BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements
Open accessAbstract
The Biopharmaceutics Classification System (BCS), based on aqueous solubility and intestinal permeability, has enjoyed wide use since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies. In 2000, the US-FDA was the first regulatory agency to publish guidance for industry describing how to meet criteria for requesting a waiver of in vivo bioavailability and bioequivalence studies for highly soluble, highly permeable (BCS Class I) drugs. Subsequently, the World Health Organization (WHO) and European Medicines Agency (EMA) published guidelines recommending how to obtain BCS biowaivers for BCS Class III drugs (high solubility, low permeability), in addition to Class I drugs. In 2015, the US-FDA became better harmonized with the EMA and WHO following publication of two guidances for industry outlining criteria for obtaining BCS biowaivers for both Class I and Class III drugs. A detailed review and comparison of the BCS Class I and Class III criteria currently recommended by the US-FDA, EMA, and WHO revealed good convergence of the three agencies with respect to BCS biowaiver criteria. The comparison also suggested that, by applying the most conservative of the three jurisdictional approaches, it should be possible for a sponsor to design the same set of BCS biowaiver studies in preparing a submission for worldwide filing to satisfy US, European, and emerging market regulators. It is hoped that the availability of BCS Class I and Class III biowaivers in multiple jurisdictions will encourage more sponsors to request waivers of in vivo bioavailability/bioequivalence testing using the BCS approach.
AI snapshot
Written from the paper’s full text.
TL;DR
This mini-review compares BCS biowaiver requirements from the US-FDA, EMA, and WHO and finds that the three agencies have largely converged, especially after the US-FDA’s 2015 draft guidances extended biowaivers to BCS Class III drugs. It concludes that sponsors can likely design one set of BCS biowaiver studies for worldwide filing by following the most conservative criteria across jurisdictions.
Key findings
- All three agencies now consider BCS Class I and Class III immediate-release solid oral dosage forms for biowaivers; the US-FDA first allowed Class I in 2000, while EMA and WHO later included Class III, and the US-FDA expanded to Class III in May 2015.
- Common positions include a high-permeability threshold of human Fa ≥85%, solubility in 250 mL or less across pH 1–6.8 at 37°C ± 1°C, and dissolution of ≥85% in 30 minutes for Class I and 15 minutes for Class III.
- Differences remain: the US-FDA uses the highest strength for solubility while EMA and WHO use the highest single therapeutic dose; the US-FDA accepts animal and in vitro permeability methods as pivotal for passively absorbed drugs while EMA and WHO treat them as supportive; and the US-FDA uses 500 mL dissolution volume versus 900 mL or less for EMA and WHO.
- From 2000 to 2015, US-FDA BCS biowaiver requests averaged about two per year, and Japan has not implemented the BCS biowaiver approach.
Methods
- The authors compared publicly available regulatory guideline criteria for BCS-based biowaivers from the US-FDA (2015 draft guidances), EMA, and WHO; agencies were selected based on a 2014 AAPS Regulatory Sciences Open Forum.
- Table I compares attributes and criteria across the three agencies and adds a column suggesting studies or conditions that could satisfy all three jurisdictions.
- The work is a narrative and tabular comparison of guidance documents, with no primary experimental data or new empirical analysis.
Limitations
- The paper does not include a formal limitations section; it acknowledges remaining dissimilarities among jurisdictions and notes that Japan has not implemented BCS biowaivers.
- Evident from the text: the comparison relies on public guidance documents and a summary table rather than on empirical submission data or regulatory outcomes.
- Evident from the text: the proposed single global filing strategy depends on applying the most conservative criteria and is not prospectively tested in the paper.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
12 of 46 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured
- Premisecitation
In 2000, the US-FDA was the first regulatory agency to publish guidance for industry describing criteria for requesting a waiver of in vivo bioavailability and bioequivalence studies for highly soluble, highly permeable (BCS Class I) drugs.
“In 2000, the US-FDA was the first regulatory agency to publish guidance for industry describing how to meet criteria for requesting a waiver of in vivo bioavailability and bioequivalence studies for highly soluble, highly permeable (BCS Class I) drugs.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [6] Shah VP, Amidon GL, Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability, Pharm Res 12, 413-420, 1995 – backstory of BCS. AAPS J. 2014;16:894–8. doi: 10.1208/s12248-014-9620-9 . source
The Introduction says the FDA published its final BCS guidance in August 2000, and WHO GUIDANCE says the FDA guidance provided biowaivers for highly soluble, highly permeable Class I products. BCS GUIDANCE describes the dissolution criteria, but the paper does not establish that the FDA was the first regulatory agency to publish such guidance; it says only that this was the first guidance with “waiver” in its title. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [11] Cook J. Impact of discordance among regulations for biopharmaceutics classification system based waivers of clinical bioequivalence studies. Dissolution Technol. 2015;22:6–10. source
The Abstract describes FDA guidance for highly soluble, highly permeable immediate-release products, and References entry 2 dates the FDA’s BCS-based waiver guidance to 2000. However, the Introduction explicitly says the FDA published the first such regulatory guidance in 2005. The paper therefore supports the guidance’s purpose but gives conflicting dates for the claim’s key year. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
Ability to waive in vivo BE requirements using the BCS biowaiver approach can be pivotal to a successful regulatory submission.
