NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

[email protected]

On Twitter @alz_gal

NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

[email protected]

On Twitter @alz_gal

NASHVILLE, TENN. – A 1 million–patient analysis of the Get With the Guidelines database found striking improvements in outcomes after ischemic stroke.

Despite the proven benefits of new-generation clot-retrieval devices, however, only about 2% of such stroke patients undergo endovascular therapy.

In a video interview at the International Stroke Conference, Dr. Bijoy Menon of the department of clinical neurosciences at the University of Calgary (Alta.), who presented the findings at the conference, discussed this apparent clinical paradox.

Dr. Menon’s study echoes findings of the landmark Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial, which found dramatically improved stroke outcomes after endovascular therapy.

But the benefits of such treatment should never outweigh the need for thoroughly screening patients and carefully considering their recovery prospects, Dr. Michael Hill, professor of neurology at the University of Calgary and primary investigator on the ESCAPE study, cautioned in another video interview at the meeting.

[email protected]

On Twitter @alz_gal

LAKE BUENA VISTA, FLA. – Trauma patients on contact isolation were nearly six times more likely to develop venous thromboembolism (VTE) as those who were not isolated, based on an analysis of 4,317 patients.

VTE occurred in 17.5% (44/251) of patients on contact isolation and 3.5% (141/4,066) of patients who were not isolated (P < .0001). Injury Severity Score (ISS), age, male gender, and obesity also were significantly associated with the risk of VTE.

The relationship between VTE risk and contact isolation remained significant after adjusting for gender, age, ISS, and comorbidities (odds ratio, 3.28; P < .0001), Dr. Robert Ferguson reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Odds ratios also were significantly elevated for obesity (OR, 2.35; P < .006), male gender (OR, 2.1; P < .0001), ISS (OR, 1.08; P < .0001), and age (OR, 1.02; P < .0001). The presence of diabetes, dementia/Alzheimer’s, history of cerebrovascular accident, psychiatric disease, cirrhosis, cancer, or alcohol abuse was not statistically significant.

The increased risk for VTE in trauma patients on contact isolation “is likely multifactorial in nature and is related but not limited to decreased ambulation, noncompliance with prophylaxis, and restricted access by staff,” said Dr. Ferguson, a third-year resident at the Virginia Tech, Roanoke.

The risk:benefit ratio of contact isolation in the trauma population needs to be reevaluated, the researchers concluded. “We encourage hospital committees to alter protocols and supplement strategies such as staff education, dedicated ambulation areas and/or isolation wards, and eliminate contact isolation following routine methicillin-resistant Staphylococcus aureus surveillance screening.”

Dr. Ferguson and his coauthors reported having no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Trauma patients on contact isolation were nearly six times more likely to develop venous thromboembolism (VTE) as those who were not isolated, based on an analysis of 4,317 patients.

VTE occurred in 17.5% (44/251) of patients on contact isolation and 3.5% (141/4,066) of patients who were not isolated (P < .0001). Injury Severity Score (ISS), age, male gender, and obesity also were significantly associated with the risk of VTE.

The relationship between VTE risk and contact isolation remained significant after adjusting for gender, age, ISS, and comorbidities (odds ratio, 3.28; P < .0001), Dr. Robert Ferguson reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Odds ratios also were significantly elevated for obesity (OR, 2.35; P < .006), male gender (OR, 2.1; P < .0001), ISS (OR, 1.08; P < .0001), and age (OR, 1.02; P < .0001). The presence of diabetes, dementia/Alzheimer’s, history of cerebrovascular accident, psychiatric disease, cirrhosis, cancer, or alcohol abuse was not statistically significant.

The increased risk for VTE in trauma patients on contact isolation “is likely multifactorial in nature and is related but not limited to decreased ambulation, noncompliance with prophylaxis, and restricted access by staff,” said Dr. Ferguson, a third-year resident at the Virginia Tech, Roanoke.

The risk:benefit ratio of contact isolation in the trauma population needs to be reevaluated, the researchers concluded. “We encourage hospital committees to alter protocols and supplement strategies such as staff education, dedicated ambulation areas and/or isolation wards, and eliminate contact isolation following routine methicillin-resistant Staphylococcus aureus surveillance screening.”

Dr. Ferguson and his coauthors reported having no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Trauma patients on contact isolation were nearly six times more likely to develop venous thromboembolism (VTE) as those who were not isolated, based on an analysis of 4,317 patients.

VTE occurred in 17.5% (44/251) of patients on contact isolation and 3.5% (141/4,066) of patients who were not isolated (P < .0001). Injury Severity Score (ISS), age, male gender, and obesity also were significantly associated with the risk of VTE.

The relationship between VTE risk and contact isolation remained significant after adjusting for gender, age, ISS, and comorbidities (odds ratio, 3.28; P < .0001), Dr. Robert Ferguson reported at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Odds ratios also were significantly elevated for obesity (OR, 2.35; P < .006), male gender (OR, 2.1; P < .0001), ISS (OR, 1.08; P < .0001), and age (OR, 1.02; P < .0001). The presence of diabetes, dementia/Alzheimer’s, history of cerebrovascular accident, psychiatric disease, cirrhosis, cancer, or alcohol abuse was not statistically significant.

The increased risk for VTE in trauma patients on contact isolation “is likely multifactorial in nature and is related but not limited to decreased ambulation, noncompliance with prophylaxis, and restricted access by staff,” said Dr. Ferguson, a third-year resident at the Virginia Tech, Roanoke.

The risk:benefit ratio of contact isolation in the trauma population needs to be reevaluated, the researchers concluded. “We encourage hospital committees to alter protocols and supplement strategies such as staff education, dedicated ambulation areas and/or isolation wards, and eliminate contact isolation following routine methicillin-resistant Staphylococcus aureus surveillance screening.”

Dr. Ferguson and his coauthors reported having no financial disclosures.

[email protected]

Diagnosing and treating illnesses are the bread and butter of hospitalist medicine. Has your bread become stale?

I used to be envious of older physicians who ‘grandfathered in’ and became exempt from the requirement to recertify every 10 years for the American Board of Internal Medicine. Preparing for the boards is extremely time consuming and, at times, incredibly stressful, but it’s what we have to do to prove that our medical knowledge is up to date, right?

Who hasn’t heard of at least one nightmare outcome after a physician treated a patient with out-of-date standards, probably the same ones he learned in medical school a long, long time ago? We may snicker at this scenario, but could we be guilty too? Could we be so set in our ways, so self-confident that we refuse to grow?

I was watching a hospital medicine CME DVD a few months ago and was shocked, as well as embarrassed, to learn that the way I was performing part of my neurological exam was antiquated. There was a new “gold standard” that I had never learned before. After all, I had been doing the exact same thing for years; too many years, it seems. I mistakenly assumed that all the physical examination skills I had learned in medical school were set in stone. But as in all aspects of medicine, even best practices for performing a basic examination have evolved over the years.

Then there is the old habit of ordering multiple blood tests on hospitalized patients every day. That’s just how many of us were trained during residency, but in real life it’s not always necessary. Sure, if there’s a reason to be concerned about specific parameters they should be followed closely, but most inpatients don’t really need chemistries and a CBC each and every day; if they weren’t already anemic, we could make them anemic with excessive blood draws. And how much of that knee-jerk reflex to order daily “routine labs” is really just defensive medicine anyway?

I recently started teaching residents and was a little apprehensive in the very beginning. After all, 2 decades later, I still remember the good (and bad) attendings, and to this very day I incorporate parts of what the good ones taught me into patient encounters. Now I would be the one who could leave a lasting, hopefully positive impression in brilliant young minds. I have found teaching residents to be motivating and eye-opening. I get to see what’s new on their burgeoning, technologically advanced horizons; and I am learning from them, too. It’s invigorating to grow in the field I love so much, to expand my mind and, sometimes, humbly acknowledge I need to switch gears and proceed in a different direction; I suspect many others would benefit from this revelation as well.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Diagnosing and treating illnesses are the bread and butter of hospitalist medicine. Has your bread become stale?

I used to be envious of older physicians who ‘grandfathered in’ and became exempt from the requirement to recertify every 10 years for the American Board of Internal Medicine. Preparing for the boards is extremely time consuming and, at times, incredibly stressful, but it’s what we have to do to prove that our medical knowledge is up to date, right?

