SFDA’s Product Specific Bioequivalence Guidance

Draft

Date of publication 17 November 2020

Date of implementation To be announced

This document is a draft SFDA guideline published for comments and suggestions purposes. It is, therefore, subject to alteration and modification and may not be referred to as SFDA guideline until approved by SFDA

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SFDA’s Product Specific Bioequivalence Guidance

Draft

Saudi Food & Drug Authority Drug Sector

Please send your comments or suggestions before 17 January 2021 to: [email protected]

Please visit SFDA’s website at http://www.sfda.gov.sa/en/drug/drug_reg/Pages/default.aspx for the latest update

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Saudi Food and Drug Authority

Vision and Mission

Vision

To be a leading international science-based regulator to protect and promote public health

Mission

Protecting the community through regulations and effective controls to ensure the safety of food, drugs, medical devices, cosmetics, pesticides and feed

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Document Control

Version Author Date Comments

Draft Executive Directorate of Products Evaluation 17 November 2020 -

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Amlodipine; Hydrochlorothiazide; Valsartan Aripiprazole ...... 52 Table of Contents ...... 32 Asenapine ...... 53 Objective: ...... 12 Amlodipine; Indapamide ...... 33 Atorvastatin Calcium...... 54 Abiraterone Acetate ...... 13 Amlodipine; Irbesartan ...... 34 Avanafil ...... 55 Aceclofenac ...... 14 Amlodipine; Lisinopril ...... 35 Azithromycin ...... 56 Acetaminophen; Oxycodone Hydrochloride 15 Amlodipine; Ramipril ...... 36 Azithromycin ...... 57 Acetaminophen; Oxycodone Hydrochloride 16 Amlodipine Besylate; Hydrochlorothiazide; Bacitracin ...... 58 Acyclovir ...... 17 Olmesartan Medoxomil ...... 37 Beclomaetasone Dipropionate ...... 59 Acyclovir ...... 18 Amlodipine Besylate; Olmesartan Medoxomil ...... 38 Benzyl alcohol ...... 60 Acyclovir ...... 19 Amlodipine Besylate; Perindopril Arginine . 39 Betahistine Dihydrochloride ...... 61 Acyclovir ...... 20 Amlodipine Besylate; Valsartan ...... 40 Betamethasone Valerate ...... 62 Agomelatine ...... 21 Amlodipine Besylate ...... 41 Bexarotene ...... 63 Alcaftadine ...... 22 Amoxicillin; Clavulanate Potassium ...... 42 Bicalutamide ...... 64 Alectinib ...... 23 Amoxicillin; Clavulanate Potassium ...... 43 Bimatoprost ...... 65 Alendronate Sodium ...... 24 Amoxicillin ...... 44 Bisoprolol Fumarate ; Hydrochlorothiazide . 66 Alendronate Sodium ...... 25 Amoxicillin ...... 45 Bisoprolol Fumarate; Perindopril Arginine .. 67 Alfuzosin Hydrochloride ...... 26 Amoxicillin ...... 46 Bisoprolol Fumarate ...... 68 Aliskiren ...... 27 Anastrozole ...... 47 Bosentan ...... 69 Alogliptin Benzoate ...... 28 Apixaban ...... 48 Bosutinib Monohydrate ...... 70 Amisulpride ...... 29 Aprepitant ...... 49 Brimonidine tartrate; Timolol maleate ...... 71 Amlodipine; Bisoprolol ...... 30 Aprepitant ...... 50 Brimonidine tartrate ...... 72 Amlodipine; Hydrochlorothiazide; Losartan Brimonidine Tartrate ...... 73 Potassium ...... 31 Aripiprazole ...... 51 5 | P a g e

Bromfenac sodium ...... 74 Cefuroxime Axetil ...... 96 Clindamycin phosphate ...... 118 Cabergoline ...... 75 Cefuroxime Axetil ...... 97 Clindamycin phosphate ...... 119 Cabozantinib ...... 76 Celecoxib ...... 98 Clobetasol Propionate ...... 120 Calcipotriene ...... 77 Chlorzoxazone ...... 99 Clobetasol Propionate ...... 121 Canagliflozin; Metformin Hydrochloride ..... 78 Cholic acid ...... 100 Clobetasol Propionate ...... 122 Canagliflozin; Metformin Hydrochloride ..... 79 Ciclopirox ...... 101 Clobetasol Propionate ...... 123 Canagliflozin ...... 80 Ciclopirox ...... 102 Clopidogrel Bisulfate ...... 124 Candesartan Cilexetil; Hydrochlorothiazide. 81 Cinacalcet Hydrochloride ...... 103 Clotrimazole ...... 125 Candesartan Cilexetil ...... 82 Ciprofloxacin; Dexamethasone ...... 104 Colchicine ...... 126 Capecitabine ...... 83 Ciprofloxacin Hydrochloride...... 105 Crizotinib ...... 127 Carbamazepine ...... 84 Ciprofloxacin hydrochloride ...... 106 Crotamiton ...... 128 Carbamazepine ...... 85 Ciprofloxacin Hydrochloride...... 107 Crotamiton ...... 129 Carbamazepine ...... 86 Ciprofloxacin Hydrochloride...... 108 Cyclobenzaprine hydrochloride ...... 130 Carglumic Acid ...... 87 Ciprofloxacin ...... 109 Cyclobenzaprine ...... 131 Cefaclor ...... 88 Citalopram Hydrobromide...... 110 Cyclosporine ...... 132 Cefdinir ...... 89 Clarithromycin ...... 111 Cyclosporine ...... 133 Cedinir ...... 90 Clarithromycin ...... 112 Dabigatran Etexilate Mesylate ...... 134 Cefixime ...... 91 Clarithromycin ...... 113 Daclatasvir Dihydrochloride ...... 135 Cefixime ...... 92 Clindamycin Hydrochloride ...... 114 Dalfampridine ...... 136 Cefixime ...... 93 Clindamycin Phosphate ...... 115 Dapagliflozin Propanediol; Metformin Cefpodoxime Proxetil ...... 94 Clindamycin phosphate ...... 116 Hydrochloride ...... 137 Cefpodoxime Proxetil ...... 95 Clindamycin phosphate ...... 117 Dapagliflozin Propanediol; Saxagliptin Hydrochloride ...... 138 6 | P a g e

Dapagliflozin Propanediol ...... 139 Divalproex Sodium ...... 160 Enzalutamide ...... 181 Dapoxetine Hydrochloride ...... 140 Docosanol ...... 161 Eperisone Hydrochloride ...... 182 Dapsone ...... 141 Dolutegravir ...... 162 Eplerenone ...... 183 Dasatinib ...... 142 Domperidone ...... 163 Erlotinib Hydrochloride ...... 184 Deferasirox ...... 143 Donepezil Hydrochloride ...... 164 Erythromycin ...... 185 Desloratadine ...... 144 Donepezil Hydrochloride ...... 165 Erythromycin ...... 186 Desloratadine ...... 145 Dorzolamide Hydrochloride ; Timolol As Erythromycin ...... 187 Desmopressin Acetate ...... 146 Maleate ...... 166 Erythromycin ...... 188 Desmopressin acetate ...... 147 Dorzolamide Hydrochloride ...... 167 Erythromycin ...... 189 Desogestrel; Ethinyl Estradiol ...... 148 Dorzolamide Hydrochloride ...... 168 Erythromycin ...... 190 Desogestrel ...... 149 Doxycycline Hyclate ...... 169 Erythromycin ...... 191 Desoximetasone ...... 150 Doxycycline Hyclate ...... 170 Escitalopram Oxalate ...... 192 Dexamethasone; Tobramycin ...... 151 Doxycycline Hyclate ...... 171 Escitalopram Oxalate ...... 193 Dexamethasone; Tobramycin ...... 152 Doxycycline Hyclate ...... 172 Esomeprazole Magnesium ...... 194 Dexamethasone ...... 153 Dronedarone ...... 173 Esomeprazole Magnesium ...... 195 Dexamethasone; Neomycin Sulfate; Drospirenone; Ethinyl Estradiol ...... 174 Eszopiclone ...... 196 Polymyxin B Sulfate ...... 154 Duloxetine Hydrochloride ...... 175 Ethinyl Estradiol; Cyproterone ...... 197 Dexamethasone; Tobramycin ...... 155 Efinaconazole ...... 176 Ethionamide ...... 198 Diclofenac sodium ...... 156 Elvitegravir ...... 177 Etodolac ...... 199 Difluprednate ...... 157 Emtricitabine; Tenofovir Disoproxil Fumarate Etodolac ...... 200 ...... 178 Divalproex Sodium ...... 158 Etodolac ...... 201 Enalapril Maleate ...... 179 Divalproex Sodium ...... 159 Etoricoxib ...... 202 Entecavir ...... 180 7 | P a g e

Everolimus ...... 203 Gemifloxacin Mesylate ...... 225 Isotretinoin ...... 246 Exemestane ...... 204 Gentamicin Sulfate ...... 226 Ivabradine Hydrochloride ...... 247 Ezetimibe ...... 205 Gentamicin Sulfate ...... 227 Ivermectin ...... 248 Febuxostat ...... 206 Gentamicin Sulfate ...... 228 Ketoconazole ...... 249 Fenofibrate ...... 207 Gestodene; Ethinylestradiol...... 229 Lacosamide ...... 250 Fexofenadine Hydrochloride ...... 208 Glibenclamide (Glyburide) ...... 230 Lamotrigine ...... 251 Fexofenadine Hydrochloride ...... 209 Gliclazide...... 231 Lamotrigine ...... 252 Fexofenadine Hydrochloride ...... 210 Glimepiride; Metformin ...... 232 Lamotrigine ...... 253 Fexofenadine Hydrochloride ...... 211 Glimepiride ...... 233 Lamotrigine ...... 254 Finasteride ...... 212 Glycopyrronium Tosylate ...... 234 Lapatinib ...... 255 Fingolimod ...... 213 Hydrochlorothiazide; Olmesartan Medoxomil Latanoprost ...... 256 Fluconazole ...... 214 ...... 235 Latanoprost ...... 257 Fluconazole ...... 215 Hydrocortisone ...... 236 Latanoprostene Bunod ...... 258 Fluocinolone Acetonide ...... 216 Hydrocortisone ...... 237 Ledipasvir; Sofosbuvir ...... 259 Fluorometholone Acetate ...... 217 Hydrogen Peroxide ...... 238 Leflunomide ...... 260 Fosinopril Sodium ...... 218 Hydroxychloroquine Sulfate ...... 239 Lenalidomide ...... 261 Gabapentin ...... 219 Imatinib ...... 240 Lercanidipine Hydrochloride ...... 262 Gabapentin ...... 220 Indapamide ...... 241 Letrozole ...... 263 Gabapentin ...... 221 Irbesartan; Hydrochlorothiazide ...... 242 Levetiracetam ...... 264 Gatifloxacin ...... 222 Irbesartan ...... 243 Levetiracetam ...... 265 Gatifloxacin ...... 223 Isoniazid ...... 244 Levocetirizine Dihydrochloride ...... 266 Gefitinib ...... 224 Isosorbide Mononitrate ...... 245 Levodopa; Carbidopa; Entacapone ...... 267

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Levofloxacin ...... 268 Mebeverine Hydrochloride ...... 290 Mirtazapine ...... 312 Levonorgestrel ...... 269 Meloxicam ...... 291 Mirtazapine ...... 313 Levothyroxine Sodium ...... 270 Meloxicam ...... 292 Mometasone Furoate ...... 314 Levothyroxine Sodium ...... 271 Memantine Hydrochloride...... 293 Montelukast Sodium ...... 315 Lidocaine ...... 272 Memantine Hydrochloride...... 294 Montelukast Sodium ...... 316 Lifitegrast ...... 273 Mesalazine (Mesalamine) ...... 295 Montelukast Sodium ...... 317 Linezolid ...... 274 Mesalazine (Mesalamine) ...... 296 Moxifloxacin Hydrochloride ...... 318 Linezolid ...... 275 Metformin; Glibenclamide (Glyburide) ..... 297 Moxifloxacin Hydrochloride ...... 319 Lisinopril ...... 276 Metformin Hydrochloride ...... 298 Mycophenolate Mofetil ...... 320 Loratadine ...... 277 Metformin Hydrochloride ...... 299 Mycophenolate Mofetil ...... 321 Loratadine ...... 278 Methotrexate ...... 300 Mycophenolate Mofetil ...... 322 Loratadine ...... 279 Metoprolol Succinate ...... 301 Naproxen; Esomeprazole ...... 323 Loratadine ...... 280 Metoprolol Tartrate ...... 302 Nepafenac ...... 324 Lornoxicam ...... 281 Metronidazole ...... 303 Netarsudil Dimesylate ...... 325 Losartan Potassium; Hydrochlorothiazide .. 282 Metronidazole ...... 304 Nystatin and Triamcinolone Acetonide ...... 326 Losartan Potassium ...... 283 Metronidazole ...... 305 Nystatin and Triamcinolone Acetonide ...... 327 Loteprednol Etabonate ...... 284 Metronidazole Benzoate ...... 306 Ofloxacin ...... 328 Loteprednol Etabonate ...... 285 Metronidazole ...... 307 Olanzapine ...... 329 Loteprednol Etabonate ...... 286 Miglustat ...... 308 Olanzapine ...... 330 Luliconazole ...... 287 Minocycline Hydrochloride...... 309 Olmesartan Medoxomil ...... 331 Lurasidone ...... 288 Minoxidil ...... 310 Olopatadine Hydrochloride ...... 332 Malathion ...... 289 Minoxidil ...... 311 Olopatadine hydrochloride ...... 333

