Fall 1937 … somewhere in Tennessee …

Little Barbara had always been a rather sickly child. You name the current popular sickness and she caught it. Three other children from town had missed church that Sunday complaining of a sore throat, so her parents knew it was only a matter of time before she had the same malady. But she was an obedient youngster and would do her best to gargle with saltwater and take whatever medicine the family had available, although she sometimes had difficulty taking pills. And the powders tasted just awful. Barb’s mother, however, had heard about a new liquid medicine that worked quickly and tasted like raspberries. And she set out that morning determined – no matter the cost – to bring this new miracle drug home.

Nobody but Almighty God and I can know what I have been through these past few days. I have been familiar with death in the years since I received my M.D. from Tulane University School of Medicine with the rest of my class of 1911. Covington County has been my home. I have practiced here for years. Any doctor who has practiced more than a quarter of a century has seen his share of death.

But to realize that six human beings, all of them my patients, one of them my best friend, are dead because they took medicine that I prescribed for them innocently, and to realize that medicine which I had used for years in such cases suddenly had become a deadly poison in its newest and most modern form, as recommended by a great and reputable pharmaceutical firm in Tennessee: well, that realization has given me such days and nights of mental and spiritual agony as I did not believe a human being could undergo and survive. I have known hours when death for me would be a welcome relief from this agony. (Letter by Dr. A.S. Calhoun, October 22, 1937)¹

Thankfully, Barbara did not take that elixir. The county’s country doctor had a habit – really more of a ritual – of religiously reading the local paper on the front porch every evening while he allowed the stench of the day, and of his sick patients, to slowly waft off him in the breeze. While annoying as all heck to his wife who just as religiously prepared dinner at the same time every evening, knowing it would remain cooling as he read, this little habit saved that county untold heartbreak. For one evening, while the wife stamped her feet and glowered at him through the window as he turned the newspaper pages, the country doctor stiffened, literally jumped off the porch and raced back to the office. When his dumbfounded spouse went to retrieve the discarded paper, she found the announcement from the AMA warning of the deadly ramifications of taking Elixir Sulfanilamide.

You may be wondering what the above stories have to do with medical devices. It is a rather interesting tale – one that begins over 30 years before the 1937 Elixir Sulfanilamide Disaster.

I. PURE FOOD AND DRUGS ACT OF 1906

Enacted in 1906, the “Wiley Act” was intended to “prevent the manufacture, sale or transportation of adulterated or misbranded or poisonous or deleterious foods, drugs, medicines and liquors, and for regulating traffic therein, and for other purposes.”² The Act defined the word “drug” to “include all medicines and preparations recognized in the United States Pharmacopoeia or National Formulary for internal or external use, and any substance or mixture of substances intended to be used for the cure, mitigation or prevention of disease of either man or other animals.”³ The term “device” did not appear in the Act, but the definition of “drug” was broad enough to allow just about anything to be characterized as a drug. For example, prior to the enactment of the FDCA, the Second Circuit held that gauze bandages were “drugs” covered by the 1906 Act.⁴ This began a rather long practice of classifying as drug items no one considered in common parlance to be a drug. But the practice allowed regulation, and courts considered regulation essential to the protection of the public health.⁵

Interestingly, the 1906 Act contained no provision requiring some sort of government approval or clearance in any manner before a drug could be marketed. The Act did set out, however, that no person could manufacture or sell any “adulterated” or “misbranded” drug; doing so was a misdemeanor and would subject the miscreant to a fine and potential imprisonment (not to exceed one year).⁶ A drug would be considered adulterated

• FIRST: If, when a drug is sold under or by a name recognized in the United States Pharmacopoeia or National Formulary, it differs from the standard of strength, quality or purity, as determined by the test laid down in the United States Pharmacopoeia or National Formulary official at the time of investigation: Provided, that no drug defined in the United States Pharmacopoeia or National Formulary shall be deemed to be adulterated under this provision if the standard of strength, quality or purity be plainly stated upon the bottle, box or other container thereof, although the standard may differ from that determined by the test laid down in the United States Pharmacopoeia or National Formulary.
• SECOND: If its strength or purity falls below the professed standard or quality under which it is sold.⁷
  And it would be considered misbranded if “the package or label of which shall bear any statement, design or device regarding such article, or the ingredients or substances contained therein which shall be false or misleading in any particular.”⁸ Today, over 100 years later, we still wrangle over what exactly is “false or misleading in any particular.”

