Bath Salts Compounds Are An Evolving Problem For DEA

This article is from NPR and can be found here.

June 30, 2012

One night a little more than two years ago, a 24-year-old man was rushed into the emergency room at Tulane University Medical Center in Louisiana. He was extremely agitated and hallucinating.
Dr. Corey Hebert figured the man was on drugs, probably PCP or a stimulant. But a few minutes later, the man became paranoid.
"He started doing some self-mutilating actions [and] was pulling out his eyebrows and eyelashes," Hebert tells weekends on All Things Considered host Laura Sullivan.

There's no legitimate use for these particular compounds that we know of.

- Arthur Berrier, Drug Enforcement Agency

Hebert then thought maybe the patient had taken methamphetamine, but his symptoms changed again. Even more surprising, a drug scan of the patient showed up clean. Hebert and his colleagues were puzzled.
After talking to the man's friends, Hebert learned he had taken a new drug that goes by the street name "bath salts."
In the months that followed, Hebert's emergency room became ground zero for bath salts patients. Every few days another patient arrived. Soon emergency rooms nationwide began seeing them, too.
The synthetic drug's popularity has been growing. National poison control centers had 304 calls about bath salts in 2010, nearly a third of them from Louisiana. Last year, there were more than 6,000 calls.
'We're Playing Whack-A-Mole'
The problem is that bath salts — which have nothing to do with the crystals you'd put in your tub — aren't one kind of drug or something you can test for and treat.
Unlike a drug like cocaine, which is made with a natural process, bath salts are made in a lab and constantly changing. The drug is designed specifically to skirt the law and test the bounds of new chemicals — with often deadly results.
"Cocaine is cocaine ... all the time, and it's always illegal," says Jill Head, a senior forensic chemist with the Drug Enforcement Agency. "But these products are continuously changing ... so what we see this week can be very different from what we're going to see a month from now."
This is a problem for police, prosecutors and the DEA, which is trying to track what the drugs are and where they come from.
Making matters worse, the compounds in the drugs aren't necessarily illegal. Because the components keep changing, drug makers can stay one step ahead of law enforcement. Even on a rush basis, it can take months to get a compound banned as a controlled substance. The DEA has gotten three compounds put on the list so far, but the agency's chemists have identified more than 60 in the past two years.
"Basically, we're playing whack-a-mole," says Arthur Berrier, a senior research chemist for the DEA. "They make one drug ... or one compound, and we smack it down, and the next week, something else pops up."
Now the scientists at a DEA lab in Northern Virginia are doing something unusual: They're making their own bath salts.
Berrier tells Sullivan that in order to fully identify a compound, scientists need what is called standard material, or an authenticated drug with a known structure.

Related NPR Stories

No 'Bath Salts' Drug Found In System Of Face-Eating AttackerJune 27, 2012

Woman Injects 'Bath Salts,' Loses Arm To Flesh-Eating BacteriaJan. 13, 2012

Florida Bans Cocaine-Like 'Bath Salts' Sold In StoresFeb. 8, 2011

"So typically what we would do is if we identify something in a bath salt material, we'd have to have a standard [to compare it to] to really identify it," he says.
The compounds scientists are finding are generally legal compounds not specifically controlled by the DEA, Berrier says. They show up in gas stations, pipe shops and all over the Internet as plant food, incense, hookah cleaner and, of course, bath salts.
Berrier says sometimes store owners know that what they're selling is really drugs, but sometimes they don't. The key for drug seekers is small packaging and the phrase "not for human consumption," which is supposed to hint at the opposite.
"[But] there's no legitimate use for these particular compounds that we know of," Berrier says.
Legal Difficulties
What DEA chemists are doing in beakers, bath salt makers are doing in vats. Officials believe many of those facilities are in China, India and Pakistan. Producers ship the drugs in bulk to the U.S., where officials suspect the final mixing and packaging is done.
To try to bring criminal cases against suppliers, sellers and users of what are essentially legal compounds, the DEA and prosecutors have had to reach way down into the annals of the nation's drug laws.
DEA lab director Jeff Comparin tells Sullivan that the challenge is that if a substance is not specifically listed in Title 21 of U.S. Code, which governs food and drugs, it can be classified as legal — but there's a loophole.
"Because of the nature of the structure, the way the chemicals are designed, the controlled-substances act also has a clause called the 'analog' part, where we can try these chemicals as if they were a controlled substance," Comparin says.
That means the agency can try to show the user or supplier intended to ingest or sell the product as a drug — usually through circumstantial evidence. Comparin says the DEA has successfully prosecuted some analog cases.
This trend of synthetic drugs is new and developing, Comparin says, and it's hard to say how long it will last.
"Who's to say what effect the ultimate control of these chemicals will have on their continued manufacture, importation and trafficking in the U.S.?" he says. "But as you can see right now, we just detect the new compounds and address the threat as best we can."
Just this week, Congress moved to ban more of the compounds the DEA's lab has identified. In the meantime, officials are hoping users will realize that if scientists in the nation's drug lab can't keep up with what drug manufacturers are making, users shouldn't be so sure what they're getting.

FDA Issues More Guidance About Makena®

In the form of Questions and Answers issued on June 29, 2012, the FDA recommends healthcare providers prescribe FDA-approved Makena (hydroxyprogesterone caproate injection) made by K-V  Pharmaceutical Company as the first-line for clinically-indicated patients. The FDA has not determined any other form of progesterone to be effective for this medical condition. The FDA also explained its enforcement policy towards compounded formulations of hydroxyprogesterone caproate. The FDA Questions and Answers state:

The FDA Questions and Answers are as follows: 

What is pharmacy compounding?