“Ability to waive in vivo BE requirements using the BCS biowaiver approach can be pivotal to a successful regulatory submission, because demonstrating that two drug formulations/products are bioequivalent is an essential drug approval requirement for both innovator and generic drug products (7).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [7] Amidon KS, Langguth P, Lennernäs H, Yu L, Amidon GL. Bioequivalence of oral products and the biopharmaceutics classification system: science, regulation, and public policy. Clin Pharmacol Ther. 2011;90:467–70. doi: 10.1038/clpt.2011.109 . source
- Premisecitation
Demonstrating that two drug formulations/products are bioequivalent is an essential drug approval requirement for both innovator and generic drug products.
“Ability to waive in vivo BE requirements using the BCS biowaiver approach can be pivotal to a successful regulatory submission, because demonstrating that two drug formulations/products are bioequivalent is an essential drug approval requirement for both innovator and generic drug products (7).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [7] Amidon KS, Langguth P, Lennernäs H, Yu L, Amidon GL. Bioequivalence of oral products and the biopharmaceutics classification system: science, regulation, and public policy. Clin Pharmacol Ther. 2011;90:467–70. doi: 10.1038/clpt.2011.109 . source
- Premisecitation
The WHO presently grants biowaivers for only Class I and Class III drugs.
“Initially, the WHO also considered granting biowaivers for some drugs of weak acids in Class II (13) but presently grants biowaivers for only Class I and Class III drugs.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [13] Kanfer I. AAPS open forum report: proposals for regulatory harmonization of a global BCS framework: challenges and opportunities. Dissolution Technol. 2015;22:58–65. source
- Premisecitation
The BCS is now widely established in the academic, industrial, and regulatory world for waiving the regulatory requirements of conducting comparative bioavailability studies to demonstrate in vivo BA/BE of immediate-release solid oral dosage forms containing BCS Class I and Class III drugs.
“Thus, the BCS is now widely established in the academic, industrial, and regulatory world for waiving the regulatory requirements of conducting comparative bioavailability studies to demonstrate in vivo BA/BE of immediate-release (IR) solid oral dosage forms containing BCS Class I and Class III drugs (5,6).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [5] Chen ML, Amidon GL, Benet LZ, Lennernäs H, The YLX, BCS. BDDCS, and regulatory guidances. Pharm Res. 2011;28:1774–8. doi: 10.1007/s11095-011-0438-1 . source
- cites [6] Shah VP, Amidon GL, Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability, Pharm Res 12, 413-420, 1995 – backstory of BCS. AAPS J. 2014;16:894–8. doi: 10.1208/s12248-014-9620-9 . source
The BCS GUIDANCE section says dissolution studies may establish bioequivalence for eligible Class I immediate-release oral products. WHO GUIDANCE says very rapidly dissolving Class III products can also be eligible for biowaivers, but it does not establish that waivers for both classes are already widely adopted across academic, industrial, and regulatory settings. The paper also notes that regulatory acceptance and harmonization will take time. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Interpretationcitation
The low rate of BCS-biowaiver submissions from 2000 to 2015 may have been due in part to these differences.
“The low rate of BCS-biowaiver submissions from 2000 to 2015 may have been due in part to these differences (11); for example, from 2000 to 2015, the number of BCS biowaiver requests submitted to the US-FDA averaged approximately two per year (Mehta M. Applicability of BCS-Based Biowaiver: Requirements and Conditions -US-FDA Perspective.European Federation for Pharmaceutical Sciences Global Bioequ”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [11] Cook J. Impact of discordance among regulations for biopharmaceutics classification system based waivers of clinical bioequivalence studies. Dissolution Technol. 2015;22:6–10. source
The Conclusions (page not available) say that differences among agency guidances may partly explain the currently low rate of biowaiver submissions. The paper does not establish that this explanation applies specifically to the stated 2000–2015 period. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Premisecitation
Initially, the WHO considered granting biowaivers for some drugs of weak acids in Class II.
