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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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D

Biologics Studied and Not
Studied in Children
*

To identify biologics that have been studied, were being studied, or were planned for study in children, the Institute of Medicine committee examined several sources of information about biologics that were approved by the Food and Drug Administration (FDA) between January 1, 1997, and December 31, 2010. FDA supplied the list of biologics for products now regulated by the Center for Drug Evaluation and Research (CDER). For the biologics that are regulated by the Center for Biologics Evaluation and Research (CBER), the committee relied on a website listing of biologics for which some supporting documentation was available. CBER staff were consulted to help the committee identify any relevant omitted products and exclude products that were approved under new drug applications (NDAs), were not being marketed, or were not new products.

As explained in Chapter 8, the committee excluded preventive vaccines and nontherapeutic biologics such as assays and reagents (e.g., products used for blood testing or blood grouping). In addition to excluding products approved before 1997, it also excluded products that were approved under new drug applications, were not approved for marketing in the United States, were not being marketed as of December 31, 2010, or were

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* Tables were prepared with the assistance of Lara Ellinger, Pharm.D., B.C.P.S., Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

not new products.1 The final list included 96 biologics. Of these, 57 were regulated by CDER and 39 were regulated by CBER. This appendix reports information from the labeling of these products and from a government registry of clinical trials.

Although the committee excluded vaccines for its more extensive analysis, it conducted a less intensive review of information on pediatric studies and labeling for vaccines. It identified 55 vaccines with supporting information that CBER had posted at http://www.fda.gov/BiologicsBloodVaccines/ucm133705.htm. The vaccines listed include approximately 20 that appear to have been approved before 1997.

A number of vaccines (e.g., vaccines for rotavirus and combination vaccines for diphtheria, tetanus, and pertussis) are labeled for pediatric use only. Of the 55 vaccines listed by CBER, three products (5 percent) were not labeled for pediatric use, had waivers of pediatric study requirements, and also did not have pediatric studies registered at ClinicalTrials.gov.

• An adenovirus type 4 and type 7 vaccine (no brand name) was developed under contract with the U.S. Department of Defense and approved by FDA in 2011 for use with military personnel ages 17 to 50 years; an earlier product had been used by the military beginning in the 1980s and ending after the sole manufacturer stopped manufacturing the product (Schrager, 2011). FDA waived the pediatric study requirement because studies were impossible or impracticable (Malarkey and Baylor, 2011).2

• An anthrax vaccine (no brand name) was approved in 1970 for use by individuals ages 18 to 65 years who are at high risk of exposure to the disease. In a 2008 approval for a new dosing interval and route of administration, FDA waived the pediatric study requirement on the grounds that studies were impossible or impracticable because the pediatric population is not at high risk of exposure (Sun, 2008).

• A herpes zoster (shingles) vaccine (Zostamax) was approved by FDA in 2006 for use by individuals 60 years of age or older. FDA waived the requirement for pediatric studies because the product

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1 The original approval dates and marketing status for biologics are not always easily determined. It is possible that one or more of the products listed had an original approval date prior to 1997. After the release of the prepublication manuscript at the end of February 2012, study staff determined that two products (Peginterferon alfa-2B; ribavirin [Pegintron/Rebetrol combo pack] and methoxy polyethylene glycol-epoetin beta [Mircera]) were not marketed as of December 31, 2010, and that one excluded product (drotrecogin alfa [Xigris]) was not discontinued until 2011. Tables D-1 and D-2 were revised to reflect this information. These revisions did not affect the report’s overall conclusions.

2 References cited in this appendix are included in the report’s reference list.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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   did not offer a meaningful therapeutic benefit over existing products and was unlikely to be used by a substantial number of children (Baylor, 2006).

In addition, FDA waived pediatric studies (without explanation) in approving a vaccine (Twinrix) for prevention of hepatitis A and B (Richman, 2007). For this product, however, ClinicalTrials.gov lists pediatric studies (see, e.g., ClinicalTrials.gov identifier: NCT00107042). For an intradermal formulation of an influenza vaccine (Fluzone), FDA waived pediatric studies because the product did not offer a meaningful therapeutic benefit over existing products and was unlikely to be used by a substantial number of children (Sun, 2011). ClinicalTrials.gov also lists pediatric studies of this product (see, e.g., ClinicalTrials.gov identifier: NCT00391391).

For the biologics including in the committee’s more extensive investigation, the committee consulted the current product labeling for references to pediatric studies; examined approval letters, if available, for references to required pediatric studies; checked FDA’s tracking database for postmarket study requirements and commitments for required studies; and searched ClinicalTrials.gov. ClinicalTrials.gov is a registry of publicly and privately supported clinical trials that is administered by the National Institutes of Health.

Table D-1, which groups CDER-and CBER-regulated products together, summarizes pediatric information found in the manufacturer’s product labeling. This information includes any pediatric use(s) for which the product is labeled; descriptions in the labeling of pediatric studies of the product (including studies that did not demonstrate efficacy); and, especially for any products without such labeling information, any warnings against pediatric use based on FDA or other analyses of adverse event reports or similar data. Information relevant to use of a product by pediatric populations may be located in several sections of the structured label (e.g., in sections on dosage, clinical pharmacology, and adverse reactions as well as in the highlights section that now appears at the start of prescription labeling). This can complicate efforts to find and summarize this information. Most of the review of labeling occurred in July and August 2011.3

Table D-2 summarizes information about pediatric studies registered at the ClinicalTrials.gov database. It first presents the information for CDER-regulated products and then presents the information for CBER-regulated

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3 After the release of the prepublication manuscript, study staff determined that Table D-1 should be revised to categorize two products (basiliximab [Simulect] and digoxin immune Fab [DigiFab]) as labeled for pediatric use. Some other summary information was edited for specificity. These revisions, based on reexamination of the manufacturer’s labeling, did not affect the report’s overall conclusions.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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products. For this table, products in certain classes (e.g., intravenous immune globulins) that are often treated as interchangeable for certain uses were grouped together because database entries often did not identify studied products by brand name. Trials for which the lower end of a participant age range was 16 years are not included. The database was checked from July to December 2011.

The brief summaries in the trials database were sometimes incorrect in indicating that a trial included children, particularly when the more detailed trial descriptions did not include an overview description of the age range but did make clear in the inclusion or exclusion criteria that only adults were eligible. These brief summaries could also be misleading about the condition to be studied, for example, by specifying transplantation rather than transplantation-related complications or disorders. A study categorized in the database as a Phase IV study, particularly one requested under the Best Pharmaceuticals for Children Act or required under the Pediatric Research Equity Act, might also fit the definition of a Phase I, II, or III study.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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TABLE D-1 Labeling Information on Pediatric Uses, Studies, and Certain Safety Warnings for Biologics Initially Approved by FDA Between January 1, 1997, and December 31, 2010 (listing for CDER-and CBER-regulated products combined)


Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Approved Indication(s) Highlights of Pediatric Information in Labeling

1. Abatacept
(Orencia)
(125118)
12/23/2005

• Adult rheumatoid arthritis

• Juvenile idiopathic arthritis (JIA)

Labeled pediatric use(s)

• ≥6 yr with moderately to severely active polyarticular JIA; may be used as monotherapy or concomitantly with methotrexate

• Not established in patients <6 yr

• Not established for diseases other than JIA



Study information

• Safety and efficacy were assessed in patients 6 to 17 yr (n = 190).

• Findings showed that the risk of disease flare in patients on Orencia was <1/3 the risk for flare in patients withdrawing from Orencia.

• Infections were the most frequent adverse events.


2. AbobotulinumtoxinA
(Dysport)
(125274)
04/29/2009

• Cervical dystonia

• Temporary improvement in glabellar lines

Cervical dystonia: Safety and effectiveness not established in pediatric patients
Glabellar lines: Not recommended for pediatric patients <18 yr

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

3. Adalimumab
(Humira)
(125057)
12/31/2002

   

• Rheumatoid arthritis

• Juvenile idiopathic arthritis (JIA)

• Psoriatic arthritis

• Ankylosing spondylitis

• Crohn’s disease

• Plaque psoriasis

   

Labeled pediatric use(s)

• Patients 4 to 17 yr for JIA

• Safety and efficacy not established for children weighing <15 kg and for conditions other than JIA



Study information

• Safety and efficacy were assessed in patients 4 to 17 yr (n = 171).

• Findings showed fewer patients in the adalimumab group than in placebo group experienced disease flare, regardless of methotrexate use.

• Malignancies have been reported in children and adolescent patients receiving treatment with tumor necrosis factor blockers, of which adalimumab is a member.

• Injection site reactions and infections are common adverse events.


4. Agalsidase beta
(Fabrazyme)
(103979)
04/24/2003

    Fabry disease    

Labeled pediatric use(s)

• Patients 8 to 16 yr with Fabry disease

• Safety and efficacy have not been evaluated in children <8 yr.



Study information

• Safety, pharmacokinetics, and pharmacodynamics were assessed in patients 8 to 16 yr (n = 16).

• Ten of 12 patients taking agalsidase beta had a reduction in globotriaosylceramide to normal levels.

• No new safety concerns were identified in pediatric patients.

• Infusion reactions were the most common adverse event.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

5. Albumin (human)
(Albumin), 5%, 25%
(125154)
10/17/2006

   

• Hypovolemia

• Hypoalbuminemia

• Prevention of central volume depletion after paracentesis

• Ovarian hyperstimulation syndrome (25% only)

• Adult respiratory distress syndrome (25%)

• Acute nephrosis (25%)

• Hemolytic disease of the newborn (25%)

   

Labeled pediatric use(s)

• Hypovolemia

• Hemolytic disease of the newborn (25%)

The product should only be administered to pediatric patients if needed.



Study information

• Data on use of albumin in children, including premature babies, are very limited.


6. Alefacept
(Amevive)
(125036)
01/30/2003

    Chronic plaque psoriasis in adult patients     Safety and efficacy of Amevive in pediatric patients have not been studied.

7. Alemtuzumab
(Campath)
(103948)
05/07/2001

    B-cell chronic lymphocytic leukemia     Safety and effectiveness in pediatric patients have not been established.

8. Alglucosidase alfa
(Lumizyme)
(125291)
05/24/2010

    Late-onset Pompe disease (α-glucosidase deficiency)    

Labeled pediatric use(s)

• Patients >8 yr with late-onset Pompe disease

• Safety and efficacy in pediatric patients <8 yrs have not been evaluated in clinical trials.