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Omeprazole; Sodium Bicarbonate ...... 334 Prasugrel Hydrochloride ...... 355 Sildenafil Citrate ...... 377 Omeprazole ...... 335 Prednisolone Acetate ...... 356 Silodosin ...... 378 Ondansetron Hydrochloride Dihydrate...... 336 Prednisolone ...... 357 Silver Sulfadiazine ...... 379 Orlistat ...... 337 Pregabalin ...... 358 Simvastatin ...... 380 Ornidazole ...... 338 Quetiapine Fumarate ...... 359 Simvastatin ...... 381 Oseltamivir Phosphate ...... 339 Quetiapine ...... 360 Sirolimus ...... 382 Oxcarbazepine ...... 340 Rabeprazole Sodium ...... 361 Sitagliptin Phosphate; Metformin Ozenoxacin ...... 341 Ramipril; Hydrochlorothiazide ...... 362 Hydrochloride ...... 383 Palbociclib ...... 342 Ramipril ...... 363 Sitagliptin Phosphate; Metformin Hydrochloride ...... 384 Pantoprazole Sodium ...... 343 Ramipril ...... 364 Sofosbuvir ...... 385 Paroxetine Hydrochloride ...... 344 Repaglenide ...... 365 Solifenacin Succinate ...... 386 Paroxetine Hydrochloride ...... 345 Ribavirin ...... 366 Sorafenib Tosylate...... 387 Pazopanib Hydrochloride ...... 346 Ribavirin ...... 367 Spinosad ...... 388 Penciclovir ...... 347 Rilpivirine Hydrochloride ...... 368 Sumatriptan Succinate ...... 389 Perindopril Arginine ...... 348 Risperidone ...... 369 Sunitinib Malate ...... 390 Perindopril Erbumine ...... 349 Risperidone ...... 370 Tacrolimus ...... 391 Pilocarpine Hydrochloride ...... 350 Rivaroxaban ...... 371 Tacrolimus ...... 392 Pioglitazon Hydrochloride; Metformine Rivastigmine Tartrate ...... 372 Tacrolimus ...... 393 Hydrochloride ...... 351 Roflumilast ...... 373 Tadalafil ...... 394 Pioglitazon Hydrochloride ...... 352 Rosuvastatin Calcium ...... 374 Tamsulosin Hydrochloride ...... 395 Pitavastatin ...... 353 Sertraline Hydrochloride ...... 375 Tamsulosin Hydrochloride; Dutasteride .... 396 Podofilox ...... 354 Sevelamer Carbonate ...... 376 Tavaborole ...... 397 10 | P a g e

Telithromycin ...... 398 Topiramate...... 413 Trimetazidine Dihydrochloride ...... 428 Telmisartan; Amlodipine Besylate ...... 399 Topiramate...... 414 Valganciclovir ...... 429 Telmisartan; Hydrochlorothiazide ...... 400 Torsemide ...... 415 Amlodipine; Hydrochlorothiazide; Valsartan Telmisartan ...... 401 Tramadol ...... 416 ...... 430 Temozolomide ...... 402 Tramadol ...... 417 Hydrochlorothiazide; Valsartan ...... 431 Tenofovir Disoproxil Fumarate ...... 403 Tramadol ...... 418 Valsartan ...... 432 Terbinafine ...... 404 Tranexamic Acid ...... 419 Vandetanib ...... 433 Terbinafine ...... 405 Tretinoin ...... 420 Varenicline Tartrate...... 434 Terbinafine ...... 406 Tretinoin ...... 421 Vemurafenib ...... 435 Testosterone ...... 407 Tretinoin ...... 422 Verdenafil ...... 436 Ticagrelor ...... 408 Tretinoin ...... 423 Verdinafil ...... 437 Timolol Maleate ...... 409 Tretinoin ...... 424 Vismodegib ...... 438 Tizanidine ...... 410 Triamcinolone Acetonide ...... 425 Vortioxetine Hydrobromide ...... 439 Tizanidine Hydrochloride ...... 411 Triamcinolone Acetonide ...... 426 Zonisamide ...... 440 Tobramycin ...... 412 Triamcinolone Acetonide ...... 427

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Objective:

To further facilitate generic pharmaceutical product availability and to support the generic pharmaceutical industry with identifying the most appropriate methodology for designing the bioequivalence/ in-vitro studies, SFDA publishes product-specific guidance describing the Authority’s current thinking and expectations on how to develop bioequivalence/ in-vitro studies for the generic pharmaceutical product.

Disclaimer: This guidance helps applicants meet the expectations of regulators in the Gulf countries for generic products. This guidance should not be understood as being legally enforceable. The applicant can use another approach if the approach satisfies the requirements of the GCC guideline of bioequivalence.

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Active ingredient Abiraterone Acetate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover

in-vivo under fasting condition.

Recommended study Analytes to measure: Abiraterone in plasma.

Bioequivalence based on (90% CI): Abiraterone.

Background: Abiraterone may consider as a highly variable drug (i.e., within- subject variability ≥ 30%).

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Active ingredient Aceclofenac

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under

fasting condition. Recommended study

Analytes to measure: Aceclofenac in plasma.

Bioequivalence based on (90% CI): Aceclofenac.

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Active ingredient Acetaminophen; Oxycodone Hydrochloride

Dosage form Extended Release Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Acetaminophen and Oxycodone in plasma.

Bioequivalence based on (90% CI): Acetaminophen and Oxycodone.

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Active ingredient Acetaminophen; Oxycodone Hydrochloride

Dosage form Tablet

1 study

Type of Study: Biowaiver option

Recommended study For more information, please refer “The SFDA guideline for biowaiver”.

Background: Acetaminophen; Oxycodone Hydrochloride Tablets are a Drug Efficacy Study implementation “DESI” effective drug for which there are no known or suspected bioequivalence problems.

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Active ingredient Acyclovir

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Acyclovir in plasma.

Bioequivalence based on (90% CI): Acyclovir.

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Active ingredient Acyclovir

Dosage form Cream; topical

Two options: In vitro studies or in vivo clinical endpoint study.

1. In Vitro approach: To qualify for the in vitro approach for this drug product the following criteria should be met:

 The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT). Or

2. Bioequivalence study with clinical endpoint.

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Active ingredient Acyclovir

Dosage form Ointment; topical

Two options: In vitro studies or in vivo clinical endpoint study.

1. In Vitro approach: To qualify for the in vitro approach for this drug product the following criteria should be met:

 The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT). Or

2. Bioequivalence study with clinical endpoint.

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Active ingredient Acyclovir

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Acyclovir in plasma.

Bioequivalence based on (90% CI): Acyclovir.

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Active ingredient Agomelatine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Agomelatine in plasma.

Bioequivalence based on (90% CI): Agomelatine.

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Active ingredient Alcaftadine

Dosage form Solution/drops; ophthalmic

Waiver option:

To qualify for the in vitro approach for this drug product the following criteria should Recommended study be met:  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

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Active ingredient Alectinib

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Recommended study Analytes to measure: Alectinib in plasma.

Bioequivalence based on (90% CI): Alectinib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Alendronate Sodium

Dosage form Effervescent Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Alendronate in plasma.

Bioequivalence based on (90% CI): Alendronate.

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Active ingredient Alendronate Sodium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Alendronate in plasma.

Bioequivalence based on (90% CI): Alendronate.

Background: Alendronate may consider as a highly variable drug (i.e., within- subject variability ≥ 30%).

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Active ingredient Alfuzosin Hydrochloride

Dosage form Extended Release Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Alfuzosin in plasma.

Bioequivalence based on (90% CI): Alfuzosin.

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Active ingredient Aliskiren

Dosage form Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Aliskiren in plasma.

Bioequivalence based on (90% CI): Aliskiren.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Alogliptin Benzoate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Alogliptin in plasma.

Bioequivalence based on (90% CI): Alogliptin.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

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Active ingredient Amisulpride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Amisulpride in plasma.

Bioequivalence based on (90% CI): Amisulpride.

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Active ingredient Amlodipine; Bisoprolol

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Amlodipine, Bisoprolol in plasma.

Bioequivalence based on (90% CI): Amlodipine and Bisoprolol.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine; Hydrochlorothiazide; Losartan Potassium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Amlodipine, Hydrochlorothiazide, Losartan, and its Carboxylic metabolite in plasma.

Bioequivalence based on (90% CI): Amlodipine, Hydrochlorothiazide and Losartan.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine; Hydrochlorothiazide; Valsartan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Amlodipine, Hydrochlorothiazide and Valsartan in plasma.

Bioequivalence based on (90% CI): Amlodipine, Hydrochlorothiazide and Valsartan.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine; Indapamide

Dosage form Tablet (Modified release for indapamide / immediate release for amlodipine)

2 studies

Type of studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Amlodipine and Indapamide in plasma.

Bioequivalence based on (90% CI): Amlodipine and Indapamide.

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Active ingredient Amlodipine; Irbesartan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Amlodipine and Irbesartan in plasma.

Bioequivalence based on (90% CI): Amlodipine and Irbesartan.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine; Lisinopril

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Amlodipine and Lisinopril in plasma.

Bioequivalence based on (90% CI): Amlodipine and Lisinopril.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine; Ramipril

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Amlodipine, Ramipril and active metabolite, Ramiprilat in Recommended study plasma.

Bioequivalence based on (90% CI): Amlodipine and Ramipril.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine Besylate; Hydrochlorothiazide; Olmesartan Medoxomil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition.

Analytes to measure: Amlodipine, Hydrochlorothiazide and Olmesartan in plasma. Recommended study Bioequivalence based on (90% CI): Amlodipine, Hydrochlorothiazide and Olmesartan.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine Besylate; Olmesartan Medoxomil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition.

Analytes to measure: Amlodipine and Olmesartan in plasma. Recommended study Bioequivalence based on (90% CI): Amlodipine and Olmesartan.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine Besylate; Perindopril Arginine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Amlodipine, Perindopril, and the active metabolite Perindoprilat in plasma.

Bioequivalence based on (90% CI): Amlodipine and Perindopril.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine Besylate; Valsartan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Amlodipine and Valsartan in plasma.

Bioequivalence based on (90% CI): Amlodipine and Valsartan.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amlodipine Besylate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Amlodipine in plasma.

Bioequivalence based on (90% CI): Amlodipine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

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Active ingredient Amoxicillin; Clavulanate Potassium

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Amoxicillin and Clavulanate acid in plasma.

Bioequivalence based on (90% CI): Amoxicillin and Clavulanate acid.

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Active ingredient Amoxicillin; Clavulanate Potassium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Amoxicillin and Clavulanic acid in plasma.

Bioequivalence based on (90% CI): Amoxicillin and Clavulanic acid.

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Active ingredient Amoxicillin

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Amoxicillin in plasma.

Bioequivalence based on (90% CI): Amoxicillin.

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Active ingredient Amoxicillin

Dosage form Extended Release Tablet

2 studies

Type of studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Amoxicillin in plasma.

Bioequivalence based on (90% CI): Amoxicillin.

45 | P a g e

Active ingredient Amoxicillin

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Amoxicillin in plasma.

Bioequivalence based on (90% CI): Amoxicillin.

46 | P a g e

Active ingredient Anastrozole

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Anastrozole in plasma.

Bioequivalence based on (90% CI): Anastrozole.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

47 | P a g e

Active ingredient Apixaban

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Apixaban in plasma.

Bioequivalence based on (90% CI): Apixaban.

48 | P a g e

Active ingredient Aprepitant

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Aprepitant in plasma.

Bioequivalence based on (90% CI): Aprepitant.

49 | P a g e

Active ingredient Aprepitant

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Aprepitant in plasma.

Bioequivalence based on (90% CI): Aprepitant.

50 | P a g e

Active ingredient Aripiprazole

Dosage form Orally Disintegrating Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Aripiprazole in plasma.

Bioequivalence based on (90% CI): Aripiprazole.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

51 | P a g e

Active ingredient Aripiprazole

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Aripiprazole in plasma.

Bioequivalence based on (90% CI): Aripiprazole.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

52 | P a g e

Active ingredient Asenapine

Dosage form Sublingual Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Asenapine in plasma.

Bioequivalence based on (90% CI): Asenapine.

Background:  Asenapine exhibits nonlinear pharmacokinetics profile.  AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

53 | P a g e

Active ingredient Atorvastatin Calcium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Atorvastatin and its active metabolites, Ortho and Para- hydroxylated atorvastatin in plasma.

Bioequivalence based on (90% CI): Atorvastatin.

Background: Atorvastatin may consider as a highly variable drug (i.e., within- subject variability ≥ 30%).

54 | P a g e

Active ingredient Avanafil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Avanafil in plasma.

Bioequivalence based on (90% CI): Avanafil.

55 | P a g e

Active ingredient Azithromycin

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Azithromycin in plasma.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

56 | P a g e

Active ingredient Azithromycin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Azithromycin in plasma.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

57 | P a g e

Active ingredient Bacitracin

Dosage form Ointment; ophthalmic

In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

58 | P a g e

Active ingredient Beclomaetasone Dipropionate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Amlodipine in plasma.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

59 | P a g e

Active ingredient Benzyl alcohol

Dosage form Lotion; topical

Two options: In vitro studies or in vivo clinical endpoint study.

1. In vitro approach: To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Equivalent comparative dosage form performance characterization ex vivo in Pediculus humanus capitis (head lice), using an appropriate pediculicide hair tuft assay with relevant controls. Or 2. Bioequivalence study with clinical endpoint.

60 | P a g e

Active ingredient Betahistine Dihydrochloride

Dosage form Tablet

Two options: Biowaiver or Bioequivalence study.

Type of Study:

1. BCS waiver option: The drug classified as BCS class I, for more information, please see “The SFDA Recommended study guideline for biowaiver”.

Or

2. Bioequivalence study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Betahistine in plasma.

Bioequivalence based on (90% CI): Betahistine.

61 | P a g e

Active ingredient Betamethasone Valerate

Dosage form Foam aerosol; topical

Two options: waiver or bioequivalence study.

1. Waiver option:

A generic betamethasone valerate foam aerosol/topical should be a solution for aerosolization; have the same active ingredient in the same concentration and dosage Recommended study form as the reference listed drug product (RLD); and must not have an inactive ingredient or other change in formulation from the RLD that may significantly affect systemic or local availability.

Or

2. Bioequivalence study with clinical endpoint.

62 | P a g e

Active ingredient Bexarotene

Dosage form Gel; topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). Or 2. Bioequivalence study with clinical endpoint.

63 | P a g e

Active ingredient Bicalutamide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Bicalutamide in plasma.

Bioequivalence based on (90% CI): Bicalutamide.

64 | P a g e

Active ingredient Bimatoprost

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach: To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. Or 2. Bioequivalence study.

65 | P a g e

Active ingredient Bisoprolol Fumarate ; Hydrochlorothiazide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Bisoprolol and Hydrochlorothiazide in plasma.

Bioequivalence based on (90% CI): Bisoprolol and Hydrochlorothiazide.

66 | P a g e

Active ingredient Bisoprolol Fumarate; Perindopril Arginine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Bisoprolol and Perindopril in plasma.