“Initially, the WHO also considered granting biowaivers for some drugs of weak acids in Class II (13) but presently grants biowaivers for only Class I and Class III drugs.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [13] Kanfer I. AAPS open forum report: proposals for regulatory harmonization of a global BCS framework: challenges and opportunities. Dissolution Technol. 2015;22:58–65. source
- Findingown data
A detailed review and comparison of the BCS Class I and Class III criteria currently recommended by the US-FDA, EMA, and WHO revealed good convergence of the three agencies with respect to BCS biowaiver criteria.
“A detailed review and comparison of the BCS Class I and Class III criteria currently recommended by the US-FDA, EMA, and WHO revealed good convergence of the three agencies with respect to BCS biowaiver criteria.”
Quote in the paperSubstantial claim - Findingreasoning
There remain some notable differences among the US-FDA, EMA, and WHO BCS biowaiver approaches.
“There remain some notable differences among these three jurisdictions.”
Quote in the paperSubstantial claim - Findingnone given
The US-FDA, EMA, and WHO presently show good convergence with respect to the types of studies and documentation needed to establish that a drug is Class I or Class III.
“The US-FDA, EMA, and WHO presently show good convergence with respect to the types of studies and documentation needed to establish that a drug is Class I or Class III.”
Quote in the paperSubstantial claim - Findingreasoning
Aspects of the US-FDA BCS biowaiver approach until the 2015 posting of the Draft Guidance contrasted dramatically with the approaches of the EMA and WHO.
“Aspects of the US-FDA BCS biowaiver approach until the 2015 posting of the Draft Guidance contrasted dramatically with the approaches of the EMA and WHO.”
Quote in the paperSubstantial claim - Findingnone given
The present BCS biowaiver approaches of the US-FDA, EMA, and WHO are in reasonably good agreement with respect to BCS Classes and IR dosage forms for which biowaivers are considered, definition of high in vivo permeability, and definition of highly soluble drug substance.
“Thus, the present BCS biowaiver approaches of the US-FDA, EMA, and WHO are in reasonably good agreement with respect to BCS Classes and IR dosage forms for which biowaivers are considered, definition of high in vivo permeability, and definition of highly soluble drug substance.”
Quote in the paperSubstantial claim - Findingcitation
From 2000 to 2015, the number of BCS biowaiver requests submitted to the US-FDA averaged approximately two per year.
“The low rate of BCS-biowaiver submissions from 2000 to 2015 may have been due in part to these differences (11); for example, from 2000 to 2015, the number of BCS biowaiver requests submitted to the US-FDA averaged approximately two per year (Mehta M. Applicability of BCS-Based Biowaiver: Requirements and Conditions -US-FDA Perspective.European Federation for Pharmaceutical Sciences Global Bioequ”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Mehta M. Applicability of BCS-Based Biowaiver: Requirements and Conditions -US-FDA Perspective.European Federation for Pharmaceutical Sciences Global Bioequivalenc e Harmonisation Initiative.Amsterdam, 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Findingnone given
The US-FDA still differs somewhat from the EMA and WHO with respect to criteria considered necessary to show high solubility, high permeability, and rapid dissolution, the latter to be performed in a smaller volume, 500 mL, compared to the EMA and WHO requirements which specify a volume of 900 mL.
“The US-FDA still differs somewhat from the other two jurisdictions with respect to criteria considered necessary to show high solubility, high permeability, and rapid dissolution, the latter to be performed in a smaller volume, 500 mL, compared to the EMA and WHO requirements which specify a volume of 900 mL.”
Quote in the paperNot a substantial claim - Premisereasoning
In 2015, the US-FDA became better harmonized with the EMA and WHO following publication of two guidances for industry outlining criteria for obtaining BCS biowaivers for both Class I and Class III drugs.
“In 2015, the US-FDA became better harmonized with the EMA and WHO following publication of two guidances for industry outlining criteria for obtaining BCS biowaivers for both Class I and Class III drugs.”
- Also stated in: § DISCUSSION · plain
“With the posting of the Draft BCS Guidance in May 2015 and a Draft Dissolution Guidance in July 2015, the US-FDA moved into better convergence with the EMA and WHO with respect to the criteria necessary for granting a BCSbased biowaiver”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [15] US Food and Drug Administration. Draft guidance for industry, dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS class 1 and class 3 drugs. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM456594.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § DISCUSSION · plain
- Interpretationreasoning
By applying the most conservative of the three jurisdictional approaches, it should be possible for a sponsor to design the same set of BCS biowaiver studies in preparing a submission for worldwide filing to satisfy US, European, and emerging market regulators.
“The comparison also suggested that, by applying the most conservative of the three jurisdictional approaches, it should be possible for a sponsor to design the same set of BCS biowaiver studies in preparing a submission for worldwide filing to satisfy US, European, and emerging market regulators.”