Who hasn’t heard of at least one nightmare outcome after a physician treated a patient with out-of-date standards, probably the same ones he learned in medical school a long, long time ago? We may snicker at this scenario, but could we be guilty too? Could we be so set in our ways, so self-confident that we refuse to grow?

I was watching a hospital medicine CME DVD a few months ago and was shocked, as well as embarrassed, to learn that the way I was performing part of my neurological exam was antiquated. There was a new “gold standard” that I had never learned before. After all, I had been doing the exact same thing for years; too many years, it seems. I mistakenly assumed that all the physical examination skills I had learned in medical school were set in stone. But as in all aspects of medicine, even best practices for performing a basic examination have evolved over the years.

Then there is the old habit of ordering multiple blood tests on hospitalized patients every day. That’s just how many of us were trained during residency, but in real life it’s not always necessary. Sure, if there’s a reason to be concerned about specific parameters they should be followed closely, but most inpatients don’t really need chemistries and a CBC each and every day; if they weren’t already anemic, we could make them anemic with excessive blood draws. And how much of that knee-jerk reflex to order daily “routine labs” is really just defensive medicine anyway?

I recently started teaching residents and was a little apprehensive in the very beginning. After all, 2 decades later, I still remember the good (and bad) attendings, and to this very day I incorporate parts of what the good ones taught me into patient encounters. Now I would be the one who could leave a lasting, hopefully positive impression in brilliant young minds. I have found teaching residents to be motivating and eye-opening. I get to see what’s new on their burgeoning, technologically advanced horizons; and I am learning from them, too. It’s invigorating to grow in the field I love so much, to expand my mind and, sometimes, humbly acknowledge I need to switch gears and proceed in a different direction; I suspect many others would benefit from this revelation as well.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Diagnosing and treating illnesses are the bread and butter of hospitalist medicine. Has your bread become stale?

I used to be envious of older physicians who ‘grandfathered in’ and became exempt from the requirement to recertify every 10 years for the American Board of Internal Medicine. Preparing for the boards is extremely time consuming and, at times, incredibly stressful, but it’s what we have to do to prove that our medical knowledge is up to date, right?

Who hasn’t heard of at least one nightmare outcome after a physician treated a patient with out-of-date standards, probably the same ones he learned in medical school a long, long time ago? We may snicker at this scenario, but could we be guilty too? Could we be so set in our ways, so self-confident that we refuse to grow?

I was watching a hospital medicine CME DVD a few months ago and was shocked, as well as embarrassed, to learn that the way I was performing part of my neurological exam was antiquated. There was a new “gold standard” that I had never learned before. After all, I had been doing the exact same thing for years; too many years, it seems. I mistakenly assumed that all the physical examination skills I had learned in medical school were set in stone. But as in all aspects of medicine, even best practices for performing a basic examination have evolved over the years.

Then there is the old habit of ordering multiple blood tests on hospitalized patients every day. That’s just how many of us were trained during residency, but in real life it’s not always necessary. Sure, if there’s a reason to be concerned about specific parameters they should be followed closely, but most inpatients don’t really need chemistries and a CBC each and every day; if they weren’t already anemic, we could make them anemic with excessive blood draws. And how much of that knee-jerk reflex to order daily “routine labs” is really just defensive medicine anyway?

I recently started teaching residents and was a little apprehensive in the very beginning. After all, 2 decades later, I still remember the good (and bad) attendings, and to this very day I incorporate parts of what the good ones taught me into patient encounters. Now I would be the one who could leave a lasting, hopefully positive impression in brilliant young minds. I have found teaching residents to be motivating and eye-opening. I get to see what’s new on their burgeoning, technologically advanced horizons; and I am learning from them, too. It’s invigorating to grow in the field I love so much, to expand my mind and, sometimes, humbly acknowledge I need to switch gears and proceed in a different direction; I suspect many others would benefit from this revelation as well.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Umbilical cord blood donation

Photo courtesy of NHS

SAN DIEGO—A product that promotes CD34 expansion has solved the problem of poor engraftment associated with umbilical cord blood transplant (UCBT), according to a speaker at the 2015 BMT Tandem Meetings.

John Wagner, MD, of the University of Minnesota in Minneapolis, supported this statement with early results from trials of HSC835, cord

blood units in which CD34 cells were expanded using the aryl hydrocarbon

receptor antagonist StemRegenin 1.

Dr Wagner and his colleagues conducted phase 1 and 2 trials of HSC835, which were supported by Novartis, the company developing the product.

Dr Wagner presented results of these trials at the BMT Tandem Meetings as abstract 29.*

The phase 1 trial included 18 patients who received double UCBT after myeloablative conditioning. They received an unmanipulated cord blood unit and an HSC835 unit.

In the phase 2 trial, 3 patients received a single HSC835 unit after myeloablative conditioning, and 3 received an HSC835 unit after non-myeloablative conditioning.

Manufacturing HSC835 took 15 days. Following expansion, the median CD34 cell dose increased 346-fold, and the median total nucleated cell (TNC) dose increased 848-fold.

Twenty-eight HSC835 products were produced, but 4 of them were not infused. Two products were contaminated, 1 was not infused due to patient relapse, and 1 product failed to expand. Dr Wagner noted that the failed unit started out at 50% viability, whereas the other units started at about 90% viability.

Phase 1

Eighteen patients were treated in the phase 1 trial. Eleven had acute lymphoblastic leukemia, 5 had acute myeloid leukemia, and 2 had myelodysplastic syndromes. The median age was 28 (range, 12 to 53).

The median TNC dose was 2.5 x 10⁷/kg for the unmanipulated cord blood unit and 5.1 x 10⁷/kg for the HSC835 unit. The median CD34 count was 0.4 x 10⁶/kg and 17.4 x 10⁶/kg, respectively. And the median CD3 count was 8.5 x 10⁶/kg and 2.5 x 10⁶/kg, respectively.

Most units were a 5/6 HLA match—50% for the unmanipulated unit and 67% for the HSC835 unit. Forty-four percent and 22% of the units, respectively, were 4/6 matches. And 6% and 11%, respectively, were 6/6 matches.

Neutrophil recovery was 100%, and the median time to recovery was 14.5 days.

Dr Wagner compared this to results in 121 matched historical controls who received UCBT with 2 unmanipulated units. Of those patients, 86% achieved neutrophil engraftment, and the median time to engraftment was 25 days (P<0.001).

In the current study, 6 patients had complete chimerism with HSC835, 6 had complete chimerism with the unmanipulated unit, and 6 had dual chimerism. In the dual-chimerism patients, both units were present, but all the T cells were derived from the unmanipulated unit.

“When we look at those patients who had engraftment of HSC835, whether it be this dual chimerism or complete chimerism, you see there is a very rapid recovery of 10.5 days, as compared to the historical control [recovery time] of 25 days,” Dr Wagner said. “And those that engrafted with the unmanipulated unit fall right where you’d expect them; that is, with the historical controls [23 days].”

Dr Wagner noted that the CD34 dose correlated with the pace of neutrophil recovery in patients who engrafted with the HSC835 unit, and patients with dual chimerism had the fastest neutrophil recovery.

Furthermore, the HSC835 unit predominated more than expected (P=0.05), winning out over the cord blood unit with a higher CD3 dose a disproportionate amount of time. The unit with a higher CD3 dose typically predominates two-thirds of the time in double UCBT.

“[These results] gave us enough information to say that [HSC835] could be a stand-alone product,” Dr Wagner said.

Phase 2

For phase 2, the researchers used a single HSC835 unit. They chose the lesser of 2 cord blood units (keeping the better unit as a backup), expanded it, and infused the resulting HSC835 unit into 3 patients who received myeloablative conditioning and 3 patients who did not.

In patients who received myeloablative conditioning, chimerism was complete at days 8, 12, and 14. Among the patients who received non-myeloablative conditioning, 1 had mixed chimerism at day 6. The other 2 had complete chimerism at days 5 and 7.

“So in conclusion, we believe that HSC835 is safe and effective in speeding neutrophil recovery after cord blood transplant,” Dr Wagner said. “These are very promising early results that compel us now to explore the single expanded product.”

Dr Wagner added that other considerations for HSC835 are that it may reduce the unit selection threshold, improve HLA match, enable re-cryopreservation (for transplant delays, backup, or multiple dosing), and perhaps allow for reduced-intensity conditioning with “mega-dose” grafts.

*Information in the abstract differs from that presented at the meeting.