Bioequivalence based on (90% CI): Bisoprolol and Perindopril.

67 | P a g e

Active ingredient Bisoprolol Fumarate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Bisoprolol in plasma.

Bioequivalence based on (90% CI): Bisoprolol.

68 | P a g e

Active ingredient Bosentan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Bosentan in plasma.

Bioequivalence based on (90% CI): Bosentan.

69 | P a g e

Active ingredient Bosutinib Monohydrate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Bosutinib in plasma.

Bioequivalence based on (90% CI): Bosutinib.

70 | P a g e

Active ingredient Brimonidine tartrate; Timolol maleate

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. Or 2. Bioequivalence study.

71 | P a g e

Active ingredient Brimonidine tartrate

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. Or 2. Bioequivalence study with clinical endpoint.

72 | P a g e

Active ingredient Brimonidine Tartrate

Dosage form Solution/drops; ophthalmic

Two options: Waiver or bioequivalence study with clinical endpoint.

Type of Study:

1. Waiver option: A generic Brimonidine tartrate ophthalmic solution product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD). Recommended study An in vivo BE study with clinical endpoint is requested for a difference of more than 5% in the amount of any inactive ingredient compared to that of the RLD, or differences in comparative physicochemical characterization data.

Or 2. Bioequivalence study with clinical endpoint.

73 | P a g e

Active ingredient Bromfenac sodium

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. Or 2. Bioequivalence study with pharmacokinetic (PK) end points.

74 | P a g e

Active ingredient Cabergoline

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Cabergoline in plasma.

Bioequivalence based on (90% CI): Cabergoline.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

75 | P a g e

Active ingredient Cabozantinib

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Cabozantinib in plasma.

Bioequivalence based on (90% CI): Cabozantinib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

76 | P a g e

Active ingredient Calcipotriene

Dosage form Solution; Topical

Two options: waiver or in vivo bioequivalence study.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Recommended study Reference Listed Drug (RLD).

Or

2. In vivo bioequivalence study.

77 | P a g e

Active ingredient Canagliflozin; Metformin Hydrochloride

Dosage form Extended Release Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And

Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Canagliflozin and Metformin in plasma.

Bioequivalence based on (90% CI): Canagliflozin and Metformin.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

78 | P a g e

Active ingredient Canagliflozin; Metformin Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Canagliflozin and Metformin in plasma.

Bioequivalence based on (90% CI): Canagliflozin and Metformin.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

79 | P a g e

Active ingredient Canagliflozin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Canagliflozin in plasma.

Bioequivalence based on (90% CI): Canagliflozin.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

80 | P a g e

Active ingredient Candesartan Cilexetil; Hydrochlorothiazide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Candesartan and Hydrochlorothiazide in plasma.

Bioequivalence based on (90% CI): Candesartan and Hydrochlorothiazide.

81 | P a g e

Active ingredient Candesartan Cilexetil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Candesartan in plasma.

Bioequivalence based on (90% CI): Candesartan.

82 | P a g e

Active ingredient Capecitabine

Dosage form Tablet

Two options: Biowaiver or Bioequivalence study.

Type of Study:

1. BCS waiver option:

The drug classified as BCS class I, for more information, please see “The SFDA Recommended study guideline for biowaiver”.

Or

2. Bioequivalence study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Capecitabine in plasma.

Bioequivalence based on (90% CI): Capecitabine.

83 | P a g e

Active ingredient Carbamazepine

Dosage form Extended Release Capsule

2 studies

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition. Recommended study And Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Carbamazepine in plasma.

Bioequivalence based on (90% CI): Carbamazepine.

Background: Carbamazepine considered as a Narrow therapeutic index (NTI) drug.

84 | P a g e

Active ingredient Carbamazepine

Dosage form Extended Release Tablet

2 studies

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition. Recommended study And Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Carbamazepine in plasma.

Bioequivalence based on (90% CI): Carbamazepine.

Background: Carbamazepine considered as a Narrow therapeutic index (NTI) drug.

85 | P a g e

Active ingredient Carbamazepine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover Recommended study in-vivo under fasting condition.

Analytes to measure: Carbamazepine in plasma.

Bioequivalence based on (90% CI): Carbamazepine.

Background: Carbamazepine considered as a Narrow therapeutic index (NTI) drug.

86 | P a g e

Active ingredient Carglumic Acid

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Carglumic acid in plasma.

Bioequivalence based on (90% CI): Carglumic acid.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

87 | P a g e

Active ingredient Cefaclor

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Cefaclor in plasma.

Bioequivalence based on (90% CI): Cefaclor.

88 | P a g e

Active ingredient Cefdinir

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Cefdinir in plasma.

Bioequivalence based on (90% CI): Cefdinir.

89 | P a g e

Active ingredient Cedinir

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Cedinir in plasma.

Bioequivalence based on (90% CI): Cedinir.

90 | P a g e

Active ingredient Cefixime

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Cefixime in plasma.

Bioequivalence based on (90% CI): Cefixime.

91 | P a g e

Active ingredient Cefixime

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Cefixime in plasma.

Bioequivalence based on (90% CI): Cefixime.

92 | P a g e

Active ingredient Cefixime

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Cefixime in plasma.

Bioequivalence based on (90% CI): Cefixime.

93 | P a g e

Active ingredient Cefpodoxime Proxetil

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Cefpodoxime in plasma.

Bioequivalence based on (90% CI): Cefpodoxime.

94 | P a g e

Active ingredient Cefpodoxime Proxetil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Cefpodoxime in plasma.

Bioequivalence based on (90% CI): Cefpodoxime.

95 | P a g e

Active ingredient Cefuroxime Axetil

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Cefuroxime in plasma.

Bioequivalence based on (90% CI): Cefuroxime.

96 | P a g e

Active ingredient Cefuroxime Axetil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Cefuroxime in plasma.

Bioequivalence based on (90% CI): Cefuroxime.

97 | P a g e

Active ingredient Celecoxib

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Celecoxib in plasma.

Bioequivalence based on (90% CI): Celecoxib.

98 | P a g e

Active ingredient Chlorzoxazone

Dosage form Tablet

Two options: Biowaiver or Bioequivalence study.

Type of Study:

1. Waiver option: The drug is listed on DESI list, for more information, please see “The SFDA guideline for biowaiver”.

Recommended study Or

2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Chlorzoxazone in plasma.

Bioequivalence based on (90% CI): Chlorzoxazone.

99 | P a g e

Active ingredient Cholic acid

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Recommended study Analytes to measure: Unconjugated cholic acid and total cholic acid (unconjugated cholic acid, glycocholic acid, and taurocholic acid) in plasma. 24 hours pre-dose baseline correction (same sampling scheme as on dosing day including meals, with individual matched sampling time-points).

Bioequivalence based on (90% CI): Baseline corrected (i) unconjugated cholic acid and (ii) total cholic acid (unconjugated cholic acid, glycocholic acid, and taurocholic acid).

100 | P a g e

Active ingredient Ciclopirox

Dosage form Shampoo; Topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization (polymeric resin). Or

2. Bioequivalence (BE) with Clinical Endpoint Study.

101 | P a g e

Active ingredient Ciclopirox

Dosage form Solution; Topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should

be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization (polymeric resin). Or

2. Bioequivalence (BE) with Clinical Endpoint.

102 | P a g e

Active ingredient Cinacalcet Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Cinacalcet in plasma.

Bioequivalence based on (90% CI): Cinacalcet.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

103 | P a g e

Active ingredient Ciprofloxacin; Dexamethasone

Dosage form Suspension; otic drops

Two options: In vitro Studies or in vivo bioequivalence study.

1. In vitro approach: To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable comparative in vitro antimicrobial kill rates.

Or

2. Bioequivalence study with pharmacokinetic (PK) endpoints.

104 | P a g e

Active ingredient Ciprofloxacin Hydrochloride

Dosage form Extended Release Tablets

2 studies

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Ciprofloxacin in plasma.

Bioequivalence based on (90% CI): Ciprofloxacin.

Note: The 500-mg strength of ciprofloxacin extended-release tablets is NOT eligible for a waiver of in-vivo testing based on an acceptable in-vivo bioequivalence study of the 1000-mg strength.

105 | P a g e

Active ingredient Ciprofloxacin hydrochloride

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study.

106 | P a g e

Active ingredient Ciprofloxacin Hydrochloride

Dosage form Ointment; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

Or

2. Bioequivalence study with clinical endpoint.

107 | P a g e

Active ingredient Ciprofloxacin Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under

fasting condition. Recommended study

Analytes to measure: Ciprofloxacin in plasma.

Bioequivalence based on (90% CI): Ciprofloxacin.

108 | P a g e

Active ingredient Ciprofloxacin

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Ciprofloxacin in plasma.

Bioequivalence based on (90% CI): Ciprofloxacin.

109 | P a g e

Active ingredient Citalopram Hydrobromide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Citalopram in plasma.

Bioequivalence based on (90% CI): Citalopram.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

110 | P a g e

Active ingredient Clarithromycin

Dosage form Extended Release Tablet

2 studies

Type of Study:

Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Clarithromycin in plasma.

Bioequivalence based on (90% CI): Clarithromycin.

111 | P a g e

Active ingredient Clarithromycin

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Clarithromycin in plasma.

Bioequivalence based on (90% CI): Clarithromycin.

112 | P a g e

Active ingredient Clarithromycin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Clarithromycin in plasma.

Bioequivalence based on (90% CI): Clarithromycin.

113 | P a g e

Active ingredient Clindamycin Hydrochloride

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Clindamycin in plasma.

Bioequivalence based on (90% CI): Clindamycin.

114 | P a g e

Active ingredient Clindamycin Phosphate

Dosage form Aerosol, Foam; Topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: A. Same active ingredient in the same concentration and dosage form as the Recommended study Reference Listed Drug (RLD) and must not have an inactive ingredient or other change in formulation from the RLD that may significantly affect systemic or local availability. B. Comparative assay of the test and reference product. Or

2. Bioequivalence (BE) Study with Clinical Endpoint.

115 | P a g e

Active ingredient Clindamycin phosphate

Dosage form Gel; Topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should

be met:

 The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). Or

2. Bioequivalence Study with Clinical Endpoint.

116 | P a g e

Active ingredient Clindamycin phosphate

Dosage form Gel; Topical

Two options: In vitro studies or in vivo clinical endpoint study.

1. In Vitro studies:

To qualify for the in vitro option for Clindamycin phosphate gel, all the following

criteria must be met:

A. The test and Reference List Drug (RLD) formulations are qualitatively and

quantitatively the same (Q1/Q2). Recommended study B. Acceptable comparative physicochemical characterization of the test and Reference Standard (RS) formulations. C. Acceptable comparative in vitro drug release rates of Clindamycin from the test and RS formulations. Or 2. Bioequivalence study with clinical endpoint.

117 | P a g e

Active ingredient Clindamycin phosphate

Dosage form Aerosol, Foam/Topical

Two options: In vitro studies or in vivo clinical endpoint study.

1. In Vitro studies:

To qualify for the in vitro option for Clindamycin phosphate gel, all the following

criteria must be met:

A. The test and Reference List Drug (RLD) formulations are qualitatively and Recommended study quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization of the test and Reference Standard (RS) formulations. C. Acceptable comparative in vitro drug release rates of Clindamycin from the test and RS formulations.

Or

2. Bioequivalence study with clinical endpoint.

118 | P a g e

Active ingredient Clindamycin phosphate

Dosage form Swab; Topical

Two options: waiver or in vivo bioequivalence study.

1. Waiver option:

To qualify for the Waiver approach for this drug product the following criteria should be met: A. Same active ingredient in the same concentration and dosage form as the Recommended study Reference Listed Drug (RLD) and must not have an inactive ingredient or other change in formulation from the RLD that may significantly affect systemic or local availability.

Or

2. Bioequivalence Study with Clinical Endpoint.

119 | P a g e

Active ingredient Clobetasol Propionate

Dosage form Shampoo; Topical

Two options: waiver or in vivo bioequivalence study.

1. Waiver option:

Recommended study The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

Or

2. In vivo bioequivalence study.

120 | P a g e

Active ingredient Clobetasol Propionate

Dosage form Aerosol, Foam; Topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: A. Same active ingredient in the same concentration and dosage form as the Reference Listed Drug (RLD) and must not have an inactive ingredient or other change in formulation from the RLD that may significantly affect systemic or Recommended study local availability. B. Comparative assay of the test and reference product.

Or

2. Bioequivalence (BE) Study with Clinical Endpoint.

121 | P a g e

Active ingredient Clobetasol Propionate

Dosage form Solution; Topical

Two options: waiver or in vivo bioequivalence study.

1. Waiver option:

Recommended study The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

Or

2. In vivo bioequivalence study with clinical endpoint.

122 | P a g e

Active ingredient Clobetasol Propionate

Dosage form Spray; Topical

Two options: waiver or in vivo bioequivalence study.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Recommended study Reference Listed Drug (RLD). Or

2. In vivo bioequivalence study with clinical endpoint.

123 | P a g e

Active ingredient Clopidogrel Bisulfate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Clopidogrel in plasma.

Bioequivalence based on (90% CI): Clopidogrel.

Background: To avoid the potential for back-conversion of the quantitatively major metabolite clopidogrel carboxylic acid to the parent drug, the analysis method should be free from methanol and/or ethanol.

124 | P a g e

Active ingredient Clotrimazole

Dosage form Solution; Topical

Two options: waiver or in vivo bioequivalence study.

1. Waiver option:

Recommended study The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

Or

2. In vivo bioequivalence study with clinical endpoint.

125 | P a g e

Active ingredient Colchicine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Colchicine in plasma.

Bioequivalence based on (90% CI): Colchicine.

Background: Colchicine considered as a Narrow therapeutic index (NTI) drug.

126 | P a g e

Active ingredient Crizotinib

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Crizotinib in plasma.

Bioequivalence based on (90% CI): Crizotinib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

127 | P a g e

Active ingredient Crotamiton

Dosage form Cream; Topical

Acceptable comparative physicochemical characterization of the test and reference

listed drug (RLD) formulations for each strength of the product to establish that the Recommended study test product is a comparable crotamiton topical cream identical in strength to the RLD.