The FDA regards pharmacy compounding as the combining or altering of the ingredients of a drug by a licensed pharmacist to produce a drug tailored to an individual patient’s particular medical needs, based on a valid prescription from a licensed medical practitioner. For example, compounding may occur if a patient needs a medication to be produced without a dye or preservative due to an allergy, or needs a medication in a liquid or suppository form because the patient cannot swallow a pill.

Should health care professionals prescribe and patients take the FDA-approved drug product rather than the compounded product?

If there is an FDA-approved drug that is medically appropriate for a patient, the FDA-approved product should be prescribed and used. Makena was approved based on an affirmative showing of safety and efficacy. The company also demonstrated the ability to manufacture a quality product. The pre-market review process included a review of the company’s manufacturing information, such as the source of the API used in the manufacturing of the drug, proposed manufacturing processes, and the firm’s adherence to current good manufacturing practice.
Compounded drugs do not undergo the same premarket review and thus lack an FDA finding of safety and efficacy and lack an FDA finding of manufacturing quality. Therefore, when an FDA-approved drug is commercially available, the FDA recommends that practitioners prescribe the FDA-approved drug rather than a compounded drug unless the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.

How will a patient know if she is receiving Makena or a compounded product?

A patient can ask her health care provider what product is being administered. A label will also be visible on the vial or syringe with information such as the patient name, prescription number, and name of the product. Typically, if the pharmacy dispenses the FDA-approved product, it will have the brand name “Makena” on the label.

Will the agency take any enforcement action against pharmacies compounding versions of hydroxyprogesterone caproate products?

The FDA may take enforcement action against compounding pharmacies if warranted. The FDA makes its enforcement decisions about compounded products on a case-by-case basis after considering the particular facts at issue. As we explained in the June 15, 2012, statement¹, the compounding of any drug, including hydroxyprogesterone caproate, should not exceed the scope of traditional pharmacy compounding.

Are pharmacies free to compound large volumes of hydroxyprogesterone caproate as long as none of their drugs are tested and found to be unsafe?

No. The FDA does not consider compounding large volumes of copies, or what are essentially copies, of any approved commercially-available drug to fall within the scope of traditional pharmacy practice. One factor that the agency considers in determining whether a drug may be compounded is whether the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.
The FDA may take enforcement action against pharmacies that compound large volumes of drugs that are essentially copies of commercially available products and for which there does not appear to be a medical need for individual patients to whom the drug is dispensed.

The FDA stated it is using a risk-based approach to enforcement action against compounding pharmacies. The FDA also stated that its investigation did not identify a major safety issue, so does that mean that the FDA does not intend to take enforcement action against the compounders of hydroxyprogesterone caproate?

No. A risk-based approach to enforcement relates to how the FDA generally prioritizes its enforcement efforts. The FDA’s June 15, 2012 statement should not be interpreted to mean that the FDA will take enforcement action only if the agency identifies a particular safety problem. We reiterate that the compounding of any drug, including hydroxyprogesterone caproate, should not exceed the scope of traditional pharmacy compounding.

Links on this page:

1. /NewsEvents/Newsroom/PressAnnouncements/ucm308546.htm

Page Last Updated: 06/29/2012 

Warning Letters Matter

Warning Letters Matter

Posted by Kim Egan  on June 27, 2012

Attached is our monthly summary of selected FDA Warning Letters recently made public by FDA. Of particular note:

FDA cited one manufacturer of drug components and its immediate shipper for violation of Import for Export provisions because of failure to provide IFE records and a report, despite multiple requests by FDA.

FDA issued a warning letter to one company for promoting unapproved new drugs that made unsubstantiated claims about treatment of a wide variety of conditions, including cancer, autism, schizophrenia, multiple sclerosis, hepatitis C, and HIV infection.

FDA cited another company for making unsubstantiated therapeutic claims, including treatment of cancer and Alzheimer’s disease, about its mushroom supplements that FDA considered unapproved new drugs. In addition to inclusion of these claims on the company’s website, they were also supplemented by metatags used to bring consumers to the site.

FDA issued a warning letter to the manufacturer of a laser system for the unapproved new use of a device, as well as violation of Electronic Product Radiation Control requirements because of failure to submit product reports and file its annual report.

FDA also cited a tobacco company for violating the agency’s regulations restricting the sale and distribution of tobacco products to minors by promoting its “No Nonsense Rewards” program, wherein customers were offered a check in exchange for providing proof of purchase of specially marked packages of the company’s moist snuff product.

FDA continues to focus on Good Manufacturing Practices and posted warning letters for the following devices: steam sterilizers, an anti-embolism wrap system, lower limb prosthetics, bone densitometers, anesthetic delivery systems and respiratory therapy equipment, contact lenses, external penile rigidity devices, infusion pumps and urological catheters, neurosurgery and hemostatic devices, wound and burn dressings, temperature indicators, dental prosthetics, plasma coagulation control devices, an enteral infusion pumps, sterile syringes, an orthogonal percussion adjusting instrument, a turning medical bed, a pharmaceutical compounding device, telemetry devices, electrocardiogram monitoring equipment and software devices, a non-sterile blood pressure monitor, a total knee replacement system, a ventricular assist system, and a powered muscle stimulator device. In addition to the cGMP violations, FDA cited twelve companies for MDR violations, two for unapproved devices, two for unapproved new uses of a device, one for Report of Corrections and Removal violations, and two for Registration and Listing violations.

FDA also posted seven warning letter for cGMP violations regarding finished pharmaceuticals and dietary supplements. In addition to the cGMP violations, FDA cited one company for labeling violations, and one company for unapproved new drugs and field alert report violations.

