Thursday, May 3, 2012

Pharmacy Purchasing and Products: State of Pharmacy Compounding, April 2012

The April 2012 edition of Pharmacy Purchasing and Products addresses the state of pharmacy compounding.  This article has charts, diagrams, and surveys of compliance with 797.  Click here to view the article.  Click here to additional charts and information.
- No comments:
Labels: , ,

The Need for Reform in Compounding Laws: The Alabama Accident


The Need for Reform in Compounding Laws

The article below appeared on the Institute for Safe Medicine Practice(ISMP) website.  It addresses the Alabama Total Parenteral Nutrition (TPN) bags that were contaminated, infected 19 patients and resulted in 9 patients' deaths.  The article addresses the lack of enforcement of laws, regulations and pharmacy board standards relating to compounding.  For example, any sterile activity should be undertaken with great care and in compliance with the United  States Pharmacopeia (USP) Chapter 797, Pharmaceutical Compounding: Sterile Preparations. The National Association of Boards of Pharmacy (NABP) has incorporated the 797 requirement into its Model State Pharmacy Act and Model Rules. As the article points out the NABP does not have authority to enforce its recommendations. State boards of pharmacy, who could enforce such laws, vary as to their position on 797.  Some states have adopted the entire chapter into laws, regulations or board policies and procedures, some have incorporated only portions of 797, and some have not taken any action and do not require compliance with 797. Another point made in the article is that most state boards have insufficient funding to send experienced and trained inspectors to pharmacy operations to ensure compliance with 797.  Deaths such as those resulting in Francks, ApotheCure, and the Alabama case, show that change in enforcement of compounding standards needs to occur before anymore deaths occur.  The question is how to best implement the reforms needed.


TPN-related deaths call for FDA guidance and pharmacy board oversight of USP Chapter <797>

