Federal Regulation of Medication Dispensing PDF

Federal Regulation of Medication: Dispensing This lecture logically follows the previous lecture in that you will see an expanded discussion of some of the topics. This slide depicts some of the actual language from the Durham Humphrey Amendment that illustrates and underscores how two classes of...

Federal Regulation of Medication: Dispensing This lecture logically follows the previous lecture in that you will see an expanded discussion of some of the topics. This slide depicts some of the actual language from the Durham Humphrey Amendment that illustrates and underscores how two classes of drugs were created, namely prescription and nonprescription. It starts out with: A drug intended for use by man (A) because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner….or (B) is limited by an earlier approved application (i.e., NDA) to use under the professional supervision of a practitioner…shall be dispensed only upon a written prescription…oral prescription, or refill… I didn’t include all the language there from the text but as I mentioned earlier, they were two of the other provisions from the Durham Humphrey Amendment that allowed a physician to phone in an oral prescription or to include refills either with the phone-in prescription or on the written prescription itself. Just to add some historical context to the Durham Humphrey Amendment. Prior to its enactment, it was generally the manufacturer that decided the prescription or over the counter status of a drug, and if the FDA didn’t like the choice, then they would sue them and challenge it. That was up until the enactment of this Amendment, when it became clear that any drug that required medical supervision required a prescription. In addition, when the FDA wanted to change the status of a previously designated over the counter drug to prescription status, a court decision held that the FDA had to prove two things: 1. That the pharmacologic and toxic effect are such that unless taken pursuant to physician’s directions, it might ham the patient, and 2. That the patient will suffer harm if he/she relies on a drug that can’t cure the condition and, accordingly, postpones their visit to the doctor Along with the passage of the Durham Humphrey Amendment, there were also some general labeling requirements that were associated with that as well.  The label cannot be false or misleading  It must not be an imitation drug  It can’t be sold under the name of another drug. For example, you can’t label something Lasix and then dispense the generic Furosemide.  The packaging and labeling must conform to official compendial standards. For example, under packaging standards, some packages are required to be packed in tight light resistant containers.  Or if it’s a drug that’s liable to deterioration, it must be packaged and labeled appropriately. Sometimes a drug is required to be labeled “keep away from moisture” because it’s subject to deterioration.   Finally, it must be packaged in conformance with the Poison Prevention Packaging Act. Some products are required to be packed in child resistant containers while others are not. The requirements under Durham Humphrey for the actual prescription label are actually a little surprising. All that Durham Humphrey required was:  the name and address of the dispenser  the serial number and date of initial prescription or its filling  the name of the prescriber  the name of the patient, if stated  and directions for use and cautionary statements Interestingly enough that the name of the drug is not even required. However, we will see that most states, Pennsylvania included, the labeling requirements are much more stringent. Pennsylvania requires on the prescription label:  the name, address, telephone number and DEA number of the pharmacy  the name of the patient  the full directions for use  the name of the prescriber  the serial number of the prescription and the date that it was originally filled In addition, the prescription label is required to include:  the trade or brand name of the drug  the strength  the dosage form and  the quantity dispensed and  and if it’s a generic, the manufacturer’s name needs to be included, or at a minimum, a suitable abbreviation of the manufacturer’s name. Finally, controlled substance prescription labels always need to contain the statement: “Caution: Federal law prohibits the transfer of this drug to any person other than the patient for whom it was prescribed.” Now shifting gears and talking about beyond-use dates, the USP does have guidelines. Keep in mind that these are guidelines--they are not actual law that you must follow but they are general guidelines. Let’s take a look at the beyond use guidelines for a typical prescription vial. The USP suggests a beyond-use date that’s not later than the expiration date on the manufacturer’s container or one year from the date that the drug is dispensed, whichever is earlier. Interestingly, the USP guidelines are not entirely adopted in Pennsylvania. Pennsylvania does not require an automatic expiration date, and the pharmacist only needs to add language such as ‘do not use after’ when the manufacturer expiration date is less than one year from the date of dispensing. This slide illustrates the actual language in the Pennsylvania Code from Title 28, Chapter 25.94. Expiration date of drug.  