News
N e ws Sublingual immunotherapy approved for grass pollen allergies
F
DA on April 1 approved the first sublingual alternative to immunotherapy injections for people 10–65 years of age who are allergic to sweet vernalgrass, orchardgrass, perennial ryegrass, timothy, or Kentucky bluegrass. Each tablet, the agency said, contains freeze-dried pollen extracts of those five perennial grasses. Manufacturer Stallergenes S.A., of France, named its biological Oralair. The product’s labeling recommends seasonal therapy, with daily treatment starting four months before the expected onset of grass pollen season. Oralair’s dose and tablet strength are expressed in terms of the potency unit Index of Reactivity (IR). FDA described the unit as Stallergenes’ inhouse reference standard for measuring potency. The labeling recommends a dosage of 300 IR/day for patients 18 years of age or older. Patients 10–17 years of age should take 100 IR on day 1, 200 IR on day 2, and 300 IR on day 3 and there-
New drugs and dosage forms Naloxone hydrochloride injection in autoinjector (Evzio, kaleo): The drug–device combination product is indicated for the emergency treatment of known or suspected opioid overdose. Phenylephrine hydrochloride ophthalmic solution (no brand name, Paragon BioTeck): The a1-adrenergic-receptor agonist is indicated to dilate the pupil. Propranolol hydrochloride oral solution (Hemangeol, Pierre Fabre): The strawberryand vanilla-flavored oral solution of the b-adrenergic blocker is indicated for the treatment of proliferating infantile hemangioma requiring systemic therapy.
770
after. All doses are taken by placing the tablet under the tongue and allowing at least one minute for the tablet to dissolve completely. No food or beverage should be ingested for five minutes after the tablet dissolves to avoid swallowing the allergens. Regardless of the strength of the first dose, it should be taken under the supervision of a physician who has experience diagnosing and treating severe allergic reactions. The labeling for the biological recommends that the patient be observed for at least 30 minutes after taking the first dose. A boxed warning in the biological’s labeling alerts health care providers to the possibility that the allergen extract can cause life-threatening allergic reactions. The boxed warning also tells health care providers to prescribe autoinjectable epinephrine to users of the biological and instruct them how to self-administer
the drug. An FDA-required Medication Guide similarly informs patients. The biological is contraindicated in patients with severe, unstable, or uncontrolled asthma or anyone who has had a severe systemic allergic reaction or severe local reaction to sublingual allergen immunotherapy. According to the labeling, the most common adverse reactions to the biological during clinical trials were itching of the mouth, ears, or tongue, throat irritation, swelling of the mouth, and cough. Oralair will be marketed as tablets containing 100 or 300 IR and packaged in blisters. Greer Laboratories Inc., a North Carolina company that specializes in allergy immunotherapy products, said it has a partnership with Stallergenes to market Oralair in this country. Distribution is planned to start in early May, said Greer’s Cheryl Reid, medical information specialist. —Cheryl A. Thompson DOI 10.2146/news140034
FDA defends generic drug labeling plan
L
awmakers on April 1 called on the chief of FDA’s drugs division to defend a proposal that would allow makers of generic drugs to unilaterally update safety information in their products’ professional labeling. Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, told members of the health subcommittee of the House Committee on Energy and Commerce that the agency’s proposed rule, issued last November, “would provide generic drug makers
Am J Health-Syst Pharm—Vol 71 May 15, 2014
with the same opportunity as brand drug makers to update their labels when they have new safety information.” If enacted, she said, the proposed rule would result in improved communication about important drug safety information for prescribers and patients. Ralph Neas, president of the Generic Pharmaceutical Association (GPhA), countered to the committee that FDA’s proposal would instead “create substanContinued on page 772
News Continued from page 770