Study information

• Safety and efficacy were assessed in 90 patients with late-onset Pompe disease, ages 10 to 70 years, in a randomized double-blind, placebo-controlled study designed to enroll patients age 8-70 years. The youngest Lumizyme-treated patient was 16 years of age, and the youngest placebo-treated patient was 10 years of age.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

9. Alglucosidase alfa
(Myozyme)
(125141)
04/28/2006

    Pompe disease (α-glucosidase deficiency)    

Labeled pediatric use(s)

• Infantile-onset Pompe disease (improvement in ventilator-free survival)

• Risks and benefits have not been established in the juvenile-onset Pompe disease population.



Study information

• One trial assessed efficacy in patients ≤7 mo with infantile-onset Pompe disease (n = 18). A greater survival without invasive ventilator support was seen in patients receiving alglucosidase alfa vs. historical control.

• A second trial assessed efficacy in patients 3 mo to 3.5 yr (n = 21). No effect of alglucosidase alfa compared with historical control could be determined.

• Most common adverse reactions were infusion related.

• Anaphylactic reactions, cardiorespiratory failure, and cardiac arrest have also occurred.

• Open-label clinical trials have been performed in older pediatric patients ranging from 2 to 16 years at the initiation of treatment juvenile-onset Pompe disease).


10. Alpha1-proteinase
inhibitor (human)
(Aralast NP)
(125039)
05/04/2007

    Congenital deficiency of α1-proteinase inhibitor with clinically evident emphysema     Safety and effectiveness in pediatric patients have not been established.

11. Alpha1-proteinase
inhibitor (human)
(Glassia)
(125325)
07/01/2010

    Emphysema due to congenital deficiency of α1-proteinase inhibitor     Safety and effectiveness in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

12. Alpha1-proteinase
inhibitor (human)
(Zemaira)
(125078)
07/08/2003

    Congenital deficiency of α1-proteinase inhibitor with clinically evident emphysema     Safety and effectiveness in pediatric patients have not been established.

13. Anakinra
(Kineret)
(103950)
11/14/2001

    Rheumatoid arthritis in adults    

Not recommended because prefilled syringes do not allow accurate dosing below 100 mg and efficacy could not be demonstrated in study because of low enrollment



Study information

• Efficacy was assessed in patients 2 to 17 yr (n = 86) with juvenile rheumatoid arthritis.

• Efficacy was not demonstrated. An adverse event profile similar to that seen in adult patients with rheumatoid arthritis was observed.


14. Antihemophilic factor (recombinant)
(ReFacto)
(103779)
03/06/2000

   

• Control and prevention of hemorrhagic episodes and for surgical prophylaxis in patients with hemophilia A

• Short-term prophylaxis of spontaneous bleeding episodes in patients with hemophilia A

   

Labeled pediatric use(s)

• Appropriate for use in children of all ages with hemophilia A, including newborns



Study information

• Safety and efficacy studies have been performed with previously untreated neonates, infants, and children <1 to 52 mo (n = 101).

• Studies were also performed with previously treated children and adolescents 5 to 18 yr (n = 31)


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

15. Antihemophilic factor (recombinant), plasma/albumin-free method
(Advate)
(125063)
07/25/2003

   

• Control and prevention of bleeding episodes in adults and children with hemophilia A

• Perioperative management in adults and children with hemophilia A

   

Labeled pediatric use(s)

• Control and prevention of bleeding episodes in adults and children with hemophilia A

• Perioperative management in adults and children with hemophilia A



Study information

• Pharmacokinetic studies were performed in patients 1 mo to <16 yr (n = 51).

• In comparison with adults, children had higher Factor VIII clearance values and thus lower half-lives and recovery of Factor VIII.

• Larger or more frequent doses should be considered in a pediatric patient population.


16. Antihemophilic factor (recombinant), plasma/albumin free (Xyntha)
(125264)
02/21/2008

   

• Control and prevention of bleeding episodes in patients with hemophilia A

• Surgical prophylaxis in patients with hemophilia A

   

Labeled pediatric use(s)

• Bleeding episodes in hemophilia A

• Surgical prophylaxis in hemophilia A

• Description of indicated uses does not mention pediatric population explicitly.



Study information

• Pharmacokinetics were studied in previously treated patients 12 to 16 yr (n = 7).

• Pharmacokinetic parameters were similar to those observed in adults.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

17. Antithrombin
(recombinant)
(ATryn)
(125284)
02/06/2009

   

• Prevention of perioperative and peripartum thromboembolic events in hereditary antithrombin-deficient patients

• Not indicated for treatment of thromboembolic events in hereditary antithrombin-deficient patients

    Safety and effectiveness in pediatric patients have not been established.

18. Anti-thymocyte globulin
(rabbit)
(Thymoglobulin)
(103869)
12/30/1998

    Acute rejection in renal transplant patients    

Safety and effectiveness in pediatric patients have not been established in controlled trials.



Study information

• Dose, efficacy, and adverse event profile are thought to be similar to those in adults, based on limited European studies and U.S. compassionate use.


19. Autologous cultured chondrocytes
(Carticel)
(103661)
08/22/1997

    Repair of symptomatic cartilage defects of the femoral condyle     Safety and effectiveness in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

20. Basiliximab
(Simulect)
(103764)
05/12/1998

    Prophylaxis of acute organ rejection in patients receiving renal transplantation    

Labeled pediatric use(s)

• Prophylaxis of acute organ rejection in renal transplant

• In pediatric patients weighing less than 35 kg, the recommended regimen is two doses of 10 mg each. In pediatric patients weighing 35 kg or more, the recommended regimen is two doses of 20 mg each.



Study information

• Safety and pharmacokinetics were assessed in 39 pediatric patients. In patients 1 to 11 years of age (n = 25), disposition parameters were not influenced to a clinically relevant extent by age, body weight, or body surface area. In adolescents (12 to 16 years of age, n = 14), disposition was similar to that in adult renal transplantation patients. No randomized, controlled trials have been conducted in pediatric patients.

• The adverse event profile was consistent with general clinical experience in pediatric renal transplantation population and with the profile in controlled adult renal transplantation studies.


21. Becaplermin
(Regranex)
(103691)
12/16/1997

    Lower-extremity diabetic neuropathic ulcers     Safety and effectiveness in pediatric patients below 16 yr have not been established.

22. Bevacizumab
(Avastin)
(125085)
02/26/2004

   

• Metastatic colorectal cancer

• Nonsquamous non-small-cell lung cancer

• Metastatic breast cancer

• Glioblastoma

• Metastatic renal cell carcinoma

    Safety, effectiveness, and pharmacokinetic profile in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

23. Botulism immune globulin intravenous
(human)
(BabyBIG)
(125034)
10/23/2003

    Treatment of infant botulism by toxin types A or B in patients <1 yr    

Labeled pediatric use(s)

• Treatment of infant botulism by toxin type A or B in patients <1 yr

• BabyBIG has not been tested in other populations.



Study information

• Efficacy and safety were assessed in an infant population (n = 129).

• BabyBIG was shown to significantly reduce hospital and intensive care unit stays, mechanical ventilation, and tube feeding.

• The only noted adverse event was a mild rash on the face or trunk.


24. C1 esterase inhibitor (human)
(Berinert)
(125287)
10/09/2009

    Treatment of acute abdominal or facial attacks of hereditary angioedema (HAE) in adult and adolescent patients    

Labeled pediatric use(s)

• Treatment of attacks of HAE in patients >12 yr

• Safety and efficacy in patients 0 to 12 yr have not been established.



Study information

• Pharmacokinetics and safety were assessed in patients 3 to 12 yr (n = 5) but numbers were insufficient to assess efficacy.


25. C1 esterase inhibitor
(Cinryze)
(125267)
10/10/2008

    Routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema (HAE)    

Labeled pediatric use(s)

• Prophylaxis of attacks of HAE in adolescent and adult patients

• Safety and effectiveness in neonates, infants, or children have not been established.



Study information

• Three patients <18 yr were included in a routine prophylaxis trial that found Cinryze to be effective in reducing days of swelling and mean severity and duration of attacks.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

26. Canakinumab
(Ilaris)
(125319)
06/17/2009

   

Cryopyrin-associated periodic syndromes (CAPS) in adults and children ≥4 yr:

• Familial cold autoinflammatory syndrome

• Muckle-Wells syndrome

   

Labeled pediatric use(s)

• CAPS in patients ≥4 yr

• Safety and effectiveness of Ilaris in patients under 4 yr have not been established.



Study information

• Safety and efficacy were assessed in the CAPS trial in patients 4 to 17 yr (n = 23).

• The majority of patients achieved improvement in clinical symptoms and objective markers of inflammation.

• Overall safety and efficacy of canakinumab in pediatric patients were comparable to those in adults.


27. Certolizumab pegol
(Cimzia)
(125160)
04/22/2008

   

• Crohn’s disease

• Rheumatoid arthritis

   

Safety and effectiveness in pediatric patients have not been established.



Boxed warning

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, of which certolizumab is a member. Certolizumab is not indicated for use in pediatric patients.


28. Cetuximab
(Erbitux)
(125084)
02/12/2004

   

• Squamous cell carcinoma of the head and neck

• Metastatic colorectal cancer

   

Safety and effectiveness in pediatric patients have not been established.



Study information

• Pharmacokinetics were assessed in patients 1 to 12 yr (n = 27) and 13 to 18 yr (n = 19).

• Pharmacokinetic profiles were similar between the age groups.

• No new safety signals were identified in pediatric patients.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

29. Coagulation factor VIIa (recombinant)
(NovoSeven)
(103665)
03/25/1999

   

• Treatment of bleeding episodes in patients with hemophilia A or B and in acquired hemophilia

• Prevention of bleeding in surgical interventions or invasive procedures in patients with hemophilia

• Treatment of bleeding episodes in patients with congenital factor VII deficiency

• Prevention of bleeding in surgical interventions or invasive procedures in patients with factor VII deficiency

   

Labeled pediatric use(s)

• All approved indications without explicit distinction by age



Study information

• Clinical trials enrolling pediatric patients were conducted, with dosing determined according to body weight and not according to age.