Drugs, which at the time of their dispensing, have full potency for less than one year, as determined by the expiration date placed on the original label by the manufacturer, may only be dispensed by a practitioner with a label that indicates said expiration date. The label should include the statement: “Do not use after (manufacturer’s expiration date)” or some type of similar wording. The beyond use dating guidelines by the USP get a little bit more complicated when we talk about unit-dose containers, which states that the beyond-use date for the unit dose container is the earlier of one year from the date of repackaging or the expiration date on the bulk container unless stability data or the manufacturer’s labeling indicates otherwise. However, this is premised on a mean temperature of 25 degrees Celsius, and the material used to be something other than PVC. That makes it a little bit difficult because many of the unit dose containers being used are often in fact PVC containers. It also gets even more complicated when we look at the FDA’s view on beyond use dating. The FDA originally issued a policy guide that reflects the USP guidelines, but it was never finalized. However, since the FDA never finalized the policy guide, the default rule now is the FDA’s previous rule, which stated that the beyond use date was not to exceed 6 months, and that the beyond use date was also not to exceed 25% of the remaining time between the date of repackaging and the expiration date on the unopened original manufacturer’s container. So if you are repackaging into a unit dose container from a manufacturer’s container that expires in one year, then the beyond use date on the unit dose container would be 3 months from the date of repackaging (i.e., 25% of the time remaining from repackaging and the manufacturer’s expiration date). Now let’s discuss the switching of a product from prescription to over-the-counter status. You can think of probably a lot of examples of drugs that were previously prescription and then became OTC, such as anti-ulcer medications and antihistamines. etc. But typically, how does that usually happen? The most common is for the manufacturer to request the FDA to make that status change through a supplemental application to the original NDA. If the FDA does grant approval for a supplemental application, and thereby allow a manufacturer to distribute a drug over the counter as opposed to prescription, that effectively grants over the counter marketing exclusivity to a manufacturer compared to a similar manufacturer, which might be marketing an identical prescription product. If that other manufacturer hadn’t also submitted and received approval for a supplemental NDA, their product would require a prescription. So, you can have situations, where you have two essentially identical products, where one will be prescription and the other will be considered over the counter. And from a dispensing perspective, you have to keep that in mind and not dispense a prescription product over the counter simply because another manufacturer’s identical product is over the counter. The second way a product can go from prescription to otc status is for the manufacturer to simply ask or petition the FDA to make it happen, instead of going through the supplemental NDA process. Or similarly, the FDA on its own, can add a monograph or amend an existing monograph. We should talk for a minute about prescription refill authorization. It’s extremely important for pharmacists to realize the difference between delegation of prescriptive authority and transmitting refill authorizations to the pharmacist. Physicians cannot delegate their prescriptive authority. A doctor can’t leave an office and leave a nurse or secretary in charge and say, for example, “you know our regular customers, so if somebody calls in for a refill, use your judgement and if you feel comfortable, grant them a refill”. That is not legal. Physicians can’t do that. However, agents can freely transmit any refill authorization to the pharmacist meaning a nurse or secretary can call from the doctor’s office and say, this is nurse so and so, doctor wants Mrs. Jones to have 3 refills on whatever drug is at issue. That’s perfectly permissible. Where it becomes a quandary for the pharmacists though, is when someone walks into the pharmacy, they are out of refills and the pharmacists calls the doctor’s office and the nurse picks up and the pharmacists asks, Mrs. Jones is here. She’s out of refills. And the nurse immediately says, ok, give her 3 more refills. So that’s an awkward situation for the pharmacist because you have to ascertain--did the person, before they came into the pharmacy, call the doctor’s office and say to expect a call from the pharmacy, or is the nurse just improperly on her own or in cahoots with the doctor having delegated prescriptive authority, which of course, is not legal or proper. Now we are going to shift gears and talk about specific prescriptive authority. Each jurisdiction will have different prescriptive authorities for different mid-level practitioners, as I believe I mentioned before. The next set of slides will be dealing with prescriptive authority as it exists in the state of Pennsylvania. You need to remember that it is the individual state that grants the authority to prescribe. It is not done on a federal level but rather on an individual state level. Make sure you also remember that a midlevel practitioner does not have unilateral prescriptive authority, and you need to know the scope of prescriptive authority of each respective midlevel practitioner such as a physician’s assistant or nurse practitioner. This slide illustrates the prescribers that are authorized to prescribe in Pennsylvania. And at the top of the slide, there are no surprises. MD, dentists, veterinarian, Doctors of Osteopathy, etc. And then at the bottom, you will see the mid-level practitioners that are authorized to prescribe in Pennsylvania, including the most recent authorization being granted to a certified nurse midwife. Then there’s the optometrist, the physician assistant and the certified registered nurse practitioner. We spoke on the previous