Monday, September 16, 2013

Compounding Pharmacy Legislation; A matter of Life and Death

U.S. Capitol Building
Glyn Lowe Photoworks, Flickr PhotoStream
Bill S 959 was introduced by Senator Tom Harkin on May 15, 2013 to address lack of oversight when pharmacies cross the line between individual prescription compounding and spontaneously starting to operate as drug manufacturers. The proposed legislation was put together in response to the New England Compounding Center’s shipping of thousands of steroid vials for spine injections on the basis of fictitious and non-existant prescriptions. Made hastily under non-sterile and deplorably putrid conditions the vials introduced a lethal pathogen in patient’s spines causing fungal meningitis. Ultimately 750 people became sick and 68 died. Meanwhile
problems continue at compounding pharmacies due to lack of enforceable standards.

Since 2001, 87 deaths have been reported amongst 1,084 patients affected by compounding contamination and errors.

S 959 will require for pharmacies that become manufacturers to be registered with the FDA and gives the regulatory agency the right to inspect such facilities, and file adverse event reports promptly.
Because of special interest lobbying the bill has been bogged down but if it, or any other version, ever passes it will probably be watered down or altered substantially from its core purpose of protecting patients from medicines made in unkempt and unsafe environments.
The government’s General Accounting Office noted in its report responding to the House of Representatives request to update its 2003 testimony on drug compounding:
“that while FDA and national pharmacy organization officials generally agreed that states regulate the practice of pharmacy and FDA regulates drug manufacturing, there was no consensus on whether compounding drugs in large quantities--in anticipation of individual prescriptions or without prescriptions--and selling those drugs across state lines falls within the practice of pharmacy or is a type of drug manufacturing that should be overseen by FDA. This lack of consensus and differing FDA authority to oversee compounded drugs across the country has resulted in gaps in oversight of drug compounding.
Until 2013, FDA limited its inspections of compounding pharmacies to those conducted in response to complaints or adverse events. However, the agency recently inspected compounding pharmacies that it identified as posing a significant threat to public health from poor sterile drug production practices in the past and found problems, such as concerns about a lack of sterility, which resulted in recalls of compounded drugs. In addition, drug manufacturers are required to register with FDA and are subject to FDA's inspection and drug approval processes; pharmacies meeting certain requirements are generally exempt from registration. However, some compounding pharmacies may have registered with FDA to market themselves as "FDA-registered" which may lead some purchasers to assume that FDA has inspected or approved their compounded drugs; whereas, according to FDA officials, this is generally not the case.
..according to national pharmacy organizations and officials from state boards of pharmacy, some states do not have the resources to inspect pharmacies on a regular basis. Instead, these states inspect pharmacies only in response to a complaint or a reported adverse drug event.”

The GAO has recommended that:
“Congress should consider clarifying FDA’s authority to oversee drug compounding. In addition, FDA should ensure its databases collect reliable and timely data on inspections associated with compounded drugs, and differentiate drug compounders from manufacturers. HHS's comments support the need to clarify FDA's authority, and stated that the information in its inspection database could be improved and that it would consider whether it can differentiate compounding pharmacies from manufacturers.”
More recently Congressman Morgan Griffith has proposed The Compounding Clarity Act H.R. 3089. It is too early to predict who will line up behind the House Bill, but ultimately something will need to be done to prevent the gray areas and overlaps between State and Federal regulation of compounding centers. And not every one will be happy.

Supporting S959, Allan Coukell, Senior Director, Drugs and Medical Devices at The PEW Charitable Trust, in his July 16, 2013 testimony to lawmakers said:
"Pew recently joined with the American Hospital Association (AHA) and the American Society of Health-System Pharmacists (ASHP) to co-host a Pharmacy Sterile Compounding Summit.
This meeting included representatives of hospitals of varying sizes, purchasing organizations, compounders, regulators, and pharmacy associations.It also included experts in pharmacy practice and drug manufacturing quality standards. These experts emphasized the enormous difference between the standards developed for traditional pharmacy practice and the Good Manufacturing Practices that apply to drug manufacturing. They emphasized that only GMPs are adequate to ensure the safety of large-scale standardized production, and that USP compounding standards, which some have suggested could be used as a national standard, were developed for use in pharmacies and are therefore not suitable for larger-scale production.cGMPs, on the other hand, are developed to ensure the proper production of large volumes of repeated batches of medicines which require standardized processes. These are the appropriate types of quality standards for large-scale compounding.For example, cGMP requires manufacturers to validate systems and processes to ensure that medicines meet consistent quality and safety standards. Process validation becomes increasingly important as the same drug is compounded in repeat batches. In addition, USP 797 does not require the testing of a drug’s starting ingredients, while cGMP does. And expiration dates are set for a manufactured drug based on extensive stability testing. But a beyond-use date for a compounded medicine may in some cases be set by referencing published studies of drugs that may not conform exactly to the compounded product.Oversight of such standards is a role for the FDA, not for state boards of pharmacy."
In finishing, Coukell clarified “One thing that characterizes pharmacy practice is that pharmacies fill prescriptions. Any business whose principal activity is the production of products without a prescription is not a traditional pharmacy.”

