DITORIAL

A Brief History of FDA Compounding Oversight

Stanford T. Shulman, MD

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• Pediatric Annals
• January 2013 - Volume 42 · Issue 1: 2-3
• DOI: 10.3928/00904481-20121221-01

This issue highlights a series of challenging pediatric dermatology cases organized by Sarah L. Chamlin, MD, an outstanding pediatric dermatologist and the dermatology section editor of Pediatric Annals. Be sure to look at each case and formulate your opinion before finding out the answer!

Fungal Meningitis Outbreak

You’ve likely heard the news about the disastrous outbreak of fungal meningitis associated with the intrathecal injection of methylprednisolone acetate for adults with chronic back pain.^1,2 The contaminated lots of steroid were compounded at a Massachusetts facility called the New England Compounding Center (NECC) and shipped to a wide area of the US.³ The vast majority of the more than 500 patients (including 36 deaths) in 19 states were infected with the rare fungus Exserohilum rostratum. Fungal contamination of unopened compounded drug vials was documented.²

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The US Food and Drug Administration (FDA) has the authority to regulate drug manufacturing, but oversight of the compounding of specific preparations for individual patient use has fallen into a gray area between federal oversight of manufacturing and state oversight of the practice of pharmacy and medicine (thus, we have state medical licenses).³

In 2002, the US Supreme Court ruled unconstitutional a law passed by Congress to enable FDA oversight of large-scale compounding. The FDA was able to salvage many aspects of that law in its policy guide, and it appears that NECC violated some of these policies.³ This entire complex story is recounted in detail in the Nov. 22, 2012 issue of The New England Journal of Medicine³ and in two original reports in the subsequent two issues.^1,2

Historical Highlights of Compounding

Originally established in 1906, the FDA has an interesting history. I recently met a very alert and healthy 82-year-old woman who was treated at Chicago’s Children’s Memorial Hospital in 1939 at the age of 8 for severe pneumococcal meningitis, and I was able to review her hospital records from that episode. She was treated with pyridine sulfanilamide and injections of rabbit type-specific pneumococcal antiserum, with an amazingly positive outcome. This is relevant because the FDA had its oversight mandate broadened in direct response to the 1937 Elixir Sulfanilamide disaster. This was the first available antibiotic to be highly effective against some infections, and it was used safely in tablet and powder form. When there was demand for a liquid formulation, the manufacturer, S.E. Massengill Co., developed a pleasant raspberry-flavored product that unfortunately used diethylene glycol, the primary ingredient in antifreeze, as a solvent. In all, there were 105 “elixir”-related deaths across 15 states. (The chemist responsible for the mixture, Harold Watkins, PhD, later committed suicide.)⁴

At that time, there was no legal requirement that medications be tested for toxicity, and the results were catastrophic. As a result, Congress passed the 1938 Food, Drug and Cosmetic Act, which increased the FDA’s authority to regulate drugs and required them to be safe and properly labeled. Amazingly, proof of drug efficacy was not a requirement until 1962, partly in response to the thalidomide tragedy in which a host of birth defects were linked to the drug.

Hopefully, the current tragedy will lead to tighter controls over the compounding industry, helping to safeguard patients throughout the US.

Source found here

Health official touts pharmacy regulations - TimesDaily.com

Health official touts pharmacy regulations - TimesDaily.com

Pharmacy board: More inspectors needed for sterile compounding

Jan. 31, 2013 5:23 PM, 

Members of the state pharmacy board called for more inspectors on Thursday amid discussions of new rules and potential legislation related to the regulation of sterile compounding.

Currently the board has five inspectors to oversee 1,905 pharmacies. Lawmakers, pharmacy experts and the board have talked in recent months about adding regulations of sterile compounding, the practice of combining multiple drugs for injection. In September, tainted compounded drugs led to a national outbreak of fungal meningitis that has stricken 693 people and led to 45 deaths.

“Until we (add more inspectors), we accomplish nothing,” board member Joyce McDaniel said.

Department of Health Assistant Commissioner for Legislative Affairs Valerie Nagoshiner discussed possible legislation related to sterile compounding that the department may pursue this legislative session. Most notably, the department is considering a bill that would require a separate license for pharmacies that practice sterile compounding.

The purpose of the separate license would be so that officials could get a handle on how many such sterile compounders have a state license. Prior to the outbreak, the board of pharmacy and the Health Department did not know the answer to that question.

