and gels. Authenticity and adulteration testing may occur during post-production as part of meeting a manufacturer's regulatory requirements, or it may be conducted at a state or national border as part of a set of international trade rules. In most cases, the testing will be done by a third party laboratory or a regulatory body.

Accreditation-led testing: In some cases, governments and other regulatory bodies provide a higher standard for a manufacturing-related laboratory process, which requires accreditation to that standard. For example, labs optionally accredited to Laboratory Accreditation for Analyses of Foods (LAAF) rules are recognized by the FDA as meeting the process requirements of the LAAF program for testing of specific sprouts, eggs, water, and certain foods being considered for import into the country. LAAF represents one of several legal and regulatory forces driving accreditation of manufacturing-related laboratories to a higher standard. It also means greater potential for more testing opportunities for the third-party lab wishing to expand into enforcement and security roles. Similarly, the previously mentioned CPSC accredits labs to perform the specific testing required by children's product safety rules. Again, as with authenticity and adulteration testing, accreditation-led testing is typically conducted by third-party labs separate from the manufacturer; however, this type of testing is a step above non-accredited labs and their methods, which may be required by certain manufacturers.

1.2.4 Tangential laboratory work

The following tangential laboratory roles aren't necessarily found directly in the manufacturing center. However, some level of laboratory work is required in these roles, which intersect with the manufacturing industry in some capacity.

Processing equipment design, monitoring, and sanitation: "Sanitation provides the hygienic conditions required to produce safe food," say Ho and Sandoval in chapter seven of Food Safety Engineering. "Improper sanitation of equipment can potentially introduce hazardous contamination to food and enhance pathogen harborage in the food-processing environment." They note the value of sanitation standard operating procedures (SSOPs) to the production facility, which dictate sanitation methods and frequencies, monitoring methods, and record keeping methods. These SSOPs are not only driven by good manufacturing practice (GMP) but also appropriate and effective laboratory testing.

While Ho and Sandoval focus on food and beverage production, the proper design, monitoring and sanitation of manufacturing equipment extends beyond that industry, into areas such as pharmaceutical production and medical device manufacturing. That foundation of laboratory testing has occurred historically with the both the experience of regulated manufacturers and those scientists engineering and standardizing hygienic solutions for manufacturing industries. Combined, these industry and laboratory experiences have driven regulations and standards on hygienic design throughout the world. Broadly speaking, this has culminated in a set of manufacturing requirements, addressing physical and chemical properties such as being nontoxic, corrosion-resistant, and non-absorbent, to mechanical properties such as being durable and smooth, and operational properties such as being cleanable and low-maintenance. In turn, these properties require laboratory and engineering knowledge about metals, alloys, plastics, and many other materials. Here we find multi-disciplinary knowledge in materials science, microbiology, chemistry, physics, and more, implying a corresponding necessity for knowledge on a wide variety of testing methods.

Calibration: Just as laboratories require their precision equipment be regularly calibrated to specific tolerances, manufacturers too require their equipment to be calibrated. Multiple types of equipment along the production line require the utmost in accuracy and consistency in order to create a finished product that is safe and fully functional. Manufacturers who fall behind on their calibration obligations are more prone to higher rates of rejected components and products, more cost overruns, more missed deadlines, and greater reputation damage. As such, manufacturers increasingly depend on industrial maintenance providers, OEM providers, and laboratories to ensure their instruments and equipment meet operational tolerances.

1.3 Safety and quality in manufacturing industries

The previous section highlighted a variety of laboratory testing activities that goes on across the three broad manufacturing-based roles, including safety and QC testing. Additionally, mention was made of standards and regulations affecting manufacturers and their QC methods (more on that in the second chapter). This focus on safety and quality in manufacturing certainly doesn't occur in a vacuum; after all, history has shown that today's focus on safety and quality are often byproducts of yesterday's people and animals injured or killed due to inadequate manufacturing processes, insufficient research, sheer incompetency, or willful neglect or malice. However, the relationships among consumers, manufacturers, and regulators haven't always been easy. In his 1988 work Consumer Safety Regulation: Putting a Price on Life and Limb, Peter Asch had the following to say about these relationships:

The anti-market position of most consumer safety advocates is necessarily severe. Consumers are believed to desire additional safety, and manufacturers to know how to produce it; yet the two groups, interacting in the marketplace, do not get the job done. Precisely why this failure occurs is seldom explained by advocates of expanded regulation.
 
