Potential Next Steps

1. Potential Next Steps Jay E. Slater, MD Director, DBPAP

2. Today’s presentations • Background • Allergenics efficacy reviews • Panel 1, 21 CFR 601.25 (1974-1979) • Panel 2, 21 CFR 601.26 (1982-1983) • Current evaluation process (2003-2011) • Safety of allergenic extracts • Assessments • Next steps

3. Internal review determinations • Table 1. Use in Diagnosis and Treatment Addressed in Literature (n = 480) • Table 2. Foods: Use in Diagnosis Addressed in Literature (n = 134) • Table 3. Non-food: Use in Diagnosis Addressed in Literature (n = 73) • Table 4. Minimal or No Literature Relating to Use in Diagnosis and Treatment (n = 566) • Table 5. Potential Safety Issues (n = 16)

4. Documents available • Review panel reports • http://www.fda.gov/BiologicsBloodVaccines/Allergenics/ucm272115.htm • Tables • http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/AllergenicProductsAdvisoryCommittee/UCM274718.pdf • FR notice (instructions for comments) • http://www.gpo.gov/fdsys/pkg/FR-2011-09-26/pdf/2011-24598.pdf

5. Discussion points • Comments on • the review process so far; • the decision to list non-standardized allergenic products in five tables according to the evidence collected; and • the possible disposition of the categories of products identified in the Tables

6. Paths forward • 21 CFR 601.25 and 601.26 • Other approaches

7. Paths forward • 21 CFR 601.25 and 601.26 • Established approach • Basis for previous efficacy/safety reviews • But - it is difficult to assess non-standardized products using data that relate to “general” product type. (For a new approval today, we would require individualized showing for a manufacturer’s product.) • These regulations apply to products licensed before 1 July 1972 – and not to those licensed after that date.

8. Assessing non-standardized products “generally” • The “general” data are comprised of: • Conclusions from case reports, not studies • Interpretation and application of cross-reactivity data • Conclusions applied “generally” to multiple manufacturers

9. Non-standardized allergenic products licensed after 1 July 1972 • Three of seven manufacturers obtained their licensed for non-standardized allergenic extracts late 1972 to 1974. http://www.fda.gov/downloads/BiologicsBloodVaccines/UCM149969.pdf

10. Paths forward • 21 CFR 601.25 and 601.26 • Other approaches: • Use other regulations to address evidence of efficacy issues (Tables 4 and 5) along with safety issues (Table 5)

11. Paths forward • Reasons to take action on the basis of efficacy evidence • Both advisory panels concluded that many allergenic extracts lack sufficient evidence of efficacy • In our current review, FDA failed to identify supportive efficacy data for hundreds of products

12. Panel recommendationsClassification panel 1974-1979 (601.25)

13. Panel recommendationsReclassification panel 1982-1983 (601.26) excludes IIIB foods/insects

14. Panel recommendationsReclassification panel 1982-1983 (601.26) includes IIIB foods/insects

15. Paths forward • Reasons to take action on the basis of efficacy evidence • Both advisory panels concluded that many allergenic extracts lack sufficient evidence of efficacy • In our current review, FDA failed to identify supportive efficacy data for hundreds of products

16. Paths forward • Other approaches • Action under other regulations • 21 CFR 601.5 • This regulation is applicable to all licensed products; unlike 601.25 and 601.26, its application is not limited to products licensed before 1 July 1972.

17. 21 CFR 601.5 § 601.5 Revocation of license. …(b)(1) The Commissioner shall notify the licensed manufacturer of the intention to revoke the biologics license, setting forth the grounds for, and offering an opportunity for a hearing on the proposed revocation if the Commissioner finds any of the following: …(vi) The licensed product is not safe and effective for all of its intended uses or is misbranded with respect to any such use.

18. 21 CFR 601.5 • FDA would focus on products where there are safety concerns and where product efficacy is not supported by data • FDA could bring actions to revoke licenses under §601.5, for allergenic extracts in Tables 4 and 5

19. Other potential actions for products in Tables 1-3 • Nomenclature corrections: work with manufacturers to • Rename ambiguous products • Eliminate redundancies based on nomenclature • Eliminate mixes • Indication corrections • Some extracts in Table 3 need to be relabeled “for diagnostic use only”

20. Paths forward • 21 CFR 601.25 and 601.26 • Other approaches: • use 21 CFR 601.5 to address evidence of efficacy along with safety issues (Tables 4 and 5) • work with manufacturers to address and correct nomenclature issues and indications (Tables 1-3)

21. Today’s presentations • Background • Allergenics efficacy reviews • Panel 1, 21 CFR 601.25 (1974-1979) • Panel 2, 21 CFR 601.26 (1982-1983) • Current evaluation process (2003-2011) • Safety of allergenic extracts • Assessments • Next steps

22. Discussion points • Comments on • the review process so far; • the decision to list non-standardized allergenic products in five tables according to the evidence collected; and • the possible disposition of the categories of products identified in the Tables