The statistics are:

- 24 letters re cGMP device violations;

- 9 letters re medical device reporting (Animas Corporation (including cGMP violations), Health Science Products, Incorporated (including cGMP violations), APC Medical Limited (including cGMP and registration and listing violations), Teh Lin Prosthetic & Orthopedic, Inc. (including cGMP violations), Sorin Group Deutschland GmbH (including cGMP violations), The Lasik Vision Institute, Newman Lasik Centers LLC, Soring Medical Technology (including cGMP violations) and Okamoto Industries Inc. (including cGMP violations));

- 7 letters re cGMP pharma violations;

- 6 letters re unapproved new drugs (Herbal Extracts Plus, LLC, Agora Publishing Inc., Natural Health Team, The hCG Drops LLC, Mushroom Wisdom, Inc., and BioAnue Laboratories, Inc.);

- 3 letters re unapproved new use of devices (Medical Quant USA (including cGMP violations), Merit Medical Ireland Ltd. and BioElectronics Corporation);

- 2 letters re unapproved new devices (Akers Biosciences, Inc., and Spencer Forrest, Inc.);

- 2 letters re tobacco product marketing and sales (The Pinkerton Tobacco Company and Tobacco Source Three LLC);

- 1 letter re an unapproved new OTC homeopathic (Schwabe North America, Inc.);

- 1 letter re an unapproved new dietary supplement (Almased USA, Inc.);

- 1 letter re unapproved new use of an OTC device (CuraeLase, Inc. (including cGMP and MDR violations));

- 1 letter re drug study violations (Betty Tuller, Ph.D.); and

- 1 letter re import for export (MedPharm, LLC).

Here is our monthly summary of selected FDA Warning Letters recently made public by FDA. The statistics for this report:

- 24 letters re cGMP device violations;

- 9 letters re medical device reporting (Animas Corporation (including cGMP violations), Health Science Products, Incorporated (including cGMP violations), APC Medical Limited (including cGMP and registration and listing violations), Teh Lin Prosthetic & Orthopedic, Inc. (including cGMP violations), Sorin Group Deutschland GmbH (including cGMP violations), The Lasik Vision Institute, Newman Lasik Centers LLC, Soring Medical Technology (including cGMP violations) and Okamoto Industries Inc. (including cGMP violations));

- 7 letters re cGMP pharma violations;

- 6 letters re unapproved new drugs (Herbal Extracts Plus, LLC, Agora Publishing Inc., Natural Health Team, The hCG Drops LLC, Mushroom Wisdom, Inc., and BioAnue Laboratories, Inc.);

- 3 letters re unapproved new use of devices (Medical Quant USA (including cGMP violations), Merit Medical Ireland Ltd. and BioElectronics Corporation);

- 2 letters re unapproved new devices (Akers Biosciences, Inc., and Spencer Forrest, Inc.);

- 2 letters re tobacco product marketing and sales (The Pinkerton Tobacco Company and Tobacco Source Three LLC);

- 1 letter re an unapproved new OTC homeopathic (Schwabe North America, Inc.);

- 1 letter re an unapproved new dietary supplement (Almased USA, Inc.);

- 1 letter re unapproved new use of an OTC device (CuraeLase, Inc. (including cGMP and MDR violations));

- 1 letter re drug study violations (Betty Tuller, Ph.D.); and

- 1 letter re import for export (MedPharm, LLC).

And of particular note:

• FDA cited one manufacturer of drug components and its immediate shipper for violation of Import for Export provisions because of failure to provide IFE records and a report, despite multiple requests by FDA.
• FDA issued a warning letter to one company for promoting unapproved new drugs that made unsubstantiated claims about treatment of a wide variety of conditions, including cancer, autism, schizophrenia, multiple sclerosis, hepatitis C, and HIV infection.
• FDA cited another company for making unsubstantiated therapeutic claims, including treatment of cancer and Alzheimer’s disease, about its mushroom supplements that FDA considered unapproved new drugs. In addition to inclusion of these claims on the company’s website, they were also supplemented by metatags used to bring consumers to the site.
• FDA issued a warning letter to the manufacturer of a laser system for the unapproved new use of a device, as well as violation of Electronic Product Radiation Control requirements because of failure to submit product reports and file its annual report.
• FDA also cited a tobacco company for violating the agency’s regulations restricting the sale and distribution of tobacco products to minors by promoting its “No Nonsense Rewards” program, wherein customers were offered a check in exchange for providing proof of purchase of specially marked packages of the company’s moist snuff product.
• FDA continues to focus on Good Manufacturing Practices and posted warning letters for the following devices: steam sterilizers, an anti-embolism wrap system, lower limb prosthetics, bone densitometers, anesthetic delivery systems and respiratory therapy equipment, contact lenses, external penile rigidity devices, infusion pumps and urological catheters, neurosurgery and hemostatic devices, wound and burn dressings, temperature indicators, dental prosthetics, plasma coagulation control devices, an enteral infusion pumps, sterile syringes, an orthogonal percussion adjusting instrument, a turning medical bed, a pharmaceutical compounding device, telemetry devices, electrocardiogram monitoring equipment and software devices, a non-sterile blood pressure monitor, a total knee replacement system, a ventricular assist system, and a powered muscle stimulator device. In addition to the cGMP violations, FDA cited twelve companies for MDR violations, two for unapproved devices, two for unapproved new uses of a device, one for Report of Corrections and Removal violations, and two for Registration and Listing violations.
• FDA also posted seven warning letter for cGMP violations regarding finished pharmaceuticals and dietary supplements. In addition to the cGMP violations, FDA cited one company for labeling violations, and one company for unapproved new drugs and field alert report violations

FTC Workshop To Look at Pet Med Pricing

FTC Workshop To Look at Pet Med Pricing

Import Alert 66-66

Import Alert 66-66

(Note: This import alert represents the Agency's current guidance to FDA field personnel regarding the manufacturer(s) and/or products(s) at issue. It does not create or confer any rights for or on any person, and does not operate to bind FDA or the public).