tial confusion for everyone in the health care system.” That confusion, he said, would result from the coexistence of different safety information in the labeling for the same drugs made by different manufacturers. And Neas predicted that the confusion would be magnified by a flood of new labeling with excessive warnings of little or no clinical relevance. Neas also said that the rule would lead to lawsuits against makers of generic drugs and substantial increases in the prices of the drugs. FDA’s plan. The proposed rule would allow manufacturers of generic drugs to submit “changes being effected” (CBE) supplements to FDA. With a CBE-0 supplement, a drug maker can update its labeling with important safety information and distribute it on FDA’s receipt of the supplement without waiting for the agency to review the material. This is in contrast to a CBE-30 supplement, which requires a 30-day interval from FDA receipt of the proposed supplemental labeling information to distribution of updated labeling by the drug maker. “This is really a procedural rule that allows a procedure that was always available to innovators to be available to generics,” Woodcock explained. Under current FDA regulations, only manufacturers of innovator, or reference, drugs may submit a CBE-0 supplement. When the maker of a generic drug discovers a safety problem, the company must notify FDA and wait for the agency and the maker of the reference drug to negotiate labeling changes before revising the generic drug’s labeling. FDA has not instituted a timeline for these revisions. Instead, FDA advises generic product makers to revise their labeling “at the very earliest time possible.” The proposed rule would establish a 30-day time frame for manufacturers to change their product labeling after FDA approves the safety changes. The proposal also describes an FDAmaintained Web-based system for logging and tracking labeling changes relat772
ed to the CBE-0 supplements that would be accessible to all drug manufacturers and the public. Safety. Subcommittee Chair Joe Pitts of Pennsylvania predicted that FDA’s proposal would result in “mass confusion” and safety problems because multiple versions of labeling for the same drug would be in circulation at the same time. In this scenario, he said, “FDAapproved labeling would become just one in a crowd.”
“This is really a procedural rule.” —Janet Woodcock, FDA But Woodcock countered that Pitts’ description better fits the current situation than the remedies in the proposed rule. “When FDA makes a label change to the innovator, there will be multiple different versions” of the labeling for the corresponding generics, she said. “Some will change their label to conform very rapidly; others may take a year or so. So that is the current situation.” Woodcock said the proposed Webbased tracking system and 30-day time frame for revising labeling “will result in less differences among brand and generic labels in the future, if this rule were to be made final.” She noted that the issue is timely because more than 80% of all prescription drugs dispensed in the United States are generics. For more than 400 drug products, only generic versions are currently marketed, and FDA expects this number to increase. Woodcock also clarified that FDA has standards in place to prevent drug manufacturers from creating a “laundry list” of potentially irrelevant warnings in product labeling. She said these standards were adopted as part of the 2006 Physician Labeling Rule, which states that manufacturers cannot put speculative information in their product labeling. Liability. Woodcock acknowledged that the claim made by Neas about the
Am J Health-Syst Pharm—Vol 71 May 15, 2014
proposed rule leading to product liability lawsuits against makers of generic drugs is likely true. A 2011 Supreme Court ruling established that makers of generic drugs cannot be subject to failure-to-warn tort claims related to safety labeling when these manufacturers are unable, per FDA regulation, to unilaterally change their products’ labeling. Manufacturers of brand-name drugs, in contrast, are not protected from such lawsuits. If the CBE-0 supplement process is made available to makers of generic drugs, as proposed by FDA, those manufacturers would no longer be shielded from these liability claims, Neas said. He cited estimates in a report from Matrix Global Advisors, an economic policy consulting firm, that FDA’s proposal would lead to $4 billion in new annual health care costs related to product liability concerns. Allison Zieve, general counsel for the consumer advocacy group Public Citizen, told the subcommittee members that GPhA’s concerns over product liability, rather than patient safety concerns, are the group’s “real objection” to FDA’s proposed rule. Zieve said Public Citizen strongly supports FDA’s proposal and believes that it will improve patient safety. ASHP, in written comments on the proposed rule, stated its support for FDA’s efforts to speed the inclusion of important new safety information in product labeling. But ASHP also expressed concerns about FDA’s ability to effectively implement the system described in the rule. The comments note that FDA has historically “faced challenges maintaining consistent and current prescription drug labeling” and has not been able to enforce its previous directives regarding labeling consistency. The comments state that existing inconsistencies in labeling and enforcement shortcomings could be magnified if manufacturers of generic drugs are allowed to independently initiate CBE-0 supplements in the way FDA has proposed. Continued on page 774
News Continued from page 772
ASHP urged FDA to update and make better use of the agency’s DailyMed drug labeling database and use that as the central portal for all labeling-related