Umbilical cord blood donation

Photo courtesy of NHS

SAN DIEGO—A product that promotes CD34 expansion has solved the problem of poor engraftment associated with umbilical cord blood transplant (UCBT), according to a speaker at the 2015 BMT Tandem Meetings.

John Wagner, MD, of the University of Minnesota in Minneapolis, supported this statement with early results from trials of HSC835, cord

blood units in which CD34 cells were expanded using the aryl hydrocarbon

receptor antagonist StemRegenin 1.

Dr Wagner and his colleagues conducted phase 1 and 2 trials of HSC835, which were supported by Novartis, the company developing the product.

Dr Wagner presented results of these trials at the BMT Tandem Meetings as abstract 29.*

The phase 1 trial included 18 patients who received double UCBT after myeloablative conditioning. They received an unmanipulated cord blood unit and an HSC835 unit.

In the phase 2 trial, 3 patients received a single HSC835 unit after myeloablative conditioning, and 3 received an HSC835 unit after non-myeloablative conditioning.

Manufacturing HSC835 took 15 days. Following expansion, the median CD34 cell dose increased 346-fold, and the median total nucleated cell (TNC) dose increased 848-fold.

Twenty-eight HSC835 products were produced, but 4 of them were not infused. Two products were contaminated, 1 was not infused due to patient relapse, and 1 product failed to expand. Dr Wagner noted that the failed unit started out at 50% viability, whereas the other units started at about 90% viability.

Phase 1

Eighteen patients were treated in the phase 1 trial. Eleven had acute lymphoblastic leukemia, 5 had acute myeloid leukemia, and 2 had myelodysplastic syndromes. The median age was 28 (range, 12 to 53).

The median TNC dose was 2.5 x 10⁷/kg for the unmanipulated cord blood unit and 5.1 x 10⁷/kg for the HSC835 unit. The median CD34 count was 0.4 x 10⁶/kg and 17.4 x 10⁶/kg, respectively. And the median CD3 count was 8.5 x 10⁶/kg and 2.5 x 10⁶/kg, respectively.

Most units were a 5/6 HLA match—50% for the unmanipulated unit and 67% for the HSC835 unit. Forty-four percent and 22% of the units, respectively, were 4/6 matches. And 6% and 11%, respectively, were 6/6 matches.

Neutrophil recovery was 100%, and the median time to recovery was 14.5 days.

Dr Wagner compared this to results in 121 matched historical controls who received UCBT with 2 unmanipulated units. Of those patients, 86% achieved neutrophil engraftment, and the median time to engraftment was 25 days (P<0.001).

In the current study, 6 patients had complete chimerism with HSC835, 6 had complete chimerism with the unmanipulated unit, and 6 had dual chimerism. In the dual-chimerism patients, both units were present, but all the T cells were derived from the unmanipulated unit.

“When we look at those patients who had engraftment of HSC835, whether it be this dual chimerism or complete chimerism, you see there is a very rapid recovery of 10.5 days, as compared to the historical control [recovery time] of 25 days,” Dr Wagner said. “And those that engrafted with the unmanipulated unit fall right where you’d expect them; that is, with the historical controls [23 days].”

Dr Wagner noted that the CD34 dose correlated with the pace of neutrophil recovery in patients who engrafted with the HSC835 unit, and patients with dual chimerism had the fastest neutrophil recovery.

Furthermore, the HSC835 unit predominated more than expected (P=0.05), winning out over the cord blood unit with a higher CD3 dose a disproportionate amount of time. The unit with a higher CD3 dose typically predominates two-thirds of the time in double UCBT.

“[These results] gave us enough information to say that [HSC835] could be a stand-alone product,” Dr Wagner said.

Phase 2

For phase 2, the researchers used a single HSC835 unit. They chose the lesser of 2 cord blood units (keeping the better unit as a backup), expanded it, and infused the resulting HSC835 unit into 3 patients who received myeloablative conditioning and 3 patients who did not.

In patients who received myeloablative conditioning, chimerism was complete at days 8, 12, and 14. Among the patients who received non-myeloablative conditioning, 1 had mixed chimerism at day 6. The other 2 had complete chimerism at days 5 and 7.

“So in conclusion, we believe that HSC835 is safe and effective in speeding neutrophil recovery after cord blood transplant,” Dr Wagner said. “These are very promising early results that compel us now to explore the single expanded product.”

Dr Wagner added that other considerations for HSC835 are that it may reduce the unit selection threshold, improve HLA match, enable re-cryopreservation (for transplant delays, backup, or multiple dosing), and perhaps allow for reduced-intensity conditioning with “mega-dose” grafts.

*Information in the abstract differs from that presented at the meeting.

Umbilical cord blood donation

Photo courtesy of NHS

SAN DIEGO—A product that promotes CD34 expansion has solved the problem of poor engraftment associated with umbilical cord blood transplant (UCBT), according to a speaker at the 2015 BMT Tandem Meetings.

John Wagner, MD, of the University of Minnesota in Minneapolis, supported this statement with early results from trials of HSC835, cord

blood units in which CD34 cells were expanded using the aryl hydrocarbon

receptor antagonist StemRegenin 1.

Dr Wagner and his colleagues conducted phase 1 and 2 trials of HSC835, which were supported by Novartis, the company developing the product.

Dr Wagner presented results of these trials at the BMT Tandem Meetings as abstract 29.*

The phase 1 trial included 18 patients who received double UCBT after myeloablative conditioning. They received an unmanipulated cord blood unit and an HSC835 unit.

In the phase 2 trial, 3 patients received a single HSC835 unit after myeloablative conditioning, and 3 received an HSC835 unit after non-myeloablative conditioning.

Manufacturing HSC835 took 15 days. Following expansion, the median CD34 cell dose increased 346-fold, and the median total nucleated cell (TNC) dose increased 848-fold.

Twenty-eight HSC835 products were produced, but 4 of them were not infused. Two products were contaminated, 1 was not infused due to patient relapse, and 1 product failed to expand. Dr Wagner noted that the failed unit started out at 50% viability, whereas the other units started at about 90% viability.

Phase 1

Eighteen patients were treated in the phase 1 trial. Eleven had acute lymphoblastic leukemia, 5 had acute myeloid leukemia, and 2 had myelodysplastic syndromes. The median age was 28 (range, 12 to 53).

The median TNC dose was 2.5 x 10⁷/kg for the unmanipulated cord blood unit and 5.1 x 10⁷/kg for the HSC835 unit. The median CD34 count was 0.4 x 10⁶/kg and 17.4 x 10⁶/kg, respectively. And the median CD3 count was 8.5 x 10⁶/kg and 2.5 x 10⁶/kg, respectively.

Most units were a 5/6 HLA match—50% for the unmanipulated unit and 67% for the HSC835 unit. Forty-four percent and 22% of the units, respectively, were 4/6 matches. And 6% and 11%, respectively, were 6/6 matches.

Neutrophil recovery was 100%, and the median time to recovery was 14.5 days.

Dr Wagner compared this to results in 121 matched historical controls who received UCBT with 2 unmanipulated units. Of those patients, 86% achieved neutrophil engraftment, and the median time to engraftment was 25 days (P<0.001).

In the current study, 6 patients had complete chimerism with HSC835, 6 had complete chimerism with the unmanipulated unit, and 6 had dual chimerism. In the dual-chimerism patients, both units were present, but all the T cells were derived from the unmanipulated unit.

“When we look at those patients who had engraftment of HSC835, whether it be this dual chimerism or complete chimerism, you see there is a very rapid recovery of 10.5 days, as compared to the historical control [recovery time] of 25 days,” Dr Wagner said. “And those that engrafted with the unmanipulated unit fall right where you’d expect them; that is, with the historical controls [23 days].”

Dr Wagner noted that the CD34 dose correlated with the pace of neutrophil recovery in patients who engrafted with the HSC835 unit, and patients with dual chimerism had the fastest neutrophil recovery.

Furthermore, the HSC835 unit predominated more than expected (P=0.05), winning out over the cord blood unit with a higher CD3 dose a disproportionate amount of time. The unit with a higher CD3 dose typically predominates two-thirds of the time in double UCBT.

“[These results] gave us enough information to say that [HSC835] could be a stand-alone product,” Dr Wagner said.

