Nearly five years ago, the compounding pharmacy profession was rocked by what would become one of the worst public health tragedies in our nation’s history: 64 deaths and 753 sickened, according to the CDC, from a fungal meningitis outbreak. The outbreak was traced to tainted steroid injections made by the New England Compounding Center (NECC), a compounding pharmacy in Framingham, MA.
The victims included young and old from all walks of life. Those fortunate enough to survive have been forced to endure years of medical treatments, debilitating pain, and an end to their life as they once knew it.
We know now that NECC was acting as a drug manufacturer – producing thousands of doses in a single run – that was disguised as a compounding pharmacy to evade the more rigorous oversight that drug makers receive.
What began after the outbreak and continues today is a much more stringent, regulated environment for compounding pharmacies. It has also created a quandary for community pharmacies that historically have done very small amounts of nonsterile compounding in order to serve their patients who might need a compounded medication. They must decide whether they are “all in” for compounding or whether they will exclude it from their practice.
One positive outcome from NECC is that the nation now has a much more consistent approach toward regulating and overseeing compounding pharmacies. The FDA’s authority to inspect and regulate those pharmacies prior to NECC, had been tested in—and limited by—the courts. The FDA lacked the clear authority to take action.
This changed for the better beginning with the Drug Quality and Security Act (DQSA), passed by Congress in 2013. Large-scale compounders—those producing doses in bulk and shipping across state lines without patient-specific prescriptions—began to register as outsourcing facilities with the FDA and became subject to FDA oversight and inspection. They now must comply with Current Good Manufacturing Practices or risk government action. As of today, more than 60 outsourcing facilities have registered with the FDA.
The DQSA enabled compounding pharmacies that did not wish to register and wanted instead to produce patient-specific medication (preparing and dispensing a medication based on a physician’s prescription) to continue to do so, subject to the oversight and regulation of their state board of pharmacy.
Most states updated and strengthened their regulations. U.S. Pharmacopeia Chapters <795> and <797> had always been the practice standards for nonsterile and sterile compounding, but until the NECC case, many states had not formally incorporated them into regulations.
Fast-forward to 2017, and the environment is vastly different. States now employ inspectors with significantly enhanced experience in compounding pharmacy practice.
In Massachusetts, home of NECC, there were 25 sterile community-based compounding pharmacies operating in 2012. Today, two high-risk sterile compounding pharmacies remain.
There is no such thing as “good enough.” There is no going halfway.
Pharmacists have a responsibility to best serve their patients, and that means putting patients first by ensuring their access to high-quality medications that can treat illness and improve quality of life.
Over the past five years, compounding pharmacy in all of its forms has progressed several generations. We have struggled through adversity to get to a better place. As a profession, we can be proud of how we meet our patients’ needs.
The International Academy of Compounding Pharmacists (IACP)’s President Baylor Rice, RPh, FIACP, explains to Drug Topics that compounding pharmacists could help in the current sodium bicarbonate shortage if they were allowed to provide office-use compounding.
Click here to read Drug Topics’ “Could Compounding Pharmacists Solve the Sodium Bicarbonate Shortage?”
“Patient harm, as a result from limited-to-no-access of a drug shortage product, can be remedied if FDA understands that access to compounded preparations goes much farther than the brick and mortar of a pharmacy,” said Rice. “Prescribers, nurses, and other health-care entities require that compounded preparations need to be available for immediate-use in emergency situations. The only way to meet this requirement is for the practitioner to house a small supply of the product in the practitioner’s office.”
Published in today’s (May 24, 2017) Inside Health Policy: “As FDA Ignores Pressure from Appropriators on DQSA, Lawmakers Push FDA to Withdraw Guidance on Compounding, Issue Rule Allowing Practice.”
Congressman Buddy Carter and the International Academy of Compounding Pharmacists (IACP) are both quoted in this piece, questioning why the Food & Drug Administration (FDA) continues to ignore the Drug Quality & Security Act’s (DQSA) Congressional intent on office-use compounding.