Other Proponents of FDA oversight include the APHA, ASHP, TFAH, and American Hospital Association.

The American Public Health Association, APHA, that claims a membership of 25,000 public health professionals, and Trust For American Health, TFAH, in a June 10 letter to Senator Tom Harkin pointed out:
"S. 959 takes important steps to make Americans safer. It would bring compounding facilities that ship interstate under federal regulation, which will allow for more uniformity of oversight and safety standards. We believe the bill will give FDA the tools to ensure safe manufacturing practices at these facilities. The legislation also protects the traditional role of pharmacists to compound individual medicines for one patient at a time.”
Making a presentation at the House Energy and Commerce Committee Subcommittee on Health Hearing on Reforming the Drug Compounding Regulatory Framework on July 16, 2013, the American Society of Health-System Pharmacists, a professional society that represents over 42,000 pharmacists who practice in hospitals, health systems, and ambulatory clinics, stated:
“We believe that compounding outsourcers that prepare customized sterile preparations that are not commercially available should be held to the highest standards for quality, including relevant Current Good Manufacturing Practices, and should be required to be registered with and routinely inspected by the FDA. Further, we believe that these entities should not copy commercially available products except in the case of drug shortages or to make a medically necessary variation that meets patient-specific needs. The drug approval process in the United States is the gold standard, and it should be maintained as such.”
Writing to the Senator on August 1, 2013 the American Hospital Association noted:
“The bill allows the compounding of Food and Drug Administration- (FDA) approved, marketed drugs as long as the drug is included on the FDA’s drug shortage list and the compounder “submits notice to the Secretary not later than three calendar days after beginning the compounding of such drug.” This is improved language from the previous draft. It is now clear this is to be a notification and not a request for approval. This instance is one of many examples where we appreciate your taking providers’ concerns into consideration and making changes to improve the bill. The process followed by the Health, Education, Labor and Pensions Committee on this legislation has been transparent, bipartisan and responsive. You and your staff are to be commended, and we are very appreciative.”
The American Association of Colleges of Pharmacy (AACP), a national organization representing pharmacy education in the United States wrote to Congress and the President in November 2012:
“We are a resource for policymakers and stakeholders in identifying a clear delineation between drug manufacturing and traditional pharmacy compounding. We will advocate for state pharmacy boards and FDA to have the resources they need for enforcement, and to ensure an appropriate balanced approach for public safety and continued access to compounded medications.”
The American Pharmacy Association APhA, with more than 62,000 practicing pharmacists, pharmaceutical scientists, student pharmacists, pharmacy technicians as members, distanced itself from the American Society of Health-System Pharmacists, same acronym different organizations, insisting they are in talks with the FDA but have not taken any positions on proposed legislation (S 959). However, in a 2008 policy paper they stated
“APhA opposes compounding when identical medications are commercially and readily available in strength and dosage form to meet patient drug therapy needs.APhA asserts that compounding is subject to regulations and oversight from state boards of pharmacy. APhA urges state boards of pharmacy to identify and take appropriate action against entities who are illegally manufacturing medications under the guise of compounding.”
Opposition to legislation is coming mainly from people who do not want FDA oversight. Arguments being used by those opposed to new legislation include complaints such as, S959 being an Anti life bill, and big pharma and FDA are in a conspiracy, etc.
Some of the detractors are:

The National Community Pharmacists Association representing pharmacist owners, managers, and employees of more than 23,000 independent community pharmacies Opposes Senate Bill 959. but has come out in support of the House Bill, The Compounding Clarity Act, H.R. 3089.

An August 1, 2013 editorial in the Minnesota Star criticized the NCPA
…..Another likely and troubling reason for the delayed action on the Senate bill: Some high-profile pharmacy industry advocates such as the National Community Pharmacists Association are trying to delay or weaken it. Action alert letters sent out recently described an FDA power grab and claimed the agency already has the authority it needs to regulate the industry……"
The PCCA (Professional Compounding Centers of America), has set up a site called Protect My Compounds which states Bill S959 has significant implications for the Autism Spectrum Disorder (ASD) community, hormone replacement therapy (HRT), and pain treatment, like patients with cancer.

The International Academy of Compounding Pharmacists (IACP), representing 3,600 compounding pharmacists is operating a website My Health My Compounds relates scenarios under which legislation becomes objectionable to them:

"….if the medicine you usually take is on back-order or shortage and your pharmacist can compound a supply for you to take until it’s available again, that information has to be sent to the FDA within 3 days of you filling that prescription. Your pharmacist would be REQUIRED to tell the federal government about your medicine. That’s unacceptable and unprecedented.
“The original intent of this legislation was to stop businesses like NECC that sent sterile medications nationwide without specific prescriptions. Out of all the confusing provisions within S. 959, the most disturbing is a complete exemption for hospitals, health-systems, and insurance companies. Those businesses can still produce and distribute sterile drugs across state lines – without patient-specific prescriptions – in any amount they wish to be used in their hospitals, nursing homes, home infusion services, even their own pharmacies.…..rather than treating all pharmacies the same, big businesses like hospitals and insurance companies that own pharmacies don’t have to have the same safeguards in place that other pharmacies will have. No pharmacy and no business should be treated differently when it comes to protecting your safety and well-being.”
The American Association of Physicians and Surgeons, AAPS, a political non medical, and non educational body, has called S 959 “ anti-patient, anti-life impact….. something very harmful to patients and the unborn and that it could shut down nearly all remaining adult stem cell treatments.

