Compounding the woes of cancer patients

Three compounding pharmacies in as many weeks have issued voluntary recalls of their sterile products, heightening concerns about the safety of compounded drugs and infusion products.

Cancer patients are among those at risk. Med Prep Consulting Inc. issued its recall after a Connecticut hospital reported particulates, later identified as fungus, floating in five 50 mL bags of magnesium sulfate IV solution. The fungus was spotted during routine surveillance of intravenous bag preparation by an oncology nurse at Smilow Cancer Hospital at Yale-New Haven (Conn.).

"We bought quite a number of medicines from Med Prep, and we removed all its products immediately from circulation across the hospital following the discovery of this particle," hospital spokesperson Robert Hutchison said in an interview.

The contaminated product did not reach patients at the hospital, but last year’s deadly meningitis outbreak from contaminated methylprednisolone, manufactured by the New England Compounding Center, highlights the dangers of contaminants that aren’t visible. Yale-New Haven Hospital is working closely with state and federal regulatory agencies on how best to move forward while seeking alternative sources for the roughly 40 different products purchased from Med Prep.

"Like many other hospitals, at Yale-New Haven we purchase certain medicines from these pharmacies because our hospital base pharmacies cannot produce the quantity of certain medicines that we require to treat our patients," Mr. Hutchinson said.

The corticosteroid dexamethasone and the antibiotics gentamicin and vancomycin were among those voluntarily recalled by Med Prep.

Societies not taking positions

The American Society of Clinical Oncology reported not being aware of any cancer patients directly affected by the recalls, but has expressed concerns that frail, immunocompromised cancer patients could be receiving contaminated products. ASCO, which has taken a strong role in the oncology drug shortage, is looking into the compounding issue but has not set a date for completing its "due diligence."*

The Hematology/Oncology Pharmacy Association also has not formulated a position on pharmacy compounding, said immediate past-president Lisa M. Holle, PharmD.

The American Cancer Society is unlikely to take up the issue unless it becomes cancer specific, said Dr. J. Leonard Lichtenfeld, deputy chief medical officer. When hospitals go to the grey market for medications, they should be able to do so with confidence that the products they receive are produced in good faith. He pointed to a counterfeit version of the cancer drug bevacizumab recently distributed in the United States without any active ingredient.

Large drug companies are not immune to recalls. Hospira Inc. issued a nationwide recall March 29 for 0.9% sodium chloride injection because brass particulates were found in the product.

Although compounding pharmacies produce only 2%-3% of U.S. prescriptions, some 70% of hospitals have outsourced at least one product, according to Christopher Topoleski, director of federal regulatory affairs for the American Society of Health System Pharmacists (ASHSP), which represents some 40,000 hospital-based pharmacists.

The society held a summit in February along with other stakeholders, including the American Hospital Association, to discuss solutions for the issues surrounding sterile compounding. It also recommended in a letter to the U.S. Department of Health and Human Services a list of characteristics – such as volume, risk level of the compound being prepared, absence of a patient and health care professional relationship, and interstate shipment – that could be used to identify compounders in need of federal oversight.

Although it’s a good starting point, Mr. Topoleski acknowledged that it won’t be easy defining this new breed of nontraditional compounder. For example, small compounding pharmacies may engage in interstate commerce in metropolitan areas like Washington D.C. that span multiple states, while multihospital systems also centrally compound and distribute across state lines. Legal ambiguity also needs to be clarified over when the Food and Drug Administration has authority under the federal Food, Drug, and Cosmetic Act and when individual states’ responsibilities pick up.

"It’s not going to be a clear cut black-and-white line," he said. "There will still be cases that will need to be looked at individually, but I think it’s going to be additional legislation we’ll need to address."

Greater regulation needed

Regulatory agencies and the pharmaceutical industry are promoting track-and-trace systems as one way to fight counterfeit drugs and to ensure that the quality-control chain of compounded products has not been broken.

