Book:LIMS Selection Guide for Manufacturing Quality Control/Introduction to manufacturing laboratories/Manufacturing labs, then and now

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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."[1] 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.[2][3][4][5]

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[6]:

  • 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)[7]:

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.[7][8][9] 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.[10] 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."[10] 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.[10][11]

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."[11] 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.[11]

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[11]:

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[10][12], openings of new pharmacy schools (though still limited in scope)[13], publishing of books[13], and additional formalization of regulating legislation (such as Britain's Apothecaries Act of 1815).[11] 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."[10] 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.[10]

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.[14] 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.[15] 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.[16]

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[17]:

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.[18] 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

From 1800 to 1900. The wonderful story of the century; its progress and achievements (1899) (14778122434).jpg

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.[19] 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."[20] 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[21]:

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[22]—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.[23][24]

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[24]:

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."[25] Kremers also touched upon another complaint popular at the time: that of pharmacy as a money-making venture.[22][25] 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[26]. 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[19], Thiesing in 1915[27], and Beal in 1919.[26] 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[26]:

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

CSIRO ScienceImage 1671 CSIR Information Stand.jpg

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.[28][29] 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."[28]

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."[30] 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.[30]

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."[14] 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."[14]

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[28]:

  • 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.[28] 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.[28] 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.[30] 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."[31] 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.[32]


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