Phase 2

For phase 2, the researchers used a single HSC835 unit. They chose the lesser of 2 cord blood units (keeping the better unit as a backup), expanded it, and infused the resulting HSC835 unit into 3 patients who received myeloablative conditioning and 3 patients who did not.

In patients who received myeloablative conditioning, chimerism was complete at days 8, 12, and 14. Among the patients who received non-myeloablative conditioning, 1 had mixed chimerism at day 6. The other 2 had complete chimerism at days 5 and 7.

“So in conclusion, we believe that HSC835 is safe and effective in speeding neutrophil recovery after cord blood transplant,” Dr Wagner said. “These are very promising early results that compel us now to explore the single expanded product.”

Dr Wagner added that other considerations for HSC835 are that it may reduce the unit selection threshold, improve HLA match, enable re-cryopreservation (for transplant delays, backup, or multiple dosing), and perhaps allow for reduced-intensity conditioning with “mega-dose” grafts.

*Information in the abstract differs from that presented at the meeting.

Mesenchymal stem cells

SAN DIEGO—Infusions of expanded mesenchymal stem cells (MSCs) can treat severe, steroid-resistant, acute graft-vs-host disease (aGVHD) in pediatric patients, according to a study presented at the 2015 BMT Tandem Meetings.

The MSC product, known as remestemcel-L, induced responses in all grades of aGVHD and all organ systems.

Response at day 28 was associated with improved survival at day 100, and clinically significant toxicities were minimal, according to investigators.

“The enrolled patients represent a very challenging population with severe graft-vs-host disease that was non-responsive to treatments, including steroids and, for many of these children, multiple immunosuppressive agents, so we believe these results are very promising,” said Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina.

Dr Kurtzberg and her colleagues reported the results in a poster presentation (abstract 492*). Three investigators involved in this research are employed by Mesoblast, Inc., the company developing remestemcel-L.

The study included 160 patients who had a median age of 10 years (range, 0.3 to 17.5 years). Eighty-four percent of patients had received an unrelated donor transplant, and 46% received a mismatched transplant.

At baseline, 19% of patients had grade B aGVHD, 28% had grade C, and 53% had grade D. Eighty-nine percent of patients had gastrointestinal involvement, 50% had skin involvement, and 29% had liver involvement. Forty-one percent of patients had 2 organs involved, and 15% had 3.

The median duration of aGVHD before study enrollment was 28 days (range, 1 to 237), and patients had failed a median of 3 immunosuppressive agents.

Treatment and outcomes

Patients received 8 bi-weekly, intravenous infusions of 2 × 10⁶ MSCs/kg for 4 weeks. They could receive additional weekly infusions if deemed eligible at day 28.

The patients received a median of 11 infusions (range, 1-20) and were exposed to the treatment for a median of 43.5 days.

Fifty-three percent of patients had at least 1 serious adverse event. Eight patients (5%) had serious events that investigators thought might be treatment-related. These included neutropenia, infusion-related reaction, pulmonary hemorrhage, respiratory distress, tachycardia, respiratory failure, and hypertension.

Three events (6%) that were considered possibly treatment-related (pulmonary hemorrhage, respiratory distress, and respiratory failure) ultimately resulted in death. Fifty-four patients (34%) died in all.

At day 28, the overall response rate (ORR) was 64%. The ORR was 74% for grade B aGVHD, 66% for grade C, and 59% for grade D. The ORR was 62% for gastrointestinal, 77% for skin, and 53% for liver aGVHD.

Response correlated with a significant improvement in survival at day 100. Eighty-one percent of patients who responded at day 28 were still alive at day 100, compared to 21% of non-responders (P<0.0001).

The investigators said this study provides support for remestemcel-L to treat aGVHD in children. A single-arm, phase 3 trial of pediatric patients with aGVHD is underway.

*Information in the abstract differs from that presented at the meeting.

Mesenchymal stem cells

SAN DIEGO—Infusions of expanded mesenchymal stem cells (MSCs) can treat severe, steroid-resistant, acute graft-vs-host disease (aGVHD) in pediatric patients, according to a study presented at the 2015 BMT Tandem Meetings.

The MSC product, known as remestemcel-L, induced responses in all grades of aGVHD and all organ systems.

Response at day 28 was associated with improved survival at day 100, and clinically significant toxicities were minimal, according to investigators.

“The enrolled patients represent a very challenging population with severe graft-vs-host disease that was non-responsive to treatments, including steroids and, for many of these children, multiple immunosuppressive agents, so we believe these results are very promising,” said Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina.

Dr Kurtzberg and her colleagues reported the results in a poster presentation (abstract 492*). Three investigators involved in this research are employed by Mesoblast, Inc., the company developing remestemcel-L.

The study included 160 patients who had a median age of 10 years (range, 0.3 to 17.5 years). Eighty-four percent of patients had received an unrelated donor transplant, and 46% received a mismatched transplant.

At baseline, 19% of patients had grade B aGVHD, 28% had grade C, and 53% had grade D. Eighty-nine percent of patients had gastrointestinal involvement, 50% had skin involvement, and 29% had liver involvement. Forty-one percent of patients had 2 organs involved, and 15% had 3.

The median duration of aGVHD before study enrollment was 28 days (range, 1 to 237), and patients had failed a median of 3 immunosuppressive agents.

Treatment and outcomes

Patients received 8 bi-weekly, intravenous infusions of 2 × 10⁶ MSCs/kg for 4 weeks. They could receive additional weekly infusions if deemed eligible at day 28.

The patients received a median of 11 infusions (range, 1-20) and were exposed to the treatment for a median of 43.5 days.

Fifty-three percent of patients had at least 1 serious adverse event. Eight patients (5%) had serious events that investigators thought might be treatment-related. These included neutropenia, infusion-related reaction, pulmonary hemorrhage, respiratory distress, tachycardia, respiratory failure, and hypertension.

Three events (6%) that were considered possibly treatment-related (pulmonary hemorrhage, respiratory distress, and respiratory failure) ultimately resulted in death. Fifty-four patients (34%) died in all.

At day 28, the overall response rate (ORR) was 64%. The ORR was 74% for grade B aGVHD, 66% for grade C, and 59% for grade D. The ORR was 62% for gastrointestinal, 77% for skin, and 53% for liver aGVHD.

Response correlated with a significant improvement in survival at day 100. Eighty-one percent of patients who responded at day 28 were still alive at day 100, compared to 21% of non-responders (P<0.0001).

The investigators said this study provides support for remestemcel-L to treat aGVHD in children. A single-arm, phase 3 trial of pediatric patients with aGVHD is underway.

*Information in the abstract differs from that presented at the meeting.

Mesenchymal stem cells

SAN DIEGO—Infusions of expanded mesenchymal stem cells (MSCs) can treat severe, steroid-resistant, acute graft-vs-host disease (aGVHD) in pediatric patients, according to a study presented at the 2015 BMT Tandem Meetings.

The MSC product, known as remestemcel-L, induced responses in all grades of aGVHD and all organ systems.

Response at day 28 was associated with improved survival at day 100, and clinically significant toxicities were minimal, according to investigators.

“The enrolled patients represent a very challenging population with severe graft-vs-host disease that was non-responsive to treatments, including steroids and, for many of these children, multiple immunosuppressive agents, so we believe these results are very promising,” said Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina.

Dr Kurtzberg and her colleagues reported the results in a poster presentation (abstract 492*). Three investigators involved in this research are employed by Mesoblast, Inc., the company developing remestemcel-L.

The study included 160 patients who had a median age of 10 years (range, 0.3 to 17.5 years). Eighty-four percent of patients had received an unrelated donor transplant, and 46% received a mismatched transplant.

At baseline, 19% of patients had grade B aGVHD, 28% had grade C, and 53% had grade D. Eighty-nine percent of patients had gastrointestinal involvement, 50% had skin involvement, and 29% had liver involvement. Forty-one percent of patients had 2 organs involved, and 15% had 3.

The median duration of aGVHD before study enrollment was 28 days (range, 1 to 237), and patients had failed a median of 3 immunosuppressive agents.

Treatment and outcomes

Patients received 8 bi-weekly, intravenous infusions of 2 × 10⁶ MSCs/kg for 4 weeks. They could receive additional weekly infusions if deemed eligible at day 28.

The patients received a median of 11 infusions (range, 1-20) and were exposed to the treatment for a median of 43.5 days.