slide about scope of authority. On an exam question or in real life, hopefully you’d be able to pick up rather readily that if you get a prescription from a podiatrist and the podiatrist is writing for acne for someone, a prescription for acne, then you should realize quite easily that that would be outside their scope of practice. Where it gets a little hairier is with situations where you have, for example, a psychiatrist or an ophthalmologist. Keep in mind that those individuals were physicians before they advanced to the specialty level. So, in theory they should be able to prescribe what a medical doctor would normally prescribe in the course of their daily practice without raising any concerns. You could also have a situation where you have a dentist writing for Tylenol with Codeine. Then you say to yourself, well, that seems pretty reasonable. Dentists have patients with pain all the time. But in the course of dispensing the prescription to the individual, in your patient counseling, you realize that the dentist had written the prescription to treat tennis elbow or something else that the dentist was just doing the person a favor by writing a prescription. Clearly that would be outside the scope of practice of the dentist and you shouldn’t dispense that medication. The proper course of action would be that once you realized what was happening to take the prescription back at the point of dispensing and just say you weren’t allowed to dispense it. Hopefully on any scope of practice exam question you get from me or on the MPJE, hopefully they won’t be that complicated. Hopefully you get a question like a podiatrist writing for acne or something. But always be on the alert whether it’s just for the exam or in real life you will realize in some situations, certain health care professionals will really try to push the envelope. And as a pharmacist, you have a duty to dispense legitimate prescriptions. So, just a word to the wise and something to keep an eye out for. CRNP’s or certified registered nurse practitioners have what’s known as a negative formulary, meaning that there’s a group of drugs from which they cannot prescribe, meaning, gold compounds, heavy metal antagonists, radioactive agents or oxytocics. Otherwise, and I don’t have them listed here, they can generally prescribe from all the other normal medical classes of drugs that are normally prescribed by, let’s say, a physician. But the easier way to look at CRNP’s, at least in my opinion, is to take a look at the negative formulary and make sure that you never dispense anything that was written by a CRNP from any of these categories. And for any mid-level practitioner, I think it’s very important that you should understand and know the prescriptive rights that they have related to controlled substances. CRNP’s, for example, can prescribe Schedule II substances for up to 30 days and Schedule III through V for up to 90 days. And inevitably these types of issues will come up in day to day practice and you really need to know the days’ supplies that a mid-level practitioner can prescribe. You should also be familiar with the requirements for the actual prescription blank from a mid- level practitioner. For a CRNP, the certification number is required as well as their printed name and signature. The DEA would be required if the CRNP was writing a controlled substance prescription. Interestingly enough, the collaborating physicians name is not required on a prescription blank for a CRNP. For physician assistants, what they can and can’t prescribe is dependent upon the written agreement that they have with the supervising physician. There used to be a negative formulary very similar to the one we saw with the CRNP’s but that was abandoned due to the development of so many levels of physician assistant specialization that it didn’t make sense to have a negative formulary when, in fact, some of those drugs on that negative formulary would be arguably prescribed by a PA depending on the type of practice that they were associated with. For the prescription blank requirements of a physician assistant, we see a familiar pattern. The license number is required, along with the printed name and signature of the PA as well as the designation PA-C, meaning certified physician assistant. The DEA number would be required if the PA is prescribing controlled substances. The prescription blank does have to include the supervising physicians printed name, but it does not have to have the signature of the supervising physician. As it relates to a PA’s controlled substance prescriptive authority, it does have a few nuances. As an overview, remember that any drugs that the PA can prescribe, including controlled substances, are governed by the agreement that they have with the supervising physician. If permitted to prescribe schedule II substances, the PA can write for an initial 72 hours supply, or alternatively a 30 days’ supply if it’s for ongoing therapy. The PA has to include on the prescription blank the actual words ‘initial’ or ‘ongoing’ therapy accordingly. In the case of a situation where the required wording is not included, it’s incumbent upon you, as a dispensing pharmacist, to call and make sure whether it is for initial or ongoing therapy. You can put the required language on the prescription yourself, as long as you notate that you phoned the PA and received a clarification from the PA, as long as you are satisfied that the prescription was written appropriately, and the failure to include the required language was simply an oversight. Finally, PA’s can prescribe schedule III through V for up to a 30-day supply and authorize up to 5 refills within a 6-month period. For optometrists prescribing, it’s very important for the pharmacist to know when in fact an