From the article – “Reps. Buddy Carter (R-GA) and Chris Stewart (R-UT) and 63 other lawmakers argued in a bipartisan letter to FDA Commissioner Scott Gottlieb Tuesday (May 23) that FDA’s compounding policy goes against congressional intent. At issue is a final guidance released in December, “Prescription Requirement under 503A of the Food, Drug and Cosmetic Act,” that requires that compounders only compound a drug for an individual patient with a prescription, or when a history of prescriptions and an established relationship allows a pharmacist to anticipate receiving a prescription.”
Click here to read the entire article.
In a considerable win for patients who need compounded medications, the International Academy of Compounding Pharmacists (IACP), working with the DQSA Coalition, is very pleased to announce that the President has signed the Congressional Omnibus bill into law, H.R. 244, which provides funding through September 30, 2017, and includes language that addresses the Memorandum of Understanding, office-use, and pharmacy inspections.
Champions in Congress have acted to preserve access to patients that turn to compounding for lifesaving medications. This bipartisan legislation includes critical language which clarifies congressional intent on several compounding regulations implementing the Drug Quality and Security Act (DQSA) of 2013. The regulations addressed are among those on which Congress had asked FDA for additional clarity and expressed strong concern that FDA implementation actions were drastically decreasing patient access to vital compounded medications.
The language calls on FDA to do the following:
- Draft a new memorandum of understanding that does not include “dispensing” within the MOU. Congress expressed concern that the FDA draft MOU includes both “dispensing” and “distribution” of compounded medications. Congress made clear in the language that FDA does not possess this authority and specifically stated, “Congress only allowed the FDA to regulate distribution” under the MOU and “Congress did not intend to include dispensing of compounded drugs over state lines within the scope of the MOU.”
- Release new guidance to allow 503A pharmacists to compound for “office-use” for prescribers, hospitals and other health systems. Congress expressed concern that patient access is decreasing to compounded medications, due to FDA’s implementation actions of prohibiting all office-use compounding even where “this practice is authorized in the vast majority of states and was intended to be allowable under DQSA.”
- Cease inspecting state-licensed 503A pharmacies under current Good Manufacturing Practices (cGMPs). Congress instructed FDA to inspect 503A pharmacies under USP standards or other applicably pharmacy inspection standards adopted by state law or regulation. Congress also stated that it “reminds the FDA that compounding pharmacies are not drug manufacturers, but rather, are state licensed and regulated health care providers that are inspected by state boards of pharmacy pursuant to state laws and regulations.” Congress further stated, “compounding pharmacies are more appropriately inspected using USP standards or other pharmacy inspection standards adopted by state law or regulation in the state in which a pharmacy is licensed.”
IACP would like to express our gratitude to the Representatives and Senators who worked tirelessly to preserve patient access to vital compounded medications, which can mean the different between life and death for the patients that depend upon these compounded medications.
IACP’s Executive Vice President John Voliva, RPh, is extensively quoted in a Drug Topics article this week, NECC and the Future of Compounding Pharmacy.
“The FDA and Massachusetts Board of Pharmacy, according to Voliva and many other members of the media, “had clear authority to investigate and take action that would have stopped the operations at New England Compounding Center, and both had been informed of problems there. Neither did.”
“The NECC tragedy provided more evidence that an increase in the communication and coordination between the FDA and the State Boards of Pharmacy was vital,” said Voliva.
Read the entire article and more of Voliva’s comments here.
IACP‘s Executive Vice President John Voliva, RPh, discusses the importance of office-use compounding for patients in an interview this week with D.C.-based publication, Inside Health Policy.
John Voliva, executive vice president of the International Academy of Compounding Pharmacists, says the final guidance, “Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act,” put limits on office-use compounding that go against congressional intent and should be rescinded.
“We’re asking for FDA to rescind it. It would be administrative from that standpoint, and then issue a proposed rule through the [Administrative Procedure Act] so we have notice and comment from the stakeholders on the public docket,” Voliva said to Inside Health Policy.
