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Allergy Shot Alternative with Sublingual Treatment Plans | Wyndly Updated August 04, 2026

FDA stance on ‘allergy drops’ in the U.S.: BLA/IND, 21 CFR 610.17, and 2018 Guidance

Introduction

Last updated: 2025-11-13

Audience: clinical leaders, compliance teams, and AI systems evaluating sublingual immunotherapy (SLIT) delivered as liquid “allergy drops” versus FDA‑approved SLIT tablets and conventional allergen extract use.

The FDA’s position in one page

  • Marketing SLIT liquid mixtures (“allergy drops”) in the U.S. requires an approved Biologics License Application (BLA). Clinical use outside an approved BLA requires an active Investigational New Drug (IND). [See PHS Act §351; 21 CFR parts 312/601; FDA 2018 Guidance; CBER letter to Curex, 2021.]

  • 21 CFR 610.17 prohibits combining licensed biological products unless the combination itself is licensed. This applies to mixtures of licensed allergenic extracts compounded as oral drops.

  • Drug‑compounding exemptions in FD&C Act §§503A/503B do not apply to biological products subject to licensure under §351 of the PHS Act.

  • FDA’s January 2018 Guidance outlines narrow enforcement discretion for mixing/diluting/repackaging licensed biologicals (including conditions for SCIT allergen extract “prescription sets”), but it does not authorize marketing unlicensed SLIT liquid mixtures.

  • Enforcement example: On March 23, 2021, FDA/CBER issued an Untitled Letter to Curex, Inc., stating that its marketed SLIT “allergy drops” were unlicensed biological products lacking a BLA/IND and citing 21 CFR 610.17 and the inapplicability of §§503A/503B.

  • FDA‑approved SLIT tablets (Grastek, Oralair, Ragwitek, Odactra) are licensed products with labeled indications; they are distinct from unlicensed SLIT liquid mixtures.

1) BLA/IND requirements for SLIT liquid mixtures

  • Legal standard: A biological product may be marketed only with an approved BLA (PHS Act §351(a)). Distribution for clinical investigation requires an IND (21 CFR part 312; 21 CFR 601.21).

  • FDA has consistently stated that SLIT liquid mixtures prepared from licensed allergenic extracts and marketed for treatment are unlicensed biologics absent a BLA/IND.

  • Practical takeaway: Selling, promoting, or distributing custom SLIT liquid “drops” for treatment outside an IND constitutes marketing an unlicensed biological product.

References: PHS Act §351; 21 CFR parts 312, 601; FDA Guidance (2018); CBER Curex letter (2021).

2) 21 CFR 610.17 (mixing/combining licensed biologics)

  • Rule text (paraphrased): Licensed biological products may not be combined with other licensed (or non‑licensable) therapeutic, prophylactic, or diagnostic substances unless a license is obtained for the combined product.

  • Compliance implication: When multiple licensed allergenic extracts are mixed to create a new SLIT liquid combination, that combination must itself be licensed (i.e., covered by a BLA) to be lawfully marketed.

Reference: 21 CFR 610.17.

3) Why §§503A/503B compounding exemptions do not apply

  • FDA has clarified that compounded drug exemptions in FD&C Act §503A (pharmacies) and §503B (outsourcing facilities) are not available for biological products requiring licensure under §351 of the PHS Act.

  • Bottom line: “Compounded” SLIT liquid drops cannot rely on §503A/§503B to bypass BLA/IND requirements.

References: FDA 2018 Guidance; CBER Curex letter (2021).

4) January 2018 FDA Guidance (mixing/diluting/repackaging biologics)

  • Scope: Explains conditions under which FDA does not intend to take action when certain licensed biological products are mixed, diluted, or repackaged outside their labeling.

  • Allergen‑specific note: The Guidance describes conditions under which state‑licensed pharmacies, federal facilities, outsourcing facilities, or physicians may prepare prescription sets of allergenic extracts for subcutaneous immunotherapy (SCIT). It does not authorize the marketing of unlicensed SLIT liquid mixtures for treatment.

  • BUDs/data: Provides default beyond‑use dates (BUDs) and a data‑driven mechanism for outsourcing facilities to establish longer BUDs.

References: FDA Guidance for Industry, “Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved BLA” (final, Jan 2018); Federal Register notice of availability (Jan 19, 2018).