The Alliance for Natural Health, ANH, have implied a conspiracy between big pharma companies and the FDA to prevent compounding by pharmacies:

“When the call for federal regulation of compounding arose, pharmaceutical companies formed the so-called Working Group on Pharmaceutical Safety to lobby for the bill. The group is led by Tommy Thompson, the former governor of Wisconsin and former Director of Health and Human Services under George W. Bush, and recently a failed Senate candidate, and Sarah Sellers, a former FDA official who worked on compounding pharmacy policy. The group represents some of the drug companies with vested interests in the compounding bill: the “participants” of the Working Group include TherapeuticsMD (a specialty pharmaceutical company), KV Pharmaceuticals, Auxilium Pharmaceuticals, and Mobius Therapeutics.
Not coincidentally, Thompson is chairman of TherapeuticsMD.And until recently, Sellers worked for Ther-RX, the marketing and distribution arm of KV Pharmaceuticals. You may recall our article on KV’s fight against the compounded version of the successful progesterone-based drug 17P, which is used to prevent premature births; KV was displeased by the FDA’s decision (due to grassroots pressure) to allow compounders to continue making the inexpensive 17P when KV wants to control the market with their high-priced version of the drug, Makena.
In other words, the Working Group on Pharmaceutical Safety and their clients have a direct financial interest in language that would allow the FDA to shut down vital compounded medications and thus a vested interest in passing S.959. Even more concerning is that TherapeuticsMD is in the process of developing a new form of the bioidentical hormones estradiol and progesterone; if these receive FDA approval and S.959 passes, it is very likely that these important hormones will no longer be available except in this new form—of unknown safety—and at what will almost certainly be outrageous prices.”
Most objections to oversight legislation are founded on business interests and made to score political points against any incumbents. The FDA is not an organization run by greedy little people making backroom deals with big money corporations, corrupt politicians focused on bringing sub par medicine to the public. People at the regulatory authority work hard to come up with standards and to enforce them with what ever little power Congress has given them. Without the FDA we would have no food and drug safety and no way of enforcing standards that help and protect lives and advise us of harmful medicines and foods. Without giving more authority and control to the FDA we are bound to have more NECC type lethal compounding disasters.

Perhaps fittingly, reflecting on current state of affairs, Terry J. Allen blogging In These Times says “Congress, in its campaign-dollar-soaked wisdom, has not granted the FDA the power to order recalls of drugs—even those proven dangerous or made in violation of federal laws.”

U.S. Government Accountability Office (U.S. GAO). "U.S. GAO - Drug Compounding: Clear Authority and More Reliable Data Needed to Strengthen FDA Oversight." Accessed September 16, 2013.
The Pew Charitable Trusts. "Testimony of Allan Coukell on Drug Compounding Regulatory Framework." Accessed September 16, 2013.
The Pew Charitable Trusts. "U.S. Illnesses and Deaths Associated With Compounded Medications." Accessed September 16, 2013.
AHA Home Page. Accessed September 16, 2013.
APHA: American Public Health Association. Accessed September 16, 2013.
American Pharmacists Association. "Compounding: The American Public Health Association (APHA) does not speak for APhA." Accessed September 16, 2013.
American Society of Health System Pharmacists. "Compounding." Accessed September 16, 2013.
AACP - Discover, Learn, Care: Improve Health. Accessed September 16, 2013. News, weather, sports from Minneapolis, St. Paul and Minnesota. "Bring drug compounding firms out of the shadows | Star Tribune." Accessed September 16, 2013.
NCPA | National Community Pharmacists Association - The Voice of the Community Pharmacist. "Pharmacists Endorse House Bill to Clarify Compounding Oversight, While Preserving Patient Access to Customized Medications." Accessed September 16, 2013.
Protect My Compounds — Speak Out. Protect Your Right to Personalized Medicine. Accessed September 16, 2013.
Home - My Health, My Compounds. "My Health, My Compounds." Accessed September 16, 2013.
AAPS | Association of American Physicians and Surgeons. "Coalition Letter Against S. 959." Accessed September 16, 2013.
The Alliance for Natural Health USA. "ANH-USA Exclusive: Drug Companies Plan to Use Compounding Bill to Take Away Your Compounded Medications." Accessed September 16, 2013.
In These Times. "Compounders Slip Through Deadly FDA Loophole." Accessed September 16, 2013.
Glyn Lowe Photoworks, Flickr PhotoStream

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