Pharmacy board members said legislation could be unnecessary, because the board could require pharmacies to alert the board during the application process if they practice sterile compounding.

At least 352 pharmacies practice sterile compounding in Tennessee, according to the preliminary results of a survey released earlier this month by the pharmacy board.

Nagoshiner also discussed legislation that would allow the Health Department commissioner to suspend a pharmacy from practicing sterile compounding. The commissioner already has the power to shut down nursing homes under an emergency suspension.

But board member Kevin Eidson worried that the commissioner was not a pharmacist and may lack the expertise to make such a call. Eidson, and other board members, suggested that the board already has the power to take such emergency action.

The tainted drugs were linked to Massachusetts-based New England Compounding Center. Eidson said too much time passed — 33 days — before the Tennessee health department gave the pharmacy board the information it needed to take action against NECC and its lead pharmacist, Barry J. Cadden.

“I feel very comfortable about what’s going on in Tennessee (in terms of sterile compounding),” Eidson said. “I’m not comfortable with what’s going on in other states.”

Board president Buddy Stephens said the board would like to inspect each of its pharmacies once per year, and sterile compounders possibly as often as once every six months.

But to accomplish these goals, more inspectors are needed. And those inspectors need to be properly trained regarding sterile compounding practices. Stephens said the board needed approval from the health department to create the new inspector positions.

He instructed the board of pharmacy staff to investigate how much licensure fees would need to increase in order to inspect each of its licensees, including those that operate out of state. At a legislative hearing on sterile compounding earlier this week, the state pharmacy association expressed support for such an increase if necessary.

Already the Iowa pharmacy board has signed off on inspecting its out-of-state pharmacies, and Stephens said Tennessee should consider following suit. Iowa will use the National Association of Boards of Pharmacies to conduct its out-of-state inspections.

Contact Nate Rau at 615-259-8094 or nrau@tennessean.com. Follow him Twitter @tnnaterau.

source found here

CDER Agenda Foreshadows Release of Guidances Long Sought by Industry

CDER Agenda Foreshadows Release of Guidances Long Sought by Industry

A.G. Schneiderman Announces $100,000 Settlement With Pharmacy Owner For Overbilling Medicaid For Ketamine Queens Pharmacy Overbilled Medicaid For Reimbursement For Larger Ketamine Dosages Than Those Used Schneiderman: Settlement Holds Pharmacy Owner Accountable For Profiting At Taxpayers’ Expense

NEW YORK - Attorney General Eric T. Schneiderman announced today a $100,000 settlement with Oleg Aronov, a co-owner of Comprehensive Pharmacy, Inc. for overbilling taxpayers relating to the dispensation of compounded medications containing the drug Ketamine. Until its closing in 2009, Comprehensive Pharmacy was an enrolled provider of health care services to New Yorkers covered by Medicaid. Through its investigation, the Attorney General’s Office discovered that Comprehensive Pharmacy had overbilled Medicaid for Ketamine.

“Medical professionals who overbill Medicaid rob the program of important resources, and deprive many New Yorkers of essential services. This settlement holds Mr. Aronov accountable for profiting at the expense of taxpayers,” said Attorney General Schneiderman. “My office will remain committed to returning any funds misspent through violations of the Medicaid program.”

In addition to providing medications in the form of a pill or as a liquid, many pharmacies supply medications to patients in the form of creams. These compounded medications are usually prepared on site by a pharmacist. With regard to compounded medications containing Ketamine, Medicaid rules and regulations dictate that a provider may only seek reimbursement for the amount of Ketamine actually used in the compounded medication. Comprehensive Pharmacy, despite these rules, billed Medicaid as if Ketamine was the entire weight of the compound, when it was not. Attorney General Schneiderman’s investigation revealed that Comprehensive Pharmacy had submitted to the program tens of thousands of dollars in erroneous claims for compounded medications containing Ketamine.

Through his settlement with the Attorney General’s Office, Aronov agrees to reimburse the State, and admits to submitting erroneous claims to Medicaid indicating Comprehensive Pharmacy had dispensed compounded medications containing more Ketamine than was actually present in the medications dispensed to Medicaid patients.