128 | P a g e

Active ingredient Crotamiton

Dosage form Lotion; Topical

Acceptable comparative physicochemical characterization of the test and reference

listed drug (RLD) formulations for each strength of the product to establish that the Recommended study test product is a comparable crotamiton topical lotion identical in strength to the RLD.

129 | P a g e

Active ingredient Cyclobenzaprine hydrochloride

Dosage form Extended release capsule

2 studies

Type of Study:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Cyclobenzaprine in plasma.

Bioequivalence based on (90% CI): Cyclobenzaprine.

130 | P a g e

Active ingredient Cyclobenzaprine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Cyclobenzaprine in plasma.

Bioequivalence based on (90% CI): Cyclobenzaprine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

131 | P a g e

Active ingredient Cyclosporine

Dosage form Emulsion; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. In vivo bioequivalence study with clinical endpoint.

132 | P a g e

Active ingredient Cyclosporine

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. In vivo bioequivalence study with clinical endpoint.

133 | P a g e

Active ingredient Dabigatran Etexilate Mesylate

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: free (non-conjugated) dabigatran and total dabigatran (non- conjugated plus conjugated dabigatran after complete alkaline cleavage of dabigatran glucuronides) in plasma.

Bioequivalence based on (90% CI): free (non-conjugated) dabigatran and total dabigatran (non-conjugated plus conjugated dabigatran).

134 | P a g e

Active ingredient Daclatasvir Dihydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Daclatasvir in plasma.

Bioequivalence based on (90% CI): Daclatasvir.

135 | P a g e

Active ingredient Dalfampridine

Dosage form Extended Release Tablet

2 studies

Type of Study:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Dalfampridine in plasma.

Bioequivalence based on (90% CI): Dalfampridine.

136 | P a g e

Active ingredient Dapagliflozin Propanediol; Metformin Hydrochloride

Dosage form Extended Release Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And

Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Dapagliflozin and metformin in plasma.

Bioequivalence based on (90% CI): Dapagliflozin and metformin.

Background: To avoid hypoglycemic episodes, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 minutes for up to 4 hours after dosing.

137 | P a g e

Active ingredient Dapagliflozin Propanediol; Saxagliptin Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Dapagliflozin, saxagliptin and its active metabolite, 5- hydroxy Recommended study saxagliptin, in plasma.

Bioequivalence based on (90% CI): Dapagliflozin and saxagliptin.

Background: To avoid hypoglycemic episodes, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 minutes for up to 4 hours after dosing.

138 | P a g e

Active ingredient Dapagliflozin Propanediol

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Dapagliflozin in plasma.

Bioequivalence based on (90% CI): Dapagliflozin.

Background: To avoid hypoglycemic episodes, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 minutes for up to 4 hours after dosing.

139 | P a g e

Active ingredient Dapoxetine Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Dapoxetine in plasma.

Bioequivalence based on (90% CI): Dapoxetine.

140 | P a g e

Active ingredient Dapsone

Dosage form Gel; Topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be:

A. Qualitatively and quantitatively the same (Q1/Q2). Recommended study B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT).

Or

2. Bioequivalence study with clinical endpoint.

141 | P a g e

Active ingredient Dasatinib

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Dasatinib in plasma.

Bioequivalence based on (90% CI): Dasatinib.

142 | P a g e

Active ingredient Deferasirox

Dosage form Dispersible Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under

fasting condition. Recommended study

Analytes to measure: Deferasirox in plasma.

Bioequivalence based on (90% CI): Deferasirox.

143 | P a g e

Active ingredient Desloratadine

Dosage form Orally Disintegrating Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Desloratadine and the active metabolite, 3- hydroxydesloratadine in plasma.

Bioequivalence based on (90% CI): Desloratadine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

144 | P a g e

Active ingredient Desloratadine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Desloratadine and its metabolite, 3-hydroxydesloratadine.

Bioequivalence based on (90% CI): Desloratadine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

145 | P a g e

Active ingredient Desmopressin Acetate

Dosage form Sublingual tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Desmopressin in plasma. Recommended study

Bioequivalence based on (90% CI): Desmopressin.

Note: - The dose should be administered sublingually without water. - Fluids should be restricted for 2 hours prior to dosing and a minimum of 8 hours post-dose. Monitor serum electrolytes regularly to identify any trend toward worsening hyponatremia prior to discharge from the study site.

146 | P a g e

Active ingredient Desmopressin acetate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Desmopressin in plasma.

Bioequivalence based on (90% CI): Desmopressin.

147 | P a g e

Active ingredient Desogestrel; Ethinyl Estradiol

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Active metabolite of Desogestrel, 3-ketodesogestrel (etonogestrel) and ethinyl estradiol in plasma.

Bioequivalence based on (90% CI): 3-ketodesogestrel (etonogestrel) and ethinyl estradiol.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

148 | P a g e

Active ingredient Desogestrel

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under

fasting condition.

Analytes to measure: Active metabolite of Desogestrel, 3-ketodesogestrel Recommended study (etonogestrel) in plasma.

Bioequivalence based on (90% CI): 3-ketodesogestrel (etonogestrel).

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

149 | P a g e

Active ingredient Desoximetasone

Dosage form Spray; topical

Two options: waiver or in vivo vasoconstrictor studies.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD). If inactive ingredients of test product differ from the RLD or are present in Recommended study significantly different amounts, the applicant must identify and characterize the formulation differences and provide information demonstrating that the differences do not affect the safety or efficacy.

Or

2. In vivo option:

Type of Studies:

A. Pilot vasoconstrictor study. And B. Pivotal vasoconstrictor study.

150 | P a g e

Active ingredient Dexamethasone; Tobramycin

Dosage form Suspension/ drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be:

A. Qualitatively and quantitatively the same (Q1/Q2). Recommended study B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable comparative in vitro antimicrobial kill rates.

Or

2. In-vivo bioequivalence study with pharmacokinetic (PK) endpoints.

151 | P a g e

Active ingredient Dexamethasone; Tobramycin

Dosage form Ointment; ophthalmic

Two options: In vitro studies or in-vivo bioequivalence study with pharmacokinetic (PK) endpoints.

1. In vitro studies: To qualify for the in vitro option for Dexamethasone; Tobramycin phosphate Ointment, all the following criteria must be met: i. The test and Reference List Drug (RLD) formulations are qualitatively and Recommended study quantitatively the same (Q1/Q2). ii. Acceptable comparative physicochemical characterization of the test and Reference Standard (RS) formulations. iii. Acceptable comparative in vitro drug release rates from the test and RS formulations.

Or

2. In-vivo bioequivalence study with pharmacokinetic (PK) endpoints.

152 | P a g e

Active ingredient Dexamethasone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Dexamethasone in plasma

Bioequivalence based on (90% CI): Dexamethasone

153 | P a g e

Active ingredient Dexamethasone; Neomycin Sulfate; Polymyxin B Sulfate

Dosage form Suspension; Ophthalmic drops

Two options: In vitro studies or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should

be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable comparative in vitro antimicrobial kill rates.

Or

2. Bioequivalence study with pharmacokinetic (PK) endpoints.

154 | P a g e

Active ingredient Dexamethasone; Tobramycin

Dosage form Suspension ; Ophthalmic

Two options: In vitro studies or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable comparative in vitro antimicrobial kill rates.

Or

2. Bioequivalence study with pharmacokinetic (PK) endpoints.

155 | P a g e

Active ingredient Diclofenac sodium

Dosage form Solution drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should

be met:

 The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

156 | P a g e

Active ingredient Difluprednate

Dosage form Emulsion ; Ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

Or

2. Bioequivalence study with pharmacokinetic (PK) endpoints.

157 | P a g e

Active ingredient Divalproex Sodium

Dosage form Delayed release tablets

2 studies

Type of Study:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Valproic acid in plasma.

Bioequivalence based on (90% CI): Valproic acid.

Background: Divalproex sodium considered as a Narrow therapeutic index (NTI) drug.

158 | P a g e

Active ingredient Divalproex Sodium

Dosage form Delayed release pellets capsule

2 studies

Type of Study:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Valproic acid in plasma.

Bioequivalence based on (90% CI): Valproic acid.

Background: Divalproex sodium considered as a Narrow therapeutic index (NTI) drug.

159 | P a g e

Active ingredient Divalproex Sodium

Dosage form Extended release tablets

2 studies

Type of Study:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Valproic acid in plasma.

Bioequivalence based on (90% CI): Valproic acid.

Background: Divalproex sodium considered as a Narrow therapeutic index (NTI) drug.

160 | P a g e

Active ingredient Docosanol

Dosage form Cream; topical

Two options: In vitro or in vivo study.

1. In vitro option:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be:

A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical/ microstructural characterizations. C. Acceptable in vitro release test (IVRT).

Or

2. Bioequivalence (BE) with Clinical Endpoint Study.

161 | P a g e

Active ingredient Dolutegravir

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Dolutegravir in plasma.

Bioequivalence based on (90% CI): Dolutegravir.

162 | P a g e

Active ingredient Domperidone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Domperidone in plasma.

Bioequivalence based on (90% CI): Domperidone.

163 | P a g e

Active ingredient Donepezil Hydrochloride

Dosage form Orally disintegrating tablet

Two options: Biowaiver or bioequivalence study. 1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA

guideline for biowaiver”.

Or

Recommended study 2. Bioequivalence study: Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Donepezil in plasma.

Bioequivalence based on (90% CI): Donepezil.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

164 | P a g e

Active ingredient Donepezil Hydrochloride

Dosage form Tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA

guideline for biowaiver”.

Or

Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Donepezil in plasma.

Bioequivalence based on (90% CI): Donepezil.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

165 | P a g e

Active ingredient Dorzolamide Hydrochloride ; Timolol As Maleate

Dosage form Solution; ophthalmic drop

Two options: Waiver or bioequivalence study with clinical endpoint.

1. Waiver option: A generic dorzolamide hydrochloride and Timolol As Maleate ophthalmic solution product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD). Recommended study Or

2. Bioequivalence study with clinical endpoint.

166 | P a g e

Active ingredient Dorzolamide Hydrochloride

Dosage form Solution; ophthalmic drop

Two options: Waiver or bioequivalence study with clinical endpoint.

1. Waiver option:

A generic dorzolamide hydrochloride ophthalmic solution product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD). Recommended study Or

2. Bioequivalence study with clinical endpoint.

167 | P a g e

Active ingredient Dorzolamide Hydrochloride

Dosage form Solution drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

168 | P a g e

Active ingredient Doxycycline Hyclate

Dosage form Capsule

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option: The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Recommended study Or

2. Bioequivalence study: Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Doxycycline in plasma.

Bioequivalence based on (90% CI): Doxycycline.

169 | P a g e

Active ingredient Doxycycline Hyclate

Dosage form Delayed release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Doxycycline in plasma.

Bioequivalence based on (90% CI): Doxycycline.

170 | P a g e

Active ingredient Doxycycline Hyclate

Dosage form Delayed release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Doxycycline in plasma.

Bioequivalence based on (90% CI): Doxycycline.

171 | P a g e

Active ingredient Doxycycline Hyclate

Dosage form Tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option: The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Recommended study Or

2. Bioequivalence study: Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Doxycycline in plasma.

Bioequivalence based on (90% CI): Doxycycline.

172 | P a g e

Active ingredient Dronedarone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Dronedarone and it active metabolite, N-debutyl dronedarone in plasma.

Bioequivalence based on (90% CI): Dronedarone.

173 | P a g e

Active ingredient Drospirenone; Ethinyl Estradiol

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Drospirenone and Ethinyl Estradiol in plasma.

Bioequivalence based on (90% CI): Drospirenone and Ethinyl Estradiol.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

174 | P a g e

Active ingredient Duloxetine Hydrochloride

Dosage form Delayed release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Duloxetine in plasma.

Bioequivalence based on (90% CI): Duloxetine.

175 | P a g e

Active ingredient Efinaconazole

Dosage form Solution; topical

Two options: In vitro or in vivo study.

1. In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

176 | P a g e

Active ingredient Elvitegravir

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Elvitegravir in plasma.

Bioequivalence based on (90% CI): Elvitegravir.

177 | P a g e

Active ingredient Emtricitabine; Tenofovir Disoproxil Fumarate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed Recommended study condition.

Analytes to measure: Emtricitabine and Tenofovir in plasma.

Bioequivalence based on (90% CI): Emtricitabine and Tenofovir.

178 | P a g e

Active ingredient Enalapril Maleate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Enalapril and active metabolite, Enalaprilat in plasma.

Bioequivalence based on (90% CI): Enalapril.

Background: Methanol and/or ethanol should not be used during sample extraction to avoid potential production of methyl ester analogue in the presence of methanol (underestimation of the parent drug), and to avoid potential for back convert of Enalaprilat to the parent drug with ethanol (overestimation of the parent drug).

179 | P a g e

Active ingredient Entecavir

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Entecavir in plasma.

Bioequivalence based on (90% CI): Entecavir.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

180 | P a g e

Active ingredient Enzalutamide

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Enzalutamide in plasma.

Bioequivalence based on (90% CI): Enzalutamide.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

181 | P a g e

Active ingredient Eperisone Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Eperisone in plasma.

Bioequivalence based on (90% CI): Eperisone.

Background: Eperisone may consider as a highly variable drug (i.e., within-subject variability ≥ 30%).

182 | P a g e

Active ingredient Eplerenone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Eplerenone in plasma.

Bioequivalence based on (90% CI): Eplerenone.

183 | P a g e

Active ingredient Erlotinib Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Erlotinib in plasma.

Bioequivalence based on (90% CI): Erlotinib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

184 | P a g e

Active ingredient Erythromycin

Dosage form Delayed release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Erythromycin in plasma.

Bioequivalence based on (90% CI): Erythromycin.

185 | P a g e

Active ingredient Erythromycin

Dosage form Gel

Acceptable comparative physicochemical characterization of the test and reference

Recommended study standard (RS) formulations of the product to establish that the test product is pharmaceutically equivalent to the RS with the identical strength.

186 | P a g e

Active ingredient Erythromycin

Dosage form Ointment; ophthalmic

In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:

Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

187 | P a g e

Active ingredient Erythromycin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Erythromycin in plasma.

Bioequivalence based on (90% CI): Erythromycin.

188 | P a g e

Active ingredient Erythromycin

Dosage form Gel; topical

Acceptable comparative physicochemical characterization of the test and reference Recommended study formulations of the product to establish that the test product is pharmaceutically equivalent to the reference product with the identical strength.

