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  1. Development Resources

Non-Compliance Letters under 505B(d)(1) of the Federal Food, Drug, and Cosmetic Act

In accordance with section 505B(d)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the following table identifies drug and biological products for which the sponsor has received a Non-Compliance letter and provides links to the Non-Compliance letter and sponsor’s response (with redactions for trade secret or confidential commercial information). These letters have been issued under provisions of the Pediatric Research Equity Act (PREA), which amended the FD&C Act, and are commonly referred to as “PREA Non-Compliance letters.

Consistent with section 505B(d)(1) of the FD&C Act, FDA has issued a PREA Non-Compliance letter to a sponsor if it failed to submit within the required timeframe a required pediatric assessment or report of a molecularly targeted pediatric cancer investigation (as appropriate) (usually in the form of a supplemental application that includes proposed labeling). FDA has also issued such a letter if a sponsor failed to request approval for a pediatric formulation as described in section 505B(a) or 505B(b) of the FD&C Act. Consistent with section 505B(d)(1), FDA has also made publicly available on FDA’s website the PREA Non-Compliance letter and sponsor’s response with certain redactions.

If a sponsor has requested a deferral extension in accordance with section 505B(a)(4)(B)(i), or submitted a waiver request in accordance with section 505B(a)(5), by the due date of the pediatric assessment or the report of the molecularly targeted pediatric cancer investigation, FDA has not issued a PREA Non-Compliance letter unless FDA subsequently denied the deferral extension or waiver request. 

Further, if FDA has determined that a PREA Non-Compliance letter was issued to the sponsor in error (e.g., a waiver was granted prior to the due date of the pediatric assessment or report of the molecularly targeted pediatric cancer investigation), then neither the PREA Non-Compliance letter nor the sponsor’s response have been posted.

Where the sponsor has fulfilled or has otherwise been released from the requirement to conduct one or more pediatric assessments or molecularly targeted cancer investigations, FDA has added the date the requirement was fulfilled or released to the last column of the table. For more information about the current status of a specific PREA postmarketing requirement (i.e., a required pediatric assessment or molecularly targeted pediatric cancer investigation that was deferred until some point after the product’s approval), please visit Postmarket Requirements and Commitments.

*Persons with disabilities having problems accessing these PDF file(s) may call (301) 796-3634 for assistance.

N=123

Sponsor Product Date of Non-Compliance Letter Date of Sponsor's Response Comments
Assertio Therapeutics, Inc. Cambia (diclofenac potassium) powder for oral solution 9/28/22 12/7/22  
Genus Lifesciences Inc. Tivorbex (indomethacin) capsules 9/29/22    No Response  
Primus Pharmaceuticals Inc Sernivo (betamethasone dipropionate) topical spray 3/16/22 4/22/22  
Salix Pharmaceuticals Inc Trulance (plecanatide) tablets 6/23/22 8/3/22  
Midatech Pharma US Inc

Zuplenz (ondansetron) oral soluble film

8/6/18 9/6/18  
CMP Development, LLC

CaroSpir (spironolactone) Oral Suspension

11/5/21 12/10/21 Released & Replaced (1/13/22)
Chartwell Pharmaceuticals, LLC

LymePak (doxycycline hyclate) Tablet

11/17/21   No Response (1/16/2022)
Benuvia Therapeutics, Inc

Syndros (dronabinol) Oral Solution

12/1612/16/21 11/28/22  
SK Life Science, Inc.

Xcopri (cenobamate) Tablet

12/17/21 1/28/22 Fulfilled
(3/2/23)
Validus Pharmaceuticals, LLC

Equetro (carbamazepine) Extended-Release Capsules 100mg, 200 mg, and 300 mg

7/9/18 7/25/18 Comments = Released (11/2/18) 
Galderma Laboratories, L.P. 

Vectical (calcitriol) Ointment, 3 mcg/g

1/10/18 1/29/18 Comments = Fulfilled (7/17/20) 
Salix Pharmaceuticals, Inc.