- Also stated in: § CONCLUSION · hedged
“Nonetheless, these differences are such that, by applying the most conservative of the three jurisdictional approaches, it should be possible for a sponsor to design the same set of BCS biowaiver studies in preparing a submission for worldwide filing to satisfy US, European, and emerging market regulators.”
Quote in the paperSubstantial claim- Rests on an assumption: Presently, many emerging markets are implementing the BCS biowaiver approach based on jurisdiction-specific guidelines or the WHO guidelines.
- Also stated in: § CONCLUSION · hedged
- Premisecitation
The two key factors governing drug absorption are aqueous solubility and intestinal permeability.
“Another premise underlying the development of the BCS is the recognition that the two key factors governing drug absorption are aqueous solubility and intestinal permeability (5).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Chen ML, Amidon GL, Benet LZ, Lennernäs H, The YLX, BCS. BDDCS, and regulatory guidances. Pharm Res. 2011;28:1774–8. doi: 10.1007/s11095-011-0438-1 . source
- Premisecitation
WHO and EMA subsequently published guidelines recommending how to obtain BCS biowaivers for BCS Class III drugs in addition to Class I drugs.
“Subsequently, the World Health Organization (WHO) and European Medicines Agency (EMA) published guidelines recommending how to obtain BCS biowaivers for BCS Class III drugs (high solubility, low permeability), in addition to Class I drugs.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [9] European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP), guideline on the investigation of bioequivalence. 2010. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [10] World Health Organization. WHO technical report series, No. 992 annex 7. Multisource (Generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. 2015. http://apps.who.int/medicinedocs/documents/s21898en/s21898en.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Regulatory agencies have long recognized that, for some drug products, in vivo BA/BE may be self-evident and can waive the requirement for in vivo evidence in certain circumstances.
“Regulatory agencies have long recognized that, for some drug products, in vivo BA/BE may be self-evident and, as such, can waive the requirement for in vivo evidence (3) in certain circumstances (to grant a biowaiver).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] US Food and Drug Administration. Title 21 code of federal regulations part 320 bioavailability and bioequivalence requirements. 2015. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=320 . Accessed 3 Dec 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
During the period from 2000 until 2015, to support granting a BCS biowaiver of a Class I drug, the US-FDA considered in vivo evidence of high permeability to be in vivo Fa ≥90%.
“Notably, during the period from 2000 until 2015, to support granting a BCS biowaiver of a Class I drug, the US-FDA expected to see solubility determinations over the pH range of 1.0 to 7.5, considered in vivo evidence of high permeability to be in vivo Fa ≥90%, and would only accept in vitro dissolution testing via USP Apparatus 1 at 100 rpm or USP Apparatus 2 at 50 rpm (no exceptions).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning
In any regulatory situation where BE studies are deemed necessary for an IR solid oral dosage form, the potential exists for a BCS-based biowaiver, provided that the appropriate BCS designation criteria are met.
“Thus, in any of these regulatory situations where BE studies are deemed necessary for an IR solid oral dosage form, the potential exists for a BCS-based biowaiver, provided that the appropriate BCS designation criteria are met.”
Quote in the paperSubstantial claim- Rests on an assumption: In new drug development, BE is used to link the commercialized, to-be-marketed formulation and the clinical-scale formulation that underwent Phase III safety and efficacy testing.
- Rests on an assumption: BE evidence is required when commercialized drug products (whether new or generic) undergo certain types of scale-up or postapproval changes.
- Premisecitation
During the period from 2000 until 2015, to support granting a BCS biowaiver of a Class I drug, the US-FDA expected to see solubility determinations over the pH range of 1.0 to 7.5.
“Notably, during the period from 2000 until 2015, to support granting a BCS biowaiver of a Class I drug, the US-FDA expected to see solubility determinations over the pH range of 1.0 to 7.5, considered in vivo evidence of high permeability to be in vivo Fa ≥90%, and would only accept in vitro dissolution testing via USP Apparatus 1 at 100 rpm or USP Apparatus 2 at 50 rpm (no exceptions).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
During the period from 2000 until 2015, to support granting a BCS biowaiver of a Class I drug, the US-FDA would only accept in vitro dissolution testing via USP Apparatus 1 at 100 rpm or USP Apparatus 2 at 50 rpm (no exceptions).
“Notably, during the period from 2000 until 2015, to support granting a BCS biowaiver of a Class I drug, the US-FDA expected to see solubility determinations over the pH range of 1.0 to 7.5, considered in vivo evidence of high permeability to be in vivo Fa ≥90%, and would only accept in vitro dissolution testing via USP Apparatus 1 at 100 rpm or USP Apparatus 2 at 50 rpm (no exceptions).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
The EMA and US-FDA publish individual BE or product-specific guidances advocating the use of BCS biowaivers.
