The Consequences of Poor Regulations

“Pi (π) Day” is March 14 (3/14, i.e., 3.14), which is a special day in Princeton, NJ, about three miles from where this author lives. The celebration of this date began in 2009 to honor Albert Einstein, whose birthday is March 14, and to celebrate mathematics. It has grown into a weeklong celebration and includes lectures, Einstein look-a-likes, tours of his home, specially priced food and other things—soup for $3.14, and a replica of his bicycle for $314.15—and of course, pie-eating contests. Reflecting on the special events of this particular week, the author considers two other events that occurred at this time: one in the U.S. and one in the EU, both of which exemplify the results of poor regulations. They are detailed here.

Compounding in the U.S.

On March 10, 2013, the CBS television network program 60 Minutes aired a segment on issues concerning the New England Compounding Center (NECC). This facility had shipped contaminated epidural steroid injections that led to a meningitis outbreak beginning in May 2012. Deaths and painful injuries were reported, and the company filed for bankruptcy in December 2012. The television broadcast, led by correspondent Scott Pelley, featured interviews with David Kessler, former U.S. Food and Drug Administration (FDA) commissioner; and Margaret Hamburg, MD, current FDA commissioner, among others. Following are some key points, taken from the show transcript.

The NECC was what is known as a compounding pharmacy. By law, compounding pharmacies are not allowed to manufacture pharmaceuticals for the mass market. That would require the oversight of the FDA. Instead, states license compounding pharmacies to make drugs for individuals. For example, a doctor might order a liquid form of a medication for a patient who cannot swallow a pill. Compounding pharmacies are bound by one rule: They must have a prescription for each individual patient.

“We became a manufacturer overnight,” said Joe Connolly, a former lab technician at NECC. “So we were basically trying to have the best of both worlds. [The company] was trying to manufacture without the oversight of a manufacturer. And it was just—we all got overtaxed and everything.”

According to the program, the NECC was growing explosively and so was the compounding industry. It started in 1998 when Congress exempted compounding pharmacies from oversight by the FDA. The theory was that mixing drugs one prescription at a time should not require federal inspection. The law passed, regardless of strong objections of then-FDA Commissioner David Kessler.

Pelley: You as FDA commissioner testified before them and you said, “Don’t do this.”

Kessler: If you’re not going to have oversight, one day people are going to die.

Pelley: That day’s arrived.

Kessler: This should not happen in 2013; maybe at the turn of the previous century, where we didn’t have institutions like the FDA. There is no reason why people had to die.

According to the television program, without FDA supervision, compounding took off and state health departments are responsible for regulating what is now nearly a $2 billion industry. Hamburg, now the FDA commissioner, said that because of the 1998 law, she does not know how many compounders there are, or what they are making.

Pelley: You know, I can just hear the folks at home saying, “Wait a minute. I thought every pharmaceutical drug in this country was approved by the FDA.” And you seem to be telling me in this interview that that’s not the case?

Hamburg: Well, compounded drugs are not FDA approved.

Pelley: So if a patient goes into a clinic and the doctor or the nurse pulls out a vial of something, that patient has no way to know whether that drug has been approved by the FDA or not?

Hamburg: Well, I think that’s right under the current system. And what I think emerged in the meningitis outbreak was that many patients and their health care providers didn’t realize that they in fact were using a compounded product.

Pelley: As commissioner of the FDA, then, you can’t tell us sitting here now that every drug being used in the United States is safe and effective?

Hamburg: No. I really cannot. Hamburg added that she now wants Congress to return authority over compounding pharmacies to her agency.

Hamburg: We need clear, strong, consistent federal standards that will be applied across the board, all 50 states. We need to be able to go in and inspect these facilities and get access to all of the information that we need.

Pelley: What are the chances of this happening again?

Hamburg: I’m sad to say that if we do not put in place the comprehensive legislation that really defines roles and responsibilities, we will have other similar problems.

Comments and Follow-up

This author believes there were several mistakes and omissions in this interview. First, the law that was cited as 1998 was actually the Food and Drug Modernization Act of 1997. This bill is well-known to the personal care industry for one particular part, stating: Not later than 18 months after the date of enactment of this Act, the Secretary of Health and Human Services shall issue regulations for over-the-counter sunscreen products for the prevention or treatment of sunburn.

