Bioequivalence and Bioavailability Forum • EMA: Draft product-specific guidances ♬

EMA: Draft product-specific guidances ♬ [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2013-11-15 16:45 (4195 d 04:45 ago) – Posting: # 11892
Views: 29,852

Dear all,

❝ ❝ Do we get Bioequivalence Recommendations for Specific Products on EMA site

❝ Not yet. But there are plans.

Today EMA published the first set of draft product-specific guidances for a three-months consultation period (until 15 Feb 2014):

Capecitabine
500 mg single dose cross-over in patients (fed state), parent in plasma (achiral),
Acceptance Range (AR) 80.00–125.00% for AUC_t and C_max (no scaling, “critical dose” drug).
Carglumic acid
200 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC₇₂ and C_max (HVD status not reviewed).
Dasatinib
140 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC_t and C_max (HVD status not reviewed).
Emtricitabine/tenofovir disoproxil
Emtricitabine 200 mg / tenofovir disoproxil 245 mg single dose cross-over in healthy subjects (fed state), parent (emtricitabine) and metabolite (tenofovir) in plasma (achiral),
AR 80.00–125.00% for AUC_t and C_max (HVD status not reviewed).
Erlotinib
150 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC₇₂ and C_max (HVD status not reviewed).
Imatinib
400 mg single dose cross-over in healthy subjects (fasting or fed state; fasting preferred, but fed acceptable according to GL/SmPC of reference), parent in plasma (achiral),
AR 80.00–125.00% for AUC₇₂ and C_max (HVD status not reviewed).
Memantine
Any strength single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC₇₂ and C_max (HVD status not reviewed).
Miglustat
100 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC_t and C_max (HVD status not reviewed).
Oseltamivir
75 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC_t and C_max (HVD status not reviewed)
Posaconazole
400 mg single dose cross-over in healthy subjects (fed state), parent in plasma (achiral),
AR 80.00–125.00% for AUC_t and C_max (scaling for C_max if CV_WR >30% demonstrated in a replicate design).
Repaglinide
2 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC_t and C_max (HVD status not reviewed).
Sirolimus
No strict dose-proportionality between 0.5 and 5 mg tablets.
0.5 and 5 mg tablets, 1 mg/ml solution (if similarity requirements not fulfilled). Single dose cross-overs in healthy subjects (fasting and fed state), parent in blood (achiral),
AR 90.00–111.11% for AUC_t (NTID) and 80.00–125.00% for for C_max.
Sorafenib
200 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC₇₂ and C_max (HVD status not reviewed).
Tadalafil
20 mg single dose cross-overs in healthy subjects (fasting and fed state), parent in plasma (achiral),
AR 80.00–125.00% for AUC₇₂ and C_max (HVD status not reviewed).
Telithromycin
400 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC_t and C_max (HVD status not reviewed).
Voriconazole
200 mg single dose cross-over in healthy subjects (fasting state), parent in plasma (achiral),
AR 80.00–125.00% for AUC_t and C_max (HVD status not reviewed).

Interesting points:

Guidances, not guidelines.
Capecitabine: 500 mg in metastatic breast or colorectal cancer patients? Unethical, IMHO.
The standard treatment scheme is 2,500 mg/m²/day in two divided doses for two weeks followed by a one week treatment-free interval. For a patient with a 2 m² body surface area a single dose is 5×500 mg – not just 500 mg.
No enantioselective analytical methods in all [sic] cases!
What does “HVD status not reviewed” mean? I always thought that one can scale the acceptance range for C_max if there are no clinical issues and CV_WR >30% is demonstrated in a reference-replicated study. Do we have to wait until the mighty oracle allows scaling in a GL?

Edit 2013-12-06: List continues here.
The complete list with the respective end of consultation here.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

Bioequivalence Recommendations for Specific Products cr.maroj 2013-09-19 11:00 [Regulatives / Guidelines]
- Bioequivalence Recommendations for Specific Products Ohlbe 2013-09-19 11:45
  - EMA: Draft product-specific guidances ♬Helmut 2013-11-15 15:45
    - EMA: Draft product-specific guidances ♬ luvblooms 2013-11-19 06:35
    - EMA: Capecitabine product-specific guidance ♬ mittyri 2013-12-10 15:33
      - EMA: Capecitabine product-specific guidance ♬ Helmut 2013-12-10 16:11
        
        Russian GL 2013: harmonisation to EMA mittyri 2013-12-14 11:57
    - EMA: Draft product-specific guidances ♬ pash413 2013-12-18 12:35
      - EMA: Use of AUC72 not dependent on t½ Helmut 2013-12-18 14:35
    - End of consultation approaching‼ Helmut 2014-02-10 18:33
      - End of consultation approaching‼ Dr_Dan 2016-01-28 09:27
        
        Guesstimates Helmut 2016-01-28 13:32
- EMA: generally no product-specific GLs Helmut 2013-09-19 11:48
  - Thank you cr.maroj 2013-09-19 13:03
  - EMA: generally no product-specific GLs The Outlaw Torn 2013-09-20 07:52
    - EMA: parent whenever possible Helmut 2013-09-20 09:02
      - EMA: parent whenever possible cr.maroj 2013-09-20 10:14
        
        EMA: parent whenever possible Helmut 2013-09-20 12:53
        
        EMA: parent whenever possible Ohlbe 2013-09-20 13:52
        
        EMA: parent whenever possible mittyri 2013-09-20 14:55
        
        EMA vs. Russia Helmut 2013-09-20 19:21
        
        FDA: Prasugrel intuitivepharma 2013-12-20 07:36
        
        FDA: Prasugrel Helmut 2013-12-20 13:46
        
        FDA: Prasugrel intuitivepharma 2013-12-24 06:38
        
        FDA: Alternative approaches… Helmut 2013-12-24 14:15
        
        FDA: Alternative approaches… intuitivepharma 2013-12-26 05:11
        
        FDA: RTR Helmut 2013-12-26 14:35
        
        FDA: RTR intuitivepharma 2013-12-31 05:34
        FDA: RTR meghalvakil20 2015-07-23 16:32
        
        WayBack Machine Helmut 2015-07-23 16:58
        
        WayBack Machine meghalvakil20 2015-07-23 17:03
        
        Old stuff Helmut 2015-07-23 17:28
        
        EMA: parent whenever possible ElMaestro 2013-09-20 19:35
        
        EMA: Sirolimus product-specific GL luvblooms 2013-11-19 13:00