"Clearly, at the provider end, it is absolutely essential that we have important drugs available to help our patients treat their cancer, manage their symptoms, and deal with any other medical conditions they have and to do it with absolute safety. Those are requirements, they’re not options," said Dr. Maurie Markman, senior vice president of clinical affairs and national director of medical oncology at Cancer Treatment Centers of America in Philadelphia. "It’s a complicated process because we’re at the giving end to the patient, but [regarding] what comes to us, we’re on the receiving end from some commercial entity. I think all of this is very disturbing. That’s all I can say."

Dr. Markman described the increasing reliance on compounding pharmacies as the flip side of the coin to drug shortages that have hit oncology patients hard, particularly shortages of generic, sterile injectable drugs. Compounding pharmacies have traditionally created custom-made products for individual patients, but they also fill gaps in the supply chain when drugs aren’t available from mainstream drug companies.

Some compounders are producing medications in advance of or without a prescription and distributing them across state lines, creating a "new breed" of specialty pharmacy compounding that "has outgrown the law, and can pose a threat to the health of the public," Food and Drug Administration Commissioner Margaret Hamburg wrote in a blog.

She argued for greater federal oversight including such "basic protections" as clear authority to examine compounding pharmacy records and prohibit compounding of "the most complex and highest risk products," including biologics.

The FDA has no data on how many compounded drugs and infusion products are earmarked for cancer patients because, under current law, compounding pharmacies that meet certain conditions are generally not required to register with the FDA or to list the drugs they compound, FDA spokesperson Christopher Kelly said.

The agency came under sharp criticism last fall for failing to take action during the meningitis outbreak, which killed 53 people in 20 states.

The FDA is targeting "higher-risk" compounding pharmacies and has issued multiple warning letters detailing violations found during 30 inspections over the last 2 months.

The FDA issued warning letters to Med Prep Consulting in 2001 and again in July 2010 after an inspection revealed the firm was repackaging sterile drugs without a patient-specific prescription, eliciting concerns about potential microbial contamination. Further details are not being released at this time because of the ongoing investigation, Mr. Kelly said.

Several regulatory proposals were recently floated in Massachusetts, including a bill by Gov. Deval Patrick that requires compounding pharmacies to obtain a special state license and creates whistleblower protections for pharmacy workers.

Last November, Rep. Edward Markey (D-Mass.) introduced the VALID ACT in an effort to strengthen federal regulations for compounding pharmacies. "It was a casualty of a completely inept session of Congress" but will be introduced again in the next 6-12 weeks, Mr. Markey’s communications director Eben Burnham-Snyder said.

The accreditation option

The American Society of Health System Pharmacists is also calling for unaccredited compounding facilities to seek accreditation by a "nationally credible accreditation body." The Pharmacy Compounding Accreditation Board (PCAB) is one possibility, but it’s up to the FDA and Congress to make an endorsement, Mr. Topoleski said.

Of the roughly 3,000 compounding pharmacies in the United States, 171 were accredited by the PCAB at the end of March. Accreditation applications during the first 2.5 months of 2013 outpaced applications for the first half of 2012, said Cindy Freberg, PCAB director of operations. Still, that is only nine more than during the height of the meningitis outbreak. Ms. Freberg said that the voluntary process takes time and involves U.S. Pharmacopeia Chapter 797 compliance for most of the PCAB standards.

"They’re looking for compliance in all of our standards," she said. "It’s not just a matter of picking one or two things."

PCAB accreditation is not recognized in the federal Food, Drug, and Cosmetic Act and "is of no regulatory significance to the FDA," noted Mr. Kelly.

Latest recall update

To date, there have been no injuries or illnesses reported to the FDA related to the Med Prep recall or to the March 25 recall of 16 sterile compounded products by Boston-based Pallimed Solutions just 5 days after Med Prep. The repackaging of bevacizumab (Avastin) into individual doses for off-label ophthalmic use, which has been a long-standing problem for the compounding industry, was tied to five serious eye infections and sparked a recall March 20 by Clinical Specialties Compounding Pharmacy. None of the three compounding pharmacies was accredited by PCAB, according to a search on its website.

*Correction, 4/11/2013: An earlier version of this story misattributed the source of this information.