This did take place exactly 18 months after the signing, which gave the industry the Final Monograph on sunscreens that was then stayed, although with some parts final; there are still parts that are unfinished.

What this author found most disturbing was that 60 Minutes did not follow up on what should have been part of the presentation. It should have asked the commissioner who wrote this terrible bill in 1997 and then tracked down the sponsors who indirectly caused what Kessler said would happen. The co-sponsors of this legislation were Congressman Richard Burr (R–North Carolina), now the Senator from North Carolina; and James Jeffords (R–Vermont), who later became an Independent in 2001 and retired from the Senate in 2008. This author believes the actions of these two people caused these tragedies just as much as management at the NECC.

Blame also needs to be put on all of Congress and the President, who signed this bill into law. Like most U.S. legislation, this Act was so large, containing more than 75 changes in FDA regulations—from re-authorizing drug users’ fees, to advertising, to sunscreens, etc.—that one may wonder whether anyone who voted for this bill had any idea of what they were supporting.

This is one time this author was glad to be late in submitting a column, although the editor may not have been glad, because it allowed me to include the impact of this television broadcast here. On April 11, 2013, Hamburg posted thoughts on her blog,1 which was also reported on April 12 in an article by Lena Sun in the Washington Post2 as a follow-up to the interview.

According to Hamburg, as a result of the NECC disaster, 53 people died and 680 were struck ill. The FDA has since inspected many compounding pharmacies that were making sterile drugs, and 30 of the 31 were given FDA 483 forms; the one exception no longer makes sterile drugs. An FDA Form 483 is issued at the conclusion of an inspection when an investigator(s) has observed any conditions that in his judgment may constitute violations of the Food Drug and Cosmetic (FD&C) or related Acts.

Republicans in the House are calling for hearings with the FDA as to why the NECC tragedy happened, but this author wonders whether the FDA will ask the members of Congress who sponsored and passed the legislation why they did. Further, will the FDA respond to these members of the House about the “Sequestration,” which has further cut FDA spending, making it even more difficult to enforce laws. The next NECC is just around the corner.

In relation, on March 21, 2013, a bill was introduced to Congress to further regulate cosmetics. So with already limited resources, the FDA is now being asked to do more to pacify nongovernmental organizations that oppose the cosmetics industry based on unfounded claims and junk science. What the FDA really needs are more resources to focus on the potential life-threatening safety of foods, drugs and medical devices. Adverse events caused by cosmetics are minimal and miniscule, yet this is what Congress will waste its time on?

EU Animal Testing Ban

The U.S. government is not alone in passing legislation that can and sometimes does lead to disasters, even if it has been warned about the consequences of its actions. The EU announced on March 11, 2013, that it has banned the sale of cosmetics containing ingredients that have been tested on animals.3 This includes imported cosmetics as well as EU-manufactured products. In 2004, the EU banned the sale of finished cosmetics tested on animals. This ban ignores the scientific fact that there are no non-animal alternatives acceptable for testing repeated-dose toxicity, including skin sensitization and carcinogenicity, reproductive toxicity and toxicokinetics. Will a cosmetic company take the risk of using a new ingredient lacking this critical safety data? I guess the EU thinks it will, or that developing new ingredients is not important to the industry, because it thinks: “Who needs another shampoo or cream, anyway?”

The better question is: Will this be enforced? A couple of examples are recently published animal safety testing studies of Aloe barbadensis leaf juice on mice and rats,4 and limonene on rat skin, for penetration research.5 Since the prohibition is forever—or until a new Amendment is published that allows animal testing—this means that no cosmetic sold in the EU can contain these ingredients, ever.

Aloe is extremely popular, especially in the natural and organic markets, and limonene is one of the most common ingredients found in fragrances, flavors and essential oils. So now, they must be banned. This author expects the EU to take one of three actions, illustrated (exaggeratedly) as follows.

1. Enforce the regulation to the fullest. Once EU Commissioner Tonio Borg hears about this crime of using ingredients tested on animals, he undoubtedly will immediately hit the EU Cosmetic Notification Portal and find all the offending products. He quickly will then notify the responsible person (RP) and Competent Authority of the Member State of this violation. However, as Article 37 requires that penalties must be “effective, proportionate and dissuasive,” what could they be? Fines? Imprisonment of the RP? Seizure of products?