• The safety and effectiveness of NovoSeven [for the indicated uses] has not been studied to determine if there are differences in various age groups, from infants to adolescents (0 to 16 yr)


30. Coagulation factor IX (recombinant)
(Benefix)
(103677)
02/01/1997

   

• Control and prevention of bleeding episodes in adult and pediatric patients with hemophilia

• Perioperative management in adult and pediatric patients with hemophilia

   

Labeled pediatric use(s)

• Control and prevention of bleeding episodes in pediatric patients with hemophilia

• Perioperative management in pediatric patients with hemophilia



Study information

• Pharmacokinetics, safety, and efficacy have been assessed in pediatric patients.

• A lower recovery is generally observed for patients <15 yr; a dose adjustment may be needed.


31. Collagenase clostridium histolyticum
(Xiaflex)
(125338)
02/02/2010

    Adult patients with Dupuytren’s contracture     Safety and effectiveness in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

32. Crotalidae polyvalent immune Fab (ovine)
(CroFab)
(103788)
10/02/2000

    Management of patients with North American crotalid (venomous snakes) envenomation    

Labeled pediatric use(s)

• Specific studies with pediatric patients have not been conducted. The absolute venom dose following snakebite is expected to be the same in children and adults; therefore, no dosage adjustment for age should be made.



Study information

• Two clinical trials using CroFab have been conducted. They were prospectively defined, open-label, multicenter trials conducted with otherwise healthy patients 11 yr or older who had suffered from minimal or moderate North American crotalid envenomation that showed evidence of progression.


33. Daclizumab
(Zenapax)
(103749)
12/10/1997

    Prophylaxis of acute organ rejection in patients receiving renal transplants    

Labeled pediatric use(s)

• Prophylaxis of acute organ rejection in patients 11 mo to 17 yr receiving renal transplants



Study information

• Pharmacokinetics, efficacy, immunogenicity, and safety were assessed in patients 11 mo to 17 yr (n = 60).

• Patient and graft survival at 1 yr posttransplant were 100% and 96.7%, respectively.

• Incidence of antidaclizumab antibodies (34%) was higher than incidence previously observed in adult patients.

• Safety profile in pediatric population was comparable to that in adult patients, with some exceptions.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

34. Darbepoetin alfa (Aranesp)
(103951)
09/17/2001

    Treatment of anemia due to chronic kidney disease (CKD) or myelosuppressive chemotherapy    

Labeled pediatric use(s)

• Treatment of anemia due to CKD in patients >1 yr and currently being treated with epoeitin alfa

• Safety and efficacy have not been assessed in initial treatment of anemic pediatric patients with CKD.

• Safety and efficacy in pediatric cancer patients have not been established.



Study information

• Pharmacokinetics were assessed in patients 3 to 16 yr (n = 12).

• Pharmacokinetic parameters were similar to those obtained in adult patients.

• Safety and the ability of darbepoetin to maintain hemoglobin concentrations in patients who had been receiving other recombinant erythropoietins were assessed in patients 1 to 17 yr (n = 123).

• Efficacy and safety in the pediatric population were similar to those in the adult population.


35. Denileukin diftitox (Ontak)
(103767)
02/05/1999

    Cutaneous T-cell lymphoma     Safety and efficacy in pediatric patients have not been established.

36. Denosumab (Prolia/Xgeva)
(125320)
06/01/2010

   

Xgeva: prevention of skeleton-related events in patients with bone metastases from solid tumors



Prolia: treatment of postmenopausal women with osteoporosis

    Safety and effectiveness of denosumab in pediatric patients have not been established. Its use is not recommended in pediatric patients, as it may impair bone growth and may inhibit eruption of dentition.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

37. Digoxin immune Fab (ovine)
(DigiFab)
(103910)
08/31/2001

    Treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose    

Labeled pediatric use(s)

Treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose including

• known suicidal or accidental consumption of fatal doses of digoxin in adults or children;

• chronic ingestion in adults and children;

• manifestations of life-threatening toxicity due to digoxin overdose



Study information

No pediatric patients were enrolled in clinical studies of DigiFab. A similar digoxin ovine Fab product, Digibind, has been used successfully to treat infants.

(Note: 2012 labeling states that safety data in pediatric population are limited and that pediatric dosing estimation is based on adult dose calculations.)


38. Drotrecogin alfa
(Xigris)
(125029)
11/21/2001

    Reduction of mortality in adult patients with severe sepsis who have a high risk of death    

A placebo-controlled trial in pediatric patients did not establish safety and effectiveness.



Study information

• Safety and efficacy were assessed in pediatric patients in the RESOLVE trial (n = 477)

• Study was terminated after interim analysis showed product was unlikely to show improvement over placebo.

• Central nervous system bleeding was greater in drotrecogin alfa-treated patients than placebo.

• All-cause mortality was similar in both treatment and placebo groups.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

39. Ecallantide
(Kalbitor)
(125277)
11/27/2009

    Acute attacks of hereditary angioedema (HAE)     Safety and effectiveness of Kalbitor in patients <16 yr have not been established.

40. Eculizumab
(Soliris)
(125166)
03/16/2007

   

• Paroxysmal nocturnal hemoglobinuria to reduce hemolysis (PNH)

   

Safety and effectiveness in pediatric patients <18 yr have not been established.


(Note: FDA approved a new indication, atypical hemolytic uremic syndrome, in September 2011 with safety and effectiveness noted to be similar to adult patients based on studies that included 25 pediatric patients ages 2 months to 17 years.)


41. Etanercept
(Enbrel)
(103795)
11/02/1998

   

• Rheumatoid arthritis (RA)

• Polyarticular juvenile idiopathic arthritis (JIA) in patients >2 yr

• Psoriatic arthritis

• Ankylosing spondylitis

• Plaque psoriasis

   

Labeled pediatric use(s)

• Polyarticular JIA in patients >2 yr

• Not established for JIA in patients <2 yr

• Safety and efficacy for plaque psoriasis in pediatric patients have not been established.



Study information

• Safety and efficacy were assessed in patients 2 to 17 yr with JIA (n = 69).

• Significantly fewer patients who remained on etanercept than those who were on placebo experienced disease flare.



Boxed warning

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, including etanercept.


42. Fibrin sealant
(TachoSil)
(125351)
04/02/2010

    Adjunct to hemostasis for use in cardiovascular surgery     Safety and effectiveness in pediatric patients undergoing cardiovascular surgery have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

43. Fibrin sealant
(Tisseel)
(103980)
05/01/1998

    Adjunct to hemostasis in surgeries involving

• Cardiopulmonary bypass

• Treatment of splenic injuries

   

Safety and effectiveness in pediatric patients have not been established.



(Note: In January 2012, FDA approved an indication extension for use as a general adjunct to hemostasis. The labeling notes that limited clinical data are available about use with children and notes that trial data on 27 revealed no differences in safety compared to the overall population studied.)


44. Fibrin sealant (human)
(Artiss)
(125266)
03/21/2008

    To adhere autologous skin grafts to surgically prepared wound beds resulting from burns in adult and pediatric populations    

Labeled pediatric use(s)

• Adherence of skin grafts to burns in patients ≥1 yr



Study information

• Safety and efficacy were assessed in patients 1 to 16 yr (n = 36).

• Safety and efficacy did not differ from those in an adult population.


45. Fibrin sealant (human)
(Evicel)
(125010)
03/21/2003

    Adjunct to hemostasis for use in patients during surgery    

Labeled pediatric use(s)

• Adjunct to hemostasis for use in patients >6 mo during surgery



Study information

• No data were available for patients 0 to 6 mo.

• Four pediatric patients were included in a study assessing use during retroperitoneal and intra-abdominal surgery; eight pediatric patients were included in a study assessing use during liver surgery.

• On the basis of these data, use of Evicel in a pediatric population is supported.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

46. Fibrinogen concentrate (human)
(RiaSTAP)
(125317)
01/16/2009

    Treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency    

Statement of indicated use does not explicitly refer to pediatric patients



Study information

• Studies included patients <16 yr.

• Patients <16 yr had shorter half-lives and faster clearance than adults.

• Small numbers of subjects limit interpretation.


47. Galsulfase
(Naglazyme)
(125117)
05/31/2005

    Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome)    

Labeled pediatric use(s)

• MPS VI in patients ≥5 yr

• Safety and efficacy in patients <5 yr have not been established.



Study information

• Clinical studies have been performed with patients 5 to 29 yr (n = 56).

• Findings showed galsulfase to be effective at improving endurance in comparison with placebo.

• An open-label study was conducted with four infants.

• Safety results are consistent with results for patients 5 to 29 yr.


48. Golimumab
(Simponi)
(125289)
04/24/2009

   

• Rheumatoid arthritis

• Psoriatic arthritis

• Ankylosing spondylitis

   

Safety and effectiveness of golimumab in pediatric patients <18 yr have not been established.



Boxed warning

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor blockers, of which golimumab is a member.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

49. Hepatitis B immune globulin intravenous (human)
(HepaGam B)
(125237)
04/06/2007

   

• Prevention of hepatitis B following liver transplantation

• Postexposure prophylaxis in the following settings: acute exposure to blood containing hepatitis B virus (HBV) surface antigen (HBsAg), perinatal exposure of infants born to HBsAg-positive mothers, sexual exposure to HBsAg-positive persons, household exposure to persons with acute HBV infection

   

Labeled pediatric use(s)

• Perinatal exposure of infants born to HBsAg-positive mothers

• Safety and effectiveness have not been established in pediatric patients. However, for postexposure prophylaxis, the safety and effectiveness of similar hepatitis B immune globulins have been demonstrated in infants and children.


50. Hepatitis B immune globulin (human)
(Nabi-HB)
(103945)
10/23/2001

   

Treatment of

• Acute exposure to blood containing hepatitis B virus (HBV) surface antigen (HBsAg)

• Perinatal exposure of infants born to HBsAg-positive mothers

• Sexual exposure to HBsAg-positive persons

• Household exposure to persons with acute HBV infection

   

Labeled pediatric use(s)

• Perinatal exposure of infants born to HBsAg-positive mothers

• Infants less than 12 mo old whose mother or primary caregiver is positive for HBsAg



Study information

• Safety and efficacy in the pediatric population have not been established. However, safety and effectiveness of similar hepatitis B immune globulins have been demonstrated in infants and children.