“The EMA and US-FDA publish individual BE or product-specific guidances advocating the use of BCS biowaivers (16,17), and the International Pharmaceutical Federation (FIP) has published 44 monographs on the subject (18).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [16] European Medicines Agency. EMA/CHMP/736403/2014 Rev 2, compilation of individual product-specific guidance on demonstration of bioequivalence. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2015/07/WC500189274.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [17] U.S. Food and Drug Administration. Guidance for industry, bioequivalence recommendations for specific products. 2010. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072872.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning
The dissimilarities among major regulatory jurisdictions present a challenge for innovator and generic companies that seek to utilize a BCS biowaiver approach for global registration of a drug product.
“However, although great advances have been made recently in harmonizing some aspects of BCS biowaiver implementation among major regulatory jurisdictions, there remain a number of dissimilarities among them (notably, in Japan, the BCS biowaiver has not been implemented at all), presenting a challenge for innovator and generic companies that seek to utilize a BCS biowaiver approach for global”
Quote in the paperSubstantial claim- Rests on an assumption: In Japan, the BCS biowaiver has not been implemented at all.
- Interpretationreasoning
The BCS is well established as a valid approach for waiving the requirements for in vivo BA and BE studies of Class I and Class III IR solid oral dosage forms in both new and generic drug development.
“The BCS is well established as a valid approach for waiving the requirements for in vivo BA and BE studies of Class I and Class III IR solid oral dosage forms in both new and generic drug development.”
Quote in the paperSubstantial claim - Premisecitation
In May 2015, the US-FDA revised its BCS Guidance to expand the biowaiver provision to Class III drugs.
“In May 2015, the US-FDA revised its BCS Guidance to expand the biowaiver provision to Class III drugs (14).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- May combine two claims. 8
- Classified as probably not a substantial claim. 17
May combine two claims.
PremisecitationThe Biopharmaceutics Classification System (BCS) is based on aqueous solubility and intestinal permeability and has been widely used since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies.
“The Biopharmaceutics Classification System (BCS), based on aqueous solubility and intestinal permeability, has enjoyed wide use since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [4] Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–20. source
- cites [5] Chen ML, Amidon GL, Benet LZ, Lennernäs H, The YLX, BCS. BDDCS, and regulatory guidances. Pharm Res. 2011;28:1774–8. doi: 10.1007/s11095-011-0438-1 . source
- cites [6] Shah VP, Amidon GL, Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability, Pharm Res 12, 413-420, 1995 – backstory of BCS. AAPS J. 2014;16:894–8. doi: 10.1208/s12248-014-9620-9 . source
The BCS Guidance section (page unavailable) defines BCS by aqueous solubility and intestinal permeability and describes biowaivers for eligible products. The copy identifies the original BCS publication as dating to 1995 but cites FDA biowaiver guidance from 2000; it does not establish that BCS was widely used to waive in vivo studies since 1995. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSimultaneous filings to multiple regulatory agencies are common within both the innovator and generic pharmaceutical industries.
“As a result, simultaneous filings to multiple regulatory agencies are common within both the innovator and generic pharmaceutical industries (2).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [2] Handoo S, Arora V, Khera D, Nandi PK, Sahu SK. A comprehensive study on regulatory requirements for development and filing of generic drugs globally. Int J Pharm Investig. 2012;2:99–105. doi: 10.4103/2230-973X.104392 . source
The Abstract says companies seek to submit a drug for approval in multiple countries, but that differing requirements make simultaneous submission challenging. The 'Filing a Generic Drug Application' section discusses agencies in various countries. Neither passage establishes that simultaneous filings are common, particularly in both the innovator and generic industries. (LLM, conf=0.83)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationThe first regulatory guidances encouraging the use of the BCS for biowaivers of Class I immediate-release solid oral dosage forms were issued by the US-FDA in 2000 and by the EMA in 2001.
“The first regulatory guidances encouraging the use of the BCS for biowaivers of Class I immediate-release (IR) solid oral dosage forms were issued by the US Food and Drug Administration (US-FDA) in 2000 (6,11) and by the European Medicines Agency (EMA) in 2001 (12).”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [6] Shah VP, Amidon GL, Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability, Pharm Res 12, 413-420, 1995 – backstory of BCS. AAPS J. 2014;16:894–8. doi: 10.1208/s12248-014-9620-9 . source
- cites [11] Cook J. Impact of discordance among regulations for biopharmaceutics classification system based waivers of clinical bioequivalence studies. Dissolution Technol. 2015;22:6–10. source
The References list the FDA’s BCS-based guidance for immediate-release solid oral dosage forms as issued in 2000. However, the Introduction says the FDA first published that guidance in 2005, and the copy does not give 2001 as the date of the EMA’s first guidance; its cited EMA guideline is dated 2010. The source therefore does not support the full chronology claimed. (LLM, conf=0.83)
Experimental — accuracy not yet measured - cites [12] European Medicines Agency. Guideline on the investigation of bioequivalence 20 Doc. Ref.: CPMP/EWP/QWP/1401/98 s.l.: Committee for Medicinal Products for Human Use (CHMP). 2001.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Findingnone givenWith respect to establishing high permeability, the US-FDA will consider in vivo and in situ animal models and in vitro methods, such as those using cultured monolayers of animal or human epithelial cells-for passively absorbed drugs only-as pivotal methods, whereas the EMA and WHO consider these methods to be supportive only.
