Imprimis Pharmaceuticals Innovates Back to Basics With Compounding

CHICAGO(TheStreet) -- Although the number of people needing custom medicines and new ways to take them is growing exponentially, there are few pharmaceuticals companies positioned to take advantage of the trend.

Enter Imprimis Pharmaceuticals (IMMY_).

The California company has a unique combination of delivery methods and partner that make it worthy of attention as more people worry about the harmful long-term effects of certain mass-produced medications.

 

For instance, nonsteroidal anti-inflammatory drugs such as Advil, Motrin and Aleve have been shown in studies to cause stomach ailments. "Gastritis, esophageal reflux disease and bleeding ulcers are all problems that can develop from NSAIDs," says Robert Hoffman, chief of rheumatology at the University of Miami's Miller School of Medicine.

Such mass-produced drugs have developed into a multibillion-dollar industry since industrialization became the norm in the 1950s. Imprimis CEO Mark Baum looks to the era before that, though, when it was common for pharmacists to blend custom prescriptions for individual customers. He thinks his company can make strides to revolutionize modern drug compounding, improving their quality and moving them swiftly through Food and Drug Administration approvals.

Imprimis has a drug delivery technology that ensures site-specific treatment via a topical cream preparation, including with Impracor, a drug entering Phase 3 approvals from the FDA in the third quarter of 2013, and a variety of others that "will enable the delivery of drugs intravenously... as well as through the mouth, through the nose, and trans-vaginally, which gives us the ability... to affect men's health, women's health, as well as [avoid] gastrointestinal conditions," Baum says.

The technology could revolutionize the way pharmaceuticals, especially analgesics, are accessed and administered, Baum says.

Imprimis already uses its Transdel technology to deliver an NSAID called ketoprofen via a cream that is rubbed on the skin, where it acts on the underlying tissues to ease pain.

Imprimis' partner in the revolution is the Professional Compounding Centers of America, "the largest player in the compounding pharmacy industry in North America," Baum says. "The PCCA has over 10,000 proprietary compounded drug formulations and ... more than a dozen proprietary drug delivery technologies," and Imprimis has an exclusive relationship with the PCCA to develop and commercialize its library of patented formulations and technologies -- to mine the library for drugs that can be developed internally or through a development partner.

This library has the potential to provide Imprimis with multiple large-market drug candidates annually, Baum says, saving cost and time. Since all the formulations have been used by the PCCA's patients, ample data are available on their performance and safety that Imprimis can use in putting drugs through the federal 505(b)(2) approval pathway.

"These are drug formulations that are typically sold by ... compounded pharmacies all over the country. Imprimis is taking them through a traditional regulated FDA process in order to bring them to the market," Baum says.

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Tennessee board adds new rules for compounding pharmacies

Tennessee board adds new rules for compounding pharmacies

Duane Morris Has Done Another Great Job of Summarizing the Revised Senate Bill Providing Federal Oversight for Compounding Pharmacies

It can be read here:  United States: Senate HELP Committee Releases Revised Senate Bill Providing Federal Oversight for Compounding Pharmacies

Last Updated: July 30 2013

Article by Rachael G. Pontikes and Elinor L. Hart

Duane Morris LLP

MUST READ--July 26, 2013 FDA Soliciting Input on Global Supply Chain Provisions in FDASIA --Meeting in August will address compounding questions

In a recent post from the FDA Voice Blog, Office of Compliance Director for FDA's Center for Drug Evaluation and Research (CDER) wrote about the agency's future activities to help combat the globalized supply chain—in particular about the Food and Drug Administration Safety and Innovation Act (FDASIA).

In addition to sharing his priorities about resolving problems regarding drug compounding, Office of Compliance Director Howard Sklamberg noted that one of his main priorities is the globalized supply chain. He noted how today, "nearly 40 percent of the drugs Americans take are imported and nearly 80 percent of the active ingredients come from overseas sources." He also recognized that a "growing number of clinical trials that test the safety and effectiveness of potential new drugs are also moving overseas, making FDA oversight more challenging."

He also identified that "counterfeit drugs are proliferating around the world and sometimes even entering the U.S. supply chain" and the "ever burgeoning worldwide use of the Internet continues to spawn avenues for illegal online sales of medicines of unknown safety and quality."

Confirming other priorities of the U.S. Department of Justice and recent FDA activities, Sklamberg also noted that "poor manufacturing practices that lead to facility shut-downs often contribute to shortages of important drugs," and another agency priority will be to "ensure that wherever drugs are made, wherever their ingredients are from, or wherever and however they are tested and sold, that they meet FDA's strict standards of quality and that they remain in adequate supply."

