User:Shawndouglas/sandbox/sublevel9

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 to 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 scarecely 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 preperations 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 1880s, further laws dictating quality and educational requirements were going into effect for pharmaceutical

The previously mentioned Charles McDowell presented his view of American research and manufacturing methods of the early 1900s, noting the following about the transition from research to manufacturing:

The definition of research is "diligent inquiry," and, if results are to be obtained, diligent inquiry is necessary; infinite patience is required. The reason for failures must be ascertained. One must learn to stand punishment; to wait; to act quickly; to differentiate between the unimportant and the worth while; and above all one must have good backing. Research chemists are often lacking in the ability to apply practically the results of their work, and a different type of man is often required for the second or small manufacturing stage. Frequently, things work well on a small scale, and failure results when mass action comes into effect. Often the reverse is true. A third type of man frequently is required when the commercial manufacturing scale is to be carried out. All of this means team work. It means not only laboratory equipment but small manufacturing equipment. In our work, we maintain a manufacturing laboratory consisting of small manufacturing units where various processes can be carried out on a manufacturing scale. This equipment consists of mills, electrical and other furnaces, pressure tanks, vacuum pans, filter presses, dryers and other machinery used in standard work, so that a process developed in the laboratory can be tried out on a small commercial scale.

McDowell goes on to classify three types of research that leads up to the manufacturing process: pure scientific inquiry, industrial research, and factory research. He notes 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. In regards to industrial research (discussed further in the next subsection), McDowell makes several observations that aptly describe the state of manufacturing research in the early 1900s. He notes that unlike pure scientific inquiry, industrial research has commercial practicality as a goal, often beginning with small-scale experiment and later seeking how to reproduce those theoretical results into large-scale manufacturing. He also reiterates 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 says, "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." As for factory research, McDowell characterizes it as full-scale factory-level operations that range from haphazard approaches to well-calculated contingency planning.

1.1.3 The rise of the industrial research lab and full-scale manufacturing

https://nap.nationalacademies.org/read/20233/chapter/4#34