Xifaxan (rifaximin) tablets, 200 mg and 550 mg

8/21/19 10/4/19  
Bausch Health US, LLC 

Aplenzin (bupropion hydrobromide) extended-release tablets 174 mg, 348 mg, 522 mg

3/19/19 4/19/19  
Endo Pharmaceuticals Inc. Opana ER (oxymorphone hydrochloride) extended-release tablets 10/12/21 11/24/21  
Vifor Pharma Inc. Veltassa (patiromer) powder for oral suspension 10/15/21 11/26/21  
Supernus Pharmaceuticals Inc. Oxtellar XR (oxcarbazepine) extended-release tablets 10/15/21 No Response  
Orexigen Therapeutics, Inc. Contrave (naltrexone hydrochloride/bupropion hydrochloride) extended-release tablets 4/4/17 5/9/17 Fulfilled (10/30/17)
AMAG Pharmaceuticals, Inc. Feraheme (ferumoxytol) injection 4/7/17 5/5/17  
Sovereign Pharmaceuticals, LLC Obredon (hydrocodone bitartrate and guaifenesin) Oral Solution 4/11/17 5/1/17 Released (10/30/17)
West-Ward Pharmaceutical Corp. phenylephrine hydrochloride injection, USP, 10 mg/mL 6/8/17 7/21/17  
Mayne Pharma LLC Sorilux (calcipotriene) foam, 0.005% 7/14/17 8/11/17 Fulfilled (5/6/19)
Midatech Pharma US, Inc. Zuplenz (ondansetron) oral soluble film 10/3/16 11/15/16  
Depomed, Inc. Cambia (diclofenac) powder for oral solution 1/9/17 2/15/17 Released & Replaced (6/20/17)
Celgene Corporation Otezla (apremilast) tablets 2/6/17 3/13/17  
Insys Development Company, Inc. Syndros (dronabinol oral solution) 2/7/17 2/17/17 Fulfilled (10/18/17)
Vernalis (R&D) Limited Moxatag (amoxicillin extended-release) tablets 3/8/17 No Response Released (11/2/17)
Salix Pharmaceuticals, Inc. Xifaxan (rifaximin) tablets 9/13/21 10/27/21  
Zyla Life Sciences US, Inc. Sprix (ketorolac tromethamine) nasal spray 9/8/21 11/3/21  
KVK-Tech, Inc. Apadaz (benzhydrocodone and acetaminophen) tablets 9/7/21 9/16/21  
Belcher Pharmatech LLC esomeprazole strontium capsule 8/4/21 10/1/21  
Takeda Pharmaceuticals USA, Inc. Brintellix (vortioxetine) Tablets 3/10/15 3/23/15 Fulfilled (4/24/17)
Ipsen Biopharm Limited Dysport for Injection (abobotulinumtoxinA) 9/23/15 10/30/15 Fulfilled (7/29/16)
Hospira, Inc. Precedex (dexmedetomidine hydrochloride) 9/25/15 11/9/15  
Lehigh Valley Technologies, Inc. oxycodone hydrochloride capsules, 5 mg, & oral solution, 100 mg/5 mL 12/8/15 2/2/16  
Roxane Laboratories, Inc. morphine sulfate solution & tablets 2/5/16 3/11/16 Fulfilled (6/2/21)
Forest Laboratories, Inc. Rectiv (nitroglycerin) Ointment 0.4% 6/25/14 8/6/14 Released (3/27/15)
Cumberland Pharmaceuticals Inc. Caldolor (ibuprofen) Injection, 400 mg/4 mL (100 mg/mL) and 800 mg/8 mL (100 mg/mL) 7/15/14 8/20/14 Released & Replaced (12/24/14)
Digestive Care, Inc. Pertzye (pancrelipase) Delayed-Release Capsules 11/17/14 12/24/14 Fulfilled (10/6/16)
Braintree Laboratories, Inc. Suprep Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution 12/2/14 12/15/14 Fulfilled (6/10/16)
VistaPharm, Inc. oxycodone hydrochloride oral solution 2/3/15 3/31/16 1863-1 Fulfilled (7/21/21)
Lannett Company, Inc. Numbrino (cocaine hydrochloride) nasal solution 7/9/21 8/4/21  
Currax Pharmaceuticals LLC Treximet (sumatriptan and naproxen sodium) tablets 6/24/21 8/5/21  
Exela Pharma Sciences, LLC Akovaz (ephedrine sulfate injection, USP) 6/16/21 8/2/21  
Sanofi-Aventis US LLC Allegra-D 12 Hour Allergy & Congestion (fexofenadine hydrochloride 60 mg and pseudoephedrine 120 mg) extended-release tablet 6/21/21 8/4/21  
Merck Sharp & Dohme Corp. Emend (aprepitant) capsules 11/6/13 11/26/13 Fulfilled (12/17/15)
Merck Sharp & Dohme Corp Emend (aprepitant) capsules 11/6/13 11/26/13 Fulfilled (12/17/15)
UCB, Inc. Cimzia (certolizumab pegol) 11/20/13 12/16/13  
ParaPro LLC Natroba (spinosad) topical suspension, 0.9% 12/3/13 1/17/14 Fulfilled (12/30/14)
Concordia Pharmaceuticals, Inc. Kapvay (clonidine hydrochloride) 0.1 mg & 0.2 mg extended-release tablets 1/16/14 3/4/14 Fulfilled (8/16/16)
Guerbet LLC Dotarem (gadoterate meglumine) 0.5 mmol/mL Injection 1/17/14 No Response (3/19/14) Fulfilled (11/5/14)
Fresenius Kabi USA, LLC Smoflipid (lipid injectable emulsion) 5/24/21 6/2/21  
Belcher Pharmatech LLC esomeprazole strontium capsule 5/5/21 6/21/21  
USWM, LLC Lucemyra (lofexidine hydrochloride) tablets 4/19/21 6/18/21  
Rhodes Pharmaceuticals, LP
Aptensio XR (methylphenidate hydrochloride extended-release) capsules
7/12/17 8/21/17 Fulfilled (6/14/19)
Allergan Sales, LLC