- See more at: http://www.policymed.com/2013/07/fda-soliciting-input-on-global-supply-chain-provisions-in-fdasia.html#sthash.qri27XjK.dpuf

Two more Michigan deaths linked to tainted steroid injections July 29, 2013

Two more Michigan residents have died in connection with a fungal meningitis outbreak that began last year and has sickened about 750 people nationwide.

A 64-year-old woman and a 75-year-old man, both of Livingston County, died after receiving tainted steroid injections. State health officials confirmed July 22 that their deaths were linked to the outbreak, said Angela Minicuci, public information officer for the Michigan Department of Community Health.

Minicuci said both people had developed epidural abscesses, or infections at the site of injection.

Beginning in May 2012, the Massachusetts-based New England Compounding Center shipped 17,000 vials of contaminated preservative-free methylprednisolone acetate to facilities in 23 states, leading to the deadly outbreak. Steroid shots are a relatively common treatment for back pain.

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Court Ruling Threatens Drug Shortage Remedy--May Effect K-V and Compounding Issues

Court Ruling Threatens Drug Shortage Remedy

By JILL WECHSLER | Published: JULY 29, 2013

The Food and  Drug Administration may no longer be able to alleviate shortages in vital drugs by permitting the import of unapproved medicines following a decision by the Court of Appeals for the District of Columbia. The ruling of July 23, 2013 also raises broader questions about when and how FDA can “exercise regulatory discretion” in deciding certain  policy and enforcement issues.

According to a unanimous decision by a three-judge panel, FDA’s action to permit import of thiopental from an unregistered foreign establishment was “not in accordance with law,” even though the aim was to address the shortage of a needed medicine. The ruling in Cook et al v. FDA (case No. 12-5176), which upholds a previous decision by a federal district court, involves a shortage of thiopental sodium, which created serious problems for state  

law enforcement

officials seeking to use it in delivering lethal injections. A group of death row inmates from three states filed suit, claiming that FDA violated the law by improperly allowing shipments of a misbranded and unapproved new drug to enter the U.S.

The Appeals Court specifically rejected FDA’s argument that it can legally address drug shortages by permitting the import of drugs approved by other regulatory authorities. Among its various tools for combating serious short supply situations, FDA also cites authority to allow distribution of a product suffering from quality problems, but found by the agency to “not cause undue risk to patients.” Other FDA relief strategies are to work with sponsors to resolve manufacturing issues, expedite inspections and reviews of short supply products, identify additional manufacturers willing to initiate or increase production, extend product expiration dates, and help firms qualify new sources of raw materials.

FDA has permitted unapproved imports 17 times in recent years, according to its announcement in May on authorizing the import of injectable total parenteral nutrition (TPN) solutions. These products are desperately needed by hospitals to treat premature infants unable to eat or drink, as well as cancer patients undergoing gastrointestinal surgeries. In this case, FDA authorized Fresenius Kabi USA to import TPN products from its Norway plant. The agency took this step after American Regent/Luitpold shut down operations at the end of 2012 to address quality issues that left particulate matter in injectable products. In this and other cases, FDA says that it evaluates the overseas drug to ensure that it is of adequate quality and informs doctors of the status of the imported product.

The July Appeals court ruling is regarded as a victory for death penalty opponents, who had pressured other manufacturers to discontinue production of thiopental and other “death drugs.” Yet state officials had urged FDA to appeal last year’s district court ruling in order to obtain needed supplies to carry out executions according to law. In that earlier lower decision, the judge accused FDA of hypocrisy, pointing out that the agency prevents consumers from purchasing medicines over the Internet because it deems the products misbranded and unapproved. The Appeals Court agreed, noting that FDA can address specific shortages through other strategies, such as designating an unapproved foreign drug as investigational to allow its importation.

This legal challenge to FDA use of enforcement discretion also could provide support for K-V Pharmaceuticals, which is challenging FDA’s failure to block competitors from producing the pre-term birth drug Makena (hydroxyprogesterone caproate injection). In this case, explains attorney Kurt Karst of Hyman, Phelps & McNamara, the D.C. District Court has sided with FDA, stating that the agency has the right to refuse to take action to stop pharmacy compounding of the drug. Kurt speculates in the FDA Law Blog that the recent Cook case will have a “huge effect” on how it deals with drug shortages [see www.fdalawblog.net July 23, 2013].

 

quoted from here

Pharmacy Compounding Primer

Pharmacy Compounding Primer
for Physicians
Prescriber Beware
Sarah Sellers1
and Wulf H. Utian2
1 q-Vigilance LLC, North Barrington, IL, USA
2 Case Western Reserve University, Cleveland, OH, USA

this article can be read here

Drug Topics Committee calls for Senate action on updated compounding bill -

 

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The U.S. Senate Health, Education, Labor and Pensions (HELP) Committee called for the Senate to act on its bill to provide clear oversight of compounding manufacturers, following the 2012 fungal meningitis outbreak, and to protect the U.S. drug supply chain from counterfeiting and theft, according to a HELP Committee statement on July 25.