Fifty-three percent of patients had at least 1 serious adverse event. Eight patients (5%) had serious events that investigators thought might be treatment-related. These included neutropenia, infusion-related reaction, pulmonary hemorrhage, respiratory distress, tachycardia, respiratory failure, and hypertension.

Three events (6%) that were considered possibly treatment-related (pulmonary hemorrhage, respiratory distress, and respiratory failure) ultimately resulted in death. Fifty-four patients (34%) died in all.

At day 28, the overall response rate (ORR) was 64%. The ORR was 74% for grade B aGVHD, 66% for grade C, and 59% for grade D. The ORR was 62% for gastrointestinal, 77% for skin, and 53% for liver aGVHD.

Response correlated with a significant improvement in survival at day 100. Eighty-one percent of patients who responded at day 28 were still alive at day 100, compared to 21% of non-responders (P<0.0001).

The investigators said this study provides support for remestemcel-L to treat aGVHD in children. A single-arm, phase 3 trial of pediatric patients with aGVHD is underway.

*Information in the abstract differs from that presented at the meeting.

Thrombus

Image by Andre E.X. Brown

The factor Xa inhibitor fondaparinux may confer a lower risk of death and bleeding after heart attack than low-molecular-weight heparin (LMWH).

In a large study, patients who received fondaparinux after non-ST-segment elevation myocardial infarction (NSTEMI) had a lower risk of major bleeding and death, both in the hospital and after discharge, compared to patients who received LMWH.

However, both arms had similar rates of subsequent heart attack or stroke.

Karolina Szummer, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden, and her colleagues disclosed these results in JAMA.

The researchers analyzed data from a Swedish registry that included 40,616 patients with NSTEMI. The patients received in-hospital treatment with fondaparinux (n=14,791; 36.4%) or LMWH (25,825; 63.6%) between September 2006 and June 2010, with follow-up through December 2010.

Patients in the fondaparinux arm were, on average, 2 years younger (72 years vs 74 years) than patients in the LMWH arm. Fondaparinux-treated patients also had fewer previous heart attacks (28.2% vs 32.2%), and fewer had been diagnosed with congestive heart failure (14.5% vs 18.7%), but more had undergone percutaneous coronary intervention (46.4% vs 38.9%).

The rate of prior bleeding events and previous hemorrhagic stroke was similar between the arms. Prior bleeding was reported in 6.1% of patients in both arms, and hemorrhagic stroke was reported in 1.4% of patients in the fondaparinux arm and 1.3% in the LMWH arm.

Following treatment, the absolute rate of severe in-hospital bleeding events was lower in the fondaparinux arm than in the LMWH arm—1.1% vs 1.8% (odds ratio [OR]=0.54).

The rate of severe bleeding while in the hospital or causing readmission was lower in the fondaparinux arm, both at 30 days—1.4% vs 2.1% (OR=0.56)—and at 180 days—1.9% vs 2.8% (OR=0.60).

In-hospital mortality was lower in the fondaparinux arm than the LMWH arm—2.7% and 4.0%, respectively (OR=0.75). The same pattern was observed for mortality at 30 days (OR=0.82) and 180 days (OR=0.76).

However, the rate of recurrent heart attack was similar in both arms. At 30 days, it was 9.0% in the fondaparinux arm and 9.5% in the LMWH arm (OR=0.94). And at 180 days, rates were 14.2% and 15.8%, respectively (OR=0.97).

Likewise, the rate of stroke did not differ significantly between the arms. At 30 days, it was 0.5% in the fondaparinux arm and 0.6% in the LMWH arm (OR=1.11). And at 180 days, rates were 1.7% and 2.0%, respectively (OR=0.98).

The results were similar in patients with varying degrees of kidney function and in the subset of patients who had undergone early percutaneous coronary intervention.

The researchers said these results provide an estimate of the treatment effect in a selected patient population. However, the effects may differ in clinical practice and should therefore be investigated in observational cohorts and in continuous registries.

Thrombus

Image by Andre E.X. Brown

The factor Xa inhibitor fondaparinux may confer a lower risk of death and bleeding after heart attack than low-molecular-weight heparin (LMWH).

In a large study, patients who received fondaparinux after non-ST-segment elevation myocardial infarction (NSTEMI) had a lower risk of major bleeding and death, both in the hospital and after discharge, compared to patients who received LMWH.

However, both arms had similar rates of subsequent heart attack or stroke.

Karolina Szummer, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden, and her colleagues disclosed these results in JAMA.

The researchers analyzed data from a Swedish registry that included 40,616 patients with NSTEMI. The patients received in-hospital treatment with fondaparinux (n=14,791; 36.4%) or LMWH (25,825; 63.6%) between September 2006 and June 2010, with follow-up through December 2010.

Patients in the fondaparinux arm were, on average, 2 years younger (72 years vs 74 years) than patients in the LMWH arm. Fondaparinux-treated patients also had fewer previous heart attacks (28.2% vs 32.2%), and fewer had been diagnosed with congestive heart failure (14.5% vs 18.7%), but more had undergone percutaneous coronary intervention (46.4% vs 38.9%).

The rate of prior bleeding events and previous hemorrhagic stroke was similar between the arms. Prior bleeding was reported in 6.1% of patients in both arms, and hemorrhagic stroke was reported in 1.4% of patients in the fondaparinux arm and 1.3% in the LMWH arm.

Following treatment, the absolute rate of severe in-hospital bleeding events was lower in the fondaparinux arm than in the LMWH arm—1.1% vs 1.8% (odds ratio [OR]=0.54).

The rate of severe bleeding while in the hospital or causing readmission was lower in the fondaparinux arm, both at 30 days—1.4% vs 2.1% (OR=0.56)—and at 180 days—1.9% vs 2.8% (OR=0.60).

In-hospital mortality was lower in the fondaparinux arm than the LMWH arm—2.7% and 4.0%, respectively (OR=0.75). The same pattern was observed for mortality at 30 days (OR=0.82) and 180 days (OR=0.76).

However, the rate of recurrent heart attack was similar in both arms. At 30 days, it was 9.0% in the fondaparinux arm and 9.5% in the LMWH arm (OR=0.94). And at 180 days, rates were 14.2% and 15.8%, respectively (OR=0.97).

Likewise, the rate of stroke did not differ significantly between the arms. At 30 days, it was 0.5% in the fondaparinux arm and 0.6% in the LMWH arm (OR=1.11). And at 180 days, rates were 1.7% and 2.0%, respectively (OR=0.98).

The results were similar in patients with varying degrees of kidney function and in the subset of patients who had undergone early percutaneous coronary intervention.

The researchers said these results provide an estimate of the treatment effect in a selected patient population. However, the effects may differ in clinical practice and should therefore be investigated in observational cohorts and in continuous registries.

Thrombus

Image by Andre E.X. Brown

The factor Xa inhibitor fondaparinux may confer a lower risk of death and bleeding after heart attack than low-molecular-weight heparin (LMWH).

In a large study, patients who received fondaparinux after non-ST-segment elevation myocardial infarction (NSTEMI) had a lower risk of major bleeding and death, both in the hospital and after discharge, compared to patients who received LMWH.

However, both arms had similar rates of subsequent heart attack or stroke.

Karolina Szummer, MD, PhD, of the Karolinska Institutet in Stockholm, Sweden, and her colleagues disclosed these results in JAMA.

The researchers analyzed data from a Swedish registry that included 40,616 patients with NSTEMI. The patients received in-hospital treatment with fondaparinux (n=14,791; 36.4%) or LMWH (25,825; 63.6%) between September 2006 and June 2010, with follow-up through December 2010.

Patients in the fondaparinux arm were, on average, 2 years younger (72 years vs 74 years) than patients in the LMWH arm. Fondaparinux-treated patients also had fewer previous heart attacks (28.2% vs 32.2%), and fewer had been diagnosed with congestive heart failure (14.5% vs 18.7%), but more had undergone percutaneous coronary intervention (46.4% vs 38.9%).

The rate of prior bleeding events and previous hemorrhagic stroke was similar between the arms. Prior bleeding was reported in 6.1% of patients in both arms, and hemorrhagic stroke was reported in 1.4% of patients in the fondaparinux arm and 1.3% in the LMWH arm.

Following treatment, the absolute rate of severe in-hospital bleeding events was lower in the fondaparinux arm than in the LMWH arm—1.1% vs 1.8% (odds ratio [OR]=0.54).