51. Ibritumomab tiuxetan
(Zevalin)
(125019)
02/19/2002

   

• Low-grade B-cell non-Hodgkin’s lymphoma (NHL)

• Follicular NHL

   

Safety and effectiveness of Zevalin in pediatric patients have not been established.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

52. Idursulfase (Elaprase)
(125151)
07/24/2006

    Hunter syndrome (Mucopolysaccharidosis II [MPS II])    

Labeled pediatric use(s)

• Hunter syndrome in patients ≥5 yr

• Safety and efficacy in pediatric patients <5 yr have not been established.



Study information

• Safety and efficacy have been evaluated in patients 5 to 31 yr (n = 96).

• Findings showed improved walking capacity in patients receiving idursulfase compared with that in patients receiving placebo.

• Children, adolescents, and adults responded similarly to treatment with idursulfase.

• Adverse effects include infusion-related reactions and hypoxemic episodes.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

53. Immune globulin injection (human), 10%, caprylate/chromatography purified (Gamunex-C)
(125046)
08/27/2003

   

• Primary humoral immunodeficiency (PI)

• Idiopathic thrombocytopenic purpura (ITP)

• Chronic inflammatory demyelinating polyneuropathy (CIDP)

   

Labeled pediatric use(s)

• PI (intravenous route) in pediatric patients

• ITP (intravenous route) in pediatric patients

• Efficacy and safety for CIDP in pediatric patients have not been established.

• Efficacy and safety by the subcutaneous route in pediatric patients have not been established.



Study information

• Intravenous Gamunex-C was evaluated for treatment of PI in pediatric patients 0 to 16 yr (n = 18).

• Pharmacokinetics, safety, and efficacy were similar to those in an adult population.

• Vomiting was more frequent in the pediatric population.

• Subcutaneous Gamunex-C was evaluated in three pediatric patients with PI; this number was too small to evaluate them separately from an adult population.

• Intravenous Gamunex-C was evaluated for the treatment of ITP in pediatric patients (n = 12).

• Pharmacokinetics, safety, and efficacy were similar to those in an adult population.

• Fever was more frequent in the pediatric population.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

54. Immune globulin intravenous (human)
(Flebogamma, 5% DIF)
(125077)
12/15/2003

    Treatment of primary humoral immunodeficiency disorders    

Efficacy and safety in pediatric patients have not been established.



Study information
Clinical trial enrolled too few children (0) and adolescents (3) to fully characterize efficacy and safety in pediatric patients. Preliminary safety data in children and adolescents with primary humoral immune deficiency has not revealed differences in safety profiles for pediatric and adult patients.


55. Immune globulin intravenous (human), 5% liquid
(Octagam)
(125062)
05/21/2004

    Treatment of primary humoral immunodeficiency diseases    

Labeled pediatric use(s)

• Primary humoral immunodeficiency in patients ≥6 yr (implicit)



Study information

• Pediatric patients 6 to 16 yr were included in a clinical study (n = 11).

• Pharmacokinetics, safety, and efficacy were similar to those in an adult population. No pediatric-specific dose requirements were necessary to achieve the desired serum IgG levels.


56. Immune globulin intravenous (human), 10% solution
(Gammagard liquid)
(125105)
04/27/2005

    Treatment of primary humoral immunodeficiency    

Labeled pediatric use(s)

• Primary humoral immunodeficiency in patients ≥2 yr

• Safety and efficacy have not been established in patients <2 yr.



Study information

• Safety and efficacy were evaluated in well-controlled studies that included pediatric patients 2 to 16 yr.

• Results were similar to those seen in adults. No adjustments in dosing were necessary.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

57. Immune globulin intravenous (human), 10% liquid
(Privigen)
(125201)
07/26/2007

   

• Primary humoral immunodeficiency

• Chronic immune thrombocytopenic purpura

   

Labeled pediatric use(s)

• Primary humoral immunodeficiency in patients ≥3 yr

• Safety and effectiveness of Privigen have not been established in pediatric patients <3 yr.

• Safety and effectiveness of Privigen have not been established in pediatric patients <15 yr with chronic immune thrombocytopenic purpura.



Study information

• Safety and efficacy were assessed in pediatric patients with PI (n = 31).

• Safety and efficacy profiles were comparable to those for adults.

• Safety, efficacy, and tolerability were established in patients 15 to 69 yr with ITP.


58. Immune globulin subcutaneous (human)
(Vivaglobin)
(125115)
01/09/2006

    Treatment of patients with primary humoral immunodeficiency    

Labeled pediatric use(s)

• Treatment of primary humoral immunodeficiency

• Safety and efficacy in pediatric subjects <2 yr have not been established.



Study information

• Two studies enrolled pediatric patients 3 to 16 yr (n = 10, n = 22).

• Safety and efficacy were similar to those seen in an adult population.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

59. Immune globulin subcutaneous (human) (IGSC), 20% liquid (Hizentra)
(125350)
03/04/2010

    Treatment of primary immunodeficiency    

Labeled pediatric use(s)

• Primary immunodeficiency in patients 2 to 16 yr

• Safety and efficacy in pediatric patients <2 yr have not been established.



Study information

• Safety and efficacy have been established in a U.S. study (n = 10) and a European study (n = 23).

• Safety and efficacy profiles were similar to those for an adult population.


60. Immune globulin intravenous (human), 5% liquid
(Gammaplex)
(125329)
09/17/2009

    Primary humoral immunodeficiency    

Implicit that safety and efficacy in a pediatric population have not been established.



Study information

• Six pediatric patients were included in a study but could not be evaluated separately because of small sample size.


61. IncobotulinumtoxinA
(Xeomin)
(125360)
07/30/2010

   

• Cervical dystonia

• Blepharospasm

    Safety and efficacy of incobotulinumtoxinA in patients <18 yr have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

62. Infliximab (Remicade)
(103772)
08/24/1998

   

• Crohn’s disease (CD)

• Ulcerative colitis

• Ankylosing spondylitis

• Psoriatic arthritis

• Plaque psoriasis

   

Labeled pediatric use(s)

• CD in patients ≥6 yr

• Use not established for patients <6 yr with CD

• Long-term safety and efficacy in pediatric CD patients not determined

• Use by pediatric patients with ulcerative colitis and plaque psoriasis not established



Study information

• Safety and efficacy have been assessed in patients 6 to 17 yr with CD (n = 112).

• Findings showed that infliximab was effective at reducing CD signs and symptoms and maintaining clinical remission.

• Safety and efficacy were assessed in patients 4 to 17 yr with juvenile rheumatoid arthritis (n = 60).

• Study failed to establish efficacy of infliximab in patients with juvenile rheumatoid arthritis.

• Findings showed high placebo response rate and higher rate of immunogenicity in pediatric patients than in adults.



Boxed warning

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, of which infliximab is a member.

• Postmarketing cases of hepatosplenic T-cell lymphoma have been reported in patients treated with TNF blockers, including infliximab. All cases were reported in patients with Crohn’s disease and ulcerative colitis, the majority of whom were adolescent or young adult males.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

63. Interferon alfacon-1
(Infergen)
(103663)
10/06/1997

    Chronic hepatitis C virus infection in patients ≥18 yr     Safety and effectiveness of interferon alfacon-1 in patients <18 yr have not been established. It is not recommended as therapy in pediatric patients.

64. Interferon beta-1A (Rebif)
(103780)
03/07/2002

    Relapsing forms of multiple sclerosis     Safety and effectiveness of interferon beta-1A in pediatric patients have not been studied.

65. Interferon gamma-1B (Actimmune)
(103836)
02/25/1999

   

• Reduction in infections in patients with chronic granulomatous disease (CGD)

• Delaying disease progression of osteopetrosis

   

Labeled pediatric use(s)

• CGD

• Osteopetrosis

• Statements of indicated uses do not explicitly refer to pediatric patients.



Study information

• Safety and efficacy were assessed in patients 1 to 44 yr with CGD (median age 14.6 yr) (n = 128).

• A statistically significant benefit in time to serious infection was found in the interferon gamma-1B group compared with placebo group.

• Safety and efficacy were assessed in patients 1 mo to 8 yr with osteopetrosis (n = 16).

• Median time to disease progression was delayed in the group receiving interferon gamma-1B plus calcitriol vs. the group receiving calcitriol alone.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

66. Laronidase (Aldurazyme)
(125058)
04/30/2003

    Hurler and Hurler-Scheie forms of mucopolysaccharidosis I (MPS I)    

Labeled pediatric use(s)

• Hurler and Hurler-Scheie forms of MPS I and for patients with the Scheie form who have moderate to severe symptoms



Study information

• Two studies assessed safety and efficacy in patients 6 to 43 yr (n = 45).

• Improvement in breathing and walking capacities were found in the laronidase group compared with placebo group.

• A third study assessed safety and efficacy in patients 6 mo to 5 yr (n = 20).

• Safety and efficacy findings were similar to those from a study that included both pediatric and adult populations.

• Common adverse events included infusion reactions and otitis media.


67. Natalizumab
(Tysabri)
(125104)
11/23/2004

   

• Relapsing forms of multiple sclerosis (MS)

• Crohn’s disease (CD)

   

Safety and effectiveness of Tysabri in pediatric patients <18 yr with MS or CD have not been established. Tysabri is not indicated for use by pediatric patients.


68. Ofatumumab
(Arzerra)
(125326)
10/26/2009

    Chronic lymphocytic leukemia     Safety and effectiveness in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

69. Omalizumab
(Xolair)
(103976)
06/20/2003

    Moderate to severe asthma    

Labeled pediatric use(s)

• Moderate to severe persistent asthma in patients ≥12 yr

• Not indicated for patients <12 yr



Study information

• Safety and effectiveness were assessed in two studies with asthma patients 6 to <12 yr (n = 926).

• Exacerbations were reduced, but other efficacy measures did not differ from those for placebo group.

• Known risk of anaphylaxis and malignancy in patients ≥12 yr outweighs benefit in children <12 yr.


70. Oprelvekin
(Neumega)
(103694)
11/25/1997

    Prevention of severe thrombocytopenia following myelosuppressive chemotherapy    

A safe and effective dose of Neumega in pediatric patients has not been established.



Study information

• A dose-escalation study involving 43 pediatric patients did not reduce need for transfusions and projected the effective dose to be higher than the maximum tolerated pediatric dose.

• Papilledema was a dose-limiting adverse effect.