information instead of creating a new database system for CBE-0 supplements. ASHP was also 1 of 21 signatories on a March 6 letter to FDA Commissioner Margaret Hamburg expressing concerns about potential adverse economic and
Hospital earns financial rewards for inpatient MTM services
A
n Oregon hospital may have cracked the code for private-payer reimbursement of inpatient medication therapy management (MTM) services provided by pharmacists. Deborah Sanchez, director of pharmacy practice and residency at 380-bed Asante Rogue Regional Medical Center in Medford, said the hospital last year billed private and public insurers for about 5000 MTM encounters. None of the expenses were reimbursed by Medicare or Medicaid. But Sanchez estimates that the MTM services continue to bring in about $50,000 per month from one private insurer with whom the hospital has negotiated rates for the services. “It’s money. It’s not nothing,” Sanchez said. “You bill a lot more than you receive, but the hospital bills a lot more than it receives overall, as well.” Sanchez said the hospital first examined the possibility of billing for inpatient MTM services about five or six years ago. She said the pharmacy and finance directors “discussed the services we were providing and if there was an opportunity to do billing for them.” Ultimately, she said, “the facility determined that the types of services that we provide in the hospital as pharmacists” fall under evaluation and management (EM) inpatient procedural codes. EM codes capture three key elements of patient care encounters—patient historytaking, physical examination, and medical decision-making—and categorize the services on the basis of complexity. 774
Sanchez said her hospital uses the SOAP (subjective data, objective data, assessment, plan) documentation style to meet state requirements for documenting pharmacists’ MTM services. Oregon state law permits pharmacists to provide MTM services and to establish collaborative practice agreements with physicians. Both of these activities require adequate documentation of the pharmacist’s encounter with the patient, and Sanchez said the SOAP process satisfies the state’s requirements. She said some of the hospital’s pharmacists weren’t familiar with SOAP charting and “needed a little bit of training” in the method and how to work it into their daily practice. “They were already doing [patient] education, so it wasn’t a huge deal” to document what they were doing, Sanchez said. Sanchez said the hospital established five billing levels for MTM services. Because the services are provided to inpatients, all encounters are face-to-face. At the low-complexity end of the spectrum are level 1 MTM services such as simple fall consultations, medication reviews, and medication reconciliation for patients who require little or no follow-up and no change to the medication regimen. Level 2 services are brief but more complex than level 1 services and are problem focused. Examples may include a fall consultation that results in a medication change, a renal function evaluation with no change to therapy, the ordering of laboratory tests, or a switch between oral and i.v. therapy.
Am J Health-Syst Pharm—Vol 71 May 15, 2014
patient safety effects of adopting the proposed rule. —Kate Traynor DOI 10.2146/news140035
Sanchez said pharmacokinetic or renal function monitoring with subsequent dosage adjustments may represent moderatecomplexity (i.e., level 3) services, and initiating warfarin therapy or evaluating a drug-induced disease may be considered level 4 services by the hospital. Level 5 services require a complete physical exam and involve extremely complex medical decision-making in patients who are critically ill. Examples may include services for intensive care unit patients with multiple medication problems or services focused on the prevention of serious adverse drug events. “It’s broken down by category, by complexity,” Sanchez said. “These all go through the biller, and the biller codes them. And they do the same thing for other nonphysician provider practitioners.” She said hospital administrators have emphasized the importance of submitting bills for services even when there is no expectation of reimbursement, because the data help establish the value of pharmacists’ clinical work. And billing the Medicare program ensures that the agency has this data available when it sets payment rates. Sanchez said other pharmacists have contacted her about billing for inpatient MTM services, but she doesn’t know if other hospitals have implemented a process like that used at her facility. She said the success depends on the willingness of insurers to reimburse for inpatient MTM services and the existence of a billing system that allows the codes to be processed for payment. She speculated that “flat-rate” or bundledpayment systems may not permit the Continued on page 776
Copyright of American Journal of Health-System Pharmacy is the property of American Society of Health System Pharmacists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