The rate of severe bleeding while in the hospital or causing readmission was lower in the fondaparinux arm, both at 30 days—1.4% vs 2.1% (OR=0.56)—and at 180 days—1.9% vs 2.8% (OR=0.60).

In-hospital mortality was lower in the fondaparinux arm than the LMWH arm—2.7% and 4.0%, respectively (OR=0.75). The same pattern was observed for mortality at 30 days (OR=0.82) and 180 days (OR=0.76).

However, the rate of recurrent heart attack was similar in both arms. At 30 days, it was 9.0% in the fondaparinux arm and 9.5% in the LMWH arm (OR=0.94). And at 180 days, rates were 14.2% and 15.8%, respectively (OR=0.97).

Likewise, the rate of stroke did not differ significantly between the arms. At 30 days, it was 0.5% in the fondaparinux arm and 0.6% in the LMWH arm (OR=1.11). And at 180 days, rates were 1.7% and 2.0%, respectively (OR=0.98).

The results were similar in patients with varying degrees of kidney function and in the subset of patients who had undergone early percutaneous coronary intervention.

The researchers said these results provide an estimate of the treatment effect in a selected patient population. However, the effects may differ in clinical practice and should therefore be investigated in observational cohorts and in continuous registries.

Patient and pharmacist

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued 5 draft documents related to drug compounding and repackaging that aim to help entities comply with public health provisions.

The agency said these draft documents are applicable to pharmacies, federal facilities, outsourcing facilities, and physicians.

The new category of outsourcing facilities was created under the Drug Quality and Security Act (DQSA), which was enacted by Congress in November 2013.

It was enacted in response to a deadly fungal meningitis outbreak that was linked to contaminated sterile compounded drug products.

Drugs compounded in an outsourcing facility that meet certain conditions may be entitled to exemptions from certain provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including the new drug approval requirements and the requirement to label drug products with adequate directions for use.

Outsourcing facilities are subject to current good manufacturing practice requirements and inspections by the FDA according to a risk-based schedule.

Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the FD&C Act, or they will be subject to all of the requirements applicable to drugs produced by conventional drug manufacturers.

“The draft guidance documents provide information to pharmacies, outsourcing facilities, healthcare entities, and others about these FDA-proposed policies, which are critical to protecting the public health,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

Descriptions of these documents follow.

Draft Guidance: For Entities Considering Whether to Register As Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

This draft guidance provides an entity considering whether to register with the FDA as an outsourcing facility with information about the regulatory impact of registering.

For example, it explains that a facility engaged in only certain activities, including repackaging human drugs and compounding non-sterile drugs, should not register as an outsourcing facility because its drug products will not qualify for the exemptions provided in section 503B, including the exemption from the new drug approval requirements.

Draft Guidance for Industry: Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities

This draft guidance describes the conditions under which the FDA does not intend to take action for certain violations of the law when state-licensed pharmacies, federal facilities, or outsourcing facilities repackage certain drug products.

Repackaged drug products are generally not exempt from any of the provisions of the FD&C Act related to the production of drugs, and the compounding provisions of the FD&C Act do not address repackaging. Therefore, the FDA is issuing guidance to describe how it intends to address repackaging when done in a state-licensed pharmacy, federal facility, or outsourcing facility.

Draft Guidance for Industry: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (BLA)

This draft guidance describes the conditions under which the FDA does not intend to take action for violations of certain sections of the Public Health Service Act (PHS Act) and the FD&C Act when state-licensed pharmacies, federal facilities, or outsourcing facilities mix, dilute, or repackage specific biological products without an approved BLA, or when such facilities or physicians prepare prescription sets of allergenic extracts without an approved BLA.

The draft guidance notes that a biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an unlicensed biological product under section 351 of the PHS Act and may not be legally marketed without an approved BLA.

Additionally, the compounding provisions of the FD&C Act do not address biological products subject to licensure under section 351 of the PHS Act. Therefore, the FDA is issuing the guidance to describe how it intends to address these practices.

Draft Guidance for Industry: Adverse Event Reporting for Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

Entities registered as outsourcing facilities are required to report adverse events to the FDA. This draft guidance explains adverse event reporting for such facilities.

Draft Memorandum of Understanding Between A State and the U.S. Food and Drug Administration Addressing Certain Distributions of Compounded Human Drug Products

The draft memorandum of understanding (MOU) under section 503A of the FD&C Act describes the responsibilities of a state that chooses to sign the MOU in investigating and responding to complaints related to compounded human drug products distributed outside the state, and in addressing the interstate distribution of “inordinate amounts” of compounded human drug products.

These documents are the latest in a series of policy documents related to FDA oversight of drugs produced by state-licensed pharmacies, federal facilities, and outsourcing facilities.

The draft guidance documents are available for public comment for 90 days. The public has 120 days to comment on the draft MOU between the states and the FDA.

Patient and pharmacist

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued 5 draft documents related to drug compounding and repackaging that aim to help entities comply with public health provisions.

The agency said these draft documents are applicable to pharmacies, federal facilities, outsourcing facilities, and physicians.

The new category of outsourcing facilities was created under the Drug Quality and Security Act (DQSA), which was enacted by Congress in November 2013.

It was enacted in response to a deadly fungal meningitis outbreak that was linked to contaminated sterile compounded drug products.

Drugs compounded in an outsourcing facility that meet certain conditions may be entitled to exemptions from certain provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including the new drug approval requirements and the requirement to label drug products with adequate directions for use.

Outsourcing facilities are subject to current good manufacturing practice requirements and inspections by the FDA according to a risk-based schedule.

Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the FD&C Act, or they will be subject to all of the requirements applicable to drugs produced by conventional drug manufacturers.

“The draft guidance documents provide information to pharmacies, outsourcing facilities, healthcare entities, and others about these FDA-proposed policies, which are critical to protecting the public health,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

Descriptions of these documents follow.

Draft Guidance: For Entities Considering Whether to Register As Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

This draft guidance provides an entity considering whether to register with the FDA as an outsourcing facility with information about the regulatory impact of registering.

For example, it explains that a facility engaged in only certain activities, including repackaging human drugs and compounding non-sterile drugs, should not register as an outsourcing facility because its drug products will not qualify for the exemptions provided in section 503B, including the exemption from the new drug approval requirements.

Draft Guidance for Industry: Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities

This draft guidance describes the conditions under which the FDA does not intend to take action for certain violations of the law when state-licensed pharmacies, federal facilities, or outsourcing facilities repackage certain drug products.

Repackaged drug products are generally not exempt from any of the provisions of the FD&C Act related to the production of drugs, and the compounding provisions of the FD&C Act do not address repackaging. Therefore, the FDA is issuing guidance to describe how it intends to address repackaging when done in a state-licensed pharmacy, federal facility, or outsourcing facility.

Draft Guidance for Industry: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (BLA)

This draft guidance describes the conditions under which the FDA does not intend to take action for violations of certain sections of the Public Health Service Act (PHS Act) and the FD&C Act when state-licensed pharmacies, federal facilities, or outsourcing facilities mix, dilute, or repackage specific biological products without an approved BLA, or when such facilities or physicians prepare prescription sets of allergenic extracts without an approved BLA.

The draft guidance notes that a biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an unlicensed biological product under section 351 of the PHS Act and may not be legally marketed without an approved BLA.

Additionally, the compounding provisions of the FD&C Act do not address biological products subject to licensure under section 351 of the PHS Act. Therefore, the FDA is issuing the guidance to describe how it intends to address these practices.

Draft Guidance for Industry: Adverse Event Reporting for Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

Entities registered as outsourcing facilities are required to report adverse events to the FDA. This draft guidance explains adverse event reporting for such facilities.

Draft Memorandum of Understanding Between A State and the U.S. Food and Drug Administration Addressing Certain Distributions of Compounded Human Drug Products

The draft memorandum of understanding (MOU) under section 503A of the FD&C Act describes the responsibilities of a state that chooses to sign the MOU in investigating and responding to complaints related to compounded human drug products distributed outside the state, and in addressing the interstate distribution of “inordinate amounts” of compounded human drug products.

These documents are the latest in a series of policy documents related to FDA oversight of drugs produced by state-licensed pharmacies, federal facilities, and outsourcing facilities.

The draft guidance documents are available for public comment for 90 days. The public has 120 days to comment on the draft MOU between the states and the FDA.

Patient and pharmacist

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has issued 5 draft documents related to drug compounding and repackaging that aim to help entities comply with public health provisions.