189 | P a g e

Active ingredient Erythromycin

Dosage form Solution; Topical

Waiver option:

Recommended study The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

190 | P a g e

Active ingredient Erythromycin

Dosage form Swab; Topical

Waiver option:

Recommended study The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

191 | P a g e

Active ingredient Escitalopram Oxalate

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Escitalopram in plasma.

Bioequivalence based on (90% CI): Escitalopram.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

192 | P a g e

Active ingredient Escitalopram Oxalate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Escitalopram in plasma.

Bioequivalence based on (90% CI): Escitalopram.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

193 | P a g e

Active ingredient Esomeprazole Magnesium

Dosage form Delayed release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Esomeprazole in plasma.

Bioequivalence based on (90% CI): Esomeprazole.

Background: Esomeprazole considered as a highly variable drug.

194 | P a g e

Active ingredient Esomeprazole Magnesium

Dosage form Powder for delayed release suspension

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under

fasting condition.

Recommended study And

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Esomeprazole in plasma, using an achiral assay.

Bioequivalence based on (90% CI): Esomeprazole.

Background: Esomeprazole considered as a highly variable drug.

195 | P a g e

Active ingredient Eszopiclone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Eszopiclone in plasma.

Bioequivalence based on (90% CI): Eszopiclone.

196 | P a g e

Active ingredient Ethinyl Estradiol; Cyproterone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Ethinyl Estradiol, Cyproterone and its major metabolite 15β- OH-Cyproterone in plasma.

Bioequivalence based on (90% CI): Ethinyl Estradiol and Cyproterone.

197 | P a g e

Active ingredient Ethionamide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Ethionamide in plasma.

Bioequivalence based on (90% CI): Ethionamide.

198 | P a g e

Active ingredient Etodolac

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Etodolac in plasma.

Bioequivalence based on (90% CI): Etodolac.

199 | P a g e

Active ingredient Etodolac

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Etodolac in plasma.

Bioequivalence based on (90% CI): Etodolac.

200 | P a g e

Active ingredient Etodolac

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed

condition. Recommended study

Analytes to measure: Etodolac in plasma.

Bioequivalence based on (90% CI): Etodolac.

201 | P a g e

Active ingredient Etoricoxib

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Etoricoxib in plasma.

Bioequivalence based on (90% CI): Etoricoxib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

202 | P a g e

Active ingredient Everolimus

Dosage form Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, four-period crossover in-vivo under fasting

condition.

And

Single-dose, two-treatment, replicate, four-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Everolimus in whole blood.

Bioequivalence based on (90% CI): Everolimus.

Background:  AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.  Everolimus may consider as a highly variable drug (i.e., within-subject variability ≥ 30%).  Everolimus considered as a Narrow therapeutic index (NTI) drug.

203 | P a g e

Active ingredient Exemestane

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Recommended study Analytes to measure: Exemestane in plasma.

Bioequivalence based on (90% CI): Exemestane.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

204 | P a g e

Active ingredient Ezetimibe

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Ezetimibe (unconjugated) and total ezetimibe (ezetimibe + Recommended study ezetimibe glucuronide) in plasma.

Bioequivalence based on (90% CI): Ezetimibe (unconjugated) and total ezetimibe (ezetimibe + ezetimibe glucuronide).

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

205 | P a g e

Active ingredient Febuxostat

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Febuxostat in plasma.

Bioequivalence based on (90% CI): Febuxostat.

206 | P a g e

Active ingredient Fenofibrate

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Recommended study Analytes to measure: Fenofibric acid in plasma.

Bioequivalence based on (90% CI): Fenofibric acid.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

207 | P a g e

Active ingredient Fexofenadine Hydrochloride

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Fexofenadine in plasma.

Bioequivalence based on (90% CI): Fexofenadine.

208 | P a g e

Active ingredient Fexofenadine Hydrochloride

Dosage form Orally disintegrating tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Fexofenadine in plasma.

Bioequivalence based on (90% CI): Fexofenadine.

209 | P a g e

Active ingredient Fexofenadine Hydrochloride

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Fexofenadine in plasma.

Bioequivalence based on (90% CI): Fexofenadine.

210 | P a g e

Active ingredient Fexofenadine Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Fexofenadine in plasma.

Bioequivalence based on (90% CI): Fexofenadine.

211 | P a g e

Active ingredient Finasteride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Finasteride in plasma.

Bioequivalence based on (90% CI): Finasteride.

212 | P a g e

Active ingredient Fingolimod

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Fingolimod and its active metabolite, Fingolimod-phosphate in Recommended study whole blood.

Bioequivalence based on (90% CI): Fingolimod.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

213 | P a g e

Active ingredient Fluconazole

Dosage form Capsule

Two options: Biowaiver or Bioequivalence study.

1. BCS waiver option: (for fluconazole in polymorphic forms II and III): The drug classified as BCS class I, for more information, please see “The SFDA guideline for biowaiver”.

Recommended study Or

2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Fluconazole in plasma.

Bioequivalence based on (90% CI): Fluconazole.

214 | P a g e

Active ingredient Fluconazole

Dosage form Tablet

Two options: Biowaiver or Bioequivalence study.

1. BCS waiver option: (for fluconazole in polymorphic forms II and III):

The drug classified as BCS class I, for more information, please see “The SFDA guideline for biowaiver”.

Recommended study Or

2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Fluconazole in plasma.

Bioequivalence based on (90% CI): Fluconazole.

215 | P a g e

Active ingredient Fluocinolone Acetonide

Dosage form Cream; topical

Acceptable comparative physicochemical characterization of the test and Reference Recommended study formulations of the product to establish that the test product is pharmaceutically equivalent to the reference product with the identical strength.

216 | P a g e

Active ingredient Fluorometholone Acetate

Dosage form Suspension/drops; ophthalmic

Two options: In vitro or in vivo study.

1. In vitro option:

To qualify for the in vitro approach for this drug product the following criteria should Recommended study be met:  The test and RLD formulations should be:

A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical/ microstructural characterizations.

Or

2. Bioequivalence (BE) with Clinical Endpoint Study.

217 | P a g e

Active ingredient Fosinopril Sodium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under

Recommended study fasting condition.

Analytes to measure: Metabolite fosinoprilat in plasma.

Bioequivalence based on (90% CI): Metabolite fosinoprilat.

218 | P a g e

Active ingredient Gabapentin

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Gabapentin in plasma.

Bioequivalence based on (90% CI): Gabapentin.

219 | P a g e

Active ingredient Gabapentin

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Gabapentin in plasma.

Bioequivalence based on (90% CI): Gabapentin.

220 | P a g e

Active ingredient Gabapentin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under Recommended study fasting condition.

Analytes to measure: Gabapentin in plasma.

Bioequivalence based on (90% CI): Gabapentin.

221 | P a g e

Active ingredient Gatifloxacin

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

222 | P a g e

Active ingredient Gatifloxacin

Dosage form Solution/drops; ophthalmic

Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD). In addition, the applicant should also submit data to Recommended study support comparable physicochemical properties.

An in vivo BE study with clinical endpoint is requested for a difference of more than 5% in the amount of any inactive ingredient compared to that of the RLD, or differences in comparative physicochemical characterization data.

223 | P a g e

Active ingredient Gefitinib

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Gefitinib in plasma.

Bioequivalence based on (90% CI): Gefitinib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

224 | P a g e

Active ingredient Gemifloxacin Mesylate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition Recommended study Analytes to measure: Gemifloxacin in plasma.

Bioequivalence based on (90% CI): Gemifloxacin.

225 | P a g e

Active ingredient Gentamicin Sulfate

Dosage form Cream; topical

Acceptable comparative physicochemical characterization of the test and reference listed drug (RLD) formulations for each strength of the product to establish that the Recommended study test product is a comparable Gentamicin topical cream identical in strength to the RLD.

226 | P a g e

Active ingredient Gentamicin Sulfate

Dosage form Ointment; topical

Acceptable comparative physicochemical characterization of the test and reference listed drug (RLD) formulations for each strength of the product to establish that the Recommended study test product is a comparable Gentamicin topical ointment identical in strength to the RLD.

227 | P a g e

Active ingredient Gentamicin Sulfate

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should

be met:

 The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

228 | P a g e

Active ingredient Gestodene; Ethinylestradiol

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Gestodene and Ethinylestradiol in plasma.

Bioequivalence based on (90% CI): Gestodene and Ethinylestradiol.

229 | P a g e

Active ingredient Glibenclamide (Glyburide)

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Glibenclamide in plasma. Recommended study

Bioequivalence based on (90% CI): Glibenclamide.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of 20% glucose solution in water. After dosing, 60 mL of 20% glucose solution should be given to each subject every 15 minutes for the following 4 hours.

230 | P a g e

Active ingredient Gliclazide

Dosage form Prolonged release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And

Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Gliclazide in plasma.

Bioequivalence based on (90% CI): Gliclazide.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

231 | P a g e

Active ingredient Glimepiride; Metformin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Glimepiride and Metformin in plasma. Recommended study Bioequivalence based on (90% CI): Glimepiride and Metformin.

Background: Each dose in the study should be administered with 240 mL of 20% glucose solution to minimize hypoglycemic effects. After dosing, 60 mL of 20% glucose solution should be given to each subject every 15 minutes for the following 4 hours.

232 | P a g e

Active ingredient Glimepiride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Glimepiride in plasma.

Recommended study Bioequivalence based on (90% CI): Glimepiride.

Background: Because of the potential for hypoglycemia from using a dose of 4 mg of glimepiride tablets, you should conduct the bioequivalence studies using the 1 mg dose. Each dose in the study should be administered with 240 mL of 20% glucose solution to minimize hypoglycemic effects. After dosing, 60 mL of 20% glucose solution should be given to each subject every 15 minutes for the following 4 hours.

233 | P a g e

Active ingredient Glycopyrronium Tosylate

Dosage form Cloth; topical

Waiver option:

Recommended study The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

234 | P a g e

Active ingredient Hydrochlorothiazide; Olmesartan Medoxomil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition. Recommended study Analytes to measure: Hydrochlorothiazide and Olmesartan in plasma.

Bioequivalence based on (90% CI): Hydrochlorothiazide and Olmesartan.

235 | P a g e

Active ingredient Hydrocortisone

Dosage form Cream; topical

Acceptable comparative physicochemical characterization of the test and reference listed drug (RLD) formulations for each strength of the product to establish that the Recommended study test product is a comparable Hydrocortisone topical cream identical in strength to the RLD.

236 | P a g e

Active ingredient Hydrocortisone

Dosage form Solution; topical

Waiver option: Recommended study The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

237 | P a g e

Active ingredient Hydrogen Peroxide

Dosage form Solution; topical

Waiver option: Recommended study The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

238 | P a g e

Active ingredient Hydroxychloroquine Sulfate

Dosage form Tablet

Waiver option:

For more information, please refer “The SFDA guideline for biowaiver”. Recommended study Background: Hydroxychloroquine Sulfate tablet is a Drug Efficacy Study implementation “DESI” effective drug for which there are no known or suspected bioequivalence problems.

239 | P a g e

Active ingredient Imatinib

Dosage form Tablet

1 study

Type of Study:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Or

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Imatinib in plasma.

Bioequivalence based on (90% CI): Imatinib.

240 | P a g e

Active ingredient Indapamide

Dosage form Sustained Release Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Indapamide in whole blood or plasma.

Bioequivalence based on (90% CI): Indapamide.

241 | P a g e

Active ingredient Irbesartan; Hydrochlorothiazide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Hydrochlorothiazide and Irbesartan in plasma.

Bioequivalence based on (90% CI): Hydrochlorothiazide and Irbesartan.

242 | P a g e

Active ingredient Irbesartan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Irbesartan in plasma.

Bioequivalence based on (90% CI): Irbesartan.

243 | P a g e

Active ingredient Isoniazid

Dosage form Tablet

Waiver option:

For more information, please refer “The SFDA guideline for biowaiver”. Recommended study Background: Isoniazid tablet is a Drug Efficacy Study implementation “DESI” effective drug for which there are no known or suspected bioequivalence problems.

244 | P a g e

Active ingredient Isosorbide Mononitrate

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under Fed condition.

Analytes to measure: Isosorbide mononitrate in plasma.

Bioequivalence based on (90% CI): Isosorbide Mononitrate.

245 | P a g e

Active ingredient Isotretinoin

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Isotretinoin in plasma. Recommended study Bioequivalence based on (90% CI): Isotretinoin.

Background: Isotretinoin is an endogenous substance, the plasma concentrations of isotretinoin should be corrected for baseline endogenous levels by subtracting the mean pre-dose baseline value (average of at least three pre-dose values, e.g. -10, -2, and 0 hours).

246 | P a g e

Active ingredient Ivabradine Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Ivabradine and its active metabolite, N-desmethylated derivative, in plasma.

Bioequivalence based on (90% CI): Ivabradine.

247 | P a g e

Active ingredient Ivermectin

Dosage form Lotion; topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

Or

2. Bioequivalence study with clinical endpoint.

248 | P a g e

Active ingredient Ketoconazole

Dosage form Foam aerosol; topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: A. Same active ingredient in the same concentration and dosage form as the Recommended study Reference Listed Drug (RLD) and must not have an inactive ingredient or other change in formulation from the RLD that may significantly affect systemic or local availability. B. Comparative assay of the test and reference product.

Or

2. Bioequivalence (BE) Study with Clinical Endpoint.

249 | P a g e

Active ingredient Lacosamide

Dosage form Tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Lacosamide in plasma.

Bioequivalence based on (90% CI): Lacosamide.

250 | P a g e

Active ingredient Lamotrigine

Dosage form Chewable dispersible tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Lamotrigine in plasma.

Bioequivalence based on (90% CI): Lamotrigine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

251 | P a g e

Active ingredient Lamotrigine

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Lamotrigine in plasma.

Bioequivalence based on (90% CI): Lamotrigine.

252 | P a g e

Active ingredient Lamotrigine

Dosage form Orally disintegrating tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Lamotrigine in plasma.

Bioequivalence based on (90% CI): Lamotrigine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

253 | P a g e

Active ingredient Lamotrigine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Lamotrigine in plasma.

Bioequivalence based on (90% CI): Lamotrigine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

254 | P a g e

Active ingredient Lapatinib

Dosage form Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Lapatinib in plasma.

Bioequivalence based on (90% CI): Lapatinib.