71. Palifermin
(Kepivance)
(125103)
12/15/2004

    Oral mucositis     Safety and effectiveness of Kepivance in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

72. Palivizumab
(Synagis)
(103770)
6/19/1998

    Prevention of lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients    

Labeled pediatric use(s)

• Prevention of lower respiratory tract disease caused by RSV in pediatric patients



Study information

• Safety and efficacy were assessed in two studies with patients ≤24 mo (n = 2,789).

• Findings showed a significant reduction in hospitalization for RSV infection in patients receiving palivizumab than those receiving placebo.


73. Panitumumab
(Vectibix)
(125147)
09/27/2006

    Metastatic colorectal carcinoma     Pharmacokinetics, safety, and effectiveness in pediatric patients have not been established.

74. Pegfilgrastim
(Neulasta)
(125031)
01/31/2002

    To decrease infections in patients receiving myelosuppressive anticancer drugs associated with febrile neutropenia    

Safety and efficacy of Neulasta in pediatric patients have not been established.



Study information

• Pharmacokinetics and safety studies were conducted with 37 pediatric patients with sarcoma.

• The most common adverse reaction was bone pain.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

75. Peginterferon alfa-2A
(Pegasys)
(103964)
10/16/2002

    Chronic hepatitis C (CHC)    

Labeled pediatric use(s)

• CHC in patients 5 yr and older with compensated liver disease not previously treated with interferon alpha and patients with histological evidence of cirrhosis and compensated liver disease was treated with Peginterferon alfa-2A. Peginterferon alfa-2A should be given in combination with Copegus unless contraindicated. Peginterferon alfa-2A contains benzyl alcohol, which has been associated with an increased incidence of neurological and other complications in neonates and infants.



Study information

• Information on safety, dosing, and efficacy from a randomized trial (114 subjects) comparing combination with monotherapy is available.

• Pediatric subjects treated with Pegasys plus Copegus combination therapy showed delays in weight and height increases after 48 wk of therapy compared with those at baseline.


76. Peginterferon alfa-2A; ribavirin
(Pegasys Copegus combination pack)
(125083)
06/04/2004

    Chronic hepatitis C     See labeling information for Pegasys.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

77. Peginterferon alfa-2B
(Pegintron)
(103949)
01/19/2001

   

Combination therapy

• In combination with ribavirin for chronic hepatitis C in patients ≥3 yr



Monotherapy

• Chronic hepatitis C in patients ≥18 yr

   

Labeled pediatric use(s)

• In combination with ribavirin for chronic hepatitis C in patients ≥3 yr

• Safety and effectiveness of peginterferon alfa-2B in combination with ribavirin in pediatric patients <3 yr have not been established.



Study information

• Safety and efficacy of peginterferon alfa-2B and ribavirin were established in patients 3 to 17 yr (n = 107)


78. Pegloticase
(Krystexxa)
(125293)
09/14/2010

    Chronic gout in adult patients     Safety and efficacy in pediatric patients <18 yr have not been established.

79. Protein C concentrate (human)
(Ceprotin)
(125234)
03/30/2007

    Prevention and treatment of venous thrombosis and purpura fulminans (PF) in congenital protein C deficiency    

Labeled pediatric use(s)

• Recommended for neonate and pediatric use



Study information

• Several retrospective and prospective studies have evaluated safety and efficacy in neonates and pediatric patients.

• A pivotal study assessed the efficacy of Ceprotin in treating PF and other thromboembolic events in patients 0 to 25 yr (n = 18).

• When compared with a historical control group, Ceprotin was more effective than fresh frozen plasma or other conventional anticoagulants.


80. Ranibizumab
(Lucentis)
(125156)
06/30/2006

   

• Macular degeneration

• Macular edema

    Safety and efficacy in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

81. Rasburicase
(Elitek)
(103946)
07/12/2002

    Management of hyperuricemia in patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid    

Labeled pediatric use(s)

• Hyperuricemia in pediatric patients with malignancies who are receiving anticancer therapy expected to result in tumor lysis



Study information

• Safety and efficacy in patients 1 mo to 17 yr were studied (n = 246).

• Children <2 yr had a lower rate of achieving normal uric acid concentrations than those 2 to 17 yr.

• Incidence of renal failure was similar between the rasburicase and allopurinol groups.


82. Rho(D) immune globulin intravenous (human)
(Rhophylac)
(125070)
02/12/2004

   

• Suppression of Rhesus (Rh) isoimmunization in

– pregnancy and obstetric conditions

– Incompatible transfusions in Rho (D)-negative individuals

• raising platelet counts in adults with idiopathic thrombocytopenic purpura

   

• Safety and effectiveness in pediatric subjects being treated for an incompatible transfusion have not been established.

• The physician should weigh the potential risks against the benefits of Rhophylac, particularly in girls whose later pregnancies may be affected if Rh isoimmunization occurs.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

83. Rilonacept
(Arcalyst)
(125249)
02/27/2008

    Cryopyrin-associated periodic syndromes (CAPS)    

Labeled pediatric use(s)

• CAPS, including familial cold autoinflammatory syndrome and Muckle-Wells syndrome in patients ≥12 yr

• Safety and efficacy in patients <12 yr have not been established.



Study information

• Pharmacokinetics, safety, and efficacy in patients 12 to 16 yr were assessed (n = 6).

• Findings showed improvement in baseline symptom scores and in markers of inflammation.

• It is unknown whether rilonacept will alter bone development in children.


84. Rimabotulinum-toxinB
(Myobloc)
(103846)
12/08/2000

    Cervical dystonia     Safety and effectiveness in pediatric patients have not been established.

85. Rituximab
(Rituxan)
(103705)
11/26/1997

   

• Non-Hodgkin’s lymphoma

• Chronic lymphocytic leukemia

• Rheumatoid arthritis

• Wegener’s granulomatosis and microscopic polyangiitis

   

• The safety and effectiveness of Rituxan in pediatric patients have not been established.

• FDA has not required pediatric studies of patients 0 to 16 yr with polyarticular juvenile idiopathic arthritis because of concerns regarding the potential for prolonged immunosuppression.


86. Romiplostim
(Nplate)
(125268)
08/22/2008

    Chronic immune (idiopathic) thrombocytopenic purpura     Safety and effectiveness in pediatric patients <18 yr have not been established.

87. Sipuleucel T
(Provenge)
(125197)
04/29/2010

    Metastatic hormone-refractory prostate cancer     No pediatric use section or other reference to children in label. By implication, safety and effectiveness not established in pediatric patients.

88. Tenecteplase
(Tnkase)
(103909)
06/02/2000

    Reduction in mortality associated with acute myocardial infarction     Safety and effectiveness in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

89. Thrombin, topical (human)
(Evithrom)
(125247)
08/27/2007

    Aid to hemostasis during surgery    

Labeled pediatric use(s)

• Aid to hemostasis during surgery in pediatric patients



Study information

• Safety and efficacy were established in a clinical trial that included 8 pediatric patients 0 to 12 yr undergoing liver surgery.


90. Thrombin, topical (recombinant)
(Recothrom)
(125248)
01/17/2008

    Aid to hemostasis during surgery    

Safety and effectiveness in a pediatric population have not been fully established.



Study information

• Recothrom was evaluated in four pediatric patients 12 to 16 yr.


91. Tocilizumab (Actemra)
(125276)
01/08/2010

   

• Rheumatoid arthritis

• Systemic juvenile idiopathic arthritis (SJIA)

   

Labeled pediatric use(s)

• SJIA

• Safety and effectiveness in pediatric patients with conditions other than SJIA have not been established.



Study information

• Efficacy and safety in pediatric patients with SJIA were assessed (n = 75).

• The response in the Actemra group was significant compared with that in the placebo group.


92. Tositumomab; iodine I 131 tositumomab
(Bexxar)
(125011)
06/27/2003

    Non-Hodgkin’s lymphoma     Safety and effectiveness of Bexxar in children have not been established.

93. Trastuzumab
(Herceptin)
(103792)
10/25/1998

   

HER2-overexpressing breast cancer

HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma

    Safety and effectiveness of Herceptin in pediatric patients have not been established.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
    Approved Indication(s)     Highlights of Pediatric Information in Labeling

94. Ustekinumab
(Stelara)
(125261)
09/25/2009

    Plaque psoriasis in adult patients     Safety and effectiveness of Stelara in pediatric patients have not been evaluated.

95. Vaccinia immune globulin intravenous
(CNJ-016)
(125109)
05/02/2005

   

• Eczema vaccinatum

• Progressive vaccinia

• Severe generalized vaccinia

• Vaccinia virus infections in patients with skin conditions

    Safety and effectiveness in the pediatric population (<16 yr) have not been established.

96. von Willebrand factor/coagulation factor VIII complex (human)
(Wilate)
(125251)
12/04/2009

    Treatment of bleeding episodes in patients with von Willebrand disease (VWD)    

Labeled pediatric use(s)

• Statement of indicated use does not explicitly refer to pediatric patients.



Study information

• Eleven pediatric patients between 5 and 16 yr with VWD (eight with type 3, one with type 2, two with type 1) were treated with Wilate for 234 bleeding episodes (BEs) in clinical studies. These studies showed that 88% of the BEs were successfully treated in this population. No dose adjustment is needed for pediatric patients, as administered dosages were similar to those used by the adult population.


Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

TABLE D-2 Pediatric Trials Registered at ClinicalTrials.gov for Biologics Initially Approved by FDA Between January 1, 1997, and December 31, 2010 (listed separately for CDER-and CBER-regulated products)


Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

1. Abatacept
(Orencia)
(125118)
12/23/2005
Juvenile rheumatoid arthritis 6 to 17 yr III
    Type 1 diabetes mellitus 6 to 45 yr II
    Acute graft-versus-host disease during transplant >12 yr II
    Wegener’s granulomatosis >15 yr I/II
    Uveitis >6 yr II

2. AbobotulinumtoxinA
(Dysport)
(125274)
04/29/2009
Spasticity in cerebral palsy 2 to 17 yr III
    Idiopathic toe walking 5 to 15 yr II
    Cerebral palsy 25 mo to 9 yr IV
    Leg length inequality; foot deformities 6 to 16 yr IV
    Torticollis 4 mo to 1 yr I
    Lower limb length discrepancy 5 to 21 yr III
    Myelomeningocele; neurogenic bladder 2 to 16 yr IV
    Cerebral palsy 1 to 17 yr I/II
    Muscle spasticity in cerebral palsy 3 to 12 yr II
    Spastic diplegic cerebral palsy 3 to 18 yr III
    Cerebral palsy 4 to 12 yr I/II
    Spasticity >2 yr III
    Cerebral palsy; drooling 6 to 21 yr n/s
    Cerebral palsy 5 to 15 yr n/s
    Idiopathic clubfoot 1 day to 2 yr n/s
    Spasticity in cerebral palsy 2 to 18 yr IV
    Clubfoot Up to 12 yr n/s
    Stroke; brain injuries; spasticity >12 yr IV
    Spinal cord injury; pain >15 yr n/s
    Cerebral palsy 2 to 18 yr I/II
    Spasticity, poststroke >2 yr n/s
    Hyperhidrosis 12 to 17 yr IV
    Cerebral palsy 10 to 17 yr II
    Esotropia Up to 5 yr n/s
    Hip pain in cerebral palsy 4 to 16 yr II
    Cerebral palsy 8 to 11 yr IV

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

3. Adalimumab
(Humira)
(125057)
12/31/2002
Juvenile rheumatoid arthritis 4 to 17 yr III
    Juvenile idiopathic arthritis 4 to 17 yr III
    Plaque psoriasis 4 to 17 yr III
    Juvenile idiopathic arthritis 4 to 17 yr n/s
    Juvenile idiopathic arthritis 2 to 4 yr III
    Enthesitis-related arthritis (ERA) 6 to 17 yr III
    Focal glomerulosclerosis 2 to 40 yr I
    Focal segmental glomerulosclerosis 1 to 50 yr II
    Uveitis; juvenile arthritis >4 yr II/III
    Crohn’s disease 6 to 17 yr III
    Crohn’s disease 15 to 75 yr II/III
    Intestinal Behcet’s disease >15 yr III
    Ankylosing spondylitis >15 yr III
    Ulcerative colitis >15 yr III
    Crohn’s disease 7 to 18 yr III
    Crohn’s disease 15 to 75 yr II/III
    Crohn’s disease-like inflammatory bowel disease in chronic granulomatous disease >10 yr I/II

4. Agalsidase beta
(Fabrazyme)
(103979)
04/24/2003
Fabry disease 7 to 15 yr II
    Fabry disease Infants IV
    Fabry disease 5 to 85 yr IV
    Fabry disease 5 to 18 yr III
    Fabry disease >15 yr IV
    Fabry disease 8 to 18 yr n/s
    Fabry disease; proteinuria 14 to 95 yr n/s

5. Alefacept
(Amevive)
(125036)
01/30/2003
Hematopoietic stem cell transplant Up to 21 yr n/s
    Type 1 diabetes mellitus 12 to 35 yr II
    Psoriasis 12 to 17 yr II
    Graft-versus-host disease 14 to 75 yr III
    Resistant chronic graft-versus-host disease Up to 70 yr I/II

6. Alemtuzumab
(Campath)
(103948)
05/07/2001
In association with stem cell transplants for various hematologic malignancies, multiple trials Various age ranges across pediatric population 0, I, II, III
    Acute lymphoblastic leukemia Up to 30 yr II
    Aplastic anemia ≥2 yr II
    Chronic lymphocytic leukemia Up to 69 yr II

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

7. Alglucosidase alfa
(Lumizyme)
(125291)
05/24/2010
Pompe disease (late onset)
Pompe disease (late onset)
Pompe disease (infantile onset)
Pompe disease (infantile onset)
Pompe disease
>8 yr
>1 yr
Up to 26 wk
6 to 36 mo
>1 mo
III
n/s
II/III
I/II
IV

8. Alglucosidase alfa
(Myozyme)
(125141)
04/28/2006
Pompe disease
Pompe disease (late onset)
Pompe disease
Pompe disease
Pompe disease (infantile onset)
Pompe disease
Pompe disease (late onset)
<18 yr
8 to 18 yr
>6 mo
Up to 24 mo
<12 mo
>8 yr
>8 yr
IV
IV
IV
IV
n/s
n/s
IV

9. Anakinra
(Kineret)
(103950)
11/14/2001
Type 1 diabetes mellitus 6 to 18 yr I/II
    Atopic dermatitis 10 to 18 yr I
    Juvenile chronic arthritis 2 to 17 yr II
    Juvenile idiopathic arthritis 2 to 20 yr II/III
    Neonatal-onset multisystem inflammatory disease Neonates  
    Relapsing polychondritis 12 to 15 yr II

10. Basiliximab
(Simulect)
(103764)
05/12/1998
Liver transplantation complications Up to 16 yr IV
    Kidney transplantation complications Up to 20 yr n/s
    Noninfectious uveitis 12 to 80 yr II
    Kidney transplantation complications 1 to 18 yr III

11. Becaplermin
(Regranex)
(103691)
12/16/1997
None    

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

12. Bevacizumab
(Avastin)
(125085)
02/26/2004
Solid tumors Up to 21 yr I
    Glial cell tumors 3 to 21 yr II
    Central nervous system tumors 18 mo to 23 yr I
    Intrinsic pontine glioma 3 to 18 yr II
    Central nervous system tumors 1 to 25 yr n/s
    Pulmonary vein stenosis No age range given; infants and children n/s
    Brain cancer Up to 21 yr II
    Gliomas 3 to 30 yr n/s
    Central nervous system tumors 3 to 21 yr II/III
    Neuroblastoma Up to 30 yr I
    Refractory solid tumors 12 mo to 20 yr I
    Medullablastoma Up to 19 yr II
    Central nervous system tumors Up to 21 yr II
    Sarcoma Up to 29 yr II
    Osteosarcoma Up to 30 yr III
    Solid tumor 1 to 30 yr I/II
    Central nervous system tumors Up to 21 yr II
    Refractory solid tumors; leukemia Up to 21 yr I
    Sarcoma 6 mo to 18 yr II
    Retinopathy of prematurity 30 wk and older n/s
    Neurofibromatosis type 2 ≥12 yr II
    Retinopathy of prematurity 30 to 36 wk I
    Sarcoma 1 to 29 yr II
    Refractory solid tumors 1 to 21 yr I
    Retinopathy of prematurity Up to 22 wk II
    Retinopathy of prematurity 30 to 36 wk II
    Retinopathy of prematurity 1 to 12 mo II/III
    Central nervous system tumors ≥15 yr I
    Sarcoma ≥13 yr II
    Neovascular glaucoma 14 to 72 yr II
    Sarcoma 1 to 29 yr n/s
    Neovascular glaucoma 10 to 80 yr n/s
    Glioma 3 to 18 yr II
    Gastrointestinal cancer ≥18 mo II
    Germ cell tumors 12 to 65 yr II
    Neuroblastoma ≥1 yr I

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

13. Canakinumab
(Ilaris)
(125319)
06/17/2009
Cryopyrin-associated periodic syndromes ≥2 yr
Up to 4 yr
≥3 yr
4 to 75 yr
III (all)
    Systemic juvenile arthritis ≥2 yr
2 to 19 yr
III (all)
    Type 1 diabetes mellitus 6 to 45 yr
6 to 35 yr
II
    Familial Mediterranean fever 4 to 20 yr
12 to 75 yr
II
    Neonatal-onset multisystem inflammatory disease 2 to 25 yr III
    Mevalonate kinase deficiency ≥2 yr II
    NALP3 mutation 4 to 75 yr II
    Tumor necrosis factor receptor-associated periodic syndromes ≥4 yr II

14. Certolizumab pegol
(Cimzia)
(125160)
04/22/2008
Crohn’s disease (several) Varying, 6 to 65 yr II (all)
    Plaque psoriasis Up to 18 yr II

15. Cetuximab
(Erbitux)
(125084)
02/12/2004
Brain cancer 3 to 21 yr II
    Refractory solid tumors 1 to 18 yr I

16. Collagenase clostridium histolyticum
(Xiaflex)
(125338)
02/02/2010
None    

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

17. Daclizumab
(Zenapax)
(103749)
12/10/1997
Immune suppression in kidney transplantation Up to 21 yr  
    Cardiac transplantation complications 1 mo to 18 yr I/II
    Cardiac transplantation complications Up to 21 yr n/s
    Juvenile idiopathic arthritis-associated uveitis 6 to 18 yr II
    Type I diabetes mellitus 8 to 45 yr III
    Type I diabetes mellitus 2 to 40 yr II
    Leukemia ≥10 yr II
    Anemia ≥2 yr II
    Ulcerative colitis ≥12 yr II
    Cardiac transplantation complications ≥13 yr IV
    Cystinosis ≥7 yr n/s
    Uveitis ≥6 yr n/s
    Uveitis ≥13 yr IV

18. Darbepoetin alfa
(Aranesp)
(103951)
09/17/2001
Anemia due to chronic renal failure Up to 17 yr III
    Anemia of prematurity Up to 49 h II
    Anemia due to chronic kidney disease 1 to 18 yr III

19. Denileukin diftitox
(Ontak)
(103767)
02/05/1999
Anaplastic large-cell lymphoma 2 to 24 yr II
    Graft-versus-host disease ≥2 yr II
    Neuroblastoma Up to 21 yr II
    Neuroblastoma Up to 21 yr I
    Graft-versus-host disease ≥6 yr II
    Refractory lymphoid malignancies Any age II
    Leukemia ≥2 yr II

20. Denosumab
(Prolia/Xgeva)
(125320)
06/01/2010
Giant-cell tumor of bone ≥12 yr II

21. Xigris
(125029)
11/21/2001
Severe sepsis Up to 17 yr III

22. Ecallantide
(Kalbitor)
(125277)
11/27/2009
Hereditary angioedema ≥10 yr n/s
    Hereditary angioedema ≥10 yr III
    Hereditary angioedema 2 to 17 yr II/III
    Hereditary angioedema ≥10 yr III

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

23. Eculizumab
(Soliris)
(125166)
03/16/2007
Hemoglobinuria 2 to 17 yr I/II
    Atypical hemolytic-uremic syndrome 12 to 18 yr II
    Atypical hemolytic-uremic syndrome 12 to 18 yr II
    Hemoglobinuria ≥12 yr II
    Hemoglobinuria ≥12 yr II
    Shiga toxin hemolytic-uremic syndrome ≥2 mo II/III
    Atypical hemolytic-uremic syndrome 1 mo to 18 yr II
    Hemolytic-uremic syndrome ≥2 yr n/s