Read the entire article here.
Take a few minutes to read this Investor’s Business Daily Commentary: A Sick Calculation About Prescription Drugs http://bit.ly/2gfvdvJ
International Academy of Compounding Pharmacists (IACP) Opinion: As America’s Pharmacy Benefit Management (PBM) industry consolidates, size and scale was supposed to reduce costs to patients, taxpayers and employers. Now, with just three PBMs dominating more than 70% of all prescription reimbursement, the promised benefits are increasingly suspect. Instead, near monopoly control of the landscape and a truly opaque business model has reaped PBM’s record profits. Meanwhile, pharmacies, prescribers, employers and patients are beleaguered a myriad of ways due to unchecked PBM actions.
The IACP Reimbursement & Insurance Committee is monitoring the activities of PBMs and working with industry partners to shine light on PBM activities. Gradually, eyes are opening in Washington D.C., and at America’s employers. If you have a story or experience of PBM abuses, contact us at email@example.com.
By John E. Voliva, RPh, IACP Executive Vice President
Last week, IACP sent out a member alert about the FDA’s notice of final rulemaking for the “list of drug products that may not be compounded under certain sections of the Food, Drug, and Cosmetic Act (FD&C Act).” This list has been commonly referred to in the pharmacy industry as the “negative list” or the “do not compound list”. Since we sent the member alert, we have received many questions about what the list means, why domperidone does not appear on the list (and if it is now allowed for compounding) and what the FDA’s next steps are for this list. This series of articles will serve as a reference point for all of the “lists” FDA has been charged with creating via the Federal law (specifically, Section 503A of the Food, Drug & Cosmetic Act) to provide clarification to the FDA’s actions and regulation on these “lists”.
First things first – why do the lists need to be created?
Section 503A directly charges the FDA to create three lists & the “positive list”, the “negative list” & the “demonstrably difficult list”. Because these lists are directly laid out in the law and the FDA is given the power of passing regulations on these lists, we now have this notice of final rulemaking for the “negative list” published in early October 2016.
Additionally, with these “lists”, the FDA must consult the Pharmacy Compounding Advisory Committee (PCAC) regarding additions or deletions from any of these lists, “unless the Secretary determines that the issuance of such regulations before consultation is necessary to protect the public health.” FDA has published that they believe passing regulations regarding the lists before consulting the PCAC will “rarely be necessary.”
Therefore, this recent action by the FDA regarding the “negative list” is not only required by Federal law, but FDA must follow certain steps to publish or change any of these lists.
The “negative list” – what does it mean?
It’s always good to look at the actual law as a starting point to fully understand what is going on when an agency passes regulations. For the “negative list”, Section 503A states (emphasis added):
“(1) Licensed pharmacist and licensed physician. A drug product may be compounded under subsection (a) if the licensed pharmacist or licensed physician –
… (C) does not compound a drug product that appears on a list published by the Secretary in the Federal Register of drug products that have been withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective;”
This paragraph is what the industry terms as the “negative list” (it’s just easier to call it that than the “list of drug products that have been withdrawn or removed from the market because such drug products… have been found to be unsafe or not effective).”
It’s important to pay attention to the emphasized text above because it gives us clear direction on how the FDA puts this list together. To appear on the list, the drug must have been available on the market, meaning, at some point in the drug’s history, it was FDA approved. This is key to the reason why drugs like domperidone are NOT on this list – the drugs have never been FDA approved. Does this mean pharmacies can now start freely compounding domperidone? Unfortunately, no, and we will explain this issue in a bit because this particular drug is covered by the “positive” list.
So, the “negative” list deals with drugs which were FDA-approved and on the market at some point in time but had been removed from the market because of safety or efficacy. The vast majority, if not all, of the list are drugs that have been removed from the market because of safety issues. Examples include cisapride, diethylstilbesterol (DES), phenformin, phenylpropanolamine (PPA), terfenidine, and chorionic gonadotropin (NOTE: PPA is not on the current list, but it will appear on the list on November 7, 2016). It is important to point out two important facts about this list:
– The “negative” list ONLY applies to compounding drugs for human use. Thus, compounding items like cisapride, DES and PPA can still be compounded for veterinary patients.