From the April 7, 2011 issue
Last week, the Alabama Department of Public Health (ADPH) reported an ongoing investigation of an outbreak of Serratia marcescens bacteremia associated with contaminated total parenteral nutrition (TPN) bags in six Alabama hospitals.(1-4) The outbreak was identified after two of the six hospitals reported an unusual number of cases of Serratia marcescens bacteremia to the ADPH and the Centers for Disease Control and Prevention (CDC). An investigation was immediately started.
A total of 19 patients from six hospitals were adversely affected after receiving the contaminated TPN. The CDC determined that all six hospitals had received TPN produced by a single compounding pharmacy, Meds IV. Nine of the 19 affected patients have died, although the CDC has not confirmed that the deaths were directly caused by the contaminated TPN.(3) Meds IV was notified about the contaminated TPN and is fully cooperating with the investigation.
To date, the investigation has uncovered traces of Serratia marcescens in the compounding room at Meds IV, although genetic testing will be required to determine whether the organisms found in the pharmacy caused the TPN contamination. Health officials also reported that seven newborns received TPN supplements from Meds IV in March, along with 41 adults. While 19 of those 41 adults got sick, none of the babies became ill.(4) Thus, the investigation is focusing on differences between compounding TPN for adults vs. neonates.
At this time, Meds IV has discontinued all production and has recalled all of its compounded preparations.
USP Chapter <797>
Any type of sterile compounding activities must be undertaken with great care and in compliance with the United States Pharmacopeia (USP) Chapter <797>, Pharmaceutical Compounding: Sterile Preparations. It is tragic events like this that compelled USP to first establish <797>, which was initially published in 2004 and revised in June 2008. Chapter <797> describes a network of systems and processes “to prevent patient harm and fatality from microbial contamination (nonsterility), excessive bacterial endotoxins, large content errors in the strength of correct ingredients, and incorrect ingredients in compounded sterile preparations (CSPs).”(5)
Increased use of compounding pharmacies for sterile preparations
In the past, most sterile compounding was completed in-house in hospital pharmacies. However, this trend has shifted over the years,(6-7) particularly after the 2008 revision of <797>, as many pharmacies found it difficult to meet all the requirements of the standard. A recent (1st quarter of 2011) survey conducted by Pharmacy Purchasing & Products showed that 66% of pharmacies outsource at least some portion of their sterile compounding. Reliance on compounding pharmacies has continued to rise due to an unprecedented escalation in shortages of parenteral drugs, including recent shortages of vitamins, electrolytes, and other pharmaceutical components of TPN.
From a safety perspective, it makes sense to outsource the compounding of CSPs. It is difficult and costly for hospitals to comply with all of the <797> standard if they prepare just a few parenteral CSPs each day. As a general rule, compounding pharmacies that prepare large quantities of CSPs may be better equipped to employ, enforce, and monitor ongoing compliance with all of the <797> standard. But should hospitals be wary of using a compounding pharmacy in light of this latest infection outbreak?
While it’s true that contamination of CSPs from a compounding pharmacy can result in large and serious outbreaks, ISMP believes the use of compounding pharmacies should not be summarily dismissed as a result of this tragic outbreak. However, we must state unequivocally that the real issue to be learned from this event is that better oversight and licensing and/or registration requirements for compounding pharmacies are required.
Enforcement of <797>
Compounding pharmacies frequently prepare very complex CSPs, many with high-alert medications intended for parenteral administration. Jay Mirtallo, A.S.P.E.N. president elect, noted in a March 30, 2011 press release on this latest infection outbreak (www.nutritioncare.org/Index.aspx?id=6174) that, “Parenteral nutrition by nature is one of the most complex sterile preparations to prepare, relying on a specific order of mixture as well as method of preparation to assure sterility, compatibility, and stability.” Thus, one might expect the Food and Drug Administration (FDA) to subject compounding pharmacies to the same strict current good manufacturing practices (cGMPs) that are routine for drug manufacturers. Or one might expect all state boards of pharmacy to hold compounding pharmacies accountable for meeting the <797> standard in its entirety. However, there is often little or no required regulatory or licensing/registration oversight of compounding pharmacies to ensure and enforce compliance with <797>.
Chapter <797> is enforceable by the FDA; the agency clearly has the authority to inspect pharmacies and enforce the standard in the interest of public health.(5) However, FDA defers to the individual states to regulate the practice of pharmacy and to perform inspections.5 In the 1970s, the National Coordinating Committee on Large Volume Parenterals (NCCLVP) of USP emerged to ensure high quality CSPs. But with the dissolution of this group in the 1980s, FDA turned to the profession of pharmacy to address problems with sterile preparation. Since the early 1990s, FDA has been aware of multiple problems with compounded preparations that have resulted in recalls, patient injuries, and deaths.(5) However, when we communicated with the FDA recently to discuss this event, no one could clearly articulate how the agency regulates compounding pharmacies.
The National Association of Boards of Pharmacy (NABP) has incorporated the <797> requirement into its Model State Pharmacy Act and Model Rules, noting that, “The board’s Good Compounding Practices Applicable to State Licensed Pharmacies, and the current USP-NF chapters on compounding and sterile pharmaceutical preparations” are to be adhered to by compounding pharmacies and pharmacists.(6) However, the Model Rules or requirements of the Model State Pharmacy Act are only enforced to the extent that they are adopted by individual states, as the NABP does not have authority to enforce its recommendations.