This is not to claim that exponents of a larger government role are necessarily wrong, or that a compelling rationale for such public expansion cannot be invoked. Rather, the case has not usually been made. The success of consumer protection advocates is, therefore, all the more remarkable.

Take the food and beverage industry, for instance. According to 2011 estimates by the CDC, "48 million people get sick, 128,000 are hospitalized, and 3,000 die from foodborne diseases each year in the United States." Whether contamination occurs in the natural growing environment of the produce farm or mechanical confines of a processed food manufacturer, these numbers point to a need for continuing to develop and modify policies and regulations that better prevent foodborne illness and encourage speedy response to such illnesses in the farm-to-fork process chain.

The drivers for this safety and quality are most obvious when viewed from the governmental level. In the U.S., several government bodies play a roll in testing and monitoring food safety and quality. For example, the USDA estimated in 2017 that some "7,500 food safety inspection personnel go to work in more than 6,000 regulated food facilities and 122 ports of entry," and "[a]nother 2,000 food safety professionals go to work in three public health laboratories, 10 district offices, and our headquarters office. These employees run test results, dispatch outbreak investigators, and unpack data to reveal telling trends and inform proactive, prevention-based policies that will lead to safer food and fewer illnesses." In another example, the CDC and its FoodNet surveillance program conducts "active surveillance; surveys of laboratories, physicians, and the general population; and population-based epidemiologic studies" for roughly 15 percent of the U.S. population. Additionally, entities like the USDA and the FDA are significant forces behind the development of regulations that affect how and when other entities—governmental and non-governmental—conduct their food and beverage testing and production activities.

In the same way, other manufacturing industries' motivations and actions towards quality and safety are driven by standards and regulations (as well as a desire to remain competitive, relevant, and profitable). From pharmaceuticals and cosmetics to gasoline and paints, manufacturers who wish to maintain a level of success in their industry will put additional focus on the safety and quality of their products, and as we learned above, that task usually falls into the domain of the manufacturing lab, be it in the manufacturing plant proper or outside the organization. That said, safety and quality labs exist not just because of regulatory controls, but also because of private incentives towards maintaining reputation and a standard of quality in the industry. Talking specifically of food safety but applicable to other industrues, Virginia Tech's John Bovay emphasized this in an August 2022 research paper:

Producers and sellers often implement private or collective standards for food safety as an investment in their own reputations. Producers who have invested in such standards can benefit from additional regulations that improve safety because these regulations can further bolster the reputation of the industry and also raise costs for rival firms. Thus, food-safety regulations may have effects on competition and certainly can have differential welfare effects.

That is all to say that reputation, standards, and regulation are interlinked in producer efforts towards safer, higher-quality products. Supporting those efforts is, in turn, quality, standardized laboratory testing that meets or exceeds the needs of the producer, as well as the overall industry. Furthering those laboratory efforts of gauging the quality of manufactured products are information management systems, which unify analytical data, help better report it, and ensure the accuracy and timeliness of that reported data. However, before we can examine the information management and informatics solutions that assist manufacturing-related laboratories in their efforts, we first need to discuss the standards and regulations affecting manufacturers and the laboratories they depend on.

References

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Citation information for this chapter

Chapter: 1. Introduction to manufacturing laboratories

Title: LIMS Selection Guide for Manufacturing Quality Control

Edition: First Edition

Author for citation: Shawn E. Douglas

License for content: Creative Commons Attribution-ShareAlike 4.0 International

Publication date: May 2023