optometrist can prescribe--either at a therapeutic level for the garden variety of products that are typically used in optometry practice--or where an optometrist is further certified in prescribing drugs that are used in the treatment of glaucoma--or if in fact they’re not certified to prescribe at all. And the real clue is always in the license. If an optometrist has an initial therapeutic certification, you will see a ‘T’ in the license. If they are glaucoma certified, that means that they previously been therapeutically certified and then obtained advanced training to be able to prescribe drugs in the treatment of glaucoma, and if you see an ‘L’ in the license, you shouldn’t be seeing it at all. You should never see a prescription from an optometrist that has an ‘L’ in the license because they are not allowed to prescribe. This slide is included solely to provide a list of typical drugs that a therapeutically certified optometrist would normally prescribe. There are no real surprises here. Anesthetics, steroids, and these are all topical, mind you, ocular lubricants, ophthalmic dyes and stains, hyperosmotic agents, autonomic agents, NSAIDS, antivirals, analgesics, antihistamines and mast cell stabilizers. There are also a handful of oral medications that an optometrist can also prescribe, including prednisone and methylprednisolone, antibacterial agents, antivirals and analgesics, including some controlled substances. This slide illustrates some other general rules that apply to optometrists who are prescribing. Any treatment of patients can’t continue beyond a 6-week period unless there is a documented consult with a licensed physician. We did go over the drugs that an optometrist could prescribe but just so there’s no confusion, a therapeutically certified optometrist cannot prescribe parenterals, beta blockers, drugs for systemic conditions, and drugs for glaucoma. This slide lists the drugs that a glaucoma certified optometrist can prescribe. As I mentioned, glaucoma certified optometrists have previously received their therapeutic certification and then gone on to advanced training, a result of which they are able to additionally prescribe the classes of drugs that you see listed there that can be used in glaucoma—beta blockers; cholinergic receptor agonists; adrenergic receptor agonists; topical carbonic anhydrase inhibitors and prostaglandin analogs. As it relates to controlled substances, optometrists are not allowed to prescribe most schedule II substances. They can prescribe hydrocodone in combination with acetaminophen or ibuprofen. They are limited to prescribing a 72-hour supply of these hydrocodone combination products. They are also permitted to prescribe certain Schedule III through IV analgesics. Of course, they must have a therapeutic license and a DEA license as well. For a complete listing of the drugs that an optometrist in Pennsylvania can prescribe, please consult the optometrist formulary available on the website listed on this slide. Now just a few things to note about the Certified nurse midwife prescriptive authority. They are the most recent addition to the mid-level practitioners in Pennsylvania that have been allowed to prescribe and what they can prescribe is largely based on the collaborative agreement with the physician. Also, they can only prescribe psychotropic drugs after consultation with the physician. Their prescription blank requires their phone number, but otherwise the requirements are similar to the CRNP, including that the physicians name is not required. And you might begin to wonder why is the physician’s name not required for either the certified nurse midwife or the CRNP? Actually, it really comes down to more of a housekeeping issue. In certain instances, whether it’s the CRNP or certified nurse midwife, they sometimes service a lot of physicians and it just becomes unwieldly to have to list all of the physicians or the particular one that they are writing for and they just figure the benefit risk is not worth it to have to mandate that as a requirement. As it relates to controlled substances a certified nurse midwife can prescribe CII through CV controlled substances. The CII prescribing is limited to 72 hours and the CIII-CV is limited to 30 days. Interestingly, controlled substances can only be prescribed to treat acute pain. So, for example, if you were presented with a prescription from a certified nurse midwife for Xanax, you can then answer the question yourself and say, wait a second, this isn’t being used to treat acute pain and you would be well within your rights to refuse to fill it. So be aware of situations like that and this interesting wrinkle as it relates to the controlled substances prescribing for a certified nurse midwife. This next slide deals with levonorgestrel emergency contraception, namely Plan B and its generic counterparts such as Next Choice One Dose, My Way, Take Action, etc. The sale of Plan B has a very long and convoluted history in terms of the age requirements and the procedural court history. In 2009 the required age to purchase the Plan B over the counter was reduced from 18 to 17. In 2013, the manufacturer of Plan B One Step obtained from the FDA the exclusive rights to sell Plan B One-Step in the over the counter aisle, meaning not behind the pharmacy counter, with no age requirement. Shortly thereafter, the generic one tablet equivalents to Plan B One- Step were also available in the over the counter aisle, however with the labeling stating that these products were for individuals 17 years of age and older. Beginning in 2014, the FDA eased up on the age restriction for the generic one tablet versions, meaning that currently, Plan B One Step and its generic equivalents are available in the regular store aisle of