Import Alert # 66-66

Published Date: 04/26/2012

Type: DWPE

Import Alert Name:

"APIs That Appear To Be Misbranded Under 502(f)(1) Because They Do Not Meet The Requirements For The Labeling Exemptions In 21 CFR 201.122"

Reason for Alert:

OASIS records indicate that a large volume of bulk chemicals which can be used as APIs in human medicines that require NDAs, ANDAs, or INDs are being offered for entry into the U.S.


NDA Imported APIs labeled for further manufacturing and processing or labeled as chemical substances are frequently destined for pharmaceutical processors that formulate finished drug products. These drug substances, consigned to individuals or processors who formulate and distribute human drugs, may be misbranded under Section 502(f)(1).

FY 2013 Food and Drug Administration Congressional Justification

The Food and Drug Administration conducts annual and multi-year budgeting in support of the nationwide public health protection programs administered by FDA.

The FDA produces three major budget submissions a year (HHS in June, OMB in September, and Congress in February). The budget documentation for Fiscal Year 2013, can be found here.

Jeffrey N. Gibbs Statement on Behalf of Dr. Gooberman's before NJ Board of Pharmacy Regarding Compounding Naltrexone Pellets

Statement
Of
Jeffrey N. Gibbs, Esq.
Hyman, Phelps & McNamara, P.C.
Washington, D.C.
Regulatory Counsel to Lance Gooberman, M.D.
Before The
New Jersey State Board of Medical Examiners
Special Committee Investigatory Hearing