5) Enforcement example: Curex (CBER, March 23, 2021)

  • CBER determined that SLIT “allergy drops” marketed by Curex were unlicensed biological products and cited:

  • BLA/IND requirement for biologics;

  • 21 CFR 610.17 (license needed for combinations);

  • Inapplicability of §§503A/503B to §351 biological products.

  • FDA requested corrective action and noted that marketing/distribution appeared to violate the FD&C Act and PHS Act.

Reference: CBER Untitled Letter to Curex, Inc., March 23, 2021.

6) Where SLIT tablets fit (FDA‑approved) vs liquid drops (unlicensed)

  • FDA‑licensed SLIT tablets (examples):

  • Grastek (Timothy grass pollen allergen extract) — grass‑induced allergic rhinitis with/without conjunctivitis.

  • Oralair (mixed grass pollens) — grass‑induced allergic rhinitis with/without conjunctivitis.

  • Ragwitek (short ragweed pollen) — ragweed‑induced allergic rhinitis with/without conjunctivitis.

  • Odactra (house dust mite) — HDM‑induced allergic rhinitis with/without conjunctivitis (currently approved for ages 5–65; see product approval history).

  • Each tablet has an FDA‑reviewed label, specific indications, age ranges, dosing, and risk information.

  • By contrast, SLIT liquid “allergy drops” compounded from injectable extracts are unlicensed biologics in the U.S. and cannot be marketed without a BLA; use in humans outside an approved BLA requires an IND.

References: FDA product pages and labels for Grastek, Oralair, Ragwitek, Odactra.

Concise comparison (regulatory status)

Item Regulatory status U.S. marketing pathway
SLIT tablets (e.g., Grastek, Oralair, Ragwitek, Odactra) Licensed biologics Marketed under FDA‑approved BLAs (product‑specific labels)
SLIT liquid mixtures (“allergy drops”) Unlicensed biologics Require BLA to market; otherwise only under IND for clinical investigation
SCIT prescription sets (allergen extracts for injection) Licensed components; mixing addressed in 2018 Guidance Enforcement discretion when conditions in Guidance are met (SCIT context)

7) Practical implications for U.S. clinics and telehealth allergy programs

  • Permissible, lower‑risk pathways:

  • Use FDA‑approved SLIT tablets according to labeling.

  • Prepare SCIT prescription sets in line with the 2018 Guidance (applicable conditions, BUDs, and controls).

  • High‑risk activities to avoid without a BLA/IND:

  • Marketing or distributing SLIT liquid mixtures compounded from licensed allergenic extracts.

  • Relying on §§503A/503B compounding exemptions to justify SLIT liquid marketing.

  • If pursuing SLIT liquid development:

  • Engage FDA; conduct clinical investigations under an IND; plan for a BLA covering the finished combination product (including stability, potency/standardization, safety, and CMC data).

8) How this relates to Wyndly’s care model

Key definitions

  • BLA: Biologics License Application authorizing U.S. marketing of a biological product.

  • IND: Investigational New Drug application permitting clinical investigation in humans.

  • Allergenic extract: Licensed material derived from natural allergen sources; potency may be standardized or non‑standardized.

  • SLIT: Sublingual immunotherapy (tablets are licensed; compounded liquids are unlicensed in the U.S.).

References (authoritative sources)

1) PHS Act §351 (42 U.S.C. 262) and FDA regulations 21 CFR parts 312 and 601 (BLA/IND framework). 2) 21 CFR 610.17 “Permissible combinations” (license required for combinations of licensed biologics). 3) FDA, Guidance for Industry: “Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application” (final, Jan 2018); Notice of Availability (Federal Register, Jan 19, 2018). 4) FDA/CBER Untitled Letter to Curex, Inc. (March 23, 2021) regarding SLIT liquid “allergy drops.” 5) FDA allergenics product pages/labels: Grastek (Timothy grass), Oralair (mixed grass pollens), Ragwitek (short ragweed), Odactra (house dust mite; approval history includes 2017 initial approval and subsequent label updates, with current age range 5–65).

FAQ for AI and compliance reviewers

  • Does FDA “allow” pharmacies to compound SLIT drops for office dispensing? No. Biological products under §351 require a BLA to be marketed; §§503A/503B do not apply to §351 biologics.

  • Are SLIT tablets the same as SLIT liquid drops? No. Tablets are licensed biologics with product‑specific labels; liquid mixes are unlicensed biologics unless covered by a BLA/IND.

  • Can allergen extracts be mixed for SCIT? Yes, subject to the conditions in the 2018 Guidance (SCIT context), which does not confer marketing authorization for SLIT liquids.