II. FEDERAL FOOD, DRUG AND COSMETIC ACT OF 1938

Eventually, the 1906 Act ran its course after several amendments, and Congress began crafting a more substantial bill. “By 1917, fraudulent medical devices, such as nose straighteners, height-stretching machines and heated rubber applicators advertised as a cure for prostate gland disorders, began flooding the market. It was clear to the FDA that the law should be expanded to include agency authority over medical devices. In its annual report to Congress that year, the FDA stated that the 1906 act ‘has its serious limitations … which render it difficult to control … fraudulent mechanical devices used for therapeutic purposes.’”⁹ One of those limitations was that the 1906 Act did not specifically define “devices,” so items that clearly were devices had to be defined as drugs just so they could be regulated. But “calling a medical device a drug, claimed a U.S. senator from Missouri at the time, was like ‘calling a sheep’s tail a leg.’”¹⁰

And so the bickering began as to how best to address this conundrum in the new Act. In an early 1934 version of the Act, a definition of “device” remained absent, but the term “drug” was defined to include “all substances, preparations and devices intended for use in the cure, mitigation, treatment or prevention of disease in man or other animals …”¹¹ This was on purpose as noted by the bill’s introducer, Senator Copeland, when discussing the 1906 Act that he hoped to fix:

The present law defines drugs as substances or mixtures or substances intended to be used for the cure, mitigation or prevention of disease. This narrow definition permits escape from legal control of all therapeutic or curative devices like electric belts, for example. It also permits the escape of preparations which are intended to alter the structure or some function of the body, as for example, preparations intended to reduce excessive weight. There are many worthless and some dangerous devices and preparations falling within these classifications. [This bill] contains ample authority to control them.¹²

But this bit of wordsmithing did not sit well with the good Senator Clark from Missouri, who later countered:

If the devices ought to be outlawed, they ought to be outlawed, and I have no objection to that; but to maintain that a purely mechanical device is a drug and to be treated as a drug in law and in logic and in lexicography is a palpable absurdity, in my opinion.¹³

Others agreed and, in order to quell the rising debate, an amendment was suggested to simply add a definition for “device.” That was done, agreed to without debate, and without further ado, the bill now had a “parallel definition” for devices.¹⁴ The bill still, however, was missing a few details:

We have found nothing in the legislative history of the Act indicating that the Congressional purpose in providing a separate definition of “devices” was anything other than to avoid the incongruity of classifying such things as electric belts as “drugs.” There was at the time no practical significance to the distinction between “drugs” and “devices,” for the operative provisions of the bill (e.g., the provision barring the introduction into interstate commerce of any food, drug, device or cosmetic that is adulterated or misbranded) applied identically to both. The bill, as late as August 1937, included no section relating to “new drugs,” and no requirement that any products covered by the bill be submitted to the government for prior approval before their introduction into interstate commerce.¹⁵

That changed, however, in 1937 because of the Elixir Sulfanilamide tragedy discussed at the beginning of this article. But it changed only for drugs – not devices. Spurred on by the deaths of nearly 100 men, women and children, new bills were introduced that included prior approval provisions for “new drugs,” but “the term ‘new drug’ was used … without any attention to the fact that the distinction between ‘drug’ and ‘device’ had thus for the first time become important.”¹⁶ Upon enactment in 1938, for the first time regulations explicitly applied to drugs – new drugs – that did not apply to devices. Also of significance was the inclusion in the definition of “drug” that it “does not include devices or their components, parts or accessories.”¹⁷

So thus continued the practice of classifying medical devices as drugs in order to deem them subject to regulation. In 1968 the Second Circuit, noting the classification of devices to be “exclusionary,” held that AMP’s new products for ligating blood vessels – an applicator, nylon ligature loop and nylon locking disk – were drugs.¹⁸ A year later, the United States Supreme Court determined that antibiotic sensitivity discs – which never came in contact with an actual patient – were drugs.¹⁹ Much like the Second Circuit, the High Court likewise referred to the device classification as an “exception” and affirmed that devices should be limited to such things as “electric belts, quack diagnostic scales and therapeutic lamps, as well as bathroom weight scales, shoulder braces, air conditioning units and crutches.”²⁰

One wonders what the Missouri senator would have thought of these legal gymnastics. Perhaps he would have suggested yet again: if you want to regulate devices, just regulate devices.

