Rho(D) Immune Globulin Shortages

Last updated July 9, 2024

This Practice Advisory is provided to specifically address settings in which human Rho(D) immune globulin (RhIg) shortages are present. This Practice Advisory was developed by the American College of Obstetricians and Gynecologists with the assistance of Manisha Gandhi, MD, and Andrea Shields, MD, MS.

(Reaffirmed March 2025)

The U.S. Food and Drug Administration, American Society of Health-System Pharmacists (ASHP), and Association for the Advancement of Blood & Biotherapies are reporting Rho(D) immune globulin (RhIg) shortages 1 2 3 .

There are currently four licensed sources of RhIg in the United States 1 :

• HyperRHO—manufactured by Grifols Therapeutics LLC

• RhoGAM—manufactured by Kedrion Biopharma Inc. 

• Rhophylac—manufactured by CSL Behring AG

• WinRho—manufactured by Kamada Ltd.

If a preferred brand of RhIg is not available, an equivalent product may be substituted 2 4 . Information posted on the FDA’s CBER-Regulated Products: Current Shortages webpage is updated as new information becomes available from the manufacturer 1 . In the event of a shortage, consider contacting the various manufacturers to determine the availability of a substitute.

If it becomes necessary to triage the administration of RhIg in locations where shortages persist despite attempts to secure the product from the four manufacturers, the American College of Obstetricians and Gynecologists (ACOG) offers the following prioritization and conservation strategies for consideration:

• Confirm neonatal Rh(D) status from umbilical cord blood before administering routine postpartum RhIg 5 .

• Avoid administering RhIg in Rh(D)-sensitized patients 5 .

• If paternity is certain and the father or sperm donor is known to be Rh(D)-negative, antenatal prophylaxis is unnecessary 5 .

• Although current ACOG guidance does not recommend routine use of noninvasive prenatal testing (NIPT) to determine fetal Rh(D) status based on cost-effectiveness analyses 5 , the use of NIPT to prioritize use of RhIg and conserve RhIg supply is a reasonable consideration in the practice setting that is experiencing RhIg shortages. Noninvasive fetal red blood cell antigen genotyping utilizing cell-free DNA (cfDNA) isolated from maternal plasma has demonstrated high sensitivity and specificity for detection of fetal Rh(D) antigen status 6 7 8 9 10 . If cfDNA testing results confirm an Rh(D)-negative fetus, RhIg would not need to be routinely administered in the antepartum period (for bleeding, abortion, pregnancy loss, or at 28 weeks of gestation). Available cfDNA testing options for Rh(D) may vary depending on location and practice setting (eg, companies offering the test; whether the test is offered as a stand-alone or combined with aneuploidy testing; timing of results; insurance coverage) and should be confirmed before implementation.

• For routine RhIg prophylaxis, prioritize postpartum patients (if indicated). If additional supply is available, continue to administer the 28-week antepartum dose as well. This approach has been used in the past and shows a reduction in alloimmunization while maximizing conservation of available RhIg 11 .

• Other indications for RhIg prophylaxis are discussed in Practice Bulletin No. 181, Prevention of Rh D Alloimmunization 5 . Prioritization of these in a shortage will depend on specifics at a local level (eg, available supply, demand, and predicted length of shortage), but in general, priority may be given to patients at later gestational durations.

As RhIg shortages continue, disparities will become more pronounced. The American College of Obstetricians and Gynecologists continues to recommend RhIg for indications as noted in existing guidance 5 12 13 14 in situations without shortages.

The American College of Obstetricians and Gynecologists will continue to actively monitor the situation and update this Practice Advisory with additional information as needed. For more information on RhIg prophylaxis, see the following ACOG guidance documents:

• Practice Bulletin No. 181, Prevention of Rh D Alloimmunization 5

• Practice Bulletin No. 192, Management of Alloimmunization During Pregnancy  12

• Practice Bulletin No. 200, Early Pregnancy Loss 13

• Practice Bulletin No. 225, Medication Abortion Up to 70 Days of Gestation 14

Please contact [email protected] with any questions.