Individual state boards of pharmacy vary in regard to the position taken with respect to <797>. Some states have adopted the chapter in its entirety, but most have chosen to incorporate only portions of <797> into laws, regulations, or board policies and procedures.(5) Some states have taken no action and do not require compliance with <797>. In addition, most state boards have insufficient funding to send experienced and trained surveyors to actually inspect pharmacy operations to ensure compliance with <797>.
While The Joint Commission (TJC) requires organizations to comply with portions of <797> that are similar to its standards, TJC views <797> as a best practice and expects organizations to review best practices for the purpose of improving systems (MM.08.01.01). Thus, surveyors may expect an improvement plan based on <797>, but it is left to the accredited organization as to what they need to improve. TJC expects organizations to comply with <797> in states that require such compliance. However, most surveyors have not been adequately trained regarding <797> and would simply ask to see the latest state inspection results.
Lessons learned: Need for future oversight
As we move forward and learn from the most recent outbreak, we are calling upon all state boards of pharmacy to expect compounding pharmacies to comply with all aspects of <797>, and to survey these pharmacies regularly to enforce compliance. To do this, state pharmacy boards must be provided with additional resources to adequately train and deploy surveyors to assess compliance. Today, many pharmacy boards are ill equipped to take on this responsibility; without additional resources, the assignment of responsibility will not result in improved oversight. The pharmacy boards that choose a limited set of criteria from the <797> standard for enforcement in their states are ill-advised regarding its benefit to public safety; partial compliance will not even partially protect patients from the risk of infection from contaminated CSPs. The <797> standard is not set out as an incremental improvement plan; it’s a bundle that must be implemented in its entirety and on an ongoing basis to be effective. Each of the state boards of pharmacy must demand and expect their licensees to comply with <797>.
We are calling upon FDA to work collaboratively with the state boards of pharmacy to provide them with the necessary support and training to survey compounding pharmacies for compliance with <797>. Further, we believe compounding pharmacies that distribute sizeable quantities (to be defined by FDA) of preparations, and those operating interstate, should be registered with FDA and subject to periodic inspections. We also encourage FDA to move forward with plans to publish guidances on Good Pharmacy Compounding Practices for Sterile Drug Products, and Outsourcer Pharmacy Operations Compliance Policy Guide (www.ismp.org/sc?k=ucm079647), to clearly articulate requirements for registration with FDA, periodic inspections, support available to the state boards of pharmacy, and expectations regarding the state boards’ role in regulating compounding pharmacies.
We are calling upon TJC to consistently survey compliance with applicable parts of the <797> standard as it relates to the type of CSPs being prepared in accredited facilities in all states.
We are calling upon all pharmacies and pharmacists/technicians who compound sterile preparations, regardless of where they work, to know and comply with <797> to the fullest extent possible. Pharmacy staff should use commercially available ready-to-use products when available, or start with sterile products whenever possible if preparing CSPs. This applies to the smallest hospitals up to the largest compounding pharmacies. We also recommend establishing an internal quality surveillance and review team to regularly monitor compounded preparations, the environment, compounding equipment, and personnel for compliance with key aspects of <797>, much like an internal peer-review process. An April 2011 supplement to Pharmacy Purchasing & Products on the state of pharmacy compounding is an excellent resource to help guide the surveillance and improvement process.(8) Any problems uncovered during surveillance require immediate stoppage of compounding, investigation, corrective action, and revalidation before resumption of activities. All pharmacy staff have a moral and legal obligation to compound preparations using the least risky processes while adhering to the highest standards possible.
We don’t have all the details about this recent outbreak, but a crucially important lesson we can take away from this tragedy is that we all need to make improvements based on the outcome of this investigation. Unfortunately, there are too many in healthcare who feel that, if it hasn’t happened to them, the adverse experiences of others do not apply. If investigation into this event uncovers some aspect (e.g., frequency of testing staff samples and environmental samples) of compounding that was overlooked in either the <797> standard or in staff practices, then let’s learn from it, incorporate necessary changes, and provide leadership and oversight to assure our patients are kept safe.
ISMP thanks Eric S. Kastango, MBA, RPh, FASHP, CEO of ClinicalIQ, for his contribution to this article.
References
1) US Food and Drug Administration (FDA). Meds IV pharmacy, IV compounded products recall: outbreak of Serratia marcescens bacteremia in Alabama hospitals. March 30, 2011. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm249099.htm
2) US Food and Drug Administration (FDA). CDC and ADPH investigate outbreak at Alabama hospitals; products recalled. March 29, 2011. www.fda.gov/Safety/Recalls/ucm249068.htm
3) Watkins T. Contaminated IV solution suspected in 9 patient deaths in Alabama. CNN Health. March 29, 2011. www.cnn.com/2011/HEALTH/03/29/alabama.hospitals.deaths/index.html?hpt=T2
4) Wolfson H. Investigators piecing together tainted IV puzzle after deaths in Alabama hospitals. The Birmingham News. April 3, 2011. http://blog.al.com/spotnews/2011/04/investigators_piecing_together.html
5) American Society of Health-System Pharmacists (ASHP). The ASHP discussion guide on USP Chapter <797> for compounding sterile preparations. www.ashp.org/s_ashp/docs/files/DiscGuide797-2008.pdf
6) National Association of Boards of Pharmacy. Model State Pharmacy Act and Model Rules of the National Association of Boards of Pharmacy. Mount Prospect, IL. August 2007.
7) Seres D, Sacks GS, Pederssen CA, Johnson D, et al. Parenteral nutrition safe practices: results of the 2003 American Society for Parenteral and Enteral Nutrition Survey. J Parenteral and Enteral Nutrition. 2006;30(3):259-65.
8) Pharmacy Purchasing & Products (PP&P). 2011 state of pharmacy compounding; PP&P’s 4th annual national survey. April 2011.
- No comments:
Labels: , , , , , ,