– Many items on the list have additional limitations. For example,
o Diethylstilbestrol: All oral and parenteral drug products containing 25 milligrams or more of diethylstilbestrol per unit dose.
o Gonadotropin, chorionic: All drug products containing chorionic gonadotropins of animal origin.
o Nitrofurazone: All drug products containing nitrofurazone (except topical drug products formulated for dermatologic application).
This is not an entire list of these special exceptions and pharmacists should frequently check and download the list for reference (note: this list will be updated with the new list on or around November 7, 2016). From the examples provided, a pharmacy can compound DES for human use as long as the unit dose does not exceed 25 mg. We receive a lot of questions about hCG, but the important distinction for this example is that in only applies to hCG of animal original – human recombinant hCG is still OK to compound. And, nitrofuazone is allowed for topical use. There are many other examples of these exceptions throughout the list.
OK – so that is the “negative” list, what about the “positive” list?
So, this list is a bit more complicated than the negative list, believe it or not. Let’s start with what Section 503A says about this list:
“A) compounds the drug product using bulk drug substances, as defined in regulations of the Secretary published at section 207.3(a)(4) of title 21 of the Code of Federal Regulations –
(III) if such a monograph does not exist and the drug substance is not a component of a drug approved by the Secretary, that appear on a list developed by the Secretary through regulations issued by the Secretary under subsection (d)”
Don’t worry about subsection d – this explains the fact that the FDA can put together these lists and must consult the PCAC.
To rewind a bit, Section 503A requires compounders to use bulk drug substances that comply with one of three “buckets” – the bulk drug substance must have a USP or NF monograph OR appear in an FDA approved drug OR appear on the “positive” list. The reason the industry calls this the “positive” list is because items appearing on the list would be allowed to be compounded with, the opposite of what appears on the “negative” list.
It’s important to note now that the FDA calls this list something different than the industry – the “bulks list”. Positive list or bulks list, we are talking about the same thing. FDA has approached the creation of this list by requesting for nominations of bulk drug substances from compounding stakeholders – the general public, pharmacies and healthcare associations. After a couple rounds of nominations, FDA has put together a master list of nominations, which can be found here. The agency has split this bulks list into three categories:
– Category 1 – Bulk Drug Substances Under Evaluation
– Category 2 – Bulk Drug Substances that Raise Significant Safety Risks
– Category 3 – Bulk Drug Substances Nominated Without Adequate Support
Category 1 represents the substances FDA is presenting to the PCAC for their consideration to either add or not add to the “positive” list. To date, the PCAC have considered over 30 different bulk drug substance for inclusion or exclusion from the positive list. We are working to put together a full chart of substances which have already been considered (and the PCAC voting results) along with other items which will be considered in future meetings.
It is important to know that the PCAC recommendation is not binding. The FDA will seriously take the Committee’s vote under consideration, but until final rulemaking is complete (much like what we recently have seen with the “negative” list), the final determination on these substances is still in a state of flux. Also, FDA has announced they will not take enforcement action on any substances appearing in Category 1 until final rulemaking is complete. Therefore, at this point, even if the Committee has voted to not add an item to the positive list, it can still be compounded until rulemaking is complete.
Items which appear in Category 2 should not be compounded and FDA will take enforcement action if a pharmacy is compounding with one of these three substances: domperidone, germanium sesquioxide and quinacrine for intrauterine use. If a pharmacy is found compounding one of these three drugs for a human patient, the FDA will issue the pharmacy a warning letter.
Category 3 is a list of items which the FDA has determined to not have enough supporting information to warrant their presentation to the PCAC. At this time, IACP is working to provide information to “clean up” this list – to remove items which clearly are not bulk drug substances and would never be used in that manner. FDA has announced they would not provide enforcement discretion for these items, however, to date, we have not seen any enforcement actions be taken in regards to these items.
