Thursday, January 31, 2013


A Brief History of FDA Compounding Oversight

Stanford T. Shulman, MD
  • Pediatric Annals
  • January 2013 - Volume 42 · Issue 1: 2-3
  • DOI: 10.3928/00904481-20121221-01
Rights and Permissions
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
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 -

Health official touts pharmacy regulations -

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 Follow him Twitter @tnnaterau.
source found here

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:

Source Found here

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

950 FL Pharmacies Called High-Risk Compounders

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


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

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

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

Resources on How Much Pharmaceutical Sales Representatives Make And Links To Job Openings

Continually Being Updated

Pharmlot  Sales Reps Not Entitled to Overtime:  Supreme Court Veterinary Pharmaceutical Sales

Job Openings

CafePharma (both pharmaceutical and veterinary) (both pharmaceutical and veterinary)

Healthcare Job (both pharmaceutical and veterinary)rd

Pharmaceutical Sales Representative Positions (Simply Hired)

Veterinary Sales Representative Positions (Simply Hired)

Discussion Boards

CafePharma has an excellent discussion boards:   for example it has a discussion board for all the major veterinary pharmaceutical companies and sales jobs with each:  discussion board and a separate discussion board for each regional sales job:  discussion board and speciality pharmacies that tends to have a lot of discussion regarding compounding:  discussion board

Wednesday, January 30, 2013

A Record Day for This Blog: We Had Well Over 500 Views; Thank you for Continuing to Read the Blog

Marketing 101: Where Have All the Good Guys and Girls Gone in the Compounding Pharmacy World

By:  Doletta Sue Tuck-Richmond

Compounding continues to take a beating in the press.  I continue to look for positive stories, and I continue to ask for someone, anyone--a doctor, a pharmacist, a veterinarian, a consumer--to tell me a positive story about compounding.    

 I have posted about the benefits of compounding  see Why We Need and Must Have Compound Medications and more specifically about the benefits of veterinary compounding.  I have asked for positive stories to be shared.  See Positive Stories About Compounding I have asked What Are All the Positives of Compounded Medications  I have posted specific stories about good compounding.  See e.g.,
Compounding pharmacist meets unique needs of patients with cystic fibrosis and Compounded pain medications ease pain and restore quality of life  I have written about 
Damage Control 101: What Does the Compounding Industry Need to Do?

I am now wondering where have all the good guys and girls gone.  Where are the defenders of good compounded preparations?  Why isn't anyone talking about how your child couldn't take a certain tablet so your pharmacist compounded a liquid formula that your child could take.  Why aren't women telling us how a pharmacist  compounded hormones that have made all the difference in their lives.  Why isn't anyone talking about people who receive injections in their knees and backs, the injections made the pain bearable and these people  were not part of the meningitis outbreak.  Why aren't veterinarians or animal owners telling us how a compounded preparation saved a pet's live. I know there must be some good stories out there just waiting to be told.  When is the compounding world going to start telling them?

News & Events CDER Forum for International Drug Regulatory Authorities, June 2013

News & Events CDER Forum for International Drug Regulatory Authorities, June 2013

Pharmacists Have Admitted That Sterile Compounds Are Often Contaminated

As deaths continue to climb in the ongoing outbreak of fungal meningitis infections caused by contaminated pain shots, a new survey of hospital pharmacists shows that they believe it could happen again.
About 13 percent of pharmacists, pharmacy technicians and others who responded to a poll from the Institute for Safe Medication Practices said that they believed contamination had occurred in the compounded sterile drugs made by their shops last year.
Those are the same types of drugs now blamed for 45 deaths and nearly 700 infections in people who received tainted injectable steroids made by the shuttered New England Compounding Center of Framingham, Mass., according to the Centers for Disease Control and Prevention.

continue reading at:
Sterile drugs often contaminated, pharmacists admit




I continue to ask readers to submit their positive stories relating to compounded medications.  If you have such a story or know of one on the Internet that I have not already posted, please feel free to either comment or email it to me.  I would love to hear from doctors, pharmacists, veterinarians, consumers or anyone else who has a positive story to tell.

Should doctors and patients be informed when high-risk pharmacy compounded products are used?

Filed Under: Michael Cohen
POSTED: Friday, January 25, 2013, 9:34 AM
The fungal meningitis outbreak that’s been gripping the country since last fall has now affected 678 patients and caused 44 deaths. Contaminated steroid injections tied to the outbreak have led to a wake-up call about a dangerous gap in regulatory oversight of compounding pharmacies that mix some injectable medications. In an earlier blog, I noted that such compounded preparations are not approved by the FDA and pharmacies also are generally not FDA-inspected.  So there is inherent risk when a compounding pharmacy acts as a manufacturer using non-sterile drug powder. In most states, including Pennsylvania, compounding pharmacy sterile processes do not undergo intensive state inspection.
Should these conditions warrant disclosure to those prescribing and administering the medication and to patients who receive the compounded medications? Do healthcare providers even consider whether they have an ethical and legal obligation to inform end users when they dispense high risk sterile products (injectables made from non-sterile ingredients) prepared by a compounding pharmacy. To do that, doctors who inject these products need to be informed of the source. We decided to probe into pharmacy staff viewpoints about whether or not such transparency should be a part of the picture.
Results of a survey the Institute for Safe Medication Practices (ISMP) conducted in the fall were released this week and provide new insights into how hospitals have been managing the preparation and/or purchase of compounded high risk sterile products. Our survey was fielded in November and December and had 412 pharmacist and pharmacy technician respondents. Results were published in the January 24, 2013 issue of the ISMP Medication Safety Alert!®.
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Another Country Viewing Blog

Added Tanzania and Ghana

Cayman Islands