255 | P a g e

Active ingredient Latanoprost

Dosage form Solution/drops; ophthalmic

Waiver option:

A generic Latanoprost ophthalmic solution product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD). Recommended study An in vivo BE study with clinical endpoint is requested for a difference of more than 5% in the amount of any inactive ingredient compared to that of the RLD, or differences in comparative physicochemical characterization data.

256 | P a g e

Active ingredient Latanoprost

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

257 | P a g e

Active ingredient Latanoprostene Bunod

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

258 | P a g e

Active ingredient Ledipasvir; Sofosbuvir

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Ledipasvir and sofosbuvir in plasma.

Bioequivalence based on (90% CI): Ledipasvir and sofosbuvir.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

259 | P a g e

Active ingredient Leflunomide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Leflunomide’s metabolite A77 1726, in plasma.

Bioequivalence based on (90% CI): The metabolite of leflunomide, A77 1726.

Background:  AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.  Since the half-life of the metabolite A77 1726 is very long, you may consider bioequivalence studies with parallel designs.

260 | P a g e

Active ingredient Lenalidomide

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Lenalidomide in plasma.

Bioequivalence based on (90% CI): Lenalidomide.

261 | P a g e

Active ingredient Lercanidipine Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: enantiomers S- and R- in plasma Lercanidipine.

Bioequivalence based on (90% CI): Both enantiomers S- and R-Lercanidipine.

Background: Lercanidipine consider as a highly variable drug (i.e., within- subject variability ≥ 30%).

262 | P a g e

Active ingredient Letrozole

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Letrozole in plasma.

Bioequivalence based on (90% CI): Letrozole.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

263 | P a g e

Active ingredient Levetiracetam

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Levetiracetam in plasma.

Bioequivalence based on (90% CI): Levetiracetam.

264 | P a g e

Active ingredient Levetiracetam

Dosage form Tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Levetiracetam using an achiral assay.

Bioequivalence based on (90% CI): Levetiracetam.

265 | P a g e

Active ingredient Levocetirizine Dihydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Levocetirizine in plasma using an achiral assay.

Bioequivalence based on (90% CI): Levocetirizine.

266 | P a g e

Active ingredient Levodopa; Carbidopa; Entacapone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Levodopa, Carbidopa and Entacapone in plasma.

Bioequivalence based on (90% CI): Levodopa, Carbidopa and Entacapone.

Background: Entacapone may consider as a highly variable drug (i.e., within- subject variability ≥ 30%).

267 | P a g e

Active ingredient Levofloxacin

Dosage form Tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Levofloxacin in plasma, using an achiral assay.

Bioequivalence based on (90% CI): Levofloxacin.

268 | P a g e

Active ingredient Levonorgestrel

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Levonorgestrel in plasma.

Bioequivalence based on (90% CI): Levonorgestrel.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

269 | P a g e

Active ingredient Levothyroxine Sodium

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, fully replicate, four-period crossover in- vivo under fasting condition. Recommended study Analytes to measure: Levothyroxine in serum.

Bioequivalence based on (90% CI): Baseline-corrected levothyroxine.

Background: Levothyroxine considered as a Narrow therapeutic index (NTI) drug.

270 | P a g e

Active ingredient Levothyroxine Sodium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, fully replicate, four-period crossover in- vivo under fasting condition.

Recommended study Analytes to measure: Levothyroxine in serum.

Bioequivalence based on (90% CI): Baseline-corrected levothyroxine.

Background: Levothyroxine considered as a Narrow therapeutic index (NTI) drug.

271 | P a g e

Active ingredient Lidocaine

Dosage form Ointment; topical

In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

272 | P a g e

Active ingredient Lifitegrast

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should

be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

273 | P a g e

Active ingredient Linezolid

Dosage form Suspension

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”. Recommended study Or

2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Linezolid in plasma.

Bioequivalence based on (90% CI): Linezolid.

274 | P a g e

Active ingredient Linezolid

Dosage form Tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA Recommended study guideline for biowaiver”.

Or

2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Linezolid in plasma.

Bioequivalence based on (90% CI): Linezolid.

275 | P a g e

Active ingredient Lisinopril

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Lisinopril in plasma.

Bioequivalence based on (90% CI): Lisinopril.

276 | P a g e

Active ingredient Loratadine

Dosage form Capsules

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Loratadine and its metabolite descarboethoxyloratadine Recommended study (desloratadine) in plasma.

Bioequivalence based on (90% CI): Loratadine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

277 | P a g e

Active ingredient Loratadine

Dosage form Chewable tablets

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Loratadine and its metabolite descarboethoxyloratadine Recommended study (desloratadine) in plasma.

Bioequivalence based on (90% CI): Loratadine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

278 | P a g e

Active ingredient Loratadine

Dosage form Orally disintegrating tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Loratadine and its metabolite descarboethoxyloratadine Recommended study (desloratadine) in plasma.

Bioequivalence based on (90% CI): Loratadine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

279 | P a g e

Active ingredient Loratadine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Loratadine and its metabolite descarboethoxyloratadine Recommended study (desloratadine) in plasma.

Bioequivalence based on (90% CI): Loratadine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

280 | P a g e

Active ingredient Lornoxicam

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Lornoxicam in plasma.

Bioequivalence based on (90% CI): Lornoxicam.

281 | P a g e

Active ingredient Losartan Potassium; Hydrochlorothiazide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Hydrochlorothiazide, losartan, and its carboxylic metabolite in plasma.

Bioequivalence based on (90% CI): Losartan and Hydrochlorothiazide.

282 | P a g e

Active ingredient Losartan Potassium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Losartan and the metabolite carboxylic acid in plasma.

Bioequivalence based on (90% CI): Losartan.

283 | P a g e

Active ingredient Loteprednol Etabonate

Dosage form Gel; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

Or

2. Bioequivalence study with clinical endpoint.

284 | P a g e

Active ingredient Loteprednol Etabonate

Dosage form Ointment; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

Or

2. Bioequivalence study with clinical endpoint.

285 | P a g e

Active ingredient Loteprednol Etabonate

Dosage form Suspension/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

Or

2. Bioequivalence study with clinical endpoint.

286 | P a g e

Active ingredient Luliconazole

Dosage form Cream; topical

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). Recommended study B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT).

Or

2. Bioequivalence study with clinical endpoint.

287 | P a g e

Active ingredient Lurasidone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Lurasidone in plasma.

Bioequivalence based on (90% CI): Lurasidone.

288 | P a g e

Active ingredient Malathion

Dosage form Lotion; Topical

Two options: waiver or in vivo bioequivalence study.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Recommended study Reference Listed Drug (RLD).

Or

2. In vivo bioequivalence study.

289 | P a g e

Active ingredient Mebeverine Hydrochloride

Dosage form Sustained release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Desmethyl mebeverine acid, Veratric acid, Mebeverine acid and Desmethyl mebeverine alcohol.

Bioequivalence based on (90% CI): Desmethyl mebeverine acid Veratric acid.

290 | P a g e

Active ingredient Meloxicam

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Meloxicam in plasma.

Bioequivalence based on (90% CI): Meloxicam.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

291 | P a g e

Active ingredient Meloxicam

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Meloxicam in plasma.

Bioequivalence based on (90% CI): Meloxicam.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

292 | P a g e

Active ingredient Memantine Hydrochloride

Dosage form Extended release capsule

2 studies

Type of Studies: Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Memantine in plasma.

Bioequivalence based on (90% CI): Memantine.

293 | P a g e

Active ingredient Memantine Hydrochloride

Dosage form Tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please see “The SFDA

guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

Analytes to measure: Memantine in plasma.

Bioequivalence based on (90% CI): Memantine.

294 | P a g e

Active ingredient Mesalazine (Mesalamine)

Dosage form Delayed Release Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition. Analytes to measure: Mesalazine in plasma.

Bioequivalence based on (90% CI): Mesalazine.

295 | P a g e

Active ingredient Mesalazine (Mesalamine)

Dosage form Extended release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

Recommended study And

Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Mesalazine in plasma.

Bioequivalence based on (90% CI): Mesalazine.

296 | P a g e

Active ingredient Metformin; Glibenclamide (Glyburide)

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Metformin and Glyburide in plasma. Recommended study Bioequivalence based on (90% CI): Metformin and Glyburide.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

297 | P a g e

Active ingredient Metformin Hydrochloride

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

And

Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Recommended study Analytes to measure: Metformin in plasma.

Bioequivalence based on (90% CI): Metformin

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

298 | P a g e

Active ingredient Metformin Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Metformin in plasma. Recommended study Bioequivalence based on (90% CI): Metformin.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

299 | P a g e

Active ingredient Methotrexate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Methotrexate in plasma.

Bioequivalence based on (90% CI): Methotrexate.

Background: Methotrexate 2.5 mg does not exhibit linearity of pharmacokinetics.

300 | P a g e

Active ingredient Metoprolol Succinate

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Metoprolol in plasma.

Bioequivalence based on (90% CI): Metoprolol.

301 | P a g e

Active ingredient Metoprolol Tartrate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Metoprolol in plasma.

Bioequivalence based on (90% CI): Metoprolol.

302 | P a g e

Active ingredient Metronidazole

Dosage form Cream; topical

Two options: In vitro or in vivo study.

1. In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT).

Or

2. Bioequivalence study with clinical endpoint.

303 | P a g e

Active ingredient Metronidazole

Dosage form Gel; Topical

Two options: In-vitro or in-vivo study.

1. In-vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

Or

2. Bioequivalence study with clinical endpoint.

304 | P a g e

Active ingredient Metronidazole

Dosage form Lotion; topical

Two options: In-vitro or in-vivo study.

1. In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT).

Or

2. Bioequivalence study with clinical endpoint.

305 | P a g e

Active ingredient Metronidazole Benzoate

Dosage form Suspension

Two options: Biowaiver or bioequivalence study

1. BCS waiver option:

The drug classified as BCS class I, for more information, please see “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

Analytes to measure: Metronidazole in plasma.

Bioequivalence based on (90% CI): Metronidazole.

306 | P a g e

Active ingredient Metronidazole

Dosage form Tablet

Two options: Biowaiver or Bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please see “The SFDA

guideline for biowaiver “ Recommended study Or

2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

Analytes to measure: Metronidazole in plasma.

Bioequivalence based on (90% CI): Metronidazole.

307 | P a g e

Active ingredient Miglustat

Dosage form Capsule

1 study

Type of Study: Single-dose, two-way crossover in-vivo under fasting condition. Recommended study Analytes to measure: Miglustat in plasma.

Bioequivalence based on (90% CI): Miglustat.

308 | P a g e

Active ingredient Minocycline Hydrochloride

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Minocycline in plasma.

Bioequivalence based on (90% CI): Minocycline.

309 | P a g e

Active ingredient Minoxidil

Dosage form Aerosol; foam/ topical

Two options: Biowaiver or in vivo study.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

If inactive ingredients of test product differ from the RLD or are present in Recommended study significantly different amounts, the applicant must identify and characterize the differences and provide information demonstrating that the differences do not affect the safety or efficacy.

Or

2. Bioequivalence study with clinical endpoint.

310 | P a g e

Active ingredient Minoxidil

Dosage form Solution; topical

Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD). Recommended study If inactive ingredients of test product differ from the RLD or are present in significantly different amounts, the applicant must identify and characterize the differences and provide information demonstrating that the differences do not affect the safety or efficacy.

311 | P a g e

Active ingredient Mirtazapine

Dosage form Orally disintegrating tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Mirtazapine in plasma.

Bioequivalence based on (90% CI): Mirtazapine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

312 | P a g e

Active ingredient Mirtazapine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

Recommended study Analytes to measure: Mirtazapine in plasma.

Bioequivalence based on (90% CI): Mirtazapine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

313 | P a g e

Active ingredient Mometasone Furoate

Dosage form Lotion; topical

Two options: Waiver or in vivo bioequivalence study.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

If inactive ingredients of test product differ from the RLD or are present in significantly different amounts, the applicant must identify and characterize the formulation differences and provide information demonstrating that the differences do Recommended study not affect the safety or efficacy.

Or

2. In vivo option:

Type of Studies:

A. Pilot vasoconstrictor study. And B. Pivotal vasoconstrictor study.

314 | P a g e

Active ingredient Montelukast Sodium

Dosage form Chewable tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition. Recommended study Analytes to measure: Montelukast in plasma.

Bioequivalence based on (90% CI): Montelukast.

315 | P a g e

Active ingredient Montelukast Sodium

Dosage form Granules

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition. Recommended study Analytes to measure: Montelukast in plasma.

Bioequivalence based on (90% CI): Montelukast.

316 | P a g e

Active ingredient Montelukast Sodium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition. Recommended study Analytes to measure: Montelukast in plasma.

Bioequivalence based on (90% CI): Montelukast.

317 | P a g e

Active ingredient Moxifloxacin Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition. Recommended study Analytes to measure: Moxifloxacin in plasma.

Bioequivalence based on (90% CI): Moxifloxacin.

318 | P a g e

Active ingredient Moxifloxacin Hydrochloride

Dosage form Solution/drops; ophthalmic

Two options: In vitro approach or in vivo bioequivalence study.

1. In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

319 | P a g e

Active ingredient Mycophenolate Mofetil

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Mycophenolate mofetil, and the active metabolite, mycophenolic acid (MPA) in plasma.

Bioequivalence based on (90% CI): Mycophenolic acid (MPA).

320 | P a g e

Active ingredient Mycophenolate Mofetil

Dosage form Suspension

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Mycophenolate mofetil, and the active metabolite, mycophenolic acid (MPA) in plasma.

Bioequivalence based on (90% CI): mycophenolic acid (MPA).

321 | P a g e

Active ingredient Mycophenolate Mofetil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Mycophenolate mofetil, and the active metabolite, mycophenolic acid (MPA) in plasma.

Bioequivalence based on (90% CI): mycophenolic acid (MPA).

322 | P a g e

Active ingredient Naproxen; Esomeprazole

Dosage form Delayed release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

And

Recommended study Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Esomeprazole in plasma using an achiral assay, and naproxen in plasma.

Bioequivalence based on (90% CI): Naproxen and Esomeprazole.

Background: Esomeprazole considered as a highly variable drug.

323 | P a g e

Active ingredient Nepafenac

Dosage form Suspension; ophthalmic

Three options

1. In vitro studies:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be:

A. Qualitatively and quantitatively the same (Q1/Q2). Recommended study B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). Or 2. Pharmacokinetic Bioequivalence studies. Or 3. Bioequivalence study with clinical endpoint.