The agency said these draft documents are applicable to pharmacies, federal facilities, outsourcing facilities, and physicians.

The new category of outsourcing facilities was created under the Drug Quality and Security Act (DQSA), which was enacted by Congress in November 2013.

It was enacted in response to a deadly fungal meningitis outbreak that was linked to contaminated sterile compounded drug products.

Drugs compounded in an outsourcing facility that meet certain conditions may be entitled to exemptions from certain provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act), including the new drug approval requirements and the requirement to label drug products with adequate directions for use.

Outsourcing facilities are subject to current good manufacturing practice requirements and inspections by the FDA according to a risk-based schedule.

Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the FD&C Act, or they will be subject to all of the requirements applicable to drugs produced by conventional drug manufacturers.

“The draft guidance documents provide information to pharmacies, outsourcing facilities, healthcare entities, and others about these FDA-proposed policies, which are critical to protecting the public health,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

Descriptions of these documents follow.

Draft Guidance: For Entities Considering Whether to Register As Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

This draft guidance provides an entity considering whether to register with the FDA as an outsourcing facility with information about the regulatory impact of registering.

For example, it explains that a facility engaged in only certain activities, including repackaging human drugs and compounding non-sterile drugs, should not register as an outsourcing facility because its drug products will not qualify for the exemptions provided in section 503B, including the exemption from the new drug approval requirements.

Draft Guidance for Industry: Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities

This draft guidance describes the conditions under which the FDA does not intend to take action for certain violations of the law when state-licensed pharmacies, federal facilities, or outsourcing facilities repackage certain drug products.

Repackaged drug products are generally not exempt from any of the provisions of the FD&C Act related to the production of drugs, and the compounding provisions of the FD&C Act do not address repackaging. Therefore, the FDA is issuing guidance to describe how it intends to address repackaging when done in a state-licensed pharmacy, federal facility, or outsourcing facility.

Draft Guidance for Industry: Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application (BLA)

This draft guidance describes the conditions under which the FDA does not intend to take action for violations of certain sections of the Public Health Service Act (PHS Act) and the FD&C Act when state-licensed pharmacies, federal facilities, or outsourcing facilities mix, dilute, or repackage specific biological products without an approved BLA, or when such facilities or physicians prepare prescription sets of allergenic extracts without an approved BLA.

The draft guidance notes that a biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an unlicensed biological product under section 351 of the PHS Act and may not be legally marketed without an approved BLA.

Additionally, the compounding provisions of the FD&C Act do not address biological products subject to licensure under section 351 of the PHS Act. Therefore, the FDA is issuing the guidance to describe how it intends to address these practices.

Draft Guidance for Industry: Adverse Event Reporting for Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act

Entities registered as outsourcing facilities are required to report adverse events to the FDA. This draft guidance explains adverse event reporting for such facilities.

Draft Memorandum of Understanding Between A State and the U.S. Food and Drug Administration Addressing Certain Distributions of Compounded Human Drug Products

The draft memorandum of understanding (MOU) under section 503A of the FD&C Act describes the responsibilities of a state that chooses to sign the MOU in investigating and responding to complaints related to compounded human drug products distributed outside the state, and in addressing the interstate distribution of “inordinate amounts” of compounded human drug products.

These documents are the latest in a series of policy documents related to FDA oversight of drugs produced by state-licensed pharmacies, federal facilities, and outsourcing facilities.

The draft guidance documents are available for public comment for 90 days. The public has 120 days to comment on the draft MOU between the states and the FDA.

Sexual assault on military campuses reached a 10-year low during the 2013-2014 academic year, according to the DoD’s Annual Report on Sexual Harassment and Violence at the Military Service Academies released on February 11, 2015. However, sexual violence remains an issue on military campuses, particularly for female cadets and midshipmen.

The report, which focuses on the U.S. Military Academy at West Point, New York; the U.S. Naval Academy in Annapolis, Maryland; and the U.S. Air Force Academy in Colorado, details that although unwanted sexual contact (USC) incident numbers in 2013-2014 were the lowest reported since the survey was first conducted in 2005, 8.2% of women enrolled at these academies and 1.1% of enrolled men experienced USC in 2013-2014. These percentages are down from the 2011-2012 program year when 12.4% of enrolled women and 2% of enrolled men reported USC.

Related: Sexual Trauma in the Military

According to a DoD press release, although incident rates of USC have declined among cadets, former Secretary of Defense Chuck Hagel stated that the mission is “far from complete.”

Although USC is decreasing, perceived sexual harassment (PSH) rates have increased. Fifty-five percent of women and 12% of men from the U.S. Marine Academy reported incidents of some PSH in 2014, up from 49% and 8%, respectively. However, 82% of women and 77% of men surveyed did not file official reports of the incidents due to perceived lack of significance.

Related: Recovering From Military Sexual Trauma

The DoD report outlines 5 initiatives to further reduce USC and PSH:

•  Establishing a forum for strategic dialogue between academies;
• Developing targeted interventions for sophomores who experience assaults at a higher rate than do other class years;
• Developing an educational program available anonymously to those coping with a history of sexual victimization;
• Improving sexual assault reporting; and
• Better addressing social and professional retaliation associated with sexual assault reporting, especially when such behavior occurs via social media.

“These survey results suggest that there were 200 fewer sexual assault victims in 2014 than in 2012,” said Major General Jeffrey J. Snow, the director of the DoD Sexual Assault Prevention and Response Program, in the DoD press release. “Although these rates are at the lowest they’ve been in the decade since the department began conducting the survey, we can and should do more. Every cadet and midshipman deserves a safe place to learn—free from sexual harassment and sexual assault.”

Sexual assault on military campuses reached a 10-year low during the 2013-2014 academic year, according to the DoD’s Annual Report on Sexual Harassment and Violence at the Military Service Academies released on February 11, 2015. However, sexual violence remains an issue on military campuses, particularly for female cadets and midshipmen.

The report, which focuses on the U.S. Military Academy at West Point, New York; the U.S. Naval Academy in Annapolis, Maryland; and the U.S. Air Force Academy in Colorado, details that although unwanted sexual contact (USC) incident numbers in 2013-2014 were the lowest reported since the survey was first conducted in 2005, 8.2% of women enrolled at these academies and 1.1% of enrolled men experienced USC in 2013-2014. These percentages are down from the 2011-2012 program year when 12.4% of enrolled women and 2% of enrolled men reported USC.

Related: Sexual Trauma in the Military

According to a DoD press release, although incident rates of USC have declined among cadets, former Secretary of Defense Chuck Hagel stated that the mission is “far from complete.”

Although USC is decreasing, perceived sexual harassment (PSH) rates have increased. Fifty-five percent of women and 12% of men from the U.S. Marine Academy reported incidents of some PSH in 2014, up from 49% and 8%, respectively. However, 82% of women and 77% of men surveyed did not file official reports of the incidents due to perceived lack of significance.

Related: Recovering From Military Sexual Trauma

The DoD report outlines 5 initiatives to further reduce USC and PSH:

•  Establishing a forum for strategic dialogue between academies;
• Developing targeted interventions for sophomores who experience assaults at a higher rate than do other class years;
• Developing an educational program available anonymously to those coping with a history of sexual victimization;
• Improving sexual assault reporting; and
• Better addressing social and professional retaliation associated with sexual assault reporting, especially when such behavior occurs via social media.

“These survey results suggest that there were 200 fewer sexual assault victims in 2014 than in 2012,” said Major General Jeffrey J. Snow, the director of the DoD Sexual Assault Prevention and Response Program, in the DoD press release. “Although these rates are at the lowest they’ve been in the decade since the department began conducting the survey, we can and should do more. Every cadet and midshipman deserves a safe place to learn—free from sexual harassment and sexual assault.”

Sexual assault on military campuses reached a 10-year low during the 2013-2014 academic year, according to the DoD’s Annual Report on Sexual Harassment and Violence at the Military Service Academies released on February 11, 2015. However, sexual violence remains an issue on military campuses, particularly for female cadets and midshipmen.

The report, which focuses on the U.S. Military Academy at West Point, New York; the U.S. Naval Academy in Annapolis, Maryland; and the U.S. Air Force Academy in Colorado, details that although unwanted sexual contact (USC) incident numbers in 2013-2014 were the lowest reported since the survey was first conducted in 2005, 8.2% of women enrolled at these academies and 1.1% of enrolled men experienced USC in 2013-2014. These percentages are down from the 2011-2012 program year when 12.4% of enrolled women and 2% of enrolled men reported USC.