24. Etanercept
(Enbrel)
(103795)
11/02/1998
Polyarticular juvenile idiopathic arthritis ≥2 mo IV
    Fanconi anemia ≥4 yr n/s
    Kawasaki disease 2 mo to 20 yr II
    Psoriasis 4 to 17 yr n/s
    Psoriasis 4 to 17 yr III
    Idiopathic pneumonia syndrome after stem cell transplant 1 to 17 yr II
    Histiocytosis Up to 65 yr II
    Type 1 diabetes mellitus 3 to 18 yr I/II
    Graft-versus-host disease, multiple trials Various age ranges across pediatric population II, III
    Dermatomyositis 4 to 16 yr II/III
    Idiopathic pneumonia syndrome after stem cell transplant ≥6 yr II
    Wegener’s granulomatosis 10 to 70 yr II
    Psoriasis n/s III
    Leukemia 2 to 18 yr III
    Uveitis Any age II

25. Galsulfase
(Naglazyme)
(125117)
05/31/2005
Mucopolysaccharidosis VI, multiple trials Various age ranges I, II, III, IV

26. Golimumab
(Simponi)
(125289)
04/24/2009
Juvenile idiopathic arthritis 2 to 18 yr III

27. Ibritumomab tiuxetan
(Zevalin)
(125019)
02/19/2002
Lymphoma Up to 21 yr I
    Non-Hodgkin’s lymphoma Up to 64 yr II

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

28. Idursulfase
(Elaprase)
(125151)
07/24/2006
Hunter syndrome ≥5 yr n/s
    Hunter syndrome ≥5 yr II/III
    Mucopolysaccharidosis II 5 to 25 yr II/III
    Hunter syndrome 3 to 18 yr n/s
    Mucopolysaccharidosis II 6 to 35 yr II/III

29. IncobotulinumtoxinA
(Xeomin)
(125360)
07/30/2010
None    

30. Infliximab
(Remicade)
(103772)
08/24/1998
Juvenile rheumatoid arthritis
Ulcerative colitis
Ulcerative colitis
Graft-versus-host disease
Graft-versus-host disease
Kawasaki disease
Kawasaki disease
Uveitis
Juvenile idiopathic arthritis
Juvenile idiopathic arthritis
Juvenile idiopathic arthritis
Spondylarthropathies
Crohn’s disease
Chronic granulomatous disease
Uveitis
4 to 18 yr
6 to 18 yr
6 to 17 yr
6 mo to 75 yr
Up to 18 yr
Up to 18 yr
Up to 17 yr
Up to 18 yr
4 to 15 yr
1 to 16 yr
4 to 18 yr
Up to 18 yr
6 to 17 yr
≥10 yr
≥9 yr
II
n/s
III
II
I
I
III
IV
III
n/s
III
II/III
III
I/II
n/s

31. Interferon
alfacon-1
(Infergen)
(103663)
10/06/1997
None    

32. Interferon beta-1A
(Rebif)
(103780)
03/07/2002
Clinically isolated syndrome 18 mo to 65 yr III

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

33. Interferon gamma-1B
(Actimmune)
(103836)
02/25/1999
Osteopetrosis 2 mo to 10 yr III
    Chronic granulomatous disease All ages IV
    HIV infection 1 to 17 yr I
    Lymphoma Up to 20 yr II/III
    Leukocyte adhesion deficiency syndrome Children, not specified II
    Pulmonary tuberculosis ≥5 yr II
    Nontuberculosis mycobacterial infections ≥5 yr II
    Cystic fibrosis ≥12 yr I/II
    Fungal infections ≥2 yr II
    Cryptococcal meningitis ≥13 yr II
    Chronic granulomatous disease Any age IV

34. Laronidase
(Aldurazyme)
(125058)
04/30/2003
Mucopolysaccharidosis I, multiple studies All ages I, II, III, IV

35. Natalizumab
(Tysabri)
(125104)
11/23/2004
Crohn’s disease 12 to 17 yr II

36. Ofatumumab
(Arzerra)
(125326)
10/26/2009
Leukemia All ages II

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

37. Omalizumab
(Xolair)
(103976)
06/20/2003
Asthma, multiple trials for moderate or severe asthma ≥ 6 yr or ≥12 yr III, IV
    Milk allergy 4 to 18 yr n/s
    Eosinophilic esophagitis 12 to 60 yr n/s
      12 to 76 yr I
    Lung disease ≥12 yr IV
    Urticaria 12 to 75 yr II
      12 to 75 yr III
      12 to 75 yr III
      12 to 75 yr III
    Cystic fibrosis ≥12 yr IV
    Hyper-immunoglobulin E syndrome 6 to 76 yr I
    Gastroenteritis 12 to 76 yr II
    Peanut allergy 6 to 75 yr II
    6 to 75 yr II
    ≥12 yr I/II
    Atopic dermatitis 12 to 60 yr IV

38. Oprelvekin
(Neumega)
(103694)
11/25/1997
Stem cell transplantation in malignancies All ages II
    Solid tumors Up to 45 yr I

39. Palifermin
(Kepivance)
(125103)
12/15/2004
Mucositis 1 to 16 yr II
    Mucositis 2 to 18 yr I
    Leukemia 1 to 16 yr I
    Severe combined immunodeficiency 2 to 20 yr I/II
    Acute myeloid leukemia; advanced myelodysplastic syndromes Up to 65 yr II
    Lymphoma 12 to 65 yr I
    Graft-versus-host disease 3 to 65 yr I/II
    Mucositis 12 to 65 yr II
    Graft-versus-host disease 3 to 65 yr I/II
    Lymphoma 12 to 70 yr II
    Epidermolysis bullosa Up to 21 yr 0
    Severe combined immunodeficiency 18 mo to 20 yr I

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

40. Palivizumab
(Synagis)
(103770)
06/19/1998
Respiratory syncytial virus infection Up to 2 yr  
    Unhealthy children with a history of prematurity 5 to 6 mo II
    Airway hyperreactivity 3 to 6 yr  
    Chronic lung disease Up to 24 mo IV
    Healthy, previously dosed children Up to 24 mo I/II
    Heart disease Up to 24 mo III
    Pain from palivizumab injection 1 mo to 2 yr IV
    Recurrent wheezing 3 mo to 1 yr n/s

41. Panitumumab
(Vectibix)
(125147)
09/27/2006
Solid tumors 1 to 17 yr I

42. Pegfilgrastim
(Neulasta)
(125031)
01/31/2002
Solid malignancies Up to 18 yr II
    Solid malignancies Up to 18 yr II
    Type 1 diabetes 12 to 45 yr I/II
    Sarcoma Up to 21 yr II

43. Peginterferon alfa-2A
(Pegasys)
(103964)
10/16/2002
Hepatitis B 3 to 17 yr III
    Hepatitis C 5 to 18 yr III
    Hepatitis C; hemophilia ≥12 yr IV
    Hepatitis C; thalassemia ≥12 yr IV
    Polycythemia vera or essential thrombothycemia ≥18 wk II
    Hepatitis C 15 to 65 yr III

44. Peginterferon alfa-2A; ribavirin (Pegasys Copegus combination)
(125083)
06/04/2004
Hepatitis C
Hepatitis C
5 to 18 yr
>12 yr
III
IV

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

45. Peginterferon alfa-2B
(Pegintron)
(103949)
01/19/2001
Neurofibromatosis 18 mo to 21 yr II
    Malignant melanoma Up to 21 yr II
    Sarcoma 5 to 40 yr III
    HIV infection 3 mo to 16 yr I
    Plexiform neurofibroma 1 to 21 yr I
    Plexiform neurofibroma 18 mo to 21 yr II
    Neurofibromatosis 2 to 30 yr II
    Chronic myeloid leukemia ≥12 yr I
    Hepatitis C 3 to 24 yr III
    HIV infection ≥15 yr II
    Glioma Up to 21 yr II

46. Pegloticase
(Krystexxa)
(125293)
09/14/2010
None    

47. Ranibizumab
(Lucentis)
(125156)
06/30/2006
None    

48. Rasburicase
(Elitek)
(103946)
07/12/2002
Hyperuricemia Up to 18 yr IV
    Leukemia; lymphoma 1 to 29 yr II
    Malignancy-induced hyperuricemia Age not specified IV
    Tumor lysis syndrome Up to 18 yr IV
    Tumor lysis syndrome ≥2 yr n/s
    Nutritional and metabolic diseases Up to 18 yr II
    Leukemia; lymphoma ≥15 yr III
    Hyperuricemia 1 to 75 yr III
    Mature B-cell lymphoma Up to 20 yr II/III

49. Rilonacept
(Arcalyst)
(125249)
02/27/2008
Juvenile idiopathic arthritis 18 mo to 19 yr II
    Familial Mediterranean fever ≥4 yr II
    Cryopyrin-associated periodic syndromes ≥7 yr III

50. RimabotulinumtoxinB
(Myobloc)
(103846)
12/08/2000
Cerebral palsy (hand functioning) 2 to 18 yr I/II

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

51. Rituximab
(Rituxan)
(103705)
11/26/1997
Leukemia; lymphoma
Lymphoproliferative disorder
Six trials specifically include young patients; others include patients of any age  
    Neuroblastoma 6 mo to 21 yr n/s
      2 mo to 18 yr  
    Hemophilia ≥18 mo II
    Thrombotic thrombocytopenic purpura ≥12 yr III
      >12 yr II/II
      ≥12 yr II
    Focal segmental glomerulosclerosis 5 to 60 yr II
    2 to 80 yr
    Transplant-related complications, multiple trials Various age ranges across pediatric population II, III, IV
    Type 1 diabetes mellitus 8 to 45 yr II/III
    8 to 45 yr IV
    Myositis ≥5 yr II
    Immunoglobulin A nephropathy ≥5 yr IV
    Nephrotic syndrome 2 to 18 yr II/III
    Wegener’s granulomatosis ≥15 yr II/III
    Aplastic anemia ≥12 mo n/s
    ≥2 yr II
    Neuromyelitis optica 12 to 86 yr I
    Central nervous system tumor 18 mo to 75 yr II
    Opsoclonus-myoclonus syndrome 6 mo to 19 yr I/II
    Chronic focal encephalitis 5 to 25 yr I
    Systemic lupus erythematosus 15 to 40 yr II
    Lymphomatoid granulomatosis ≥12 yr n/s