While Ketamine, a general anesthesia, has a number of legitimate uses, it is also abused and is known as a “date rape” drug because of its ability to induce a dissociative state. Ketamine is classified as a Schedule III controlled substance. The Attorney General’s investigation did not uncover any evidence that the compounded medications prepared and erroneously billed by Comprehensive Pharmacy were being used for any illegal or illicit purposes.”

The Attorney General’s investigation originated from a referral by the New York State Office of the Medicaid Inspector General (OMIG). Attorney General Schneiderman would like to thank OMIG for its assistance in resolving this matter.

The case was handled by Deputy Regional Director Thomas O’Hanlon and Special Assistant Attorney General Samuel Yee, under the supervision of Assistant Deputy Attorney General Paul Mahoney and Special Deputy Attorney General Monica Hickey-Martin. The investigation was conducted by Senior Special Investigator Thomas Dowd, under the supervision of Chief Investigator Thaddeus Fischer, and by Special Auditor Investigator Olga Sunitsky, under the supervision of Supervising Special Auditor Emmanuel Archer and the Medicaid Fraud Control Unit’s New York City Regional Chief Auditor Thomasina Piccolo-Smith. 

A copy of today’s settlement can be found here: www.ag.ny.gov/pdfs/Oleg-2013.pdf

Source Found here

Pharmacy Practice News - Is Compounding ‘Denial Coma’ Over?

Pharmacy Practice News - Is Compounding ‘Denial Coma’ Over?

Florida Article Is a Must Read: Gives Ideas for States to Improve Regulation and It Notes Anytime FDA Has attempted to Rein In Compounders Who Act As Manufacturers Courts Have Blocked IT

See prior post or read article entitled 950 FL Pharmacies Called High-Risk Compounders
  here 

950 FL Pharmacies Called High-Risk Compounders

By Carol Gentry

Originally published on Thu January 31, 2013 1:19 pm

Almost 950 Florida-licensed pharmacies engage in “sterile compounding,” the type of high-risk drug-making that led to a deadly fungal meningitis epidemic last year, according to a Department of Health survey released last week.
Sterile compounders are now given priority for state inspections, but it’s going to be a daunting task to check them all, judging from the survey report and interviews with pharmacists and health department officials. There are  two reasons:
--One-third of the 950 are based out of state, like the New England Compounding Center, the source of contaminated drugs that caused the epidemic. Florida law doesn’t give health officials any authority over out-of-state licensees.
--While the state has 18 inspectors for pharmacies, the health department said, only five of them are licensed pharmacists. And even the pharmacists need extra training to inspect the high-risk sterile compounders, officials said