Wednesday, May 2, 2012

FDA's Final Strategic Plan: Key Initiatives Relating to Compounding


The FDA's Final Strategic Plan for the Foods and Veterinary Program, which was announced on April 23, 2012, provides the following initiatives related to compounding:

7.2 – Reduce availability of substandard and illegally marketed animal drugs.
The FVM Program is concerned about the number of unapproved animal drug products that are being sold and marketed to animal owners and veterinarians. To reduce the risk of harm from substandard and illegally marketed animal drugs, the program will identify new regulatory frameworks and enforcement strategies to combat this growing area of concern.

Key Initiatives
7.2.1: Develop risk‐based frameworks that assure quality and safety for animal drug products that are currently being marketed without FDA approval.
7.2.2: Develop and implement an enforcement strategy that addresses the illegal compounding of new animal drugs and removes unsafe, ineffective or copycat animal drugs from the market.
- No comments:
Labels:

FDA Announces Final Strategic Plan for the Foods and Veterinary Medicine Program


FDA Announces Final Strategic Plan for the Foods and Veterinary Medicine Program

April 23, 2012
The U.S. Food and Drug Administration (FDA) announces the release of the final Strategic Plan for the Foods and Veterinary Medicine Program (FVM) for 2012-2016. The plan addresses the responsibilities of the Center for Food Safety and Applied Nutrition and the Center for Veterinary Medicine while including activities supported by the Office of Regulatory Affairs. The plan illustrates the breadth and complexity of the program’s work and identifies priority initiatives. It outlines seven strategic program goals, each encompassing its own key objectives, as well as nearly 100 specific initiatives aimed at achieving goals and objectives.
The draft Strategic Plan was published on September 30, 2011, with a thirty-day comment period. The FDA carefully reviewed and considered all submitted comments before issuing this final Strategic Plan.

Click here to view the final plan.
- No comments:
Labels: ,

FDA Website with Index to Major Warning Letters


FDA's website http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/

PharmacyCompounding/default.htm contains an index with links to major compliance 

actions and major warning letters issued to compounder through March 2011.  Anyone

considering doing business with a compounder should check to see if warning letter or 

action has been taken by the FDA or the state pharmacy boards.    The index for the FDA

website  appears as follows:

Pharmacy Compounding


Pharmacy Compounding News


Significant Compliance Actions



Compounding Surveys

- No comments:
Labels: ,

Tuesday, May 1, 2012

DOJ/FDA reply to Franck's and Amici Waiver Argument

In addressing the waiver argument raised by Franck's and amici, DOJ/FDA contends:
The government's brief cites numerous instances in the record where it argued and documented that the factual basis of this action for injunctive relief is that Franck's animal drug compounding activities exceed the bounds of traditional pharmacy compounding and are indicative of large-scale drug manufacturing, as described in CPG 608.400.
DOJ/FDA also explains that this case involves a question of law--not the specific facts--of the case.  It  states,  "To be sure, the fundamental issue in this case is a question of law, the resolution of which depends on analysis of the FDCA, not on any specific facts."  Nonetheless, DOJ/FDA argues it is both necessary and logical to discuss FDA's enforcement policy and application of that policy to the facts on which the complaint for injunctive relief was based.  DOJ/FDA argues it has not waived the argument because it has not belatedly raised a new theory.  More specifically, its brief contains the following argument:
Contrary to Franck's claims, the government has not belatedly raised an "alternative theory" of its case – that compounded animal drugs are unlawful only when prepared in an operation resembling manufacturing. There is but one theory of this case: New animal drugs compounded by pharmacies are not exempt from the FDCA and never were, and they are accordingly subject to FDA's enforcement authority. However, FDA recognizes that compounded animal drugs can serve beneficial public health purposes. Thus, pursuant to its consistent, longstanding policy, FDA undertakes enforcement action against compounding pharmacies only when the scope and nature of their activities "raise the kinds of concerns normally associated with a drug manufacturer and result in significant [FDCA] violations." CPG 608.400, Doc. 17-2, Ex. A at 4. Because Franck's animal drug compounding operations raise such concerns, the government brought this action to enjoin Franck's further violations of the Act. That has been the government's position throughout this litigation. 
Ultimately, DOJ/FDA contends that government counsel's previous comments at the district court level are not sufficient to show waiver:
Citing excerpts from government counsel's responses to questions during district court oral argument, Franck's Lab contends further that FDA has waived certain other arguments, e.g., the relevance of AMDUCA and other FDCA provisions to the statutory interpretation question at issue. As FDA's opening brief notes (at 41 & n.15), government counsel's comments do not support Franck's waiver claim. Moreover, this Court has held that "waivers and concessions made in appellate oral arguments need to be unambiguous before they are allowed to change the outcome of an appeal," and such comments should be considered in the context of the party's briefs and entire presentation. Crowe v. Coleman, 113 F.3d 1536, 1542 (1997). See also Moose Lodge v. Irvis, 407 U.S. 163, 170, 92 S. Ct. 1965, 1970 (1972) ("We are loath to attach conclusive weight to the relatively spontaneous responses of counsel to equally spontaneous questioning from the Court during oral argument."). That same principle should apply to counsel's comments during district court arguments.Thus, considering the government's complaint, arguments in support of its motions for a preliminary injunction and summary judgment, declarations, and other evidence, snippets of government counsel's argument in district court cannot reasonably be construed as concessions or waivers of any legal arguments. Cf. Savoury v. U.S. Attorney General, 449 F.3d 1307, 1318-19 (11th Cir. 2006) (even if estoppel applies to government, willfulness and negligence, inter alia, must be shown). 
- No comments:
Labels: , ,

Summary in DOJ's Reply Brief in Franck's


Here is the introduction and summary from the government's reply brief in Franck's:


INTRODUCTION AND SUMMARY 

    Like the definition of "new drug" for human use, the definition of "new animal drug" in the Federal Food, Drug, and Cosmetic Act ("FDCA" or "the Act") is sweeping and straightforward – "any drug intended for use for animals other than man" that "is not generally recognized * * * as safe and effective under the conditions prescribed." 21 U.S.C. § 321(v)(1) (emphasis added); compare id. § 321(p)(1) ("new drug" definition). When a pharmacy compounds a drug for animal use, it creates a Case: 11-15350 Date Filed: 05/01/2012 "new animal drug" because the compounded product is not generally recognized by experts as safe and effective, and it has not been subjected to the controlled clinical trials that are necessary to establish its safety and effectiveness. Even a drug that is a copy of an approved animal drug is a "new animal drug" that must be independently established as safe and effective when produced by a party other than the one that holds FDA approval for the drug. Although Congress has carved out a few exceptions to the "new animal drug" definition and the FDCA's approval and other requirements for such drugs, it has enacted no unconditional exemption for new animal drugs compounded by pharmacies.   