the pharmacy without any age restrictions. This next slide discusses when patient package inserts are required. And if you’ll notice the list is rather small. It’s only for oral and injectable contraceptives, estrogen-containing drugs like Premarin and diethylstilbestrol and finally for intrauterine contraceptive devices. Now that’s not to say that the FDA only wants patients to be informed on these few select drugs but rather there’s been a shift in the policy at the FDA to shift from patient package inserts to medication guides, which we will discuss in a minute. But before we leave the topic of patient package inserts, what are the rules for pharmacists in dispensing a package insert along with the product? Well, the traditional rule in retail pharmacy is that you would have to include the patient package insert with each dose of the product. But what do you do if you are in a hospital situation? Hospitals and other institutions can certainly provide a package insert to the inpatient every time they get the dose but you can see how impractical that might be. So they developed a rule whereby the institution or hospital can provide the insert prior to the administration of the first dose and then once every 30 days thereafter, which certainly seems a more practical application. As I mentioned, the patient package inserts have been abandoned in favor of medication guides. The list keeps growing and growing for those products which a medication guide is required. And rather than list slide after slide of those drugs requiring a medication guide, perhaps the best way to familiarize yourself with that would be to go to www.fda.gov and then simply list under the search function, medication guides. You’ll see the list of over 300 products that are included. How does the FDA determine when a medication guide is required? They use three simple rules. They require a medication guide when issuing a medication guide would prevent serious adverse effects or where the risk information included in the medication guide could affect someone’s decision to use or continue to use the product. There might be a sufficient number of dangers included in the medication guide, for example, someone might just say, gee that’s too dangerous, I’m not even going to take it. And then thirdly, they would use or require a medication guide when patient adherence to direction is critical to the value of taking the product. And of course, the manufacturer, when issuing a medication guide, needs to obtain approval for the language in the guide from the FDA and certainly the pharmacy is under an obligation to dispense the medication guide each time the product is dispensed. Our discussion now shifts to approved drugs being used for unlabeled indications. And why does this occur in the first place? You would think that the manufacturer would, when submitting to the FDA originally, include the approved indications or the indications they would like the drug to be used for in the original NDA application. Well, a couple factors get in the way here. First of all, the drug approval process lags way behind the discovery of new uses for drugs. New uses are being discovered all the time for drugs that are on the market and the FDA approval process for those new indications is years behind typically. Also, sometimes manufacturers, realize that the approval process is faster if they include fewer indications on their original NDA application. They are thinking that down the road, that they can add supplemental NDA’s for submission to the FDA for any added indications. In the real world, how does it work out when a physician prescribes a drug for an unlabeled indication? Well, the FDA stance is that a prescriber may prescribe an approved drug for an unapproved use or in a dosage not recommended by the labeling and the pharmacist can certainly dispense such a prescription without violating federal law. Obviously though, the pharmacist has to exercise due diligence in keeping up with the literature to make sure that it is currently in place in the medical community that they’re being prescribed for that unlabeled use or unapproved dosage. Where the FDA has a problem is with manufacturers who try to push the envelope and promote a drug in an unapproved or unlabeled indication. And if you’ve been following the news over the last 5-10 years, there have been settlements in totaling billions of dollars where manufacturers have illegally tried to promote their drugs for some unlabeled uses. The bottom line is that it’s appropriate for doctors to prescribe and pharmacists to dispense medication for unlabeled indications. But the manufacturers are not allowed to promote any indications other than those in the package insert. Now we will discuss prescription compounding, which unfortunately can be a little complicated. With the enactment of the Food and Drug Administration Modernization Act, there came an attempt legislatively to clarify the distinction between compounding and manufacturing. What do we mean by that? Basically, we mean clarifying the traditional compounding role of a pharmacist so that it isn’t confused with manufacturing. With FDAMA, traditional pharmacy compounding became exempt from GMP requirements, meaning that pharmacists who did traditional compounding didn’t have to abide by GMP’s. Pharmacists didn’t have to worry about the adequate directions for use requirements on a label and finally didn’t have to submit an NDA, which obviously would be ludicrous and very onerous on a typical pharmacy to have to submit an NDA anytime they did any compounding. Unfortunately, with the passage of FDAMA, it also included restrictions on soliciting or advertising the compounding of any particular drug, class of drug or type of drug. A district court ruled that