324 | P a g e

Active ingredient Netarsudil Dimesylate

Dosage form Solution/drops; ophthalmic

In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be:

Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

An in vivo BE study is requested for a difference of more than 5% in the amount of any inactive ingredient compared to that of the RLD, or differences in comparative physicochemical characterization data.

325 | P a g e

Active ingredient Nystatin and Triamcinolone Acetonide

Dosage form Cream; topical

Acceptable comparative physicochemical characterization of the test and reference Recommended study formulations of the product to establish that the test product is pharmaceutically equivalent to the reference product with the identical strength.

326 | P a g e

Active ingredient Nystatin and Triamcinolone Acetonide

Dosage form Ointment; topical

Acceptable comparative physicochemical characterization of the test and reference Recommended study formulations of the product to establish that the test product is pharmaceutically equivalent to the reference product with the identical strength.

327 | P a g e

Active ingredient Ofloxacin

Dosage form Solution/drops; ophthalmic

In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

An in vivo BE study is requested for a difference of more than 5% in the amount of any inactive ingredient compared to that of the RLD, or differences in comparative Physicochemical.

328 | P a g e

Active ingredient Olanzapine

Dosage form Orally disintegrating tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition.

Analytes to measure: Olanzapine in plasma. Recommended study

Bioequivalence based on (90% CI): Olanzapine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

329 | P a g e

Active ingredient Olanzapine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Olanzapine in plasma.

Bioequivalence based on (90% CI): Olanzapine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

330 | P a g e

Active ingredient Olmesartan Medoxomil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, crossover in vivo under fasting condition. Recommended study Analytes to measure: Olmesartan in plasma.

Bioequivalence based on (90% CI): Olmesartan.

331 | P a g e

Active ingredient Olopatadine Hydrochloride

Dosage form Solution/drops; ophthalmic

Two options: In vitro or in vivo bioequivalence study.

1. In vitro option: To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

332 | P a g e

Active ingredient Olopatadine hydrochloride

Dosage form Solution/drops; ophthalmic

In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

An in vivo BE study is requested for a difference of more than 5% in the amount of any inactive ingredient compared to that of the RLD, or differences in comparative physicochemical

333 | P a g e

Active ingredient Omeprazole; Sodium Bicarbonate

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Omeprazole in plasma.

Bioequivalence based on (90% CI): Omeprazole.

Background: Omeprazole considered as a highly variable drug.

334 | P a g e

Active ingredient Omeprazole

Dosage form Delayed release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

And

Recommended study Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Omeprazole in plasma.

Bioequivalence based on (90% CI): Omeprazole.

Background: Omeprazole considered as a highly variable drug.

335 | P a g e

Active ingredient Ondansetron Hydrochloride Dihydrate

Dosage form Tablet

Two options: Biowaiver or bioequivalence study

1. BCS waiver option: The drug classified as BCS class I, for more information, please see “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study: Type of Study: Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

Analytes to measure: Ondansetron in plasma.

Bioequivalence based on (90% CI): Ondansetron.

336 | P a g e

Active ingredient Orlistat

Dosage form Capsule

1 study

Type of Study: In vivo bioequivalence (BE) study with pharmacodynamic (PD) Recommended study Endpoints, Multiple-dose, 3-way crossover consisting of two doses of reference product and at least one dose of the test product. The product should be administered as per the reference product labeling.

337 | P a g e

Active ingredient Ornidazole

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Ornidazole in plasma.

Bioequivalence based on (90% CI): Ornidazole.

338 | P a g e

Active ingredient Oseltamivir Phosphate

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Oseltamivir and its metabolite, oseltamivir carboxylate in plasma.

Bioequivalence based on (90% CI): Oseltamivir.

339 | P a g e

Active ingredient Oxcarbazepine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Oxcarbazepine and active metabolite 10-monohydroxy derivative (MHD) in plasma.

Bioequivalence based on (90% CI): Oxcarbazepine.

340 | P a g e

Active ingredient Ozenoxacin

Dosage form Cream; topical

Two options: In vitro or in vivo study.

1. In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be:

Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT).

Or

2. Bioequivalence study with clinical endpoint.

341 | P a g e

Active ingredient Palbociclib

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Recommended study Analytes to measure: Palbociclib in plasma.

Bioequivalence based on (90% CI): Palbociclib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

342 | P a g e

Active ingredient Pantoprazole Sodium

Dosage form Delayed release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

And

Recommended study Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Pantoprazole in plasma.

Bioequivalence based on (90% CI): Pantoprazole.

Background: Pantoprazole considered as a highly variable drug.

343 | P a g e

Active ingredient Paroxetine Hydrochloride

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Paroxetine in plasma.

Bioequivalence based on (90% CI): Paroxetine.

344 | P a g e

Active ingredient Paroxetine Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Paroxetine in plasma.

Bioequivalence based on (90% CI): Paroxetine.

345 | P a g e

Active ingredient Pazopanib Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Pazopanib in plasma. Recommended study Bioequivalence based on (90% CI): Pazopanib.

Background: - AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”. - For drugs with a less than proportional increase in AUC with increasing dose over the therapeutic dose range, bioequivalence should in most cases be established both at the highest strength and at the lowest strength (or a strength in the linear range), i.e. in this situation, two bioequivalence studies are needed.

346 | P a g e

Active ingredient Penciclovir

Dosage form Cream; topical

In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT).

347 | P a g e

Active ingredient Perindopril Arginine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Perindopril and the active metabolite, perindoprilat in plasma.

Bioequivalence based on (90% CI): Perindopril.

348 | P a g e

Active ingredient Perindopril Erbumine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Perindopril and the active metabolite, perindoprilat in plasma.

Bioequivalence based on (90% CI): Perindopril.

349 | P a g e

Active ingredient Pilocarpine Hydrochloride

Dosage form Solution; ophthalmic

Two options: Waiver or in vivo bioequivalence study.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Recommended study Reference Listed Drug (RLD).

Or

2. In vivo bioequivalence study.

350 | P a g e

Active ingredient Pioglitazon Hydrochloride; Metformine Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Pioglitazone and its active metabolite M-IV and Metformin in Recommended study plasma.

Bioequivalence based on (90% CI): Pioglitazone and Metformin.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

351 | P a g e

Active ingredient Pioglitazon Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Pioglitazone and active metabolite M-IV in plasma.

Bioequivalence based on (90% CI): Pioglitazone.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

352 | P a g e

Active ingredient Pitavastatin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Pitavastatin in plasma.

Bioequivalence based on (90% CI): Pitavastatin.

353 | P a g e

Active ingredient Podofilox

Dosage form Solution; topical

Two options: Waiver or bioequivalence study with clinical endpoint.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

Recommended study If inactive ingredients of test product differ from the RLD or are present in significantly different amounts, the applicant must identify and characterize the formulation differences and provide information demonstrating that the differences do not affect the safety or efficacy.

Or

2. Bioequivalence study with clinical endpoint.

354 | P a g e

Active ingredient Prasugrel Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Metabolite R-138727 and metabolite R-95913 in plasma.

Bioequivalence based on (90% CI): Metabolite R-138727 and metabolite R-95913 in plasma.

Background: Active metabolite (R-138727) is not stable in aqueous solution and plasma. Provide detailed information for sample collection, processing, stabilization, and validation of analysis.

355 | P a g e

Active ingredient Prednisolone Acetate

Dosage form Suspension; ophthalmic drops

Two options: In vitro or in vivo bioequivalence study with pharmacokinetic (PK) endpoints.

1. In vitro option: To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

Or

2. In vivo bioequivalence study with pharmacokinetic (PK) endpoints.

356 | P a g e

Active ingredient Prednisolone

Dosage form Effervescent tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option: The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Prednisolone in plasma.

Bioequivalence based on (90% CI): Prednisolone.

357 | P a g e

Active ingredient Pregabalin

Dosage form Tablet

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Pregabalin in plasma.

Bioequivalence based on (90% CI): Pregabalin.

358 | P a g e

Active ingredient Quetiapine Fumarate

Dosage form Extended release tablets

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in vivo under fed condition.

Analytes to measure: Quetiapine in plasma.

Bioequivalence based on (90% CI): Quetiapine.

359 | P a g e

Active ingredient Quetiapine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Quetiapine in plasma.

Bioequivalence based on (90% CI): Quetiapine.

360 | P a g e

Active ingredient Rabeprazole Sodium

Dosage form Delayed release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Rabeprazole in plasma.

Bioequivalence based on (90% CI): Rabeprazole.

Background: Rabeprazole considered as a highly variable drug.

361 | P a g e

Active ingredient Ramipril; Hydrochlorothiazide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Ramipril and its metabolite, ramiprilat and Hydrochlorothiazide in plasma. Recommended study

Bioequivalence based on (90% CI): Ramipril and Hydrochlorothiazide.

Background: If ramipril can be reliably measured, a confidence interval approach for bioequivalence determination should be used for ramipril. If ramipril cannot be reliably measured, a confidence interval approach for bioequivalence determination should be used for ramiprilat.

362 | P a g e

Active ingredient Ramipril

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Ramipril and the metabolite, ramiprilat in plasma.

Bioequivalence based on (90% CI): Ramipril.

Background: If ramipril can be reliably measured, a confidence interval approach for bioequivalence determination should be used for ramipril. If ramipril cannot be reliably measured, a confidence interval approach for bioequivalence determination should be used for ramiprilat.

363 | P a g e

Active ingredient Ramipril

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Ramipril and the metabolite, ramiprilat in plasma. Recommended study Bioequivalence based on (90% CI): Ramipril.

Background: If ramipril can be reliably measured, a confidence interval approach for bioequivalence determination should be used for ramipril. If ramipril cannot be reliably measured, a confidence interval approach for bioequivalence determination should be used for ramiprilat.

364 | P a g e

Active ingredient Repaglenide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Repaglenide in plasma.

Bioequivalence based on (90% CI): Repaglenide.

Background: To avoid hypoglycemic episodes in healthy volunteers, the drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 min for up to 4 hours after dosing.

365 | P a g e

Active ingredient Ribavirin

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Ribavirin in plasma.

Bioequivalence based on (90% CI): Ribavirin.

366 | P a g e

Active ingredient Ribavirin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Ribavirin in plasma.

Bioequivalence based on (90% CI): Ribavirin.

367 | P a g e

Active ingredient Rilpivirine Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Recommended study Analytes to measure: Rilpivirine in plasma.

Bioequivalence based on (90% CI): Rilpivirine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

368 | P a g e

Active ingredient Risperidone

Dosage form Orally disintegrating tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Risperidone in plasma.

Bioequivalence based on (90% CI): Risperidone.

369 | P a g e

Active ingredient Risperidone

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Risperidone in plasma.

Bioequivalence based on (90% CI): Risperidone.

370 | P a g e

Active ingredient Rivaroxaban

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed/fasting condition. (refer to the below information)

Recommended study Analytes to measure: Rivaroxaban in plasma.

Bioequivalence based on (90% CI): Rivaroxaban.

Background: Since there is a different food effect resulting in different food recommendations for the lower (2.5 and 10 mg) and the higher (15 and 20 mg) strengths, fasting study should be conducted for the lower strengths, and fed study for the higher strengths.

371 | P a g e

Active ingredient Rivastigmine Tartrate

Dosage form Capsule

Two options: BCS waiver or Bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

OR Recommended study

2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Rivastigmine in plasma.

Bioequivalence based on (90% CI): Rivastigmine.

372 | P a g e

Active ingredient Roflumilast

Dosage form Tablet

1 study

Type of Study: Single-dose, two-way, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Roflumilast in plasma.

Bioequivalence based on (90% CI): Roflumilast.

373 | P a g e

Active ingredient Rosuvastatin Calcium

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Rosuvastatin in plasma.

Bioequivalence based on (90% CI): Rosuvastatin.

374 | P a g e

Active ingredient Sertraline Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Sertraline in plasma.

Bioequivalence based on (90% CI): Sertraline.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

375 | P a g e

Active ingredient Sevelamer Carbonate

Dosage form Tablet

Two in vitro studies

Type of Studies:

In vitro equilibrium binding study with and without acid pre-treatment at pH 4 and pH 7.

And Recommended study In vitro kinetic binding study with and without acid pre-treatment at pH 4 and pH 7.

Analytes to measure: Unbound phosphate in filtrate (to calculate phosphate bound to resin)

Bioequivalence based on (90% CI): The Langmuir binding constant k2 from the equilibrium binding study.

376 | P a g e

Active ingredient Sildenafil Citrate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Sildenafil and active metabolite, piperazine N- desmethylsildenafil in plasma.

Bioequivalence based on (90% CI): Sildenafil.

377 | P a g e

Active ingredient Silodosin

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Silodosin and its active metabolite, glucouronide conjugate Recommended study (KMD-3213G).

Bioequivalence based on (90% CI): Silodosin.

Background: - Due to safety concerns, the study should be performed using the 4 mg strength. - Subjects should be closely monitored for hypotension.

378 | P a g e

Active ingredient Silver Sulfadiazine

Dosage form Cream; topical

In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

379 | P a g e

Active ingredient Simvastatin

Dosage form Orally disintegrating tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Simvastatin and its beta-hydroxyacid metabolite in plasma.

Bioequivalence based on (90% CI): Simvastatin.

380 | P a g e

Active ingredient Simvastatin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Simvastatin and its beta-hydroxyacid metabolite in plasma.

Bioequivalence based on (90% CI): Simvastatin.

381 | P a g e

Active ingredient Sirolimus

Dosage form Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, full replicate, four-period crossover in-vivo under fasting condition.

And

Single-dose, two-treatment, full replicate, four-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Sirolimus in whole blood.

Bioequivalence based on (90% CI): Sirolimus.

Background: - Sirolimus considered as a Narrow therapeutic index (NTI) drug. - For tablets, dose proportionality has been demonstrated between 2 mg and 5 mg doses. 0.5 mg tablets are not strictly bioequivalent with the higher strengths in

terms of Cmax.

382 | P a g e

Active ingredient Sitagliptin Phosphate; Metformin Hydrochloride

Dosage form Extended release tablets

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Sitagliptin and metformin in plasma.

Bioequivalence based on (90% CI): Sitagliptin and metformin.

Background: The drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 minutes for up to 4 hours after dosing.

