jag009
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NJ,
2024-07-17 22:29
(109 d 00:53 ago)

Posting: # 24080
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 Brazil, Mexico: Proc GLM or Proc Mixed? [Regulatives / Guidelines]

Hi everyone,

A dumb question... Does anyone know if Brazil or Mexico accepts bioequivalence study with statistics based on Proc GLM or Proc Mixed?

Thx
J


Edit: Category changed and subject line changed. [Helmut]
Helmut
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Vienna, Austria,
2024-07-18 11:01
(108 d 12:21 ago)

@ jag009
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 Brazil, Mexico: Proc GLM?

Hi John,

❝ Does anyone know if Brazil or Mexico accepts bioequivalence study with statistics based on Proc GLM or Proc Mixed?


Not knowing, only guessing…
  • Brazil accepts for HVD(P)s reference-scaling by Average Bioequivalence with Expanding Limits (ABEL)1 like the EMA2 and the WHO.3 That means a model with all effects fixed (ANOVA).4 In SAS-lingo that’s Proc GLM. By analogy – though not stated in the guideline – also for ABE.
  • Mexico accepts widening the limits in case of high with-subject variability. No details about the statistical method (also about ABE) are given in the guideline of 2013.5 No idea whether a more recent guideline exists.


  1. ANVISA. Dispõe sobre os critérios para a condução de estudos de biodisponibilidade relativa/bioequivalência (BD / BE) e estudos farmacocinéticos. Brasilia. 17 August 2022. Online [Portuguese].
  2. EMA. Guideline on the Investigation of Bioequivalence. London. 20 January 2010. Online.
  3. WHO. Essential Medicines and Health Products. Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. WHO Technical Report Series, No. 1003, Annex 6. Geneva. 28 April 2017. Online.
  4. EMA. Clinical pharmacology and pharmacokinetics: questions and answers. 3.1 Which statistical method for the analysis of a bioequivalence study does the Agency recommend? London. 21 September 2016. Online.
  5. Secretario del Salud. NORMA Oficial Mexicana NOM-177-SSA1-2013, Que establece las pruebas y procedimientos para demostrar que un medicamento es intercambiable. 20 September 2013. Web Archive 18 November 2017 [Spanish].

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Ohlbe
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France,
2024-07-18 11:40
(108 d 11:41 ago)

@ Helmut
Posting: # 24082
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 Mexico: new guideline

Dear John and Helmut,

❝ Mexico accepts widening the limits in case of high with-subject variability. No details about the statistical method (also about ABE) are given in the guideline of 2013.5 No idea whether a more recent guideline exists.


I found one from January 2023. Refers to RSABE in the text, to the EMA guideline in the bibliography.

Regards
Ohlbe
Helmut
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2024-07-18 12:42
(108 d 10:40 ago)

@ Ohlbe
Posting: # 24083
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 Mexico: ABEL

Dear Ohlbe,

❝ I found one from January 2023. Refers to RSABE in the text, to the EMA guideline in the bibliography.


THX for this goody!
Following the bullet points of Section 4), RSABE in this context is a misnomer. It should be SABE. RSABE* (preferred by the US FDA and China’s CDE) is one approach and ABEL another. See also this article.

@John: Since the references of the guideline are the EMA’s (in the previous post #2 and #4), an ANOVA (Proc GML). Scaling only for Cmax if \(\small{CV_\text{wR}>30\%}\), upper cap of scaling at \(\small{CV_\text{wR}=50\%}\) (maximum expansion 69.84 – 143.19%), point estimate constraint 80.00 – 125.00%. Likely an ANOVA also for ABE.


  • Why the FDA recommends Proc Mixed for partial replicate designs and Proc GLM for full replicate designs is beyond me. For ABE Proc Mixed is recommended for any design.

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NK
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India,
2024-07-19 09:30
(107 d 13:52 ago)

@ Helmut
Posting: # 24084
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 Mexico: ABEL

Dear HS,

❝ * Why the FDA recommends Proc Mixed for partial replicate designs and Proc GLM for full replicate designs is beyond me. For ABE Proc Mixed is recommended for any design.


corrected statement

FDA recommends Proc GLM for partial replicate designs and Proc MIXED for full replicate designs.

Regards
NK
Helmut
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2024-07-19 11:26
(107 d 11:55 ago)

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Posting: # 24085
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 Mexico: ABEL

Hi NK,

❝ FDA recommends Proc GLM for partial replicate designs and Proc MIXED for full replicate designs.


THX, you are right.

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jag009
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NJ,
2024-07-23 21:43
(103 d 01:39 ago)

@ Helmut
Posting: # 24093
Views: 1,193
 

 Mexico: ABEL

Thank you all!
J
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