this particular section of FDAMA was unconstitutional because it was an impermissible restriction on free speech. So, they basically threw out all the compounding provisions and not just the provisions on soliciting or advertising. Ultimately the Supreme Court upheld the violations of free speech and agreed with the district court in that regard, but they didn’t comment on the remainder of the compounding provisions. So at the district court level they threw out everything related to compounding in FDAMA but the Supreme Court was silent on it. So this left the FDA in a dilemma as to how they were going to proceed with monitoring prescription compounding. So, under these confusing circumstances, the FDA announced that they were simply going to revert back to an earlier Compliance Policy Guide, which re-emphasized to the pharmacist community that the FDA will continue to defer to state authorities unless there were violations related to compounding that were enumerated in the policy guide. So let’s review some of those impermissible activities that the FDA would take action against. The first is the FDA looked very suspect at any pharmacy that was compounding in anticipation of receiving prescriptions, unless done in limited quantities that were consistent with past dispensing practices. So, if the FDA looked in your back room and you had stockpiled with drug upon drug of compounded product, then they would strongly suspect and likely investigate further to determine if you were a manufacturer as opposed to a traditional compounding pharmacy. The FDA was also concerned to make sure that you weren’t compounding using any drugs that have been previously removed from the market for safety reasons. Or compounding drugs from bulk active ingredients that weren’t components of FDA approved drugs. Or receiving, storing or using drug substances without making sure that the supplier was a FDA registered facility. Some other violations that the FDA would be prone to investigate would be using drug components that didn’t meet official compendial requirements. Using commercial equipment in your compounding arena. This next one’s an interesting one – compounding drugs for 3 rd parties who resell to individual patients or offering compounded drug products at wholesale to other state licensed persons or commercial entities for resale. So here the FDA was coming out and saying a traditional compounding pharmacy couldn’t resell to either another pharmacy, for example, or to a physician practice for subsequent resale to patients. One very serious violation in the eyes of the FDA was the next bullet point. Compounding drug products that are commercially available in the marketplace. So if you were just making or compounding a drug just because you could make it cheaper than an existing drug in the market place, that would be considered a serious offense on the part of the FDA, however it would be permissible if you had that same product and you compounded it and you just simply removed a dye, perhaps, that was in that product that someone might be allergic to, that would be certainly permissible. And then finally, a general failure to operate in conformance with state law regulating the practice of pharmacy. All of the confusion surrounding the compounding provisions that were in FDAMA were finally resolved with the passage of the Drug Quality and Security Act, specifically Title I which was called the Compounding Quality Act. We already spoke previously about the NECC disaster which prompted the passage of this Act and what it basically did was reinstate the compounding provisions in § 503A of FDAMA minus the unconstitutional sections, of course. § 503A deals with traditional compounding. The specific provisions of § 503A of FDAMA are quite similar to those in the FDA compliance policy guide that we reviewed in the previous slides. They are listed in your text and you will be responsible for knowing them for the class exam. Title I of the Drug Quality and Security Act also included § 503B which allowed for the creation of outsourcing facilities which we also spoke of previously. Now for a further discussion on the Prescription Drug Marketing Act that we have discussed a little bit earlier. This was enacted based on concerns and a realization that many drugs that consumers were using were probably adulterated and misbranded because they didn’t come from normal distribution channels. They realized that sales reps of manufacturers were storing a lot of drugs in the wrong places – in their garages, in their trunks – and they weren’t always being delivered to the ultimate patient in the traditional context of issuing samples. There was a realization that a lot of drugs that were purchased by hospitals at an inexpensive price were finding their way out the back door and being sold to other entities. So, what Congress did was institute a 3-pronged attack. They were going to do their best to regulate the distribution of samples and also regulate the purchase and resale of drugs that were purchased by non-profit entities such as hospitals, etc., at inexpensive prices to make sure that they didn’t end up being sold at higher prices for other individuals. And then finally to require wholesalers to be licensed at the state level. So, let’s start our discussion with the regulation of samples. What were some of the specific provisions in the PDMA? First of all, the sale, purchase or trade of samples was strictly prohibited including even the offer to sell. If you made an offer to sell and the sale wasn’t made, that would still be considered a violation of the PDMA. Also, the sale, purchase or trade or counterfeiting of drug coupons is also prohibited. And the way it worked to establish a much more careful paper trail, practitioners who