[email protected]

Three compounding pharmacies in as many weeks have issued voluntary recalls of their sterile products, heightening concerns about the safety of compounded drugs and infusion products.

Cancer patients are among those at risk. Med Prep Consulting Inc. issued its recall after a Connecticut hospital reported particulates, later identified as fungus, floating in five 50 mL bags of magnesium sulfate IV solution. The fungus was spotted during routine surveillance of intravenous bag preparation by an oncology nurse at Smilow Cancer Hospital at Yale-New Haven (Conn.).

"We bought quite a number of medicines from Med Prep, and we removed all its products immediately from circulation across the hospital following the discovery of this particle," hospital spokesperson Robert Hutchison said in an interview.

The contaminated product did not reach patients at the hospital, but last year’s deadly meningitis outbreak from contaminated methylprednisolone, manufactured by the New England Compounding Center, highlights the dangers of contaminants that aren’t visible. Yale-New Haven Hospital is working closely with state and federal regulatory agencies on how best to move forward while seeking alternative sources for the roughly 40 different products purchased from Med Prep.

"Like many other hospitals, at Yale-New Haven we purchase certain medicines from these pharmacies because our hospital base pharmacies cannot produce the quantity of certain medicines that we require to treat our patients," Mr. Hutchinson said.

The corticosteroid dexamethasone and the antibiotics gentamicin and vancomycin were among those voluntarily recalled by Med Prep.

Societies not taking positions

The American Society of Clinical Oncology reported not being aware of any cancer patients directly affected by the recalls, but has expressed concerns that frail, immunocompromised cancer patients could be receiving contaminated products. ASCO, which has taken a strong role in the oncology drug shortage, is looking into the compounding issue but has not set a date for completing its "due diligence."*

The Hematology/Oncology Pharmacy Association also has not formulated a position on pharmacy compounding, said immediate past-president Lisa M. Holle, PharmD.

The American Cancer Society is unlikely to take up the issue unless it becomes cancer specific, said Dr. J. Leonard Lichtenfeld, deputy chief medical officer. When hospitals go to the grey market for medications, they should be able to do so with confidence that the products they receive are produced in good faith. He pointed to a counterfeit version of the cancer drug bevacizumab recently distributed in the United States without any active ingredient.

Large drug companies are not immune to recalls. Hospira Inc. issued a nationwide recall March 29 for 0.9% sodium chloride injection because brass particulates were found in the product.

Although compounding pharmacies produce only 2%-3% of U.S. prescriptions, some 70% of hospitals have outsourced at least one product, according to Christopher Topoleski, director of federal regulatory affairs for the American Society of Health System Pharmacists (ASHSP), which represents some 40,000 hospital-based pharmacists.

The society held a summit in February along with other stakeholders, including the American Hospital Association, to discuss solutions for the issues surrounding sterile compounding. It also recommended in a letter to the U.S. Department of Health and Human Services a list of characteristics – such as volume, risk level of the compound being prepared, absence of a patient and health care professional relationship, and interstate shipment – that could be used to identify compounders in need of federal oversight.

Although it’s a good starting point, Mr. Topoleski acknowledged that it won’t be easy defining this new breed of nontraditional compounder. For example, small compounding pharmacies may engage in interstate commerce in metropolitan areas like Washington D.C. that span multiple states, while multihospital systems also centrally compound and distribute across state lines. Legal ambiguity also needs to be clarified over when the Food and Drug Administration has authority under the federal Food, Drug, and Cosmetic Act and when individual states’ responsibilities pick up.

"It’s not going to be a clear cut black-and-white line," he said. "There will still be cases that will need to be looked at individually, but I think it’s going to be additional legislation we’ll need to address."

Greater regulation needed

Regulatory agencies and the pharmaceutical industry are promoting track-and-trace systems as one way to fight counterfeit drugs and to ensure that the quality-control chain of compounded products has not been broken.