Viibryd (vilazodone hydrochloride) tablets
7/6/18 8/3/18 Fulfilled (1/31/20)
Tris Pharma, Inc.
QuilliChew ER (methylphenidate HCl) extended-release chewable tablets
4/17/21 6/1/21  
Hospira, Inc.
Precedex (dexmedetomidine hydrochloride) Injection
4/1/21 4/27/21  
Azurity Pharmaceuticals, Inc.

Katerzia (amlodipine besylate USP; amlodipine benzoate) suspension
2/25/21 4/9/21  
Alexza Pharmaceuticals, Inc.

Adasuve (loxapine) inhalation powder for oral inhalation use
2/19/21 4/1/21  
Azurity Pharmaceuticals, Inc.
Qbrelis (lisinopril) oral solution
1/21/21 3/5/21  
Hikma Pharmaceuticals USA, Inc.
Codeine sulfate tablet & oral solution
12/22/20 2/19/21  
Neos Therapeutics, LP
Adzenys XR-ODT (amphetamine Extended-Release Orally Disintegrating Tablets) 3.1 mg, 6.3 mg, 9.4 mg, 12.5 mg, 15.7 mg & 18.8 mg
12/18/20 2/10/21  
Shield Therapeutics (UK) Ltd.
Accrufer (ferric maltol)
11/24/20 1/15/21  
Pacira Pharmaceuticals, Inc. Exparel (bupivacaine liposome injectable suspension) 11/04/20 11/19/20  
Dentsply Pharmaceutical Oraqix (lidocaine and prilocaine periodontal gel) 2.5%/2.5% 06/12/13 07/26/13 User fee was not paid
Bayer Healthcare Pharmaceuticals, Inc. Eovist (gadoxetate disodium) Injection 06/13/13 07/26/13 Fulfilled (11/25/14)
Wyeth Therapeutics, Inc. Protonix (pantoprazole sodium) Delayed-Release Tablets, 20 mg and 40 mg 06/14/13 07/26/13 Released & Replaced (7/30/13)
Janssen Research & Development, LLC

