How US drug legislation comes about and reaches the writer
In the United States the most significant changes in legislative policy, most readily those in the laws that govern drugs, have been driven by a response to tragedy or public outrage. A statute then reaches a medical writer's work through the regulations that implement it.
Tragedy as a driver of legislation
In the United States the most significant changes in legislative policy have been driven by a response to tragedy or public outrage, most readily observed in the laws that govern drugs, medical devices and biologics, and medical communicators in the regulatory field are acutely aware of it. One regulatory affairs writer holds that for medical communicators who work in the industry or are interested in its opportunities, it is of ever-increasing importance to understand how historical events have affected food and drug law and how developments in the public and business landscape continue to shape US regulatory policy.
The 1906 and 1938 food and drug acts
The 1906 Pure Food and Drug Act was created in response to public outrage after the publication of Upton Sinclair's The Jungle, a book about unsanitary conditions in the meat-packing industry. The act formed the beginning of the US FDA and remained in place for decades, although by the 1930s legislators widely recognised it as obsolete. In the 1930s the distribution and sale of drugs went largely unregulated, and nearly anyone could obtain sulfanilamide, one of the first widely available antibiotics, over the counter.
Sulfanilamide was used to treat streptococcal infections, and in pill form physicians prescribed it for a range of bacterial infections, including venereal disease. Many disliked swallowing medicine in tablet form, and to boost sales the S. E. Massengill Company created a more palatable liquid formulation. In 1937 a chemist made the liquid formulation by dissolving the drug in a sweet glycol. In one account the glycol was ethylene glycol, sweet but extremely poisonous, and the formulation caused the deaths of more than 100 people. In another the chemist was Harold Watkins and the glycol was diethylene glycol, a clear, odourless, sweet compound, and Watkins was either unaware of, or disregarded, warnings that diethylene glycol was not safe for human consumption.
The company introduced Elixir Sulfanilamide in early September 1937, with direct shipments to hospitals, retail pharmacies and doctors' offices spurred on by its sales force. News then travelled slowly: radio stations served mostly local news, rural newspapers did not cover national events extensively, long-distance calls were expensive and the post was slow. On Saturday 9 October 1937 a group of physicians in Tulsa, Oklahoma, wired the editor of a respected medical journal to report at least six deaths among their patients after prescribing the elixir. They noted a consistent progression of anuria, acute nephritis and liver degeneration, with severe abdominal pain, nausea and vomiting, ending in stupor. Because sulfanilamide in pill form had proven safe and efficacious, diethylene glycol became the prime suspect for the deaths appearing across the nation. FDA inspectors visited the company's headquarters to investigate the recipe and initiate a recall. FDA officials sought to remove the drug from the market despite stonewalling and subterfuge by doctors and pharmacists, but at least 100 deaths were attributed to the elixir in the intervening weeks.
The resulting publicity aroused public anger, and despite heavy lobbying by industry, President Franklin Roosevelt signed the 1938 Federal Food, Drug, and Cosmetic Act, which required drug manufacturers to prove the safety of products before marketing them to the public. The incident hastened the act's final enactment, and the act remains the statutory basis for FDA regulation of the products it covers. By 2015 hardly a week passed without a nearly instantaneous recall of defective products, medications among them, with the news spread through tweets, cable news and websites, and as a result, and spurred by legislation, dangerous and deadly products were removed from circulation quite rapidly.
Compounding and the Drug Quality and Security Act
More than 100 years after the 1906 act, tragic circumstances were still needed to pass needed regulation. In 2012 a multistate outbreak of meningitis, with 722 cases and 64 deaths, was traced back to the New England Compounding Center.
A compounding facility mixes, combines or alters the ingredients of a drug to create a medication tailored to the needs of an individual patient. Such a facility is not allowed to produce large batches to market to physicians or clinics, so it is exempt from the laws that regulate drug manufacturing facilities. Because it is typically a pharmacy, or at least supervised by a pharmacist, state pharmacy boards have primary responsibility for its day-to-day oversight, and the FDA does not scrutinise it to verify that its products are safe and effective.