January 17, 2000
This statement is provided on behalf of Dr. Lance Gooberman, M.D. It describes the legal and regulatory status of the practice of pharmacy compounding. It is offered to demonstrate that the practice of pharmacy compounding is legal under both federal law and New Jersey state law, that the regulatory requirements for ensuring the safety and effectiveness of compounded drugs differ significantly from the requirements for manufactured drug products, and that Dr. Gooberman's practice of compounding naltrexone pellets for subcutaneous implantation in patients undergoing opiate detoxification is consistent with those requirements.
Introduction
Compounding is an integral part of the practice of pharmacy. It is legal in all fifty states. Tens of thousands of compounded dosage forms are dispensed each day in the United States.¹
In New Jersey, compounding is defined as "the act of preparing pharmaceutical components into medications, pursuant to an authorized prescriber's medication order, including, but not limited to prescription compounding, and intravenous admixture preparation."² Like other states, New Jersey state law imposes specific requirements on the practice of compounding. For example, specific New Jersey Statutes require compounded prescriptions to be filled in the amount and with the drugs as prescribed by the practitioners.³ limit who may compound drugs and under what conditions,⁴ and establish training,⁵ documentation,⁶ and handling and delivery requirements for compounded prescriptions.⁷
However, nothing in New Jersey law says that a pharmacist must have a specified amount of data before compounding a drug, or that a physician must have a specified amount of data before prescribing a Compound drug. And, in fact, requiring a specified amount of data in advance is entirely incompatible with compounding. Physicians often prescribe a compounded drug to meet the unique needs of a single patient. Obviously, there can be no prior clinical experience in that situation.
The practice of pharmacy compounding is distinctly different from the process of drug manufacturing. The U.S. Pharmacopoeia (USP), an authoritative reference for establishing drug standards, describes the characteristics that differentiate compounding from manufacturing. They include: "the existence of specific practitioner-pharmacist-patient relationships; the quantity of medication prepared in anticipation of receiving a prescription or a prescription order; and the conditions of sale, which are limited to specific prescription orders."⁸
The USP has established a monograph that describes the standards for pharmacy compounding. USP took this action in express recognition of the importance of compounding. Significantly, although USP sets our detailed standards for compounding, it does not require that there be test done before a drug is compounded.
Similarly; the National Association of Boards of Pharmacy (NABP), to which most state boards of pharmacies belong, has created detailed standards for drug compounding, NABP's standards have been widely adopted by the states. However, the NABP's standards do not require that a pharmacist or physician possess any clinical data before compounding.
Compounding is most frequently necessary when the patient requires a drug that is not available commercially. Because approval of a new drug application is a time consuming and expensive process, manufacturers generally only develop drugs in the strengths and dosage forms that are most likely to ensure a return on their investment. If a particular patient needs a drug in a different strength or dosage form, compounding is the means by which the physician can provide the drug to that patient. Compounding is also useful for medications that are not stable and which must be prepared in small quantities, or when the patient is allergic to something (e.g. a dye) in the commercially available form of the drug.
In 1938, Congress passed the first statute regulating the distribution of drugs. As subsequently amended, federal law requires that before the drug may be marketed, the drug company must demonstrate that he drug is safe and effective for its intended use. As a result, drug companies must undertake one or more clinical studies of sufficient size to demonstrate the safety and effectiveness of the product.⁹ By contrast, a compounded drug is not intended for general use. Thus, the regulatory scheme for ensuring the safety and effectiveness of compounded drugs is necessarily different than that for manufactured drug products.
In 1997, Congress established the regulatory scheme that now governs the practice of pharmacy compounding. The strategies selected by Congress to ensure the safety and effectiveness of compounded drugs clearly reflect the characteristic differences between compounded and manufactured drug products. The federal regulatory scheme focuses on controlling the process of compounding. It does not require a statistically significant assessment of the safety and effectiveness of the final drug product, as that assessment would be irrelevant to the needs of the patient for whom the compounded prescription was prescribed.
Pharmacy Compounding: The Federal Regulatory Requirements
Prior to 1997, the Food and Drug Administration (FDA) had taken the position that pharmacies that compounded were subject to the new drug approval (NDA) and good manufacturing practice (GMP) requirements of the Federal Food, Drug, and Cosmetic Act (FDC Act). According to the FDA, every time a pharmacy compounded a drug, it needed to comply with the GMP and NDA provisions of the FDC Act. While FDA said that in the exercise of its enforcement discretion, it would normally not require pharmacies to comply with the GMP and NDA requirements, the agency also said that it had the power to compel compliance. Under those standards, compounded drugs were - n theory - subject to the same standards for safety and efficacy as drugs manufactured for use in the general population. Congress disagreed with that approach.
In 1997, Congress amended the FDC Act by adding Section 503A which governs the practice of pharmacy compounding. Section 503A which governs the practice of pharmacy compounding. Section 503A exempts compounded drugs from the new drug approval and good manufacturing practice requirements of the FDC Act, provided that the drugs are compounded in accordance with specified criteria.
These criteria include limiting compounding to licensed pharmacists and physicians, and restricting the type and quality of the materials that may be used. It is through adherence to these criteria that the safety and efficacy of compounded drug products is achieved. Therefore, a pharmacist who compounds a drug in accordance with these criteria is exempt from the NDA, GMP and labeling provisions that govern the development of drug products manufactured for use in a broader population of patients.¹⁰ Thus, there are no requirements for evaluating the safety or efficacy of the final compounded drug in animal or human trials. The statute does not require test data even if a compounded drug is widely prescribed and dispensed to thousands of patients.
In enacting the pharmacy legislation, Congress was well aware of the fact that new drugs generally require controlled clinical trials. Nevertheless, Congress exempted compounded drugs from the need to meet this standard. Congress recognized that compounding, by its very nature, should not have to meet the safety and efficacy standards that apply to manufactured drugs.
Compounding of Depo-Naltrexone Pellets
Dr. Gooberman's practice of compounding depo-naltrexone in pellet form for subcutaneous implantation in patients undergoing opiate detoxification is consistent with the criteria established by Congress for pharmacy compounding in Section 503A. Section 503A provides that compounding may only be performed by a licensed pharmacist or licensed physician subject to receipt of a valid prescription for an identified Patient. Dr. Gooberman complies with this requirement because he, as a licensed physician, prescribes compounded depo-naltrexone in pellet form form for subcutaneous implantation in individually identified patients.
Section 503A also places limits on the type of drugs that may be used in compounding. According to Section 503A(b), a licensed pharmacist may compound a drug product using bulk drug substances that comply with the applicable USP or National Formulary (NF) monograph, when a monograph exists, as well as the USP chapter on pharmacy compounding. Naltrexone is covered by a USP monograph.
Any drug withdrawn from the market because it was found to be unsafe or not effective, or any drug which presents "demonstrable difficulties" for compounding that reasonably demonstrate an adverse effect on the safety or effectiveness of that drug product, may not be used in compounding.¹¹ Naltrexone is an FDA approved drug that has not been withdrawn from the market for reasons concerning its safety or effectiveness, nor has it been identified by FDA as a drug which presents "demonstrable difficulties" for compounding. Therefore, it meets these criteria.
Section 503A also places limits on the quantity of drug that may be compounded. This includes a prohibition on "regular" compounding, or compounding in "inordinate" amounts, of drug products which are essentially copies of commercially available drugs.¹²
Naltrexone is not commercially available in the pellet form prescribed by Dr. Gooberman. Orally administered forms of the drug are commercially available and are currently used as adjunctive therapy during the detoxification process for the purpose of blocking the pharmacological effects of exogenously administered opioids. The utility of orally administered naltrexone is limited, however, as dosing is dependent upon patient compliance. Because the drug is prescribed for patients whose lifestyles may make compliance extraordinarily difficult, the rate of relapse is high. Depo-naltrexone in the pellet form is considered significantly different from oral naltrexone. Thus, compounding of the drug in this form is not considered compounding of a drug that is otherwise commercially available, and this limitation therefore does not apply to the pellets compounded by Dr. Gooberman.
While compounding may be limited to a single formulation for a single patient, that is not necessarily the case. Under Section 503A, a pharmacist can compound larger quantities of a drug, such as depo-naltrexone, for multiple patients and still not need FDA approval. Accordingly, Dr. Gooberman's prescription of depo-naltrexone for multiple patients is not inconsistent with Section 503A.
The law also intends there to be limits on the quantity of compounded drugs that may be shipped across state lines by individual pharmacists or pharmacies. Specifically, Section 503A seeks to limit the interstate distribution of "inordinate amount" in this context is to be established by FDA with each state through a Memorandum of Understanding (MOU). FDA has said that it will not enforce this provision until an MOU is adopted. FDA has not yet adopted an MOU.
Thus, Dr. Gooberman's prescriptions for compounded depo-naltrexone comply with FDA's requirements. He therefore does not need to have clinical data to prescribe this compounded medication.
___________________________
1. International Academy of Compounding Pharmacists, The Art and Skill of Compounding,http://iacprx.org/about_compounding.htm.
2. N.J.A.C. § 13:39-1.2(1999).
3. N.J.A.C. § 45:14-16(1999).
4. N.J.A.C. § 13:39-9.8(1999).
5. N.J.A.C. § 13:39-11.7(1999).
6. N.J.A.C. § 13:39-11.10(1999).
7. N.J.A.C. § 13:39-11.13(1999).
8. United States Pharmacopeia, Pharmacy Compounding Practices, USP 24-NF 19,2118.
9. 21 U.S.C. § 355(d)
10. 21 U.S.C. § 353a.
11. 21 U.S.C. § 503A(b)(1)(D).
12. 21 U.S.C.§ 503A(b)(1)(D)