And what about consumers in the EU? Suddenly their favorite cosmetics are no longer available, the store shelves are 90% empty due to violations, and they can no longer obtain their favorite cosmetics. Ah yes, but they can always order them online. What will the cosmetic industry do? By the time this column is published, cosmetics will already be labeled “aloe-free” and “limonene-free”. There will also be great demand for little leaping bunny labels and other symbols to indicate testing for “purity.”

2. Ignore the regulation. Possibly the easiest thing for Commissioner Borg to do is ignore this and hope it goes away. However, People for the Ethical Treatment of Animals (PETA) will pull out its old bunny suits from the late 1970s, or don new rat, mice and guinea pig ones, and storm the stores with television cameras flashing, condemning the industry again for violating the will of the public by testing on animals. Consumers will see this on the evening news and boycott these “horrible” cosmetics, until they discover there are no more cosmetics … leading them back to making their own products at home.

But where will they get aloe? The crash in demand by the personal care industry will cause farmers to cease production, as there are no sales. They will now raise Cyamopsis tetragonoloba instead for its guar gum because there is growing demand for it in hydraulic fracturing, or fracking. So will at-home gardeners discontinue growing certain other illegal plants in their basements, to plant aloe instead?

3. The third option is politely called the “shuffle.” This is what politicians do when they are caught saying or doing things that undermine their reputation and need to come up with a story they hope will explain their decision. There were warnings on March 11, 2013, when the animal testing ban became official, that the ban left a loophole. And shortly after the official announcement, Dagmar Roth-Behrendt, a Socialist lawmaker from Germany who helped steer a measure through the European Parliament resulting in the 2004 ban, said companies could still use ingredients from tests on animals as long as the tests were carried out for non-cosmetic products like pharmaceuticals or chemicals. Roth-Behrendt said she did not know if the loophole “followed pressure from the industry,” but added “this is wrong.”

When this author attended a meeting some years ago in the EU about animal testing bans, there were questions regarding animal testing to comply with REACH. The “shuffle” was that REACH was for environmental safety, not cosmetic safety. This author asked: “How does the animal know the difference?”


Readers should note: This author knows he has poked fun at the EU. It is only meant to convey the possible results of poor legislation. Do not take it personally, it is meant in jest. Readers must understand that what has happened in the U.S. due to poor regulation can also happen in the EU; it is the law of unintended consequences.

Due to the animal testing ban, the EU will not have inhalation safety studies of aerosols, therefore the FDA should immediately require that all aerosols imported from the EU, or any other country that prohibits animal testing, have a mandated safety warning known as the 740.10.

The Code of Federal Regulations 21CFR740.10 states:

Sec. 740.10 Labeling of cosmetic products for which adequate substantiation of safety has not been obtained.

(a) Each ingredient used in a cosmetic product and each finished cosmetic product shall be adequately substantiated for safety prior to marketing. Any such ingredient or product whose safety is not adequately substantiated prior to marketing is misbranded unless it contains the following conspicuous statement on the principal display panel: Warning —The safety of this product has not been determined.

This author feels such labeling must be required, because why should one industry, in this case, the U.S., suffer from performing safety tests that its competition is not? Especially when untested products could eventually injure consumers? This essentially harms an industry trying to do the “right” thing. As the old adage goes, “No good deed goes unpunished.”

Finally, as an aside, this author feels compelled to comment on the new H.R. 1385 Bill introduced by Representative Jan Schakowsky (D-Illinois) on March 21, 2013. Can any reader please explain to me why a politician would introduce legislation that could effectively ban almost all hair dyes, when she dyes her hair?

Remember to celebrate “Pi Day” next year!

Send e-mail to All websites accessed Apr 15, 2013.
1. proactive-inspections-further-highlight- need-for-new-authorities-for-pharmacy- compounding/
2. science/fda-finds-widespread-safety-issues-at-compounding-pharmacies/2013/04/11/5321e17a-a20d-11e2-be47-b44febada3a8_ story.html?wpisrc=nl_headlines
4. I Sehgal et al, Safety assessment of decolorized whole leaf aloe vera juice, J Toxicol (online) (Mar 11, 2013)
5. YW Kim et al, Safety evaluation of limonene, J Toxicol Environ Health B Crit Rev 16(1) 17–38 (2013)

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