With all of this, we come to a bit of quandary, especially in regards to Category 2. While these items are not on the “negative” list, the FDA still feels these items should not be compounded because of safety risks. Why, then, do these three drugs not appear on the negative list? The answer is pretty simple: they were never FDA approved and never appeared on the market as such. Remember, the “negative” list are items which have been withdrawn from the market for safety or efficacy reason. For them to be removed from the market, they must have first appeared on the market. Thus, the items in Category 2 will most likely never appear on the “negative” list, however, they still should not be compounded or the pharmacy runs the risk of enforcement actions by the FDA.
Great – so we have covered “negative” & “positive” lists – what’s this about demonstrably difficult?
Once again, Section 503A provide for the FDA to put together a list of categories of drugs they feel are too difficult for compounders to make. From the law:
“(3) Drug product.–A drug product may be compounded under subsection (a) only if–
(A) such drug product is not a drug product identified by the Secretary by regulation as a drug product that presents demonstrable difficulties for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product;”
Thus, again, the FDA will put together a list, via consultation with the PCAC and via final rulemaking, a list of drug products (or categories) which compounders should not try to make. So far, the PCAC has considered to categories of drugs to add to this list: Metered Dose Inhalers and Dry Powders for Inhalation. Both categories of drugs were voted to be placed on the list. Additionally, the Committee will consider transdermal delivery systems (TDS) at the November 2016 meeting – but don’t worry – the types of transdermal drugs which will be considered are those which utilize reservoir or matrix type delivery systems. They are NOT considering transdermals which are liquids or semisolids, like gels, creams, lotions, foams, ointments or sprays. IACP fully expects the committee to recommend to add TDS to the list of demonstrably difficult drugs.
Please continue to watch for further communications from IACP regarding these “lists” and the actions of the PCAC as we continue to monitor FDA’s enforcement of Section 503A.
IACP has submitted comments to the Food & Drug Administration (FDA) regarding the Draft Guidance:Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act
“IACP understands and supports the need to protect public health. However, when providing guidance, it is essential that FDA adheres to the plain language of statutes and Congressional intent to preserve patient and prescriber access to vital compounded medications. Providing clear direction as to the FDA’s thoughts regarding this important subject help not only guide Agency investigators during inspections but gives additional insight to the pharmacy industry as a whole on what the FDA expects from this practice of pharmacy.
IACP is concerned with several main points of the proposed guidance, which we outline below, and we look forward to starting a dialog with the Agency on proposed solutions to the issues raised by our Academy.”
Please click here to view IACP’s entire comments to FDA.
Email firstname.lastname@example.org with any questions.
International Academy of Compounding Pharmacists
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IACP has submitted comments to FDA regarding the Draft Guidance for Industry: Insanitary Conditions at Compounding Facilities.
“IACP understands and supports the need to protect public health. However, when providing guidance, it is essential that FDA adheres to the plain language of statutes and Congressional intent that preserve patient and prescriber access to vital compounded medications. Ensuring compounded medications are not prepared under insanitary conditions should be of the upmost importance, however, Guidance to the matter for state licensed pharmacies should ensure that proper adherence to State law and USP General Chapters <795> and <797> are not superseded.
The current draft guidance fails to follow Congressional intent, current State laws or regulations and USP General Chapters <795> and <797> as it pertains to pharmaceutical compounding. It also appears to attempt to exert current Good Manufacturing Practices (cGMP) on pharmacies which are clearly exempt from these requirements via Section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act).
IACP is concerned, both from the language contained in this guidance and from the agency’s recent announcement on inspections, effective August 1, 2016, that the FDA will attempt to use findings regarding insanitary conditions as a mechanism to find a pharmacy not compliance with Section 503A and hold the pharmacy as an unregistered Outsourcing Facility or Manufacturer.”