FDA Information for Veterinarians

The FDA website contains an information just for Veterinarians. The FDA Vetrinarian page is found here. The following links are available on the FDA's website:

Information for Veterinarians

How can I tell if a drug is FDA-approved for animals?1

How can I tell if a drug is FDA-approved for people?2

How can I use an online database of drug labels to tell if a drug is FDA-approved?3

Should I report to FDA an adverse event for an unapproved animal drug?4

How can I tell if a flea and tick product is legitimate?5

“Dear Veterinarian” Letters6

Potassium Bromide: Is It Safe for Dogs?7

A Systematic Review of the Safety of Potassium Bromide in Dogs (JAVMA, Vol 240, No. 6, March 15, 2012)8

Concerns about marketed but unapproved animal drugs9

Bodybuilding.com and Jeremy DeLuca: Criminal Charges

Food and Drug Administration Office of Criminal Investigations

	U.S. Department of Justice Press Release

For Immediate Release May 22, 2012	United States Attorney District of Idaho Contact: Pamela Bearg Public Information Officer Wendy J. Olson U.S. Attorney Kevin T. Maloney Assistant U.S. Attorney (208) 334-1211

BOISE – U.S. Attorney Wendy J. Olson announced today that Bodybuilding.com, LLC, and Jeremy DeLuca, former president and vice president of Bodybuilding.com, LLC, pled guilty this morning in federal court in Boise to misdemeanor counts of introduction and delivery for introduction of misbranded drugs into interstate commerce. The charges are all violations of the Food, Drug and Cosmetic Act. As part of the plea, Bodybuilding.com, LLC agreed to pay a $7 million fine and DeLuca agreed to pay a $600,000 fine. The United States agreed to recommend that DeLuca receive probation and not be sentenced to any prison term. The plea agreements state that between March 2006 and September 2009, Bodybuilding.com, LLC, sold five products misbranded as dietary supplements, when they were actually drugs. The five products were: I Force Methadrol, Nutra Costal D-Stianozol, I Force Dymethazine, Rage RV5, and Genetic Edge Technologies (GET) SUS500. According to the plea agreements, the products were drugs because they contained synthetic anabolic steroids or synthetic chemical “clones” of anabolic steroids that were not dietary supplements and because they were labeled and promoted as products intended to affect the structure and function of the human body (building muscle mass). Jeremy DeLuca's plea agreement states that during the time period charged, he was president or vice president of Bodybuilding.com, LLC, and had authority over products offered for sale on the company's webstore. “Dietary supplements” must contain one or more “dietary ingredients.” A “dietary ingredient” is a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of one or more of these dietary ingredients. Bodybuilding.com, LLC, is the largest internet retailer of supplements in the world. It does not manufacture dietary supplements, but only retails products made by others. The plea agreement further states that from 2007 to 2009, the FDA compliance officer at Bodybuilding.com, LLC informed company management, including Jeremy DeLuca, that some prohormone products carried on its website contained ingredients that did not qualify as dietary supplements. Olson stated that Bodybuilding.com, LLC and DeLuca were the fifth and sixth defendants to plead guilty in the District of Idaho's investigation into distribution of misbranded drugs through Bodybuilding.com's website. Product manufacturers Tribravus Enterprises, the makers of I Force Methadrol and I Force Dymethazine; R&D Holdings; and DDC, LLC, doing business as Advanced Muscle Science, pled guilty to corporate felonies for introduction and delivery for introduction of misbranded drugs into interstate commerce, with the intent to mislead and defraud. Bodybuilding.com, LLC, founder and CEO Ryan DeLuca pled guilty on April 9, 2012, to misdemeanor charges. “Today's guilty pleas signal that retailers, as well as manufacturers, of products sold as dietary supplements have a clear responsibility under the law to ensure that the products they are selling are indeed dietary supplements, and not synthetic steroids or steroid clones masquerading as dietary supplements,” said Olson. “Bodybuilding.com, LLC, Ryan DeLuca and Jeremy DeLuca have now all accepted responsibility for these violations of the Food, Drug and Cosmetic Act.” Olson said that today's pleas are the culmination of a detailed and thorough investigation that included the execution of search warrants in September 2009 at Bodybuilding.com, LLC's Boise warehouse and Meridian headquarters. “Since the execution of the search warrants, Bodybuilding.com, LLC has worked cooperatively with the FDA and the U.S. Attorney's Office to ensure that it no longer sells products that do not qualify as dietary supplements,” said Olson. “We were able to resolve this case through misdemeanor charges in part because of the actions Bodybuilding.com, LLC, its current management and its general counsel's office have taken over the last two and a half years to prioritize regulatory compliance. We are confident that Bodybuilding.com has put into place procedures to eliminate products with these ingredients from its product line.” Under federal sentencing law, corporations convicted of violating the Food, Drug and Cosmetic Act can be fined up to twice the gross gain from sales of the misbranded product. According to its plea agreement, Bodybuilding.com, LLC had gross gain of $3.5 million from misbranded prohormone products, including those specifically identified in the plea agreement. Thus, Bodybuilding.com, LLC, agreed to pay a $7 million fine. Jeremy DeLuca has agreed to pay a $100,000 fine for each of the six counts with which he is charged. “The FDA’s Office of Criminal Investigations is fully committed to investigating and supporting the prosecution of those who sell synthetic steroids or steroid clones but call them dietary supplements. We commend the U.S. Attorney’s Office for their diligence in prosecuting this case,” said Thomas Emerick, Special Agent in Charge, FDA’s Office of Criminal Investigations, Los Angeles Field Office. Sentencing is set for August 1, 2012, in Boise before Chief U.S. District Judge B. Lynn Winmill. The Food and Drug Administration, Office of Criminal Investigations investigated the case. Assistant United States Attorney Kevin Maloney and Special Assistant United States Attorney Jim Smith, Associate Chief Counsel of the Food and Drug Administration, prosecuted the case.

