Literature data are reviewed regarding the scientific advisability of allowing a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing either diclofenac potassium and diclofenac sodium. Within the biopharmaceutics classification system (BCS), diclofenac potassium and diclofenac sodium are each BCS class II active pharmaceutical ingredients (APIs). However, a biowaiver can be recommended for IR drug products of each salt form, due to their therapeutic use, therapeutic index, pharmacokinetic properties, potential for excipient interactions, and performance in reported BE/bioavailability (BA) studies, provided: (a) test and comparator contain the same diclofenac salt; (b) the dosage form of the test and comparator is identical; (c) the test product contains only excipients present in diclofenac drug products approved in ICH or associated countries in the same dosage form, for instance as presented in this paper; (d) test drug product and comparator dissolve 85% in 30 min or less in 900 mL buffer pH 6.8, using the paddle apparatus at 75 rpm or the basket apparatus at 100 rpm; and (e) test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8.

Background Ritonavir (RTV) tablets were not available in Thailand until they were manufactured by the Government Pharmaceutical Organization of Thailand. We assessed pharmacokinetics (PK), safety and efficacy of generic RTV-boosted atazanavir (ATV) in virologically suppressed HIV-1-infected Thai adults. Methods Virologically suppressed HIV-1-infected Thai adults who currently use ATV (either 200 or 300 mg) with Norvir® soft gel capsule (SGC) 100-mg-based regimen were enrolled into this prospective, 48-week single-arm study. Participants switched from Norvir® SGC to generic RTV. Plasma trough concentration (C) was assessed at trough baseline before switching to generic RTV and week 24 in all participants, with the target ATV C of 0.15 mg/l. trough Plasma HIV-1 RNA and other laboratory safety parameters were assessed until week 48. Results Of 100 participants (51% male) enrolled, 50% was using ATV 200 mg and 50% was using 300 mg at the time RTV SGC were changed into generic tablets. All participants used two nucleoside reverse transcriptase inhibitors (NRTIs) as backbone. There were no significant changes in mean (sd) Ctrough of RTV (0.20 [0.33] versus 0.23 [0.39]; P=0.21) and ATV (0.83 [0.93] versus 0.88 [0.95]; P=0.62) between baseline and week 24. From entry to week 48, median alanine aminotransferase significantly increased from 25 to 30 IU/l (P=0.001) and total bilirubin significantly decreased from 1.7 to 1.3 (P=0.04). One study drug related grade 3 adverse event was reported. All but one participant maintained plasma HIV-1 RNA <50 copies/ml after 48 weeks. Conclusions Generic RTV-boosted ATV showed adequate levels, good tolerability and great efficacy after 48 weeks.

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