Related: Sexual Trauma in the Military

According to a DoD press release, although incident rates of USC have declined among cadets, former Secretary of Defense Chuck Hagel stated that the mission is “far from complete.”

Although USC is decreasing, perceived sexual harassment (PSH) rates have increased. Fifty-five percent of women and 12% of men from the U.S. Marine Academy reported incidents of some PSH in 2014, up from 49% and 8%, respectively. However, 82% of women and 77% of men surveyed did not file official reports of the incidents due to perceived lack of significance.

Related: Recovering From Military Sexual Trauma

The DoD report outlines 5 initiatives to further reduce USC and PSH:

•  Establishing a forum for strategic dialogue between academies;
• Developing targeted interventions for sophomores who experience assaults at a higher rate than do other class years;
• Developing an educational program available anonymously to those coping with a history of sexual victimization;
• Improving sexual assault reporting; and
• Better addressing social and professional retaliation associated with sexual assault reporting, especially when such behavior occurs via social media.

“These survey results suggest that there were 200 fewer sexual assault victims in 2014 than in 2012,” said Major General Jeffrey J. Snow, the director of the DoD Sexual Assault Prevention and Response Program, in the DoD press release. “Although these rates are at the lowest they’ve been in the decade since the department began conducting the survey, we can and should do more. Every cadet and midshipman deserves a safe place to learn—free from sexual harassment and sexual assault.”

Bellafill

Suneva Medical, Inc, announces US Food and Drug Administration approval of the polymethylmethacrylate collagen filler Bellafill for the correction of moderate to severe, atrophic, distensible facial acne scars on the cheek in patients older than 21 years. Bellafill adds volume to the skin to lift and smooth out pitted acne scars to the level of the surrounding skin. Bellafill also is indicated for correction of nasolabial folds. For more information, visit www.bellafill.com.

Benzac

Galderma Laboratories, LP, launches Benzac Acne Solutions, an over-the-counter 3-step acne regimen consisting of a skin balancing foaming cleanser, intensive spot treatment, and blemish clearing hydrator. In addition to salicylic acid, Benzac also contains Kakadu plum (an antioxidant) to brighten the skin, lemon myrtle (an astringent) to reduce excess oil, and zinc to act as a barrier against skin moisture loss. Benzac contains pharmaceutical-grade East Indian sandalwood oil to calm and soothe the skin. For more information, visit www.benzac.com.

The Promius Promise App

Promius Pharma, LLC, marketers of Zenatane (isotretinoin capsules), launches The Promius Promise App designed to help educate and guide patients through the iPLEDGE program from the first visit to the last visit. The app is free for patients who have received a Zenatane prescription through The Promius Promise program. Patients can easily find important information, which may help with treatment compliance. The app will be useful for young adults and teenagers as well as their parents. For more information, visit www.zenatane.com/toolkit/Promius-Promise-Enrollment-Form.php.

Soolantra

Galderma Laboratories, LP, announces US Food and Drug Administration approval of Soolantra Cream 1% for the once-daily treatment of inflammatory lesions of rosacea. Ivermectin, the active ingredient in Soolantra, has both anti-inflammatory and antiparasitic activity. The basis for the cream formulation is Cetaphil Moisturizing Cream. Soolantra offers patients improvement as early as week 2 of treatment. For more information, visit www.soolantra.com/hcp.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].

Bellafill

Suneva Medical, Inc, announces US Food and Drug Administration approval of the polymethylmethacrylate collagen filler Bellafill for the correction of moderate to severe, atrophic, distensible facial acne scars on the cheek in patients older than 21 years. Bellafill adds volume to the skin to lift and smooth out pitted acne scars to the level of the surrounding skin. Bellafill also is indicated for correction of nasolabial folds. For more information, visit www.bellafill.com.

Benzac

Galderma Laboratories, LP, launches Benzac Acne Solutions, an over-the-counter 3-step acne regimen consisting of a skin balancing foaming cleanser, intensive spot treatment, and blemish clearing hydrator. In addition to salicylic acid, Benzac also contains Kakadu plum (an antioxidant) to brighten the skin, lemon myrtle (an astringent) to reduce excess oil, and zinc to act as a barrier against skin moisture loss. Benzac contains pharmaceutical-grade East Indian sandalwood oil to calm and soothe the skin. For more information, visit www.benzac.com.

The Promius Promise App

Promius Pharma, LLC, marketers of Zenatane (isotretinoin capsules), launches The Promius Promise App designed to help educate and guide patients through the iPLEDGE program from the first visit to the last visit. The app is free for patients who have received a Zenatane prescription through The Promius Promise program. Patients can easily find important information, which may help with treatment compliance. The app will be useful for young adults and teenagers as well as their parents. For more information, visit www.zenatane.com/toolkit/Promius-Promise-Enrollment-Form.php.

Soolantra

Galderma Laboratories, LP, announces US Food and Drug Administration approval of Soolantra Cream 1% for the once-daily treatment of inflammatory lesions of rosacea. Ivermectin, the active ingredient in Soolantra, has both anti-inflammatory and antiparasitic activity. The basis for the cream formulation is Cetaphil Moisturizing Cream. Soolantra offers patients improvement as early as week 2 of treatment. For more information, visit www.soolantra.com/hcp.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].

Bellafill

Suneva Medical, Inc, announces US Food and Drug Administration approval of the polymethylmethacrylate collagen filler Bellafill for the correction of moderate to severe, atrophic, distensible facial acne scars on the cheek in patients older than 21 years. Bellafill adds volume to the skin to lift and smooth out pitted acne scars to the level of the surrounding skin. Bellafill also is indicated for correction of nasolabial folds. For more information, visit www.bellafill.com.

Benzac

Galderma Laboratories, LP, launches Benzac Acne Solutions, an over-the-counter 3-step acne regimen consisting of a skin balancing foaming cleanser, intensive spot treatment, and blemish clearing hydrator. In addition to salicylic acid, Benzac also contains Kakadu plum (an antioxidant) to brighten the skin, lemon myrtle (an astringent) to reduce excess oil, and zinc to act as a barrier against skin moisture loss. Benzac contains pharmaceutical-grade East Indian sandalwood oil to calm and soothe the skin. For more information, visit www.benzac.com.

The Promius Promise App

Promius Pharma, LLC, marketers of Zenatane (isotretinoin capsules), launches The Promius Promise App designed to help educate and guide patients through the iPLEDGE program from the first visit to the last visit. The app is free for patients who have received a Zenatane prescription through The Promius Promise program. Patients can easily find important information, which may help with treatment compliance. The app will be useful for young adults and teenagers as well as their parents. For more information, visit www.zenatane.com/toolkit/Promius-Promise-Enrollment-Form.php.

Soolantra

Galderma Laboratories, LP, announces US Food and Drug Administration approval of Soolantra Cream 1% for the once-daily treatment of inflammatory lesions of rosacea. Ivermectin, the active ingredient in Soolantra, has both anti-inflammatory and antiparasitic activity. The basis for the cream formulation is Cetaphil Moisturizing Cream. Soolantra offers patients improvement as early as week 2 of treatment. For more information, visit www.soolantra.com/hcp.

If you would like your product included in Product News, please e-mail a press release to the Editorial Office at [email protected].

In hepatitis C, people born with the IL28B CC genotype can count themselves luckier than those born with CT or TT.

To read the full article, go to the Cleveland Clinic Journal of Medicine:  http://www.ccjm.org/home/article/genetics-and-hepatitis-c-its-good-to-be-cc/0afbe8ada94cdbab08fd0663c76e460e.html.

In hepatitis C, people born with the IL28B CC genotype can count themselves luckier than those born with CT or TT.

To read the full article, go to the Cleveland Clinic Journal of Medicine:  http://www.ccjm.org/home/article/genetics-and-hepatitis-c-its-good-to-be-cc/0afbe8ada94cdbab08fd0663c76e460e.html.

In hepatitis C, people born with the IL28B CC genotype can count themselves luckier than those born with CT or TT.

To read the full article, go to the Cleveland Clinic Journal of Medicine:  http://www.ccjm.org/home/article/genetics-and-hepatitis-c-its-good-to-be-cc/0afbe8ada94cdbab08fd0663c76e460e.html.