     Thus, the consistent position of the Food and Drug Administration ("FDA" or "the agency") – based on the Act's plain language and documented in litigation, FDA's Compliance Policy Guides ("CPG"), and regulations – has been that pharmacy-compounded drugs for human and animal use are "new drugs" and "new animal drugs" that require FDA approval before they can be lawfully distributed in interstate commerce.  At the same time, however, FDA recognizes that drug compounding is part of traditional pharmacy practice, and, when compounded pursuant to valid prescriptions for individual patients, compounded drugs can serve important public health purposes by meeting the needs of patients for whom approved, commercially available drugs are inadequate. For that reason, FDA has 2 Case: 11-15350 Date Filed: 05/01/2012 historically declined, and continues to decline, to take enforcement action against pharmacies engaged in traditional compounding activities. However, when evidence shows (as in this case) that a pharmacy's activities substantially exceed the bounds of traditional compounding, and the pharmacy is effectively engaged in drug manufacturing masquerading as compounding, without compliance with FDCA approval and other requirements, the agency takes enforcement action. 

     Three other circuits have squarely held that pharmacy-compounded animal drugs are "new animal drugs" under the Act and are therefore subject to FDA's enforcement authority. Med. Ctr. Pharmacy v. Mukasey, 536 F.3d 383, 408 (5th Cir. 2008) ("Medical Center"); United States v. Algon Chem. Inc., 879 F.2d 1154, 1158, 1160 (3d Cir. 1989); United States v. 9/1 Kg. Containers, 854 F.2d 173, 179 (7th Cir. 1988), cert. denied, 489 U.S. 1010, 109 S. Ct. 1118 (1989). No circuit has held otherwise.  Moreover, the Supreme Court has discussed approvingly FDA's enforcement policy and affirmed that "the Government needs to be able to draw a line between small-scale compounding and large-scale drug manufacturing." Thompson v. W. States Med. Ctr., 535 U.S. 357, 361-63, 370, 122 S. Ct. 1497, 1501-02, 1505 (2002) ("Western States"). 

     This appeal presents the same fundamental question of law answered by the courts in Medical Center, Algon, and 9/1 Kg. That question arises in the context of 3 Case: 11-15350 Date Filed: 05/01/2012 a rare civil enforcement action initiated by FDA against a pharmacy whose compounding activities have demonstrably exceeded the bounds of traditional pharmacy practice and resemble large-scale drug manufacturing. The undisputed record supporting FDA's request for injunctive relief (largely overlooked by the district court) shows that the animal drug compounding activities of Franck's Lab – as its name, extensive product catalog, operations, and documented history of FDCA violations over several years suggest – is more indicative of a manufacturer than the corner drugstore that compounds a lifesaving medication for the family dog pursuant to a veterinarian's individualized prescription. 

    Thus, this case is not about whether traditional pharmacy compounding can serve important public health purposes; it can and does. This appeal concerns whether Congress has authorized FDA to take enforcement action against pharmacies when their compounding activities pose a threat to public health because they are manufacturing drugs, but evading the FDCA's approval and other requirements that Congress enacted to protect public health. 

     Franck's Lab acknowledges, as it did in district court, that FDA has authority to take enforcement action against entities engaged in unlawful drug manufacturing, but it fails to identify the source of that authority and to explain where the "line between small-scale compounding and large-scale drug manufacturing" lies. Western 4 Case: 11-15350 Date Filed: 05/01/2012 States, 535 U.S. at 370, 122 S. Ct. at 1505. Those failures are fatal to Franck's Franck's Lab and its amici grossly misrepresent FDA's position (see, e.g., Franck's Br. 10), characterizing it as extreme, when, in fact, this action represents a judicious exercise of the agency's enforcement authority against a pharmacy that has repeatedly flouted the law and FDA warnings. 
     
