# Presentation: 130999

## Advisory Committee on Blood Safety and Availability

FDA Blood Product Advisory Committee May 2008

Jerry A. Holmberg, Ph.D.

- FDA Blood Product Advisory Committee May 2008
- Jerry A. Holmberg, Ph.D.

## Assistant Secretary for Health

- Joxel Garcia, M.D., M.B.A.
- Admiral, United States Public Health Service
- Donald Wright, M.D., M.P.H.
- Principal Deputy Assistant Secretary for Health
- Anand Parekh, M.D., M.P.H.
- Deputy Assistant Secretary for Health
- (Science and Medicine)

## Recommendations(2000-2008)

- Posted on web site:  _[www.hhs.gov/bloodsafety](http://www.hhs.gov/bloodsafety)_
- Since 2000 there have been:
- 42 Recommendation Topic Groups
- Over 100 actions by the Department and Operating Divisions
- CDC
- CMS
- FDA
- HRSA
- NIH,NHLBI

## Erythropoiesis Stimulating Agents (ESA)

- The Committee believes that there is inadequate information to accurately assess the impact of CMS’s National Coverage Determination (NCD) for Erythropoiesis Stimulating Agents (ESA) on the management of anemia in the general patient population and in cancer patients.

**Notes:**
Whereas, the revised position on ESA coverage may increase blood demand, ACBSA recommends HHS perform an analysis of the impact of ESA NCD on blood demand in affected patient populations. The information needed should be derived from prospective data collection. 

Whereas current demand for transfusion in various patient groups is not well characterized and varies with local practices, including adherence or non adherence with available transfusion guidelines, the ACBSA recommends HHS support studies to identify and characterize transfusion practices in relation to clinical outcomes in patient groups affected by the NCD, e.g., survival, quality of life (using validated instruments), adverse events, including cardiovascular events.
FDA’s Oncologic Drugs Advisory Committee (ODAC) on Erythropoiesis-Stimulating Agents (ESA) therapy for Chemotherapy-Induced Anemia (CIA).   Over the last 9 months I have been in communications with both FDA’s CDER and CMS related to the impact of the blood supply based on lower hemoglobin requirement.  It has been a pleasure to work with my colleagues in these agencies with the focus on public health, safety and reasonable reimbursement guidelines.

The drug companies (J&J and Amgen) have used the blood supply to leverage support for their drug.  The impact on the blood supply is minimal and any additional demand can be compensated by local recruitment for donors.   Our biannual survey and BASIS provided needed data to support our position.

The real issue has been the safety issue of ESA agents when given to oncology patients in order to avoid transfusion.  The hemoglobin trigger level, hemoglobin ceilings, dose and length of exposure in various types of cancers have been related to adverse outcomes in patients.  ESAs affect on cancer promotion, probably through EPO receptor sites has been documented and thrombotic events have also been reported at higher hemoglobin levels.  

Regarding the efficacy of the ESA over blood transfusion, there have not been data collected in the controlled studies to measure adverse events to transfusion. It seems that this is a glaring omission for a claim that ESAs have a benefit over transfusion in symptomatic patients.  Hemoglobin levels and fatigue are usually the only two parameters for indication.  

Summary of the ODAC discussion and voting:

The Committee recommended continued marketing of ESAs for the treatment of anemic due to concomitant cancer chemotherapy. (13 Yes, 1 No) 
Product labeling 
The Committee was divided on whether the indication for use be modified to restrict use only to patients with small cell lung cancer.  (Yes 6, No 8) 
The Committee supported a label change to include a statement that ESA use is not indicated for patients receiving potentially curative treatment. (Yes 11, No 2, Ab 1) 
The Committee was divided but the majority supported a label change to include a statement that ESA use is not indicated for patients with breast and/or head &neck cancer.  There was discussion by the Committee to include the qualifying word ”metastatic” in front of the cancers.  (Yes 9, N 5) 
Although the Committee did not vote on a specific hemoglobin level to trigger ESA initiation, the Committee was asked to discuss.   Dr. Stronchek from the Clinical Center Transfusion Medicine Department related that 10 grams may have been the level in the 1990 but now must hospital practices have a trigger of 8 and some even lower.  There was also discussion on the use in asymptomatic patients.  Generally the Committee was receptive to lowering the trigger to < 10 grams or even lower.   Note:  This discussion supports CMS’s National Coverage Determination (NCD) to 10 grams administered for 8 weeks. 
The Committee was asked to vote on several strategies to reduce risk. 
The Committee was divided (Yes 8, No 5 and Ab1) on a requirement to obtain written informed consent/patient agreement for he treatment of CIA with ESAs. 
.The Committee defeated the suggestion that FDA mandate a restricted distribution system for oncology patients receiving ESA (Yes 1, No 10, Ab 2)

## Recommendations August 2007

- The Committee recommends that HHS:
- Establish sufficient hospital and blood center participation in inventory reporting Develop comprehensive models
- Define shortage scenarios that would require implementation of alternative strategies for blood collection, distribution, and use.
- Support operations research to characterize and recruit potential donors who do not now routinely donate.

**Notes:**
Whereas the blood supply is a critical part of the Nation’s healthcare infrastructure, the HHS ACBSA believes that knowledge of real-time national blood and blood product inventory and its dynamics is essential for emergency preparedness and response. The committee finds that blood center data are extensive, but not comprehensively aggregated nor available to HHS; hospital data reporting is essential, but limited.  Although the blood supply is elastic, it is unclear whether it is sufficiently elastic to address potential disasters. 

## Slide 6

## Recommendations January 2008

- The ACBSA finds that accumulating evidence for the efficacy and safety of pathogen reduction warrants a commitment and concerted effort to add this technology as a broadly applicable safeguard which additionally would provide a reasonable protection against potential emerging infectious diseases. This would result in a pro-active, pre-emptive strategy that would broadly render most known agents non-infectious and prevent emerging agents from becoming transfusion risks. To achieve this goal, government, industry, blood organizations and public stakeholders need to work in concert to commit the required financial and technical resources.

**Notes:**
The Committee recommends that the Secretary:
Adopt as a high priority the urgent development of safe and effective pathogen reduction technologies for all blood transfusion products and implementation as they become available;
Provide resources to overcome current barriers to development and validation of pathogen reduction technologies;
Ensure adequate safety monitoring of pathogen reduced blood products post- marketing using an active national hemovigilance system
Ensure that other efforts to improve blood safety and availability are not compromised by these efforts. 

## Next ACBSA

- May 29 & 30, 2008
- Update on safety of transfusion and transplantation
- Updates on HBOC and rule making associated with vascularized composite allographs.
- Discussion of transfusions associated with older red cells.

## Nominations to ACBSA

- Federal Registry Notice, April 15, 2008
- Nominations due June 30, 2008