wanted samples had to request them in writing each time. They couldn’t have any standing orders, for example, please deliver me X number of samples each month. And finally, the PDMA strictly mandates storage, handling and record keeping requirements for samples. So, in essence, you had a paper trail from the moment it left the manufacturer to the time it wound up in the patient’s hands. That was all accounted for on paper. Some other provisions regarding samples. I spoke earlier of the problem that retail pharmacies are prohibited from having samples. If a sample wound up or was found in a retail pharmacy, that would be considered tantamount to admitting that a violation of the PDMA had occurred. Hospital pharmacies, on the other hand, are allowed to have samples. However, accompanying the sample, there must be a receipt of the name and address of the doctor that prescribed it or requested it, the name of the hospital designated to receive the sample, name, address and title of the person acknowledging receipt of that sample, the established name of the drug, quantity, lot number and delivery date. So you can see that with the passage of the PDMA, they were very serious about the elaborate record keeping that had to be in place to make sure that samples were not being diverted. Also, under the PDMA, as previously mentioned, the PDMA prohibits the sale, purchase or trade or, as we saw in the case of the samples, even the offer to sell these types of products offering to sell prescription drugs that had been purchased by hospitals, healthcare entities or charitable organizations, which obviously typically are able to purchase drugs at a less expensive price, than the traditional retail pharmacy. There are certain exceptions to the prohibition on resale that you should be familiar with. The first is that the PDMA does allow resales of hospital purchases from a group purchasing organization or from another member hospital or sales or purchases to/from non-profit affiliates, or between hospitals or healthcare entities under common control. And the reason that these re- sales are allowed is because all of these organizations are technically obtaining the same price. There’s no chance for diversion. They are all getting the drug at the same price. The next one is an important one in that emergency sales can be permitted from a hospital to a community pharmacy to alleviate a temporary drug shortage. So that’s an important consideration. And then finally, PDMA does allow the selling or dispensing of prescriptions pursuant to prescription. And that the important distinction to make here is that this would mean that a drug that was purchased inexpensively at that hospital could be sold or dispensed in the outpatient pharmacy of that hospital, but not in the retail pharmacy of that hospital. And that’s an important consideration. Many hospitals these days have established retail pharmacies to compete with the community pharmacy down the block. In those cases, a firewall has to be set up, separate inventories, separate buying and everything. So make sure you understand that distinction. As you can see from this slide, there are very serious penalties for violating the Prescription Drug Marketing Act. For any penalty, you could be imprisoned for not more than 10 years or fined not more than $250,000 or both. For manufacturers, it’s particularly challenging in that if a manufacturer decides to use a sales rep instead of the mail to distribute the samples, and there’s any violations of the statute, initially there is a civil penalty of not more than $50,000 for each of the first two violations in a 10-year period, and beyond a 2 nd violation, there would be a civil penalty of not more than $1,000,000 in that 10 year period. As you can see, Congress takes this very seriously and you should be very cautious in your practice to make sure that you don’t commit any violations of the PDMA. On this slide, let’s introduce the concept of pedigree. Just what is a pedigree? It’s a statement that identifies each prior sale of a given drug product. Its purchase, any trade, including all dates of transactions, names, addresses of all parties to them. So in essence, a pedigree is nothing more than an elaborate paper trail indicating very specifically where the drug was, (i.e., in whose hands it was prior to your obtaining it in a pharmacy). The PDMA allowed the FDA to require a pedigree if the individual or the entity was not the manufacturer or an authorized distributor of record. What is an authorized distributor of record? That would be considered, typically, the main wholesalers – McKesson, Amerisource Bergen, Cardinal Health. Anyone beyond that would be considered a secondary wholesaler to which this pedigree requirement applied. A lot of secondary wholesalers went to the courts seeking injunctions saying it was grossly unfair to require the secondary wholesaler to have a pedigree and not require that of the primary wholesalers. The court agreed and invalidated this pedigree requirement because of the severe economic impact. The situation finally got resolved with the enactment of the Drug Supply Chain Security Act (DSCSA), which is Title II of the Drug Quality Security Act of 2013. The DSCSA established various timelines that ultimately by 2023 would create a fully electronic, interoperable track and trace program whereby all partners in the chain from the manufacturer to the pharmacy would be required to electronically track and trace all products using a unique product identifier, most likely the FDA recommended standardized numerical identification or SNI. And what it typically will be, will be the NDC number of the product plus an individualized 20-digit serial number that will accompany it. Also, beginning in January 