 The updated legislation, S. 959, known as the “Pharmaceutical Quality, Security, and Accountability Act,” includes the “Pharmaceutical Compounding and Quality and Accountability Act” (Title 1) and the “Drug Supply Chain Security Act” (Title 2).

Under Title 1, the bill distinguishes between traditional compounding for humans that will continue to be regulated by state boards of pharmacy and compounding manufacturers that will be regulated by FDA. Compounding manufacturers are defined as manufacturers that produce sterile products without, or in advance of, a prescription and then sell across state lines.

Title 1 still allows traditional compounding pharmacies to compound for healthcare practitioners for office use, but sets the limit to 10% of products that the compounding pharmacy can dispense. Within 14 days of dispensing, the pharmacies must reconcile the names of patients who will receive the office use product, the HELP Committee noted.

FDA will be able to develop a list of drugs that cannot be compounded and bulk ingredients that cannot be used in compounded products. Also, there is be streamlined notice for compounding during a drug shortage, which allows for a single notice by the compounder that is copying an FDA-approved drug, according to Title 1.

Compounding manufacturers will only be able to compound nonsterile drugs from a list developed by FDA. However, they will be allowed to repackage biologics without a prescription. All compounding manufacturers will be listed on the FDA’s website, including the state where they are registered. When compounding manufacturers register, they must include a list of products that they produced in the last 6 months.

“This bill is about saving lives, plain and simple. The most recent compounding outbreak resulted in 61 deaths. More than 700 people continue to suffer from tainted compounded medicine. We must find reasonable ways to prevent further death or illness due to confusion over who has oversight of compounding pharmacies,” said Sen. Pat Roberts (R-Kan.) during the release

JUL 29, 2013

 of this updated bill.

Under Title 2, within 4 years of enactment of this legislation, all prescription drugs will be tracked from the manufacturer to the pharmacy. Manufacturers will have to serialize their products, provide transaction information, transaction history, and transaction statements in an electronic format to their trading partners.

“This bill establishes a uniform system that improves the security and safety of drugs for consumers,” Sen. Richard Burr (R-N.C.) said during the release of the updated legislation.

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Senators Propose Amendments To S. 959-RX Trace

As many of you pointed out to me in private emails last Friday after I had claimed that things had been quiet, there had indeed been some significant activity on S. 959, “Pharmaceutical Quality, Security, and Accountability Act” (PQSA) that occurred last week.  Even though the bill was awaiting action on the Senate floor, the bill managers in the Senate are apparently able to pull it back and amend it, and that’s what they did.  The bill is a combination of the “Pharmaceutical Compounding Quality and Accountability Act” and the “Drug Supply Chain Security Act” and my interest is in the latter so I will limit my analysis to that part of the current bill.

The amendments are fairly light and sprinkled throughout.  Most have little to no affect on the meaning or implementation of the bill–these include reformatting, corrections and minor logical adjustments–but there are a few things that are notable.

Most significantly, manufacturers would be required to provide their transaction information, transaction history, and transaction statement in a single document only in electronic formstarting 4 years after enactment.  Prior to that point they could provide it in either electronic or paper form.  What’s interesting about this change is how it would trickle down the supply chain.

On the surface you would expect that the authors of the bill would need to include a similar requirement on the wholesalers, dispensers and repackagers, but they did not do that.  It is not necessary because, wholesalers were already required to receive that information from the manufacturer.  Once the manufacturer can only provide it in electronic form 4 years after enactment, then wholesalers must be able to receive and store it electronically to remain in compliance at that same time.

Once wholesalers begins to receive the transaction information, history and statements from the manufacturers in electronic form it appears that the bill would allow them to convert them to paper whenever they need to pass them on to their customer.  That is, at least until the enhanced drug distribution security provisions would kick in 10 years after enactment.  By that time, everyone would have to create, store and exchange these documents electronically.

But this brings me to the next significant amendment to the bill.  There is a new and poorly worded section under the Product Tracing section called “Trading Partner Agreements”.  The section says:

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FDA CDER Schedule for Guidance Agenda: for 2013

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 Impuritiesin 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 Version: 07.26.13. Guidances with (*) indicates an addition since previous posting.
CATEGORY —Clinical/Antimicrobial
• Antibacterial Therapies for Patients with Limited or No Alternative Therapies for the Treatment of
Serious Bacterial Disease
• 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
• Standards for Clinical Trial Imaging Endpoints
CATEGORY – CMC and CLINICAL/MEDICAL
• Immunogenicity Assessment for Therapeutic Protein Products
CATEGORY —Clinical Pharmacology
• Bioanalytical Methods Validation