Finally, that happened.

III. MEDICAL DEVICE AMENDMENTS ACT OF 1976

As history shows, sometimes tragedies ensue before action occurs. The FDA notes that “during 1972 and 1973, pacemaker failures were reported. And in 1975, hearings took place on problems that had been reported with the Dalkon Shield intrauterine device, which caused thousands of reported injuries. Those two incidents helped underscore the need for the Medical Device Amendments, enacted in 1976.”²¹ The MDA created a classification scheme for devices that correlated in general to the level of risk and the concomitant level of FDA regulatory oversight²² (e.g., Class I, Class II and Class III), and gave the FDA authority over device development, marketing and post-marketing activities. As President Ford said when signing it into law, “The Medical Device Amendments of 1976 eliminate the deficiencies that accorded the FDA ‘horse and buggy’ authority to deal with ‘laser age’ problems.”²³

Specifically focusing on pre-approval authority, the MDA sets out the underpinnings of the 510(k) and PMA processes. Whether a device falls under the parameters of the 510(k) paradigm, the PMA process or neither depends on its classification. And classifications are mutually exclusive – a device is either I, II or (never “and”) III.

If Class I, the device is not subject to any sort of preapproval process, but simply falls under what are known as “general controls.” General controls apply to all medical devices, but they are the only controls that apply to Class I devices. They are the basics, governing such things as adulteration, misbranding, device registration and listing, and good manufacturing practices. Essentially, if determined to be a Class I device, the FDA has decided that it needs only general controls to assure itself of the safety and effectiveness of the device. Of interest, “when initially classifying devices, the FDCA requires that the least restrictive classification must first be considered, and only when the device in question cannot meet the definition of a less restrictive class can more restrictive classifications be considered.”²⁴

The Class II devices fall under the 510(k) system. In order to equalize competition with respect to pre-amendment devices that could continue being marketed²⁵ as “grandfathered” until the FDA classified them, Congress said that new devices that were “substantially equivalent” (SE) to a pre-amendment device also could be legally marketed. But nowhere was the term “substantially equivalent” defined – until 1986 when the FDA issued a Guidance addressing the matter.²⁶ Although a lot of attention has been paid to the SE term, legislative history makes clear that Congress’s intent was to base the SE determination on another SE finding: safety and effectiveness.²⁷ Class II devices are those that require a few more standards, or performance standards, in addition to general controls, in order for the FDA to be satisfied that the device is safe and effective.²⁸

Lastly, the Class III devices require approval of a Premarket Approval Application (PMA) before they may be legally marketed.²⁹ These are devices that are “intended to be used in supporting or sustaining human life or preventing impairment of human health, or that may present a potential unreasonable risk of illness or injury for which general controls and special controls are insufficient to provide reasonable assurance of the safety and effectiveness of a device, or for which there is insufficient information to make such a determination.”³⁰ In summary, when general controls and special controls are not enough, or the FDA simply does not know if they are enough, the device is classified as Class III.

Keep in mind as well that the FDA may down-classify a device when its current classification constitutes “overregulation.”

As experience and knowledge about a device increase, the original classification can be adjusted via the process of reclassification. Changes in classification are based on the FDA’s receipt of new information about a device. The FDA may, on its own, or in response to an outside petition, change a device’s classifcation by regulation. A manufacturer who wishes to have a device reclassified to a lower class must convince the FDA that the less stringent class requirements will be sufficient to provide reasonable assurance of safety and effectiveness.³¹

Regardless of the class, the focus has always been, and remains today, the safety and effectiveness of the device. And in 1990, the FDA was given additional authority to ensure safety and effectiveness.