Role of the pharmacist in preventing distribution of counterfeit meds - American Pharmacists Association

American Pharmacists Association - Article March 24, 2012: - Role of the pharmacist in preventing distribution of counterfeit meds

"Summary: The taskforce recommends that pharmacists (1) purchase medications from known, reliable sources; (2) warn patients of the dangers of purchasing medications over the Internet; (3) confirm with distributors that products were purchased from manufacturers or other reliable sources; (4) monitor counterfeit product alerts; (5) examine products for suspicious appearance; (6) work with the pharmaceutical industry, distributors, and the Food and Drug Administration (FDA) to close gaps in the supply chain, especially for drugs in short supply; (7) use scanning technology in the pharmacy as part of a prescription verification process; (8) educate themselves, coworkers, and patients about the risks of counterfeit medications; and (9) report suspicious medications to FDA, the distributor, and the manufacturer.

Conclusion: The consequence of a patient receiving a counterfeit medication in the United States could be catastrophic, and pharmacists must play an active role in preventing such an event from occurring."

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Protocols To Minimize Risk of Errors When Compounding

Errors When Preparing Medications

Michael J. Gaunt, PharmD

Published Online: Sunday, October 24, 2010

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Pharmacies must implement and maintain protocols to minimize the risk of errors when compounding and mixing medications.

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Compounding. A pediatric infectious disease physician prescribed Videx (didanosine) 10 mg/mL suspension for a 6-year-old HIV patient. Instructions from the physician directed that the prescription be compounded using “200 mL of distilled water, 200 mL of Maalox cherry antacid, and adding Videx 4ng solution to equal 400 mL.” The pharmacist who initially filled the prescription contacted a pharmacist at the prescribing facility for directions on properly compounding the medication. These instructions were handwritten and attached to the original prescription and were also entered into the pharmacy computer system.

The patient continued to take the Videx suspension as prescribed for the next 4 years. The prescriptions were filled at the same community pharmacy and all, except for the one initially dispensed, were compounded by 1 of 2 pharmacists. One of the pharmacists compounded the prescription correctly, while his partner mixed 4 packages of Videx 4-g solution in each prescription he compounded, doubling the Videx concentration to 20 mg/mL rather than 10 mg/mL.

The error was discovered when the pharmacist found a note from his partner stating that the patient was owed 200 mL of Videx at no charge. The pharmacist was puzzled by this entry. He discovered that his partner had been improperly compounding the medication over the 4-year period that it was dispensed. The partner erroneously believed that each bottle of Videx made 200 mL and that, therefore, it took 2 bottles of Videx to make the 400 mL as directed in the prescription.

The partner attributed the error to ambiguous instructions written by the pharmacist who filled the original prescription. These instructions reportedly gave no milligram strength, just the final volume of the suspension. However, the partner acknowledged that he never reviewed the Videx package insert for instructions, nor did he seek clarification from his partner and/or the prescriber.

To ensure patient safety, physicians and pharmacists must proactively assess the accuracy and safety of compounded medications. Before dispensing, clear, accurate, step-by-step recipes should be on file. Institute a process to ensure that all compounding recipes undergo a documented approval process prior to use, as well as an updated review every year. Establish an independent double-check process for all calculations completed each time a compound is made. A compounding logbook should be maintained documenting each compound made, the recipe followed, and all ingredients, including quantities, used. This logbook should be reviewed weekly and with each refill dispensed as a quality control check.

Mixing. An 8-month-old girl was prescribed amoxicillin/clavulanate potassium suspension to treat an ear infection. The prescription was taken to the family’s local community pharmacy, where a stock medication bottle labeled with instructions to give the child a half teaspoonful twice daily by mouth was dispensed. When the family arrived home, they measured a half teaspoonful of the powder and administered it to the girl. The pharmacy had failed to mix the powder prior to dispensing the medication. The girl was rushed to the emergency department, where she was treated for the antibiotic overdose.

To reduce the risk of this type of error, consider placing new prescriptions for oral liquid medications, especially those that need to be reconstituted, in a separate area away from other prescriptions waiting to be picked up. Mark the area as “not to be dispensed without speaking to the pharmacist.” Include specific product descriptions on the prescription label (eg, orange-flavored, white, opaque liquid). Review the label, route of administration, and directions for use with the patient; open the bottle with the patient and/or caregiver. Ensure that oral syringes (without caps) or other appropriate measuring devices are provided or are available for purchase. Provide education to patients regarding proper use and cleaning of the measuring device. Have the patient demonstrate how to measure and administer the dose to validate learning.

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Dr. Gaunt is a medication safety analyst and the editor of ISMP Medication Safety Alert! Community/ Ambulatory Care Edition. 

This article can be found here.

Pharmacists Included as "Health Care Providers" Under Pennsylvania Health Care Records Law

This article appears in the Pennsylvania Pharmacists Association news:

Diana Yap, APhA - April 10, 2012 - Pennsylvania appeals court opinion declares pharmacists are ‘health care providers’ under the law, citing state Pharmacy Practice Act and state board of pharmacy regulations. Calling pharmacists “health care providers” for the purposes of the Pennsylvania Medical Records Act (MRA), the Superior Court of Pennsylvania on March 23 issued an opinion important to pharmacy in the case of Landay v Rite Aid. The ruling reversed a lower court decision holding that the state’s MRA didn’t apply to pharmacies because a pharmacy customer was not a “patient.” “We find the fact that the court concluded that a pharmacist is a health care provider and that the recipient of prescription medication is a patient very interesting and promising, especially in light of the fact that certain government entities and others sometimes like to argue that pharmacists are not providers,” Patricia A. Epple, CAE, CEO of the Pennsylvania Pharmacists Association, told pharmacist.com. Read more: http://www.pharmacist.com/AM/Template.cfm?Section=Pharmacy_News&Template=/CM/ContentDisplay.cfm&ContentID=28264 