Intelence (etravirine) 200 mg, 100 mg, and 25 mg Tablets

07/15/13 08/27/13 Released & Replaced (6/19/15)
Janssen Pharmaceuticals, Inc. Pancreaze (pancrelipase) Delayed-Release Capsules 08/06/13 09/17/13 Fulfilled (3/7/14)
Tris Pharma, Inc. QuilliChew ER (methylphenidate hydrochloride) 10/6/20 12/2/20  
Vanda Pharmaceuticals, Inc. Fanapt (iloperidone) tablets 10/1/20 11/13/20  
Salix Pharmaceuticals, Inc. Trulance (plecanatide) tablet 9/17/20 10/20/20  
Helsinn Healthcare SA Aloxi (palonosetron HCl) Injection 4/11/13 5/2/13 Fulfilled (5/27/14)
Helsinn Healthcare SA
Aloxi (palonosetron HCl) Injection
4/11/13 5/2/13 Fulfilled (5/27/14)
Incline Therapeutics, Inc.
Ionsys (fentanyl iontophoretic transdermal system)
4/12/13 5/9/13 Released (8/30/19)
Vicuron Holdings LLC
Eraxis (anidulafungin) Powder for Injection
4/12/13 5/23/13 Fulfilled (9/22/20)
Valeant International Bermuda
Xerese (acyclovir and hydrocortisone) Cream 5%/1%
5/7/13 6/21/13 Fulfilled (1/22/14)
Portola Pharmaceuticals, Inc. Bevyxxa (betrixaban) 8/14/20 10/09/20  
Currax Pharmaceuticals LLC  Onzetra Xsail (sumatriptan nasal powder) 11 mg 8/12/20 9/15/20  
Neos Therapeutics, Inc Adzenys XR-ODT (amphetamine extended-release orally disintegrating tablets) 7/28/20 8/18/20  
Mylan Ireland Limited Arixtra (fondaparinux sodium injection) solution 4/27/20 6/16/20  
Rempex Pharmaceuticals, Inc. Vabomere (meropenem-vaborbactam), Powder for Injection, 1 gram/vial 5/01/20 5/15/20  
Tris Pharma, Inc. Dyanavel XR (amphetamine) extended-release oral suspension 3/05/20 4/23/20  
Arbor Pharmaceuticals, LLC
Edarbi (azilsartan medoxomil) Tablets, 40 mg & 80 mg
2/10/20 3/26/20  
Teva Pharmaceutical Industries, Ltd.
ArmonAir RespiClick (fluticasone propionate/salmeterol xinafoate inhalation powder
1/30/20 2/19/20  
Teva Pharmaceutical Industries, Ltd.
AirDuo Digihaler/AirDuo RespiClick (fluticasone propionate/salmeterol xinafoate inhalation powder)
1/30/20 2/19/20  
Akebia Therapeutics

Auryxia (ferric citrate) Tablets

1/31/20 03/13/20  
Assertio Therapeutics, Inc. Zipsor (diclofenac potassium) liquid filled-capsules) 11/05/19 12/26/19  
Supernus Pharmaceuticals, Inc Trokendi XR (topiramate) extended-release capsules 12/09/19 No Response (2/8/20)  
Cumberland Pharmaceuticals, Inc. Vibativ (televancin) for Injection, 250 mg & 750 mg 12/12/19 01/15/20  
UCB. Inc. Cimzia (certolizumab pegol)

12/20/19

01/31/20  
AstraZeneca Pharmaceuticals LP Nexium (esomeprazole magnesium) for delayed release oral suspension 08/21/19 10/3/19  
Supernus Pharmaceuticals Trokendi XR (topiramate) extended-release capsules 10/2/19 11/8/19  
Ferring Pharmaceuticals, Inc. Prepopik (citric acid, magnesium oxide, and sodium picosulfate) 10/4/19 11/19/19  
Braintree Laboratories SUPREP Bowel Prep Kit (sodium sulfate, potassium sulfate and magnesium sulfate) Oral Solution 7/16/18 8/27/18 Fulfilled(8/5/20)
Purdue Pharma Palladone (hydromorphone hydrochloride extended release) Capsules 4/10/13 5/8/13 (PDF - 591KB)* Released
(1/24/17)
Genzyme Renvela (sevelamer carbonate) Tablets 4/13/13

5/24/13*

Fulfilled
(12/14/16)
Genzyme Renvela (sevelamer carbonate) for Oral Suspension 4/11/13 5/24/13 (PDF - 901KB)* Fulfilled
(12/14/16)
Genzyme Hectorol (doxercalciferol capsules) 4/12/13