N e ws Sublingual immunotherapy approved for grass pollen allergies
F
DA on April 1 approved the first sublingual alternative to immunotherapy injections for people 10–65 years of age who are allergic to sweet vernalgrass, orchardgrass, perennial ryegrass, timothy, or Kentucky bluegrass. Each tablet, the agency said, contains freeze-dried pollen extracts of those five perennial grasses. Manufacturer Stallergenes S.A., of France, named its biological Oralair. The product’s labeling recommends seasonal therapy, with daily treatment starting four months before the expected onset of grass pollen season. Oralair’s dose and tablet strength are expressed in terms of the potency unit Index of Reactivity (IR). FDA described the unit as Stallergenes’ inhouse reference standard for measuring potency. The labeling recommends a dosage of 300 IR/day for patients 18 years of age or older. Patients 10–17 years of age should take 100 IR on day 1, 200 IR on day 2, and 300 IR on day 3 and there-
New drugs and dosage forms Naloxone hydrochloride injection in autoinjector (Evzio, kaleo): The drug–device combination product is indicated for the emergency treatment of known or suspected opioid overdose. Phenylephrine hydrochloride ophthalmic solution (no brand name, Paragon BioTeck): The a1-adrenergic-receptor agonist is indicated to dilate the pupil. Propranolol hydrochloride oral solution (Hemangeol, Pierre Fabre): The strawberryand vanilla-flavored oral solution of the b-adrenergic blocker is indicated for the treatment of proliferating infantile hemangioma requiring systemic therapy.
770
after. All doses are taken by placing the tablet under the tongue and allowing at least one minute for the tablet to dissolve completely. No food or beverage should be ingested for five minutes after the tablet dissolves to avoid swallowing the allergens. Regardless of the strength of the first dose, it should be taken under the supervision of a physician who has experience diagnosing and treating severe allergic reactions. The labeling for the biological recommends that the patient be observed for at least 30 minutes after taking the first dose. A boxed warning in the biological’s labeling alerts health care providers to the possibility that the allergen extract can cause life-threatening allergic reactions. The boxed warning also tells health care providers to prescribe autoinjectable epinephrine to users of the biological and instruct them how to self-administer
the drug. An FDA-required Medication Guide similarly informs patients. The biological is contraindicated in patients with severe, unstable, or uncontrolled asthma or anyone who has had a severe systemic allergic reaction or severe local reaction to sublingual allergen immunotherapy. According to the labeling, the most common adverse reactions to the biological during clinical trials were itching of the mouth, ears, or tongue, throat irritation, swelling of the mouth, and cough. Oralair will be marketed as tablets containing 100 or 300 IR and packaged in blisters. Greer Laboratories Inc., a North Carolina company that specializes in allergy immunotherapy products, said it has a partnership with Stallergenes to market Oralair in this country. Distribution is planned to start in early May, said Greer’s Cheryl Reid, medical information specialist. —Cheryl A. Thompson DOI 10.2146/news140034
FDA defends generic drug labeling plan
L
awmakers on April 1 called on the chief of FDA’s drugs division to defend a proposal that would allow makers of generic drugs to unilaterally update safety information in their products’ professional labeling. Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, told members of the health subcommittee of the House Committee on Energy and Commerce that the agency’s proposed rule, issued last November, “would provide generic drug makers
Am J Health-Syst Pharm—Vol 71 May 15, 2014
with the same opportunity as brand drug makers to update their labels when they have new safety information.” If enacted, she said, the proposed rule would result in improved communication about important drug safety information for prescribers and patients. Ralph Neas, president of the Generic Pharmaceutical Association (GPhA), countered to the committee that FDA’s proposal would instead “create substanContinued on page 772
News Continued from page 770