     Franck's Lab and its amici contend that FDA has changed its policy and has acted inconsistently. Not so; the agency's position here is fully consistent with the position that it has repeatedly taken in other litigation over many decades and that is set forth in FDA's publicly available enforcement guidance. Franck's Lab claims that the federal government's action here clashes with sovereign State interests, but, notably, Franck's Lab has not, and cannot, identify any such tension. Finally, Franck's claim that the government has conceded or waived certain arguments is baseless.

- No comments:
Labels: ,

DOJ's Reply Brief in Franck's

The government's reply brief in Franck's has been filed.  Click here to view brief.
- No comments:
Labels: ,

Benefits and Risks of Pharmacy Compounding


This article appears on the United States Food and Drug Administration Website.  Although published in 2007 and geared toward drugs for humans, it contains key points as to why compounding of medication is needed, the special risks of pharmacy compounding if the rules and regulations are not followed, red flags to watch for and a checklist for consumers:

The Special Risks of Pharmacy Compounding

On this page:
Pharmacy compounding is an age-old practice in which pharmacists combine, mix, or alter ingredients to create unique medications that meet specific needs of individual patients.
It's also a practice that is under FDA scrutiny—mainly because of instances where compounded drugs have endangered public health.
"In its traditional form, pharmacy compounding is a vital service that helps many people, including those who are allergic to inactive ingredients in FDA-approved medicines, and others who need medications that are not available commercially," says Kathleen Anderson, Pharm.D, Deputy Director of the Division of New Drugs and Labeling Compliance in FDA's Center for Drug Evaluation and Research (CDER).
Compounded medications are also prescribed for children who may be unable to swallow pills, need diluted dosages of a drug made for adults, or are simply unwilling to take bad-tasting medicine.
"But consumers need to be aware that compounded drugs are not FDA-approved," Anderson says. "This means that FDA has not verified their safety and effectiveness."
Steve Silverman, Assistant Director of CDER's Office of Compliance, says that poor practices on the part of drug compounders can result in contamination or in products that don't possess the strength, quality, and purity required. "And because patients who use these drugs may have serious underlying health conditions," he says, "these flawed methods pose special risks."
Unlike commercial drug manufacturers, pharmacies aren't required to report adverse events associated with compounded drugs. "FDA learns of these through voluntary reporting, the media, and other sources," says Silverman.
The Agency knows of more than 200 adverse events involving 71 compounded products since 1990. Some of these instances had devastating repercussions.
  • Three patients died of infections stemming from contaminated compounded solutions that are used to paralyze the heart during open-heart surgery. FDA issued a warning letter in March 2006 to the firm that compounded the solutions.
  • Two patients at a Washington, D.C., Veterans Affairs hospital were blinded, and several others had their eyesight damaged, by a compounded product used in cataract surgery. The product was contaminated with bacteria. In August 2005, FDA announced a nationwide recall of this Trypan Blue Ophthalmic Solution. Contaminated solution had been distributed to hospitals and clinics in eight states.
  • In March 2005, FDA issued a nationwide alert concerning a contaminated, compounded magnesium sulfate solution that caused five cases of bacterial infections in a New Jersey hospital. A South Dakota patient treated with the product developed sepsis and died.

A Troubling Trend

The emergence over the past decade of firms with pharmacy licenses making and distributing unapproved new drugs in a way that's clearly outside the bounds of traditional pharmacy is of great concern to FDA.
"The methods of these companies seem far more consistent with those of drug manufacturers than with those of retail pharmacies," says Silverman. "Some firms make large amounts of compounded drugs that are copies or near copies of FDA-approved, commercially available drugs. Other firms sell to physicians and patients with whom they have only a remote professional relationship."
FDA highlighted these concerns in August 2006, when it warned three firms to stop manufacturing and distributing thousands of doses of compounded, unapproved inhalation drugs nationwide.
Inhalation drugs are used to treat diseases including asthma, emphysema, bronchitis, and cystic fibrosis. "These are potentially life-threatening conditions for which numerous FDA-approved drugs are available," says Silverman. "Compounded inhalation drugs may be distributed to patients in multiple states, and patients and their doctors may not understand that they are receiving compounded products."