“With respect to establishing high permeability, the US-FDA will consider in vivo and in situ animal models and in vitro methods, such as those using cultured monolayers of animal or human epithelial cells-for passively absorbed drugs only-as pivotal methods, whereas the EMA and WHO consider these methods to be supportive only.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenWith respect to establishing rapid or very rapid dissolution, the US-FDA now requests that dissolution testing use a volume of 500 mL, whereas the EMA and WHO request using the typical compendial volume of 900 mL or less.
“With respect to establishing rapid or very rapid dissolution, the US-FDA now requests that dissolution testing use a volume of 500 mL, whereas the EMA and WHO request using the [typical] compendial volume of 900 mL or less.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Findingnone givenWith respect to establishing high solubility, the US-FDA appears to have the most stringent recommendations for which pH values to test.
“With respect to establishing high solubility, the US-FDA appears to have the most stringent recommendations for which pH values to test.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenThe US-FDA asks that the highest strength be used for establishing high solubility, whereas the EMA and WHO ask that the highest therapeutic dose be used.
“By contrast, the US-FDA asks that the highest strength be used for establishing high solubility, whereas the EMA and WHO ask that the highest therapeutic dose be used.”
Quote in the paperSubstantial claimMay combine two claims.
Findingnone givenAlthough great advances have been made recently in harmonizing some aspects of BCS biowaiver implementation among major regulatory jurisdictions, there remain a number of dissimilarities among them.
“However, although great advances have been made recently in harmonizing some aspects of BCS biowaiver implementation among major regulatory jurisdictions, there remain a number of dissimilarities among them (notably, in Japan, the BCS biowaiver has not been implemented at all), presenting a challenge for innovator and generic companies that seek to utilize a BCS biowaiver approach for global”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
PremisecitationAccess and affordability to medicines for all patients can be facilitated by global pharmaceutical development programs.
“Ideally, access and affordability to medicines for all patients can be facilitated by global pharmaceutical development programs (1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] Liberti L, Breckenridge A, Eichler HG, Peterson R, McAuslane N, Walker S. Expediting patients’ access to medicines by improving the predictability of drug development and the regulatory approval process. Clin Pharmacol Ther. 2010;87:27–31. doi: 10.1038/clpt.2009.179 . source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationApplication of the BCS in waiving BA/BE requirements is based on premises that if two immediate-release drug formulations/products behave as oral solutions within the GI tract due to high solubility and rapid dissolution, no precipitation occurs in the GI tract once the API is dissolved, and the two IR formulations have the same in vivo dissolution profile under all intestinal luminal conditions,则
“Application of the BCS in waiving BA/BE requirements is based on premises that if (1) two immediate-release (IR) drug formulations/products behave as oral solutions within the GI tract due to high solubility and rapid dissolution, (ii) no precipitation occurs in the GI tract once the API is dissolved, and (iii) the two IR formulations have the same in vivo dissolution profile under all intestinal”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–20. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationFor stability and quality controls dissolution testing of Class I and III drugs, the US-FDA presently recommends that applicants use 500 mL of 0.01 M HCl aqueous media.
“By contrast, for stability and quality controls dissolution testing of Class I and III drugs, the US-FDA presently recommends that applicants use 500 mL of 0.01 M HCl aqueous media, USP Apparatus I at 100 rpm or USP Apparatus II at 75 rpm, a single point dissolution specification of Q = 80% in 30 min for BCS Class I drugs, and a single point dissolution specification of Q = 80% in 15 min for BCS”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] US Food and Drug Administration. Draft guidance for industry, dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS class 1 and class 3 drugs. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM456594.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe US-FDA now recommends that, for drug products in both BCS Class I and III, USP disintegration testing can be used in lieu of the dissolution test if the product is shown to meet a dissolution specification of Q = 80% in 15 min.