tial confusion for everyone in the health care system.” That confusion, he said, would result from the coexistence of different safety information in the labeling for the same drugs made by different manufacturers. And Neas predicted that the confusion would be magnified by a flood of new labeling with excessive warnings of little or no clinical relevance. Neas also said that the rule would lead to lawsuits against makers of generic drugs and substantial increases in the prices of the drugs. FDA’s plan. The proposed rule would allow manufacturers of generic drugs to submit “changes being effected” (CBE) supplements to FDA. With a CBE-0 supplement, a drug maker can update its labeling with important safety information and distribute it on FDA’s receipt of the supplement without waiting for the agency to review the material. This is in contrast to a CBE-30 supplement, which requires a 30-day interval from FDA receipt of the proposed supplemental labeling information to distribution of updated labeling by the drug maker. “This is really a procedural rule that allows a procedure that was always available to innovators to be available to generics,” Woodcock explained. Under current FDA regulations, only manufacturers of innovator, or reference, drugs may submit a CBE-0 supplement. When the maker of a generic drug discovers a safety problem, the company must notify FDA and wait for the agency and the maker of the reference drug to negotiate labeling changes before revising the generic drug’s labeling. FDA has not instituted a timeline for these revisions. Instead, FDA advises generic product makers to revise their labeling “at the very earliest time possible.” The proposed rule would establish a 30-day time frame for manufacturers to change their product labeling after FDA approves the safety changes. The proposal also describes an FDAmaintained Web-based system for logging and tracking labeling changes relat772
ed to the CBE-0 supplements that would be accessible to all drug manufacturers and the public. Safety. Subcommittee Chair Joe Pitts of Pennsylvania predicted that FDA’s proposal would result in “mass confusion” and safety problems because multiple versions of labeling for the same drug would be in circulation at the same time. In this scenario, he said, “FDAapproved labeling would become just one in a crowd.”
“This is really a procedural rule.” —Janet Woodcock, FDA But Woodcock countered that Pitts’ description better fits the current situation than the remedies in the proposed rule. “When FDA makes a label change to the innovator, there will be multiple different versions” of the labeling for the corresponding generics, she said. “Some will change their label to conform very rapidly; others may take a year or so. So that is the current situation.” Woodcock said the proposed Webbased tracking system and 30-day time frame for revising labeling “will result in less differences among brand and generic labels in the future, if this rule were to be made final.” She noted that the issue is timely because more than 80% of all prescription drugs dispensed in the United States are generics. For more than 400 drug products, only generic versions are currently marketed, and FDA expects this number to increase. Woodcock also clarified that FDA has standards in place to prevent drug manufacturers from creating a “laundry list” of potentially irrelevant warnings in product labeling. She said these standards were adopted as part of the 2006 Physician Labeling Rule, which states that manufacturers cannot put speculative information in their product labeling. Liability. Woodcock acknowledged that the claim made by Neas about the
Am J Health-Syst Pharm—Vol 71 May 15, 2014
proposed rule leading to product liability lawsuits against makers of generic drugs is likely true. A 2011 Supreme Court ruling established that makers of generic drugs cannot be subject to failure-to-warn tort claims related to safety labeling when these manufacturers are unable, per FDA regulation, to unilaterally change their products’ labeling. Manufacturers of brand-name drugs, in contrast, are not protected from such lawsuits. If the CBE-0 supplement process is made available to makers of generic drugs, as proposed by FDA, those manufacturers would no longer be shielded from these liability claims, Neas said. He cited estimates in a report from Matrix Global Advisors, an economic policy consulting firm, that FDA’s proposal would lead to $4 billion in new annual health care costs related to product liability concerns. Allison Zieve, general counsel for the consumer advocacy group Public Citizen, told the subcommittee members that GPhA’s concerns over product liability, rather than patient safety concerns, are the group’s “real objection” to FDA’s proposed rule. Zieve said Public Citizen strongly supports FDA’s proposal and believes that it will improve patient safety. ASHP, in written comments on the proposed rule, stated its support for FDA’s efforts to speed the inclusion of important new safety information in product labeling. But ASHP also expressed concerns about FDA’s ability to effectively implement the system described in the rule. The comments note that FDA has historically “faced challenges maintaining consistent and current prescription drug labeling” and has not been able to enforce its previous directives regarding labeling consistency. The comments state that existing inconsistencies in labeling and enforcement shortcomings could be magnified if manufacturers of generic drugs are allowed to independently initiate CBE-0 supplements in the way FDA has proposed. Continued on page 774
News Continued from page 772
ASHP urged FDA to update and make better use of the agency’s DailyMed drug labeling database and use that as the central portal for all labeling-related
