Switching medication products during the treatment of psychiatric illness

Figures & data

Table 1. Bioequivalence study parameters in Canada, United States, and Europe.

Comparative assessment of study parameters^a
Parameter	Canada	United States	Europe
Study design	Nonreplicated, randomized, crossover	Nonreplicated, randomized, crossover	Nonreplicated, randomized, crossover
Fasting/fed	Fasting	Fasting and fed	Fasting
Volunteers	>80% power of acceptance criteria	Sufficient to achieve adequate power	>12 (min 80% power of acceptance criteria)
Study dose	Made by manufacturer	Made by manufacturer	Made by manufacturer
Test Reference	Canadian reference product	Reference listed drug in USA	European reference product
Sampling points	12–18 samples per subject/dose	12–18 samples (more collected at Tmax to be continued up to 3+ half-lives	At least 2 samples before expected Tmax, 3–4 terminal log-linear phase
Analytical method validation parameters	Accuracy	Accuracy	Accuracy
	LOQ	Calibration curve	Detection
	Precision	LLOQ	Limit of quantitation
	Recovery	Precision	Intermediate precision specificity
	Specificity	Reproducibility	Linearity range
	Stability	Selectivity	Precision
	Standard curves	Sensitivity	Repeatability
		Stability
Moieties to be measured in plasma	Active drug	Active drug	Active drug
	Metabolites if applicable	Metabolites if applicable	Metabolites if applicable
PK parameters	Cmax	Cmax	Cmax
	Tmax	Tmax	Tmax
	AUC0-t and AUC0-∞	AUC0-t and AUC0-∞	AUC0-t and AUC0-∞
	t1/2	t1/2	t1/2
	γz	γz	γz
Criteria for bioequivalence	90% CI 80%–125% for Cmax, AUC0-t, AUC0-∞	90% CI 80%–125% for Cmax, AUC0-t, AUC0-∞	90% CI 80%–125% for Cmax, AUC0-t, AUC0-∞ (for highly variable drugs 75%–133%)
GCP requirements	ICH GCP guidelines	ICH GCP guidelines	ICH GCP guidelines

Data from Nation & Sansom, 1994; Borgheini 2003; Galgatte, Jamdade, and Aute, & Chaudhari, 2013. Reprinted from Galgatte et al., 2014.

AUC_0-t: denotes area under the plasma concentration-time curve from time zero to the last measurable concentration; AUC_0-∞: denotes area under the concentration curve from zero to infinity; C_max: denotes maximum serum concentration; GCP: denotes good clinical practice; ICH: denotes International Council for Harmonisation; LOQ: denotes limit of quantitation; LLOQ: denotes lower limit of quantitation; T_max: denotes time to reach maximal concentration; t_1/2: denotes terminal elimination half-life; γz: denotes terminal or elimination rate constant.

^aAll follow International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, with some minor variation.

Nation, R. L., & Sansom, L. N. (1994). Bioequivalence requirements for generic products. Pharmacology Therapeutics, 62, 41–55. doi:10.1016/0163-7258(94)90004-3

 PubMed Web of Science ®Google Scholar

Borgheini, G. (2003). The bioequivalence and therapeutic efficacy of generic versus brand-name psychoactive drugs. Clinical Therapeutics, 25, 1578–1592. doi:10.1016/S0149-2918(03)80157-1

 PubMed Web of Science ®Google Scholar

Galgatte, U. C., Jamdade, V. R., Aute, P. P., & Chaudhari, P. D. (2013). Study on requirements of bioequivalence for registration of pharmaceutical products in India, South-Africa and Australia. American Journal of PharmTech Research, 3, 289–305.

 Google Scholar

Galgatte, U. C., Jamdade, V. R., Aute, P. P., & Chaudhari, P. D. (2014). Study on requirements of bioequivalence for registration of pharmaceutical products in USA, Europe and Canada. Saudi Pharmaceutical Journal, 22, 391–402. doi:10.1016/j.jsps.2013.05.001

 PubMed Web of Science ®Google Scholar