“In addition, the US-FDA now recommends that, for drug products in both BCS Class I and III, USP disintegration testing can be used in lieu of the dissolution test if the product is shown to meet a dissolution specification of Q = 80% in 15 min.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] US Food and Drug Administration. Draft guidance for industry, dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS class 1 and class 3 drugs. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM456594.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn July 2015, the US-FDA posted a new draft Guidance for Industry which provided recommendations for in vitro dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS Class I and Class III drugs.
“Subsequently, in July 2015, the US-FDA posted a new draft Guidance for Industry which provided recommendations for in vitro dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS Class I and Class III drugs (15).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] US Food and Drug Administration. Draft guidance for industry, dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS class 1 and class 3 drugs. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM456594.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe International Pharmaceutical Federation (FIP) has published 44 monographs on BCS biowaivers.
“The EMA and US-FDA publish individual BE or product-specific guidances advocating the use of BCS biowaivers (16,17), and the International Pharmaceutical Federation (FIP) has published 44 monographs on the subject (18).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] International Pharmaceutical Federation (FIP). Biowaiver monographs. 2015. http://www.fip.org/bcs_monographs . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe two different draft guidances distinguish between dissolution testing to establish BCS Class versus dissolution testing that, together with chemistry, manufacturing, and controls (CMC) data, characterizes the quality and performance of the drug product to be marketed.
“The two different draft guidances distinguish between dissolution testing to establish BCS Class versus dissolution testing that, together with chemistry, manufacturing, and controls (CMC) data, characterizes the quality and performance of the drug product to be marketed (20,21).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [20] U.S. Food and Drug Administration. Guidance for industry, dissolution testing of immediate release solid oral dosage forms. 1997. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070237.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [21] United States Pharmacopeia. <1092> The dissolution procedure: development and validation. USP 36. Rockville: USP; 2015, p. 735.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTo establish BCS Class I or III, the US FDA presently recommends that applicants use a media volume of 500 mL.
“Thus, to establish BCS Class I or III, the US FDA presently recommends that applicants use the following: media of three pH values as noted in Table I; media volume of 500 mL: USP Apparatus I at 100 rpm or USP Apparatus II at 50 rpm or 75 rpm when justified; appropriate sampling times for dissolution profile generation; and statistical methods for comparing dissolution profiles.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationFor stability and quality controls dissolution testing of Class I and III drugs, the US-FDA presently recommends that applicants use USP Apparatus I at 100 rpm or USP Apparatus II at 75 rpm.
“By contrast, for stability and quality controls dissolution testing of Class I and III drugs, the US-FDA presently recommends that applicants use 500 mL of 0.01 M HCl aqueous media, USP Apparatus I at 100 rpm or USP Apparatus II at 75 rpm, a single point dissolution specification of Q = 80% in 30 min for BCS Class I drugs, and a single point dissolution specification of Q = 80% in 15 min for BCS”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] US Food and Drug Administration. Draft guidance for industry, dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS class 1 and class 3 drugs. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM456594.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
PremisecitationUntil the posting of the 2015 Draft BCS Guidance, the US-FDA would only grant biowaivers for Class I pharmaceutically equivalent IR oral dosage forms and would not consider biowaivers for Class III IR drug products.
“Until the posting of the 2015 Draft BCS Guidance, the US-FDA would only grant biowaivers for Class I pharmaceutically equivalent IR oral dosage forms and would not consider biowaivers for Class III IR drug products.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTo establish BCS Class I or III, the US FDA presently recommends that applicants use media of three pH values as noted in Table I.
“Thus, to establish BCS Class I or III, the US FDA presently recommends that applicants use the following: media of three pH values as noted in Table I; media volume of 500 mL: USP Apparatus I at 100 rpm or USP Apparatus II at 50 rpm or 75 rpm when justified; appropriate sampling times for dissolution profile generation; and statistical methods for comparing dissolution profiles.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTo establish BCS Class I or III, the US FDA presently recommends that applicants use USP Apparatus I at 100 rpm or USP Apparatus II at 50 rpm or 75 rpm when justified.
“Thus, to establish BCS Class I or III, the US FDA presently recommends that applicants use the following: media of three pH values as noted in Table I; media volume of 500 mL: USP Apparatus I at 100 rpm or USP Apparatus II at 50 rpm or 75 rpm when justified; appropriate sampling times for dissolution profile generation; and statistical methods for comparing dissolution profiles.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationFor stability and quality controls dissolution testing of Class I and III drugs, the US-FDA presently recommends a single point dissolution specification of Q = 80% in 30 min for BCS Class I drugs.