information instead of creating a new database system for CBE-0 supplements. ASHP was also 1 of 21 signatories on a March 6 letter to FDA Commissioner Margaret Hamburg expressing concerns about potential adverse economic and
Hospital earns financial rewards for inpatient MTM services
A
n Oregon hospital may have cracked the code for private-payer reimbursement of inpatient medication therapy management (MTM) services provided by pharmacists. Deborah Sanchez, director of pharmacy practice and residency at 380-bed Asante Rogue Regional Medical Center in Medford, said the hospital last year billed private and public insurers for about 5000 MTM encounters. None of the expenses were reimbursed by Medicare or Medicaid. But Sanchez estimates that the MTM services continue to bring in about $50,000 per month from one private insurer with whom the hospital has negotiated rates for the services. “It’s money. It’s not nothing,” Sanchez said. “You bill a lot more than you receive, but the hospital bills a lot more than it receives overall, as well.” Sanchez said the hospital first examined the possibility of billing for inpatient MTM services about five or six years ago. She said the pharmacy and finance directors “discussed the services we were providing and if there was an opportunity to do billing for them.” Ultimately, she said, “the facility determined that the types of services that we provide in the hospital as pharmacists” fall under evaluation and management (EM) inpatient procedural codes. EM codes capture three key elements of patient care encounters—patient historytaking, physical examination, and medical decision-making—and categorize the services on the basis of complexity. 774
Sanchez said her hospital uses the SOAP (subjective data, objective data, assessment, plan) documentation style to meet state requirements for documenting pharmacists’ MTM services. Oregon state law permits pharmacists to provide MTM services and to establish collaborative practice agreements with physicians. Both of these activities require adequate documentation of the pharmacist’s encounter with the patient, and Sanchez said the SOAP process satisfies the state’s requirements. She said some of the hospital’s pharmacists weren’t familiar with SOAP charting and “needed a little bit of training” in the method and how to work it into their daily practice. “They were already doing [patient] education, so it wasn’t a huge deal” to document what they were doing, Sanchez said. Sanchez said the hospital established five billing levels for MTM services. Because the services are provided to inpatients, all encounters are face-to-face. At the low-complexity end of the spectrum are level 1 MTM services such as simple fall consultations, medication reviews, and medication reconciliation for patients who require little or no follow-up and no change to the medication regimen. Level 2 services are brief but more complex than level 1 services and are problem focused. Examples may include a fall consultation that results in a medication change, a renal function evaluation with no change to therapy, the ordering of laboratory tests, or a switch between oral and i.v. therapy.
Am J Health-Syst Pharm—Vol 71 May 15, 2014
patient safety effects of adopting the proposed rule. —Kate Traynor DOI 10.2146/news140035
Sanchez said pharmacokinetic or renal function monitoring with subsequent dosage adjustments may represent moderatecomplexity (i.e., level 3) services, and initiating warfarin therapy or evaluating a drug-induced disease may be considered level 4 services by the hospital. Level 5 services require a complete physical exam and involve extremely complex medical decision-making in patients who are critically ill. Examples may include services for intensive care unit patients with multiple medication problems or services focused on the prevention of serious adverse drug events. “It’s broken down by category, by complexity,” Sanchez said. “These all go through the biller, and the biller codes them. And they do the same thing for other nonphysician provider practitioners.” She said hospital administrators have emphasized the importance of submitting bills for services even when there is no expectation of reimbursement, because the data help establish the value of pharmacists’ clinical work. And billing the Medicare program ensures that the agency has this data available when it sets payment rates. Sanchez said other pharmacists have contacted her about billing for inpatient MTM services, but she doesn’t know if other hospitals have implemented a process like that used at her facility. She said the success depends on the willingness of insurers to reimburse for inpatient MTM services and the existence of a billing system that allows the codes to be processed for payment. She speculated that “flat-rate” or bundledpayment systems may not permit the Continued on page 776
Copyright of American Journal of Health-System Pharmacy is the property of American Society of Health System Pharmacists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