IV. SAFE MEDICAL DEVICES ACT OF 1990

Per the FDA, the “Safe Medical Devices Act (SMDA) was passed in 1990, and represents the first reform of medical device law since the 1976 amendments. This law modified the amendments to give the public greater protection against dangerous medical devices.”³² And how did it accomplish that? These are just a few ways:

• The SMDA formally memorialized the FDA’s methods for determining substantial equivalence as had been set out in the 1986 Guidance.
• Substantial equivalence was actually defined and included safety and effectiveness.
• Any marketed device could be a predicate – not just a pre-amendment device.
• Regulation of Class II devices was enhanced with the use of performance standards and special controls.
• Special controls can be such things as specific labeling requirements or FDA Guidances.
• Mandatory event reporting for certain events, such as death.
• Mandatory post-market surveillance for certain devices.

V. CONCLUSION . . . FOR NOW

For now, our story pauses. But the tale continues with more on the SMDA, FDAMA in 1997, MDUFMA in 2002, FDAAA and MDUFA II in 20

---

[i] U.S. Food and Drug Administration, “Taste of Raspberries, Taste of Death – The 1937 Elixir Sulfanilamide Incident,” FDA Consumer Magazine, June 1981, Available at http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation /SulfanilamideDisaster/default.htm. Last accessed May 20, 2014.

[ii] http://www.fda.gov/RegulatoryInformation/Legislation/ucm148690.htm; Public Law Number 59-384; 34 Stat.768 (1906) (repealed in 1938 by 21 U.S.C. 329(a)).

[iii] Id. at Sec. 6 (emphasis added).

[iv] AMP Inc. v. Gardner, 389 F.2d 825, 830 n.12 (2d Cir. 1968) (citing United States v. 48 Dozen Packages, More or Less, of Gauze Bandage Labeled in Part Sterilized, 94 F.2d 641 (2d Cir. 1938)).

[v] Id. at 829 (noting products must be classified according to Congressional purpose, which here “was, very clearly, to keep inadequately tested medical and related products which might cause widespread danger to human life out of interstate commerce.”).

[vi] 34 Stat. 768, Sec. 1, 2.

[vii] Id. Sec. 7.

[viii] Id. Sec. 8.

[ix] U.S. Food and Drug Administration, “Medical Device and Radiological Health Regulations Come of Age,” FDA Consumer Magazine, January-February 2006.

[x] Id.

[xi] Gardner, 389 F.2d at 827-28.

[xii] Id. at 828.

[xiii] Id. at 828.

[xiv] Id. at 829.

[xv] Id.

[xvi] Id.

[xvii] Id. at 829-30. http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/MedicalDeviceand
RadiologicalHealthRegulationsComeofAge/default.htm. The premarket regulation of devices again was delayed in 1962 with the aftermath of the thalidomide disaster in Europe. While the 1962 Amendments specifically allowed FDA to regulate some devices as drugs (i.e., sutures and contact lenses), the majority remained unregulated. Flaherty, Defending Substantial Equivalence: An Argument for the Continuing Validity of the 510(k) Premarket Notifi cation Process, 63 Food Drug L. J. 901, 905 (2008) (Flaherty Article).

[xviii] Id. at 830.

[xix] United States v. An Article of Drug … Bacto-Unidisk…., 394 U.S. 784 (1969).

[xx] Id. at 799-800. Last accessed February 7, 2014.

[xxi] U.S. Food and Drug Administration, “Medical Device and Radiological Health Regulations Come of Age,” FDA Consumer Magazine, January-February 2006. Last accessed May 20, 2014.

[xxii] FDA describes it a little differently: “Devices are classified according to the degree of difficulty in assuring their safety and effectiveness.” See http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/Generaland
SpecialControls/ucm055910.htm.

[xxiii] Id.

[xxiv] Flaherty Article at 906.

[xxv] Id. at 907.

[xxvi] Id. at 907-08 (discussing Guidance on the CDRH Premarket Notifi cation Review Program).

[xxvii] Id. (“The Committee believes that the term should be construed narrowly where necessary to assure the safety and effectiveness of a device but not so narrowly where differences between a new device and a marketed device do not relate to safety and effectiveness.”)

[xxviii] See http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/Generaland
SpecialControls/default.htm.

[xxix] Id.

[xxx] Id.

[xxxi] See http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/ucm080412.htm.

[xxxii] U.S. Food and Drug Administration, “Medical Device and Radiological Health Regulations Come of Age,” FDA Consumer Magazine, January-February 2006. Available at http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/MedicalDeviceand
RadiologicalHealthRegulationsComeofAge/default.htm. Last accessed May 20, 2014.

Finis