383 | P a g e

Active ingredient Sitagliptin Phosphate; Metformin Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Sitagliptin and metformin in plasma. Recommended study

Bioequivalence based on (90% CI): Sitagliptin and metformin.

Background: The drug products should be administered with 240 mL of a 20% glucose solution in water, followed by 60 mL of the glucose solution administered every 15 minutes for up to 4 hours after dosing.

384 | P a g e

Active ingredient Sofosbuvir

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Sofosbuvir in plasma.

Bioequivalence based on (90% CI): Sofosbuvir.

385 | P a g e

Active ingredient Solifenacin Succinate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period, two-way crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Solifenacin in plasma.

Bioequivalence based on (90% CI): Solifenacin.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

386 | P a g e

Active ingredient Sorafenib Tosylate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Sorafenib in plasma.

Bioequivalence based on (90% CI): Sorafenib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

387 | P a g e

Active ingredient Spinosad

Dosage form Suspension; topical

Two options: In vitro or in vivo bioequivalence study with clinical endpoint.

1. In vitro option:

To qualify for the in vitro approach for this drug product the following criteria should be met: Recommended study  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization.

Or

2. Bioequivalence study with clinical endpoint.

388 | P a g e

Active ingredient Sumatriptan Succinate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study Analytes to measure: Sumatriptan in plasma.

Bioequivalence based on (90% CI): Sumatriptan.

389 | P a g e

Active ingredient Sunitinib Malate

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Sunitinib in plasma.

Bioequivalence based on (90% CI): Sunitinib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

390 | P a g e

Active ingredient Tacrolimus

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

Analytes to measure: Tacrolimus in whole blood. Recommended study Bioequivalence based on (90% CI): Tacrolimus.

Background: - AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”. - Tacrolimus considered as a Narrow therapeutic index (NTI) drug.

391 | P a g e

Active ingredient Tacrolimus

Dosage form Extended release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

And

Recommended study Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fed condition.

Analytes to measure: Tacrolimus in whole blood.

Bioequivalence based on (90% CI): Tacrolimus.

Background: Tacrolimus considered as a Narrow therapeutic index (NTI) drug.

392 | P a g e

Active ingredient Tacrolimus

Dosage form Ointment; topical

Two options: In vitro or in vivo bioequivalence study with clinical endpoint.

1. In vitro option:

To qualify for the in vitro option for this drug product the following criteria should be met:  The test and RLD formulations should be: A. Qualitatively and quantitatively the same (Q1/Q2). Recommended study B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT). D. Acceptable in vitro permeation test (IVPT).

Or

2. Bioequivalence study with clinical endpoint.

393 | P a g e

Active ingredient Tadalafil

Dosage form Tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And

Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Tadalafil in plasma.

Bioequivalence based on (90% CI): Tadalafil.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

394 | P a g e

Active ingredient Tamsulosin Hydrochloride

Dosage form Controlled release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Tamsulosin in plasma.

Bioequivalence based on (90% CI): Tamsulosin.

395 | P a g e

Active ingredient Tamsulosin Hydrochloride; Dutasteride

Dosage form Capsule

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Dutasteride and tamsulosin in plasma.

Bioequivalence based on (90% CI): Dutasteride and tamsulosin.

396 | P a g e

Active ingredient Tavaborole

Dosage form Solution; topical

Two options: Waiver or bioequivalence study with clinical endpoint.

1. Waiver option:

The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the

Reference Listed Drug (RLD).

If inactive ingredients of test product differ from the RLD or are present in Recommended study significantly different amounts, the applicant must identify and characterize the formulation differences and provide information demonstrating that the differences do not affect the safety or efficacy.

Or

2. Bioequivalence study with clinical endpoint.

397 | P a g e

Active ingredient Telithromycin

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Telithromycin in plasma.

Bioequivalence based on (90% CI): Telithromycin.

398 | P a g e

Active ingredient Telmisartan; Amlodipine Besylate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

Analytes to measure: Telmisartan and Amlodipine in plasma. Recommended study Bioequivalence based on (90% CI): Telmisartan and Amlodipine.

Background: - AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”. - Telmisartan considered as a highly variable drug.

399 | P a g e

Active ingredient Telmisartan; Hydrochlorothiazide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

Analytes to measure: Telmisartan and Hydrochlorothiazide in plasma.

Recommended study Bioequivalence based on (90% CI): Telmisartan and Hydrochlorothiazide.

Background: - AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”. - Telmisartan considered as a highly variable drug.

400 | P a g e

Active ingredient Telmisartan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, replicate, three or four-period crossover in-vivo under fasting condition.

Analytes to measure: Telmisartan in plasma. Recommended study

Bioequivalence based on (90% CI): Telmisartan.

Background: - AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”. - Telmisartan considered as a highly variable drug.

401 | P a g e

Active ingredient Temozolomide

Dosage form Capsule

Two options: Biowaiver or bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Temozolomide in plasma.

Bioequivalence based on (90% CI): Temozolomide.

402 | P a g e

Active ingredient Tenofovir Disoproxil Fumarate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Tenofovir in serum.

Bioequivalence based on (90% CI): Tenofovir.

403 | P a g e

Active ingredient Terbinafine

Dosage form Cream; topical

1 study Recommended study Type of Study: Bioequivalence study with clinical endpoint.

404 | P a g e

Active ingredient Terbinafine

Dosage form Granules

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Terbinafine in plasma.

Bioequivalence based on (90% CI): Terbinafine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

405 | P a g e

Active ingredient Terbinafine

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Terbinafine in plasma.

Bioequivalence based on (90% CI): Terbinafine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

406 | P a g e

Active ingredient Testosterone

Dosage form Solution; metered/ transdermal

Waiver option:

To qualify for a waiver of the in vivo bioequivalence study requirement, generic product should: A. Be a solution for application to the skin.

Recommended study B. Contain the active drug ingredient, testosterone, in the same concentration and dosage form as the Reference Listed Drug (RLD).

C. Contain no differing inactive ingredient or other change in formulation from the RLD that may significantly affect absorption of the active drug ingredient or active moiety.

407 | P a g e

Active ingredient Ticagrelor

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Ticagrelor and its active metabolite in plasma.

Bioequivalence based on (90% CI): Ticagrelor.

408 | P a g e

Active ingredient Timolol Maleate

Dosage form Solution; ophthalmic drops

Two options: Waiver or in vivo bioequivalence study.

1. Waiver option:  The test product should be qualitatively (Q1) and quantitatively (Q2) the same Recommended study as the Reference Listed Drug (RLD).  Acceptable comparative physicochemical characterization.

Or

2. In vivo bioequivalence study with clinical endpoints.

409 | P a g e

Active ingredient Tizanidine

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Tizanidine in plasma.

Bioequivalence based on (90% CI): Tizanidine.

410 | P a g e

Active ingredient Tizanidine Hydrochloride

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Tizanidine in plasma.

Bioequivalence based on (90% CI): Tizanidine.

411 | P a g e

Active ingredient Tobramycin

Dosage form Ointment; ophthalmic

In vitro approach:

To qualify for the in vitro approach for this drug product the following criteria should be met:  The test and RLD formulations should be: Recommended study A. Qualitatively and quantitatively the same (Q1/Q2). B. Acceptable comparative physicochemical characterization. C. Acceptable in vitro release test (IVRT).

412 | P a g e

Active ingredient Topiramate

Dosage form Extended release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Topiramate in plasma.

Bioequivalence based on (90% CI): Topiramate.

413 | P a g e

Active ingredient Topiramate

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Topiramate in plasma.

Bioequivalence based on (90% CI): Topiramate.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

414 | P a g e

Active ingredient Torsemide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Torsemide in plasma.

Bioequivalence based on (90% CI): Torsemide.

415 | P a g e

Active ingredient Tramadol

Dosage form Extended release capsule

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure (in appropriate biological fluid): Tramadol in plasma.

Bioequivalence based on (90% CI): Tramadol.

416 | P a g e

Active ingredient Tramadol

Dosage form Extended release tablet

2 studies

Type of Studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure (in appropriate biological fluid): Tramadol in plasma.

Bioequivalence based on (90% CI): Tramadol.

417 | P a g e

Active ingredient Tramadol

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting conditions. Recommended study

Analytes to measure (in appropriate biological fluid): Tramadol in plasma.

Bioequivalence based on (90% CI): Tramadol.

418 | P a g e

Active ingredient Tranexamic Acid

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Tranexamic Acid in plasma.

Bioequivalence based on (90% CI): Tranexamic Acid.

419 | P a g e

Active ingredient Tretinoin

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition

Recommended study Analytes to measure: Tretinoin in plasma.

Bioequivalence based on (90% CI): Tretinoin.

Background: Baseline concentrations of tretinoin should be measured. (3 samples taken before the drug products are administered).

420 | P a g e

Active ingredient Tretinoin

Dosage form Cream

1 study

Type of Study: Randomized, double blind, parallel, placebo controlled, in vivo Bioequivalence (BE) with Clinical Endpoint Study. Recommended study

Analytes to measure: Not Applicable.

Bioequivalence based on (90% CI): Clinical endpoint.

421 | P a g e

Active ingredient Tretinoin

Dosage form Gel

1 study

Type of Study: Randomized, double blind, parallel, placebo controlled, in vivo Bioequivalence (BE) with Clinical Endpoint Study. Recommended study

Analytes to measure: Not Applicable.

Bioequivalence based on (90% CI): Clinical endpoint.

422 | P a g e

Active ingredient Tretinoin

Dosage form Solution; topical

1 study

Type of Study: Randomized, double blind, parallel, placebo controlled, in vivo Bioequivalence (BE) with Clinical Endpoint Study. Recommended study

Analytes to measure: Not Applicable.

Bioequivalence based on (90% CI): Clinical endpoint (in vivo option).

423 | P a g e

Active ingredient Tretinoin

Dosage form Solution; Topical

Two options: Waiver or bioequivalence study with clinical endpoint.

1. Waiver option: The test product should be qualitatively (Q1) and quantitatively (Q2) the same as the Reference Listed Drug (RLD).

If inactive ingredients of test product differ from the RLD or are present in Recommended study significantly different amounts, the applicant must identify and characterize the formulation differences and provide information demonstrating that the differences do not affect the safety or efficacy.

Or

2. Bioequivalence study with clinical endpoint.

424 | P a g e

Active ingredient Triamcinolone Acetonide

Dosage form Cream; topical

Acceptable comparative physicochemical characterization of the test and reference listed drug (RLD) formulations for each strength of the product to establish that the Recommended study test product is a comparable triamcinolone acetonide topical cream identical in strength to the RLD.

425 | P a g e

Active ingredient Triamcinolone Acetonide

Dosage form Lotion; topical

Acceptable comparative physicochemical characterization of the test and reference listed drug (RLD) formulations for each strength of the product to establish that the Recommended study test product is a comparable triamcinolone acetonide topical cream identical in strength to the RLD.

426 | P a g e

Active ingredient Triamcinolone Acetonide

Dosage form Ointment; topical

Acceptable comparative physicochemical characterization of the test and reference Recommended study standard (RS) formulations of the product to establish that the test product is pharmaceutically equivalent to the RS with the identical strength.

427 | P a g e

Active ingredient Trimetazidine Dihydrochloride

Dosage form Extended release tablet

2 studies

Type of studies:

Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

And Recommended study Single-dose, two-treatment, two-period crossover in-vivo under fed condition.

Analytes to measure: Trimetazidine in plasma.

Bioequivalence based on (90% CI): Trimetazidine.

428 | P a g e

Active ingredient Valganciclovir

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study Analytes to measure: Valganciclovir and ganciclovir in plasma.

Bioequivalence based on (90% CI): Valganciclovir.

429 | P a g e

Active ingredient Amlodipine; Hydrochlorothiazide; Valsartan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Amlodipine, Hydrochlorothiazide and Valsartan in plasma.

Bioequivalence based on(90%CI): Amlodipine, Hydrochlorothiazide and Valsartan.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

430 | P a g e

Active ingredient Hydrochlorothiazide; Valsartan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Hydrochlorothiazide and Valsartan in plasma.

Bioequivalence based on (90% CI): Hydrochlorothiazide and Valsartan.

431 | P a g e

Active ingredient Valsartan

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Valsartan in plasma.

Bioequivalence based on (90% CI): Valsartan.

432 | P a g e

Active ingredient Vandetanib

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover or parallel in-vivo under fasting condition.

Recommended study Analytes to measure: Vandetanib in plasma.

Bioequivalence based on (90% CI): Vandetanib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

433 | P a g e

Active ingredient Varenicline Tartrate

Dosage form Tablet

Two options: Biowaiver or Bioequivalence study.

1. BCS waiver option:

The drug classified as BCS class I, for more information, please refer to “The SFDA guideline for biowaiver”.

Or Recommended study 2. Bioequivalence study:

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Analytes to measure: Varenicline in plasma.

Bioequivalence based on (90% CI): Varenicline.

434 | P a g e

Active ingredient Vemurafenib

Dosage form Tablet

1 study

Type of Study: Multiple-dose, two-treatment, two-period crossover in-vivo under fed condition. Recommended study

Analytes to measure: Vemurafenib in plasma.

Bioequivalence based on (90% CI): Vemurafenib.

435 | P a g e

Active ingredient Verdenafil

Dosage form Orally disintegrating tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Vardenafil in plasma.

Bioequivalence based on (90% CI): Vardenafil.

Background: The drug should be placed on the tongue where it will disintegrate. The drug should be administered without water.

436 | P a g e

Active ingredient Verdinafil

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition. Recommended study

Analytes to measure: Vardenafil in plasma.

Bioequivalence based on (90% CI): Vardenafil.

437 | P a g e

Active ingredient Vismodegib

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Vismodegib (total) in plasma.

Bioequivalence based on (90% CI): Vismodegib.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

438 | P a g e

Active ingredient Vortioxetine Hydrobromide

Dosage form Tablet

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Vortioxetine in plasma.

Bioequivalence based on (90% CI): Vortioxetine.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

439 | P a g e

Zonisamide Active ingredient

Dosage form Capsule

1 study

Type of Study: Single-dose, two-treatment, two-period crossover in-vivo under fasting condition.

Recommended study Analytes to measure: Zonisamide in serum.

Bioequivalence based on (90% CI): Zonisamide.

Background: AUC truncated at 72 h could be used and accepted according to “The GCC Guidelines for Bioequivalence”.

440 | P a g e