Enforcement

"FDA historically hasn't directed enforcement against pharmacies engaged in traditional compounding," says Anderson. "Rather, we've focused on establishments whose activities raise the kinds of concerns normally associated with a drug manufacturer and whose compounding practices result in significant violations of the new-drug, adulteration, or misbranding provisions of the Federal Food, Drug, and Cosmetic Act."
FDA counts compounded drugs among the new drugs that are covered under the Act. "We consider them new because they're not generally recognized among experts as safe and effective," says Anderson.
She adds that FDA recognizes that states have a central role in regulating pharmacy compounding. "We refer complaints to the states, support them when they request it, and cooperate in investigations and follow-up actions. But there are cases when states are unable to act, and we proceed without them," Anderson says.

Red Flags

In a May 29, 2002, Compliance Policy Guide devoted to human pharmacy compounding, FDA identifies factors that it considers in deciding upon enforcement action. These factors include instances where pharmacists are:
  • compounding drug products that have been pulled from the market because they were found to be unsafe or ineffective.
  • compounding drugs that are essentially copies of a commercially available drug product.
  • compounding drugs in advance of receiving prescriptions, except in very limited quantities relating to the amounts of drugs previously compounded based on valid prescriptions.
  • compounding finished drugs from bulk active ingredients that aren't components of FDA-approved drugs, without an FDA-sanctioned, investigational new-drug application.
  • receiving, storing, or using drug substances without first obtaining written assurance from the supplier that each lot of the drug substance has been made in an FDA-registered facility.
  • failing to conform to applicable state law regulating the practice of pharmacy.

What You Can Do

What can consumers do to protect themselves against inappropriate drug-compounding practices? Ilisa Bernstein, Pharm.D, J.D., Director of Pharmacy Affairs in FDA's Office of the Commissioner, offers these tips:
  • Ask your doctor if an FDA-approved drug is available and appropriate for your treatment.
  • Check with the pharmacist to see if he or she is familiar with compounding the product in your prescription.
  • Get information from your doctor or pharmacist about proper use and storage of the compounded product.
  • If you receive a compounded product, ask the pharmacist if the doctor asked for it to be compounded.
  • If you experience any problems or adverse events, contact your doctor or pharmacist immediately and stop using the product.
  • Report any adverse events experienced while using the product to FDA's MedWatch program5.
Date Posted: May 31, 2007
Page Last Updated: 03/14/2012 
- No comments:
Labels: , ,

Government's Reply Brief in Franck's Case Due Today

The Department of Justice (DOJ), who represents the United States Food and Drug Administration, reply brief is due today, May 1, 2012, in the Franck's case.  A reply brief is normally limited both in page number (15 pages or no more than 7,000 words) See Fed. R. App. P. 28.1(e)(1) and 28.1(e)(3); 37(a)(7)(b)(ii) and arguments in that the party replying normally can address only the arguments the other party made and is generally prohibited from raising any new arguments.  See Fed. R. App. P. 27(a)(4) ("A reply must not present matters that do not relate to the response).  Franck's most likely will not be able to file a brief in response to DOJ's reply brief.  See Fed. R. App.  P. 28(c)("Unless the court permits, no further briefs may be filed.").   The parties filing as amicus also cannot file a reply brief without permission from the court.  See Fed. R. App. P. 29(f).   DOJ has until midnight in the court's time zone (Eastern Time Zone)  to file the reply.  See Fed. R. App. P. 26(a)(4)(a).  As soon as DOJ's reply brief is filed and available, it will be posted here.
- No comments:
Subscribe to: Posts (Atom)