52. Romiplostim
(Nplate)
(125268)
08/22/2008
Idiopathic thrombocytopenic purpura 12 mo to 17 yr III
    Idiopathic thrombocytopenic purpura 12 mo to 17 yr I/II
    Idiopathic thrombocytopenic purpura 1 to 18 yr III
    Idiopathic thrombocytopenic purpura ≥1 yr III

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

53. Tenecteplase
(Tnkase)
(103909)
06/02/2000
Restoration of function in dysfunctional central venous catheters (2 studies, including subjects weighing <10 kg) n/s III

54. Tocilizumab
(Actemra)
(125276)
01/08/2010
Systemic juvenile idiopathic arthritis Up to 19 yr III
    Systemic juvenile idiopathic arthritis 2 to 17 yr III
    Systemic juvenile idiopathic arthritis Up to 24 mo I

55. Tositumomab; iodine I 131 tositumomab
(Bexxar)
(125011)
06/27/2003
None    

56. Trastuzumab
(Herceptin)
(103792)
10/25/1998
Osteosarcoma
Recurrent osteosarcoma
<30 yr
Any age
II
II

57. Ustekinumab
(Stelara)
(125261)
09/25/2009
Psoriasis 12 to 18 yr III

Biologics Under the Jurisdiction of the Center for Biologics Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

1. Albumin (human)
(Albumin)
(125154)
10/17/2006
Cardiac surgery 2 to 12 yr IV
    Cardiac surgery Up to 36 mo n/s

2. Alpha1-proteinase inhibitor (human)
(Aralast NP)
(125039)
05/04/2007
Type 1 diabetes mellitus 8 to 35 yr II
    Type 1 diabetes mellitus 8 to 35 yr II
    Type 1 diabetes mellitus 6 to 45 yr I

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

3. Alpha1-proteinase inhibitor (human)
(Glassia)
(125325)
07/01/2010
Type 1 diabetes mellitus 10 to 25 yr I/II

4. Alpha1-proteinase inhibitor (human)
(Zemaira)
(125078)
07/08/2003
None    

5. Antihemophilic factor (recombinant), plasma/albumin free method
(Advate)
(125063)
07/25/2003
Hemophilia A (multiple studies) Age ranges vary for specific studies but collectively cover the pediatric age range I, II, III, IV

6. Antihemophilic factor (recombinant)
(ReFacto)
(103779)
03/06/2000

7. Antihemophilic factor (recombinant), plasma/albumin free
(Xyntha)
(125264)
02/21/2008

8. Antithrombin (recombinant)
(ATryn)
(125284)
02/06/2009
Postoperative hemorrhage in cardiopulmonary bypass surgery Up to 30 days I
    Postoperative hemorrhage in cardiopulmonary bypass surgery Up to 30 days III

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

9. Anti-thymocyte globulin (rabbit)
(thymoglobulin)
(103869)
12/30/1998
Transplant-related complications, multiple trials Various age ranges across pediatric population I, II, III, IV
    Type 1 diabetes mellitus 12 to 45 yr I, II
      12 to 35 yr II
    Aplastic anemia ≥2 yr II
      ≥12 yr II
      ≥15 yr II
    Systemic sclerosis Up to 64 yr II
    Myelodysplastic syndrome All ages II
    Toxicities of total body irradiation Up to 21 yr IV

10. Autologous cultured chondrocytes
(Carticel)
(103661)
08/22/1997
None    

11. Botulism immune globulin intravenous (human)
(BabyBIG)
(125034)
10/23/2003
Infant botulism Up to 1 yr n/s

12. C1 esterase inhibitor (human)
(Berinert)
(125287)
10/09/2009
Hereditary angioedema ≥6 yr II/III
    Hereditary angioedema ≥6 yr III

13. C1 esterase inhibitor (Cinryze)
(125267)
10/10/2008
Hereditary angioedema
Hereditary angioedema
2 to 11 yr
≥6 yr
II
II

14. Coagulation factor VIIa (recombinant)
(NovoSeven)
(103665)
03/25/1999
Hemophilia A Up to 8 yr II
    Cardiopulmonary bypass Up to 30 days n/s
    Hemophilia A ≥2 yr n/s
    Hemophilia Up to 20 yr IV
    Hemophilia A, B ≥2 yr II
    Hemophilia A, B ≥2 yr n/s
    Factor VII deficiency Up to 90 yr n/s

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

15. Coagulation factor IX (recombinant)
(Benefix)
(103677)
02/01/1997
Hemophilia B (multiple studies) Age ranges vary for specific studies but collectively cover the pediatric age range III, IV

16. Crotalidae polyvalent immune Fab (ovine)
(CroFab)
(103788)
10/02/2000
Snakebite 2 to 80 yr III
    Snakebite ≥1 yr IV

17. Digoxin immune Fab (ovine)
(DigiFab)
(103910)
08/31/2001
None    

18. Fibrin sealant (human)
(Artiss)
(125266)
03/21/2008
None    

19. Fibrin sealant (human)
(Evicel)
(125010)
03/21/2003
Surgical blood loss n/s III

20. Fibrin sealant
(TachoSil)
(125351)
(04/02/2010)
Local bleeding, liver surgery Up to 6 yr II/III
    Local bleeding, liver surgery All ages III

21. Fibrin sealant
(Tisseel)
Baxter
(103980)
05/01/1998
Burns ≥6 yr I/II
    Burns Up to 65 yr III

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

22. Fibrinogen concentrate (human)
(RiaSTAP)
(125317)
01/16/2009
Cardiac surgical procedures Up to 18 yr II
    Fibrinogen deficiency ≥6 yr II

23. Hepatitis B immune globulin intravenous (human)
(HepaGam B)
(125237)
04/06/2007
Nonea    

24. Hepatitis B immune globulin (human)
(Nabi-HB)
(103945)
10/23/2001
Nonea    

25. Immune globulin intravenous (human)
(Flebogamma 5% DIF [dual inactivation plus nanofiltration])
(125077)
12/15/2003
Trials for infections (both bacterial and viral); pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; neonatal infection; recurrent infections and immunoglobulin G subclass deficiency; HIV infection; Rasmussen encephalitis Various age ranges across the pediatric age spectrum I, II, III, IV

26. Immune globulin intravenous (human) 10% solution
(Gammagard liquid)
(125105)
04/27/2005
Multiple trials for primary immunodeficiencies
Trials for transplantation-related complications

27. Immune globulin intravenous (human) 5% liquid
(Gammaplex)
(125329)
09/17/2009
Other trials for abnormal muscle movement in neuroblastoma; sickle cell pain crisis; hyperbilirubinemia; idiopathic thrombocytopenic purpura; postpolio syndrome

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

28. Immune globulin injection (human) 10% caprylate/chromatography purified
(Gamunex-C)
(125046)
08/27/2003

29. Immune globulin subcutaneous (human) (IGSC) 20% liquid
(Hizentra)
(125350)
03/04/2010

30. Immune globulin intravenous (human) 5% liquid
(Octagam)
(125062)
05/21/2004

31. Immune globulin intravenous (human) 10% liquid
(Privigen)
(125201)
07/26/2007

32. Immune globulin subcutaneous (human)
(Vivaglobin)
(125115)
01/09/2006

33. Protein C concentrate (human)
(Ceprotin)
(125234)
03/30/2007
Protein C deficiency ≤6 mo II/III
    Protein C deficiency n/s IV

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

34. Rho(D) immune globulin intravenous (human)
(Rhophylac)
(125070)
02/12/2004
None    

35. Sipuleucel T
(Provenge)
(125197)
04/29/2010
None    

36. Thrombin, topical (human)
(Evithrom, a component of Evicel)
(125247)
08/27/2007
Aid to hemostasis during surgery
Aid to hemostasis during skin graft surgery
Up to 17 yr
2 to 75 yr
IV
II

37. Thrombin, topical (recombinant)
(Recothrom)
(125248)
01/17/2008

38. Vaccinia immune globulin intravenous
(CNJ-016)
(125109)
05/02/2005
Corneal scarring associated with vaccinia complication ≥1 yr II
    Prevention of vaccinal infection n/s I

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

Biologics Under the Jurisdiction of the Center for Drug Evaluation and Research

Generic Name
(Trade Name)
(BLA Number)
Original Approval Date
Condition Ages of Trial Participants Trial Phase

39. von Willebrand factor/coagulation factor VIII complex (human)
(Wilate)
(125251)
12/04/2009
Bleeding prevention in surgery ≥6 yr III
    Von Willebrand disease n/s n/s
    Hemophilia A Any age n/s

     a For the hepatitis B immune globulin products, none of the pediatric study listings involving this type of product cited either brand name.

NOTES: For age, n/s indicates a study for which the trial description did not state age explicitly but included children’s hospital sites or had inclusion criteria or other information text that indicated the inclusion of pediatric patients (e.g., references to trial patients <10 kg). For trial phase, n/s indicates that the phase was not specified in the description. Search terms included a combination of the generic “biologic name AND children” or the “trade name AND children” to capture all registered studies that used that agent. Some biologic agents that are often treated as interchangeable have been grouped together by their generic name (e.g., immune globulin intravenous). For each product that has relevant studies for the class of drug, at least one study identifies that brand name. The listings for each product may not be exhaustive of trials for the same condition, age group, and phase.

Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×

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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Page 365
Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
×
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Page 375
Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Suggested Citation:"Appendix D: Biologics Studied and Not Studied in Children." Institute of Medicine. 2012. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. Washington, DC: The National Academies Press. doi: 10.17226/13311.
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Next: Appendix E: Written Requests for Studies of Pediatric Hypertension: Longitudinal Changes in FDA Specifications »
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The Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) were designed to encourage more pediatric studies of drugs used for children. The FDA asked the IOM to review aspects of pediatric studies and changes in product labeling that resulted from BPCA and PREA and their predecessor policies, as well as assess the incentives for pediatric studies of biologics and the extent to which biologics have been studied in children. The IOM committee concludes that these policies have helped provide clinicians who care for children with better information about the efficacy, safety, and appropriate prescribing of drugs. The IOM suggests that more can be done to increase knowledge about drugs used by children and thereby improve the clinical care, health, and well-being of the nation's children.

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