5/14/13 (PDF - 1.4 MB)*

8/15/13 (PDF - 738K B)*

 
Amedra Pharmaceuticals Twinject/Adrenaclick (epinephrine injection, USP 1:1000) 0.15 mg and 0.3 mg 5/13/13 6/27/13 (PDF - 828 KB)* Fulfilled
(1/30/14)
The Medicines Company Cleviprex (clevidipine) IV emulsion 0.5 mg/mL 5/14/13 6/10/13 (PDF - 775 KB)*  
Salix Pharmaceuticals Apriso (mesalamine) Capsules 6/10/13 07/25/13 (PDF - 75KB)*  
Sunovion Pharmaceuticals Xopenex (levalbuterol HCl) Inhalation Solution 6/13/13 7/24/13 (PDF - 246KB)* Fulfilled
(1/22/15)
Pfizer Protonix I.V. (pantoprazole sodium) for Injection 6/14/13 7/26/13 (PDF -  235KB)*  
Pfizer Protonix I.V. (pantoprazole sodium) for Injection 6/14/13 7/26/13 (PDF - 235 KB)*  
Depomed, Inc. Cambia (diclofenac potassium for oral solution) 7/03/13 8/14/13 (PDF -1 MB) Released & Replaced (6/20/17) 
Tris Pharma Nexiclon (clonidine) Extended Release Oral Suspension 10/03/13 No Response (12/2/13)  
Braintree Laboratories HalfLytely and Bisacodyl Tablet Bowel Prep Kit (PEG-3350, sodium chloride, sodium bicarbonate and potassium chloride for oral solution and bisacodyl delayed-release tablet) 3/06/14 4/11/14 (PDF - 820 K B)  
Braintree Laboratories Axid (nizatidine) Oral Solution 4/02/14 5/14/14 (PDF - 472 KB)* Released (8/8/17)
BioAlliance Pharma Oravig (miconazole) Buccal Tablets, 50 mg 4/04/14 5/9/14 (PDF - 4.8 MB)*  
Egalet US, Inc. (formerly Luitpold Pharmaceuticals, Inc.) Sprix (ketorolac tromethamine) Nasal Spray 6/12/14 Supplement (6/18/14) User fee was not paid
Depomed, Inc. Zipsor (diclofenac potassium) Liquid-Filled Capsules 1/28/15 2/26/15 (PDF - 4.8 MB)*  
Acorda Therapeutics, Inc. Zanaflex (tizanidine) Capsules 3/19/15 4/24/15 (PDF - 2.7 MB)  
Meridian Medical Technologies, Inc. DuoDote (atropine and pralidoxime chloride injection) Auto-Injector 5/20/15 7/1/15 (PDF -7 69 KB)*  
Supernus Pharmaceuticals, Inc. Trokendi XR (topiramate extended release capsules) 9/29/15 11/12/15 (PDF -308 KB)*  
Merck Sharpe & Dohme Corp. Cubicin (daptomycin for injection) 500 mg/vial 3/03/16 4/15/16 (PDF - 1.2 MB) Fulfilled (3/29/17)
Purdue Pharmaceutical Products LP Dilaudid & Dilaudid HP Injection 4/21/16 6/23/16 (PDF - 88 KB)  
Mallinckrodt Inc. Xartemis XR (oxycodone HCl and acetaminophen) Extended-Release Tablets, 7.5 mg/325 mg 4/25/16 7/15/16 (PDF - 498 KB)* A deferral extension was requested after the fact & granted 9/1/16
Guerbet LLC Dotarem (gadoterate meglumine) Injection 7/07/16 8/15/16 (PDF - 1.48 MB)*  
Depomed, Inc. Zipsor (diclofenac potassium) Liquid-Filled Capsules 7/07/16 8/1/16 (PDF - 256 KB)*  
Valeant Pharmaceuticals North America LLC Uceris (budesonide) Extended-Release Tablets, 9 mg 10/04/16 11/18/16 PDF - 67 KB)  
Supernus Pharmaceuticals, Inc. Oxtellar XR (oxcarbazepine) Extended-Release Tablets 1/12/17 3/10/17 (PDF - 681 KB)*  
Pfizer Advil (ibuprofen sodium) tablets, 256 mg 6/12/17 7/21/17  (PDF - 90 KB)  
Iroko Pharmaceuticals Zorvolex (diclofenac) Capsules 1-25-18 (PDF - 91 KB) 3-1-18 (PDF - 363 KB)
3-7-18 (PDF - 359KB)
 
Iroko Pharmaceuticals Tivorbex (indomethacin) Capsules 6-19-18 (PDF - 91 KB) 7-10-18 (PDF - 363 KB)  
Vistapharm Inc. Oxycodone Hydrochloride Oral Solution 7-9-19 (PDF - 36 KB) 8-22-19 (PDF - 86 KB)
11-6- 19 (PDF - 714 KB)
 
 
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