2015, manufacturers, wholesalers, repackagers and dispensers had to have a system in place that to be able to quarantine, investigate and notify the FDA of any suspect drug product that they had obtained. We spoke previously about the DSCSA eliminating the pedigree requirement. The DSCSA replaced the pedigree requirement with much more robust requirements. The DSCSA requires the same information in a pedigree, but in addition it requires more details about the product and a statement of legitimacy. Basically, the DSCSA requires a transaction report broken down into 3 sections, namely transaction information; transaction history; and transaction statement: Transaction Information Name of the product Strength and dosage Specific NDC# Number of containers Lot number of the specific product Date of transaction and shipment Business name and address of the trading partner sending/receiving the product Transaction History The recording of the product’s entire transaction history (Pedigree) starting with the manufacturer. _ Transaction Statement Records the following information and requires that the trading partner transferring ownership of the specific product adhere to the following information. Is authorized under the DSCSA Received the product from a trading partner that is also authorized under the DSCSA Received the transaction information and statement from the trading partner Did not knowingly ship a suspect or illegitimate product Has systems in place to comply with verification requirements Did not provide false transaction information or knowingly alter the transaction history In most circumstances, it is illegal for individuals to import drugs into the U.S. for personal use because these products purchased from other countries often have not been approved by the FDA. The FDA does allow some exceptions: Prescription product that is used for the treatment of a serious condition:   for which effective treatment may not be available domestically in the US.  There is no known promotion of the product to persons residing in the U.S.  The product does not represent an unreasonable risk.  The consumer affirms in writing that the product is for personal use.  The quantity is generally limited to not more than a three-month supply and the consumer either: o Provides the name and address of the doctor licensed in the U.S. responsible for treatment, or o Provides evidence that the product is for the continuation of a treatment begun in a foreign country. For controlled substances, An individual can enter or depart the US with a controlled substance if it is in the original container in which it was dispensed and the individual declares it to a customs officer by stating the CS is for personal use and either the trade name and CS schedule appears on the container label, or the name and address of the pharmacy or practitioner who dispensed it is on the label along with the prescription number. A US resident may import into the US no more than 50 dosage units combined of all CS in the individual’s possession that were obtained abroad for personal medical use. The 50-dosage unit limit does not apply to CS’s lawfully obtained in the US pursuant to a prescription issued by a DEA registrant. Now a word or two about FDA inspections. The most important thing to remember about an FDA inspection should you ever be confronted with one is that you can’t refuse it, otherwise, you will face possible jail time and/or a huge fine. The good news about FDA inspections is that they have to be conducted at a reasonable time, in a reasonable manner and be reasonably limited. What this means is that you won’t get the knock at 3 o’clock in the morning like you could in the event of a DEA search warrant. So, the thing to remember about FDA inspections, they are reasonable but do not refuse them. This is the last slide in this particular presentation and it deals with tax free alcohol, which can be a confusing topic, which hopefully I can try and make some sense out of it for you. Tax free alcohol is not the grain alcohol that you can obtain at a liquor store, which is sometimes used in a retail pharmacy for compounding. The tax-free alcohol that we are discussing on this slide is alcohol that’s obtained tax free that’s typically used in a hospital setting. Could be used for sterilizing solutions, sometimes compounding prescriptions and/or preparing of specimens. The rule associated with tax free alcohol is that it cannot be sold but a separate charge may be added for medicines compounded on the premises and dispensed to patients for use on the premises. What this means is, let’s say, a hospital pharmacy is compounding a preparation for an inpatient. Any amount of tax free alcohol they use in that compounding process, they can’t charge the patient for. However, it does allow the hospital pharmacy to charge the individual inpatient for the actual medicine that is part of that compound. There are some other restrictions on tax free alcohol. It can’t be given to patients as a beverage or used as food. And that’s not to say that in a hospital setting the doctor sometimes won’t order some kind of alcohol before bedtime for example. But that would not be the tax-free alcohol. That would just be the traditional alcohol that you would get at a liquor store. Make sure you make that distinction. And then finally, any medicines compounded using tax free alcohol cannot be sold to either outpatients or the public. So, again, this reiterates that the only time you could use tax free alcohol in a compounding arena is in a hospital setting and when you are doing it for an inpatient. Again, you cannot use tax free alcohol when you are compounding if the ultimate product is going to be given either to an outpatient or the public. It would only be used for inpatients.