The New England Compounding Center was manufacturing product in bulk and marketing it to clinics without linking it to real patient prescriptions, under patient names that included Sliver Surfer, Octavius and Mickey Mouse. Proper sterilisation took a back seat to increased production: product that was supposed to be sterilised for at least 20 minutes was sterilised for only 15, to produce two extra batches a day. Air and surface samples had detected contamination, but employees were ordered to forgo decontaminating the rooms so as not to incur production downtime, and to falsify documents suggesting the rooms had been cleaned. These failings still might not have put the public at risk had the facility followed the requirement to test that the finished product was sterile, but it ignored that requirement too.
Over seven weeks starting in June 2012, more than 6,500 vials of injectable steroids were shipped to customers around the country. In August 2012 a 56-year-old autoworker from Smyrna, Tennessee, was diagnosed with community-acquired meningitis, given antibiotics and sent home. After his continued decline, with headaches, agitation and seizures, the hospital tested for a rarer, fungal form of meningitis, and the result came back positive for Aspergillus fumigatus, a fungus usually found in decaying organic matter such as a compost heap. The source of the infection was contaminated steroid injections produced by the New England Compounding Center. The outbreak sickened and killed patients in 20 states before all the product could be recalled. Fourteen executives, owners and staff were arrested for crimes including racketeering, fraud, conspiracy and violating federal drug laws, and two executives, Glenn Chin and Barry Cadden, were charged with murder.
After the outbreak, Congress passed the Drug Quality and Security Act on 27 November 2013. Its Title I, the Compounding Quality Act, requires additional oversight of compounding pharmacies in several ways. Section 503B of the Compounding Quality Act created a new entity, the outsourcing facility, which is much larger than a traditional compounding facility and can supply compounded medications to hospitals. Outsourcing facilities must report adverse events on all compounded medications to the FDA twice a year, and they are subject to current Good Manufacturing Practice requirements and FDA inspection.
Facilities under Section 503A, which are not outsourcing facilities, are exempt from current Good Manufacturing Practice requirements as long as they comply with that section's conditions. Among those conditions, the facility compounds products "for an identified individual patient based on the unsolicited receipt of a valid prescription", "does not compound regularly or in inordinate amounts…any drug products that are essentially copies of commercially available drug product", and "does not advertise or promote the compounding of any particular drug".
The Compounding Quality Act also puts new penalties in place for activities such as intentionally falsifying a prescription for a compounded medication and failing to report adverse events. It requires cross-communication between state pharmacy boards and the FDA: a board must inform the FDA when it sends a compounding facility a warning letter, imposes sanctions on it, or revokes or suspends its pharmacy licence, and the FDA must inform the boards if a compounding facility is found violating Section 503A.
These safeguards are meant to protect against the kind of tragedy that unfolded in 2012. The outbreak shows how tragedy affects legislation, and that such events are not confined to the distant past.
Implementing a statute through regulations
The Affordable Care Act ran to 2,400 pages, and health care providers, institutions and patients devoted significant time to working out what it meant. The act and its reconciliation package used legal jargon, and much of their text consisted of amendments to existing provisions of other statutes, including the Internal Revenue Code, the Public Health Service Act, the Social Security Act, the False Claims Act, the Employee Retirement Income Security Act, the Indian Health Care Improvement Act and several provisions of the US Criminal Code. Many of its provisions were unreadable unless read side by side with those statutes. Unlike earlier reform bills such as Medicare Part D, it had no conference committee notes to work from, because there had been no conference.
Implementing the act would take time. One study put the mean time to complete a regulation from start to finish at 831 days, about 2 years and 4 months. Because the act was immensely complicated, many anticipated that parts of it might take longer still.
As agencies began working out the regulations that implement sections of the act, the difficulties were clearly going to lie in the details. Agencies must nevertheless post their proposals for comment and take industry's comments into account before adopting final rules. One policy commentator urged all health care providers and medical communicators to stay engaged during implementation and make their presence known at the US Department of Health and Human Services. Whatever a writer's position before the reforms passed, the reforms would affect the profession.