"Clearly, at the provider end, it is absolutely essential that we have important drugs available to help our patients treat their cancer, manage their symptoms, and deal with any other medical conditions they have and to do it with absolute safety. Those are requirements, they’re not options," said Dr. Maurie Markman, senior vice president of clinical affairs and national director of medical oncology at Cancer Treatment Centers of America in Philadelphia. "It’s a complicated process because we’re at the giving end to the patient, but [regarding] what comes to us, we’re on the receiving end from some commercial entity. I think all of this is very disturbing. That’s all I can say."

Dr. Markman described the increasing reliance on compounding pharmacies as the flip side of the coin to drug shortages that have hit oncology patients hard, particularly shortages of generic, sterile injectable drugs. Compounding pharmacies have traditionally created custom-made products for individual patients, but they also fill gaps in the supply chain when drugs aren’t available from mainstream drug companies.

Some compounders are producing medications in advance of or without a prescription and distributing them across state lines, creating a "new breed" of specialty pharmacy compounding that "has outgrown the law, and can pose a threat to the health of the public," Food and Drug Administration Commissioner Margaret Hamburg wrote in a blog.

She argued for greater federal oversight including such "basic protections" as clear authority to examine compounding pharmacy records and prohibit compounding of "the most complex and highest risk products," including biologics.

The FDA has no data on how many compounded drugs and infusion products are earmarked for cancer patients because, under current law, compounding pharmacies that meet certain conditions are generally not required to register with the FDA or to list the drugs they compound, FDA spokesperson Christopher Kelly said.

The agency came under sharp criticism last fall for failing to take action during the meningitis outbreak, which killed 53 people in 20 states.

The FDA is targeting "higher-risk" compounding pharmacies and has issued multiple warning letters detailing violations found during 30 inspections over the last 2 months.

The FDA issued warning letters to Med Prep Consulting in 2001 and again in July 2010 after an inspection revealed the firm was repackaging sterile drugs without a patient-specific prescription, eliciting concerns about potential microbial contamination. Further details are not being released at this time because of the ongoing investigation, Mr. Kelly said.

Several regulatory proposals were recently floated in Massachusetts, including a bill by Gov. Deval Patrick that requires compounding pharmacies to obtain a special state license and creates whistleblower protections for pharmacy workers.

Last November, Rep. Edward Markey (D-Mass.) introduced the VALID ACT in an effort to strengthen federal regulations for compounding pharmacies. "It was a casualty of a completely inept session of Congress" but will be introduced again in the next 6-12 weeks, Mr. Markey’s communications director Eben Burnham-Snyder said.

The accreditation option

The American Society of Health System Pharmacists is also calling for unaccredited compounding facilities to seek accreditation by a "nationally credible accreditation body." The Pharmacy Compounding Accreditation Board (PCAB) is one possibility, but it’s up to the FDA and Congress to make an endorsement, Mr. Topoleski said.

Of the roughly 3,000 compounding pharmacies in the United States, 171 were accredited by the PCAB at the end of March. Accreditation applications during the first 2.5 months of 2013 outpaced applications for the first half of 2012, said Cindy Freberg, PCAB director of operations. Still, that is only nine more than during the height of the meningitis outbreak. Ms. Freberg said that the voluntary process takes time and involves U.S. Pharmacopeia Chapter 797 compliance for most of the PCAB standards.

"They’re looking for compliance in all of our standards," she said. "It’s not just a matter of picking one or two things."

PCAB accreditation is not recognized in the federal Food, Drug, and Cosmetic Act and "is of no regulatory significance to the FDA," noted Mr. Kelly.

Latest recall update

To date, there have been no injuries or illnesses reported to the FDA related to the Med Prep recall or to the March 25 recall of 16 sterile compounded products by Boston-based Pallimed Solutions just 5 days after Med Prep. The repackaging of bevacizumab (Avastin) into individual doses for off-label ophthalmic use, which has been a long-standing problem for the compounding industry, was tied to five serious eye infections and sparked a recall March 20 by Clinical Specialties Compounding Pharmacy. None of the three compounding pharmacies was accredited by PCAB, according to a search on its website.

*Correction, 4/11/2013: An earlier version of this story misattributed the source of this information.