Continue reading here

NEW & REVISED DRAFT GUIDANCE CDER FDA PLANS TO PUBLISH in 2013: COMPOUNDING IS ON THE LIST

Guidance Agenda:
New & Revised Draft Guidances CDER is
Planning to Publish During
Calendar Year 2013
(See the Good Guidance Practices (GGPs) regulation on this Web page or
21 CFR 10.115 for details about the Guidance Agenda.)
CATEGORY — Advertising
•
Considerations for Regulatory Submissions of Promotional Labeling and Advertising Materials including Submissions in Electronic Format
CATEGORY — Animal Rule
•
Product Development Under the Animal Rule
CATEGORY — Biopharmaceutics
•
Food-Effect Bioavailability and Fed Bioequivalence Studies---Bioavailability and Bioequivalence Studies for Orally Administered Drug Products Submitted in New Drug Applications General Consideration
CATEGORY — Biosimilarity
•
Submission of Clinical Pharmacology Data as Evidence of Biosimilarity for Biologics and Protein Products
CATEGORY — Chemistry
•
Allowable Excess Volume and Labeled Vial Fill Size
•
Bioequivalence Studies with Pharmacokinetic Endpoints for Drug Products Submitted in Abbreviated New Drug Applications
•
CMC Postapproval Manufacturing Changes Reportable in Annual Reports for Specified Biological Products
•
Comparability Protocols for Approved Drugs: Chemistry, Manufacturing, and Controls Information
•
Elemental Impurities in Drug Products Marketed in the United States
•
Immunogenicity Considerations for Low Molecular Weight Heparin
•
Liposome Drug Products: CMC, Human Pharmacokinetic and Bioavailability; and Labeling Documentation
•
Size and Physical Attributes of Generic Tablets
Version: 01.31.13
CATEGORY — Clinical/Antimicrobial
•
Antibacterial Therapies for Patients with Limited or No Alternative Therapies for the Treatment of Serious Bacterial Diseases
•
Community-Acquired Bacterial Pneumonia: Developing Drugs for Treatment
•
Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment
•
Pulmonary Tuberculosis: Developing Drugs for Treatment
CATEGORY — Clinical/Medical
•
Alzheimer’s Disease: Developing Drugs for the Treatment of Early State Disease
•
Common Issues in Drug Development for Rare Diseases
•
Developing Drug and Biological Products for Analgesic Indications
•
Modifications and Revisions of Risk Evaluation and Mitigation Strategies (REMS)
•
Pregnant Women in Clinical Trials – Scientific and Ethical Considerations
CATEGORY – CMC and CLINICAL/MEDICAL
•
Immunogenicity Assessment for Therapeutic Protein Products
CATEGORY — Clinical Pharmacology
•
Bioanalytical Methods Validation
•
Clinical Pharmacogenomics: Study Design and Premarketing Evaluation
•
Clinical Pharmacology Consideration for Therapeutics Proteins
•
General Clinical Pharmacology Considerations for Pediatrics Studies for Drugs and Biological Products
CATEGORY — Clinical/Statistical
•
Multiple Endpoints in Clinical Trials
CATEGORY — Current Good Manufacturing Practices (CGMPs)/Compliance
•
Quality Systems Approach to Pharmaceutical cGMP Regulation (OMPQ)
•
Uniformity of In-Process Mixtures (OMPQ)
•
Control of Highly Potent Compounds (OMPQ)
•
Contract Manufacturing Arrangements for Drugs: Quality Agreements
•
Submission of Field Alert Reports and Biological Product Deviation Reports (OMPQ)
•
Pre-Launch Activities Importation Request (PLAIR)
Version: 01.31.13
CATEGORY — Drug Safety Information
•
Best Practices in Developing Proprietary Names to Minimize Medication Errors
•
Providing Postmarket Safety Reports in the ICH E2C(R2) Format (Periodic Benefit-Risk Evaluation Report)
•
Safety Considerations in Product Design to Minimize Medication Errors.
•
Securing the Drug Supply Chain—Standards for Tracking and Tracing Prescription Drug Packages
•
Safety Considerations for Container Label and Carton Labeling Design to Minimize Medication Errors
CATEGORY — Electronic Submissions
•
Providing Regulatory Submissions in Electronic Format – General Considerations
•
Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
•
Providing Regulatory Submissions in Electronic Format – Postmarketing Safety Reports
•
Providing Regulatory Submissions in Electronic Format – Standardized Study Data
•
Providing Submissions in Electronic Format – Summary Level Clinical Site Data for CDER’s Inspection Planning
•
Providing Submissions in Electronic Format – Postmarket Non-Expedited Individual Case Safety Reports; Technical Questions and Answers
CATEGORY — IND
•
Adverse Events: Collection and Reporting for Secondary Endpoints
CATEGORY — Labeling
•
Drug Names and Dosage Forms
•
Pediatric Information: Incorporating into Human Prescription Drug and Biological Products Labeling
CATEGORY – Pharmacology/Toxicology
•
Endocrine Disruption Potential of Drugs: Non Clinical Evaluation
CATEGORY — Procedural
•
Applying the Criteria for Requiring a Risk Evaluation and Mitigation Strategy (REMS)
•
Expedited Programs for Serious Conditions, Drugs and Biologics
•
Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants
•
Integrated Summary of Safety
•
Investigational New Drug Applications prepared and submitted by Clinical Sponsor Investigators
•
Pediatric Product Development
Version: 01.31.13
Version: 01.31.13
•
Pharmacy Compounding of Human Drugs Under Section 503A of the Federal Food, Drug, and Cosmetic Act
•
Public Disclosure of FDA-Sponsored Studies
•
Prescription Drug Marketing Act (PDMA) Requirements
•
Reporting Drug Sample Distribution Under Section 6004 of the Affordable Care Act
•
Use of a Master File for Shared System Risk Evaluation and Mitigation Strategies
•
Electronic Source Data in Clinical Investigations
Note: Agenda items reflect guidances under development as of the date of this posting.

Source found  here

Pharmalot Discussion on Supreme Court's Ruling that Pharmaceutical Sales Representatives Are Not Entitled To Overtime Pay

To read this excellent review, click here