Georgia law regarding office use

Georgia law regarding office use of compounded drugs is as follows: It is illegal for any person or entity to purchase compounded medications within the state or out of state for office use or dispensing unless the company you are purchasing from has all necessary federal and state manufacturing licenses and all applicable state wholesale licenses. All compounded medications must be patient specific. This can be found at http://SOS.Georgia.gov/plb/pharmacy

Import Alert 61-07

Import Alert 61-07

The Role and Education of the Veterinary Pharmacist

A interesting article entitled, The Role and Education of the Veterinary Pharmacist, Am. J. Pharm. Educ. 2009 February 19; 73(1): 16, notes that the practice of veterinary pharmacy is an emerging field in the United States.  That entire article can be read by clicking here.

More retailers offering pet prescriptions--But Are Retailers A Safe Place From Which To Buy Your Pet Medications

The recent article below points out that a number of retailers are now offering pharmacy services for sick pets. However, it may not be a good idea to buy your pet prescriptions from retailers. As the article points out: "The problem pet owners face is that pharmacists at these stores aren't trained about the medication and how it can affect the animals," Lund said. "The pharmacist or some website isn't going to help you when you're having a reaction at 10 p.m."

The author of this blog believes there is a great need for trained, specialized pharmacist in veterinary medicine. We need more colleges and universities that offer a specialized degree in veterinary pharmacy. To ensure a pet's safety and wellbeing, pet owners should check out the pharmacy and pharmacist they are doing business with. A good place for a pet owner to start their research is with the state board of pharmacy to see if the pharmacy or pharmacist has ever been disciplined or fined.  Another area to examine is whether the pharmacy and pharmacist are knowledge of veterinary medications.

More retailers offering pet prescriptions

BY JUSTINE GRIFFIN - SUN SENTINEL

FORT LAUDERDALE, Fla. -- Retailers are making it easier and cheaper for pet owners to get the medication they need to care for their sick cats and dogs.

Winn-Dixie is the latest chain to extend its pharmacy services to reach sick pets. The Jacksonville, Fla.-based grocery chain began offering pet prescriptions recently when it partnered with Center Pet Pharmacies, a Washington, D.C.-based company that specializes in pet medication. Target launched its pet refills program at stores with pharmacies in 2010, and Wal-Mart began in March of this year.

"We already had a nice size business of pet owners at our pharmacies who used our services to get discounted prices on antibiotics and other cross-over drugs," said Mike LeBlanc, director of pharmacy business development for Winn-Dixie. "It just seemed natural to provide drugs for pets at the same time."

Most often pet owners get their prescription medications from their veterinarian's office or online through sites like 1-800-PetMeds.com. But veterinarians like Kristy Lund at Lund Animal Hospital in Boca Raton, Fla., are seeing more patients opt to have refills sent to places like Wal-Mart or Target, where cheaper generic alternatives are offered.

"In today's economy, more people have to bargain-shop, and this provides a service for those who may be struggling with care costs," Lund said.

In 2012, American pet owners are expected to spend nearly $53 billion on their animals, according to the American Pet Products Association. Pet owners will spend more than $13 billion on medical care costs alone, which is an expected 1.3 percent increase from the total spent in 2011.

"The problem pet owners face is that pharmacists at these stores aren't trained about the medication and how it can affect the animals," Lund said. "The pharmacist or some website isn't going to help you when you're having a reaction at 10 p.m."

Most veterinarian practices have pharmacies inside their offices. Veterinarians are required to attend seminars every two years to keep their drug administering licenses active. Retailers, like Winn-Dixie, partner with pet compounding pharmacies which specialize in developing drugs in smaller dosages for animals, which does not require their employees to have special training to administer animal prescriptions.

Pet supplies chains like Petsmart and Petco do not sell prescription medications. Walgreens and CVS Pharmacy do not sell pet medicines either.

Although Publix doesn't offer pet-specific medications, "cross-over" drugs, which are treatments like antibiotics or anti-inflammatory capsules used by both pets and humans, can be picked up from its pharmacies.

Most cross-over prescriptions can be filled in the same day, LeBlanc said. Specialized pet medications take 24 to 48 hours to fill. Pet prescriptions filled by Winn-Dixie pharmacies also will include personalized instructions similar to when human prescriptions are filled and delivered. About 75 percent of all Winn-Dixie locations have pharmacies.

"These services make our shopper's lives easier," LeBlanc said. "They're already purchasing pet food inside the store, and now they have the opportunity to take care of another pet need here too."

Pet medicines can come in bacon or other flavors, and or be switched from a capsule to a gel depending on a pet owner's needs, said Kenny Kramm, owner of Center Pet Pharmacies.

Read more here: http://www.newsobserver.com/2012/06/28/2165994/more-retailers-offering-pet-prescriptions.html#storylink=cpy

Read more here: http://www.newsobserver.com/2012/06/28/2165994/more-retailers-offering-pet-prescriptions.html#storylink=cpy

Government Regulation of Compounding

There is much disagreement about whether states, the federal govenment, or both should regulate compounding.  Here are a two general articles on government regulation:

1.  Meron, Daniel (2007) "Balancing Government Regulation Against Access to
Drugs," Address to Seton Hall University School of Law, February 16, 2007.  Read here

2.  Lewyn, Michael (2010) "Character Counts: The “Character of the Government Action" in Regulatory Takings Actions," Seton Hall Law Review: Vol. 40: Iss. 2, Article 4. Read here