[email protected]

Three compounding pharmacies in as many weeks have issued voluntary recalls of their sterile products, heightening concerns about the safety of compounded drugs and infusion products.

Cancer patients are among those at risk. Med Prep Consulting Inc. issued its recall after a Connecticut hospital reported particulates, later identified as fungus, floating in five 50 mL bags of magnesium sulfate IV solution. The fungus was spotted during routine surveillance of intravenous bag preparation by an oncology nurse at Smilow Cancer Hospital at Yale-New Haven (Conn.).

"We bought quite a number of medicines from Med Prep, and we removed all its products immediately from circulation across the hospital following the discovery of this particle," hospital spokesperson Robert Hutchison said in an interview.

The contaminated product did not reach patients at the hospital, but last year’s deadly meningitis outbreak from contaminated methylprednisolone, manufactured by the New England Compounding Center, highlights the dangers of contaminants that aren’t visible. Yale-New Haven Hospital is working closely with state and federal regulatory agencies on how best to move forward while seeking alternative sources for the roughly 40 different products purchased from Med Prep.

"Like many other hospitals, at Yale-New Haven we purchase certain medicines from these pharmacies because our hospital base pharmacies cannot produce the quantity of certain medicines that we require to treat our patients," Mr. Hutchinson said.

The corticosteroid dexamethasone and the antibiotics gentamicin and vancomycin were among those voluntarily recalled by Med Prep.

Societies not taking positions

The American Society of Clinical Oncology reported not being aware of any cancer patients directly affected by the recalls, but has expressed concerns that frail, immunocompromised cancer patients could be receiving contaminated products. ASCO, which has taken a strong role in the oncology drug shortage, is looking into the compounding issue but has not set a date for completing its "due diligence."*

The Hematology/Oncology Pharmacy Association also has not formulated a position on pharmacy compounding, said immediate past-president Lisa M. Holle, PharmD.

The American Cancer Society is unlikely to take up the issue unless it becomes cancer specific, said Dr. J. Leonard Lichtenfeld, deputy chief medical officer. When hospitals go to the grey market for medications, they should be able to do so with confidence that the products they receive are produced in good faith. He pointed to a counterfeit version of the cancer drug bevacizumab recently distributed in the United States without any active ingredient.

Large drug companies are not immune to recalls. Hospira Inc. issued a nationwide recall March 29 for 0.9% sodium chloride injection because brass particulates were found in the product.

Although compounding pharmacies produce only 2%-3% of U.S. prescriptions, some 70% of hospitals have outsourced at least one product, according to Christopher Topoleski, director of federal regulatory affairs for the American Society of Health System Pharmacists (ASHSP), which represents some 40,000 hospital-based pharmacists.

The society held a summit in February along with other stakeholders, including the American Hospital Association, to discuss solutions for the issues surrounding sterile compounding. It also recommended in a letter to the U.S. Department of Health and Human Services a list of characteristics – such as volume, risk level of the compound being prepared, absence of a patient and health care professional relationship, and interstate shipment – that could be used to identify compounders in need of federal oversight.

Although it’s a good starting point, Mr. Topoleski acknowledged that it won’t be easy defining this new breed of nontraditional compounder. For example, small compounding pharmacies may engage in interstate commerce in metropolitan areas like Washington D.C. that span multiple states, while multihospital systems also centrally compound and distribute across state lines. Legal ambiguity also needs to be clarified over when the Food and Drug Administration has authority under the federal Food, Drug, and Cosmetic Act and when individual states’ responsibilities pick up.

"It’s not going to be a clear cut black-and-white line," he said. "There will still be cases that will need to be looked at individually, but I think it’s going to be additional legislation we’ll need to address."

Greater regulation needed

Regulatory agencies and the pharmaceutical industry are promoting track-and-trace systems as one way to fight counterfeit drugs and to ensure that the quality-control chain of compounded products has not been broken.