“By contrast, for stability and quality controls dissolution testing of Class I and III drugs, the US-FDA presently recommends that applicants use 500 mL of 0.01 M HCl aqueous media, USP Apparatus I at 100 rpm or USP Apparatus II at 75 rpm, a single point dissolution specification of Q = 80% in 30 min for BCS Class I drugs, and a single point dissolution specification of Q = 80% in 15 min for BCS”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] US Food and Drug Administration. Draft guidance for industry, dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS class 1 and class 3 drugs. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM456594.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationFor stability and quality controls dissolution testing of Class I and III drugs, the US-FDA presently recommends a single point dissolution specification of Q = 80% in 15 min for BCS Class III drugs.
“By contrast, for stability and quality controls dissolution testing of Class I and III drugs, the US-FDA presently recommends that applicants use 500 mL of 0.01 M HCl aqueous media, USP Apparatus I at 100 rpm or USP Apparatus II at 75 rpm, a single point dissolution specification of Q = 80% in 30 min for BCS Class I drugs, and a single point dissolution specification of Q = 80% in 15 min for BCS”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] US Food and Drug Administration. Draft guidance for industry, dissolution testing and specification criteria for immediate-release solid oral dosage forms containing BCS class 1 and class 3 drugs. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM456594.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTo establish BCS Class I or III, the US FDA presently recommends that applicants use statistical methods for comparing dissolution profiles.
“Thus, to establish BCS Class I or III, the US FDA presently recommends that applicants use the following: media of three pH values as noted in Table I; media volume of 500 mL: USP Apparatus I at 100 rpm or USP Apparatus II at 50 rpm or 75 rpm when justified; appropriate sampling times for dissolution profile generation; and statistical methods for comparing dissolution profiles.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTo establish BCS Class I or III, the US FDA presently recommends that applicants use appropriate sampling times for dissolution profile generation.
“Thus, to establish BCS Class I or III, the US FDA presently recommends that applicants use the following: media of three pH values as noted in Table I; media volume of 500 mL: USP Apparatus I at 100 rpm or USP Apparatus II at 50 rpm or 75 rpm when justified; appropriate sampling times for dissolution profile generation; and statistical methods for comparing dissolution profiles.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] US Food and Drug Administration. Draft guidance for industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system. 2015. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf . Accessed 3 Dec 2015.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
The paper relies on this without support.
Worldwide drug marketing approvals may be delayed due to region-specific regulatory requirements or dissimilar regulatory review outcomes from agencies of different jurisdictions.
“Although, in theory, simultaneous dossier submissions can greatly streamline the drug approval process, in practice, worldwide drug marketing approvals may be delayed due to region-specific regulatory requirements or dissimilar regulatory review outcomes from agencies of different jurisdictions.”
The paper relies on this without support.
In new drug development, BE is used to link the commercialized, to-be-marketed formulation and the clinical-scale formulation that underwent Phase III safety and efficacy testing.
“In new drug development, BE is used to link the commercialized, to-bemarketed formulation and the clinical-scale formulation that underwent Phase III safety and efficacy testing.”
The paper relies on this without support.
BE evidence is required when commercialized drug products (whether new or generic) undergo certain types of scale-up or postapproval changes.
“BE evidence is also required when commercialized drug products (whether new or generic) undergo certain types of scale-up or postapproval changes.”
The paper relies on this without support.
Presently, many emerging markets are implementing the BCS biowaiver approach based on jurisdiction-specific guidelines or the WHO guidelines.
“Presently, many emerging markets are implementing the BCS biowaiver approach based on jurisdiction-specific guidelines or the WHO guidelines.”
The paper relies on this without support.
In Japan, the BCS biowaiver has not been implemented at all.
“(notably, in Japan, the BCS biowaiver has not been implemented at all)”
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- Authors
- Davit, B. M., Kanfer, I., Tsang, Y. C., & Cardot, J.-M.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Rhodes University (ZA)
- Apotex (Canada) (CA)
- Université Clermont Auvergne (FR)
- Corresponding author
- Davit, Barbara M.
- Venue
- The AAPS Journal
- Published
- 2016-03-04
- Volume
- 18
- Issue
- 3
- Pages
- 612-618
- ISSN
- 1550-7416 (ISSN-L)
- PMC
- PMC5256598
- OpenAlex
- W2291667458
- Cited by
- 92
- References
- 10
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 7 · 2023: 7 · 2022: 12 · 2021: 15 · 2020: 9 · 2019: 6 · 2018: 12 · 2017: 7 · 2016: 3
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- Locations
- The AAPS Journal (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Physical Sciences › Chemistry › Spectroscopy › Analytical Chemistry and Chromatography
- Keywords
- Biopharmaceutics Classification System, bioequivalence, bioavailability, regulatory guidelines, regulatory harmonization, EMA, FDA, World Health Organization
- MeSH terms
- Animals, Biological Availability, Biopharmaceutics, Pharmaceutical Preparations, Europe, Humans, Solubility, Therapeutic Equivalency
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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