"Clearly, at the provider end, it is absolutely essential that we have important drugs available to help our patients treat their cancer, manage their symptoms, and deal with any other medical conditions they have and to do it with absolute safety. Those are requirements, they’re not options," said Dr. Maurie Markman, senior vice president of clinical affairs and national director of medical oncology at Cancer Treatment Centers of America in Philadelphia. "It’s a complicated process because we’re at the giving end to the patient, but [regarding] what comes to us, we’re on the receiving end from some commercial entity. I think all of this is very disturbing. That’s all I can say."

Dr. Markman described the increasing reliance on compounding pharmacies as the flip side of the coin to drug shortages that have hit oncology patients hard, particularly shortages of generic, sterile injectable drugs. Compounding pharmacies have traditionally created custom-made products for individual patients, but they also fill gaps in the supply chain when drugs aren’t available from mainstream drug companies.

Some compounders are producing medications in advance of or without a prescription and distributing them across state lines, creating a "new breed" of specialty pharmacy compounding that "has outgrown the law, and can pose a threat to the health of the public," Food and Drug Administration Commissioner Margaret Hamburg wrote in a blog.

She argued for greater federal oversight including such "basic protections" as clear authority to examine compounding pharmacy records and prohibit compounding of "the most complex and highest risk products," including biologics.

The FDA has no data on how many compounded drugs and infusion products are earmarked for cancer patients because, under current law, compounding pharmacies that meet certain conditions are generally not required to register with the FDA or to list the drugs they compound, FDA spokesperson Christopher Kelly said.

The agency came under sharp criticism last fall for failing to take action during the meningitis outbreak, which killed 53 people in 20 states.

The FDA is targeting "higher-risk" compounding pharmacies and has issued multiple warning letters detailing violations found during 30 inspections over the last 2 months.

The FDA issued warning letters to Med Prep Consulting in 2001 and again in July 2010 after an inspection revealed the firm was repackaging sterile drugs without a patient-specific prescription, eliciting concerns about potential microbial contamination. Further details are not being released at this time because of the ongoing investigation, Mr. Kelly said.

Several regulatory proposals were recently floated in Massachusetts, including a bill by Gov. Deval Patrick that requires compounding pharmacies to obtain a special state license and creates whistleblower protections for pharmacy workers.

Last November, Rep. Edward Markey (D-Mass.) introduced the VALID ACT in an effort to strengthen federal regulations for compounding pharmacies. "It was a casualty of a completely inept session of Congress" but will be introduced again in the next 6-12 weeks, Mr. Markey’s communications director Eben Burnham-Snyder said.

The accreditation option

The American Society of Health System Pharmacists is also calling for unaccredited compounding facilities to seek accreditation by a "nationally credible accreditation body." The Pharmacy Compounding Accreditation Board (PCAB) is one possibility, but it’s up to the FDA and Congress to make an endorsement, Mr. Topoleski said.

Of the roughly 3,000 compounding pharmacies in the United States, 171 were accredited by the PCAB at the end of March. Accreditation applications during the first 2.5 months of 2013 outpaced applications for the first half of 2012, said Cindy Freberg, PCAB director of operations. Still, that is only nine more than during the height of the meningitis outbreak. Ms. Freberg said that the voluntary process takes time and involves U.S. Pharmacopeia Chapter 797 compliance for most of the PCAB standards.

"They’re looking for compliance in all of our standards," she said. "It’s not just a matter of picking one or two things."

PCAB accreditation is not recognized in the federal Food, Drug, and Cosmetic Act and "is of no regulatory significance to the FDA," noted Mr. Kelly.

Latest recall update

To date, there have been no injuries or illnesses reported to the FDA related to the Med Prep recall or to the March 25 recall of 16 sterile compounded products by Boston-based Pallimed Solutions just 5 days after Med Prep. The repackaging of bevacizumab (Avastin) into individual doses for off-label ophthalmic use, which has been a long-standing problem for the compounding industry, was tied to five serious eye infections and sparked a recall March 20 by Clinical Specialties Compounding Pharmacy. None of the three compounding pharmacies was accredited by PCAB, according to a search on its website.

*Correction, 4/11/2013: An earlier version of this story misattributed the source of this information.

[email protected]