Minimum therapeutic dose

Dear All

We are generally manufacturing cortico-steroids (API) which is mainly used for skin lotion or ointment. So is there any method how to find out the minimum therapeutic dose.

[quote=jogendar.dubey]Dear All

We are generally manufacturing cortico-steroids (API) which is mainly used for skin lotion or ointment. So is there any method how to find out the minimum therapeutic dose.[/quote]

You should consult Guidance for the testing Cosmetics Ingredients and their safety evaluation for the european comisision,

O well I recomended to you:
http://pharmtech.findpharma.com/pharmtech/Article/Setting-Cleaning-Validation-Acceptance-Limits-for-/ArticleStandard/Article/detail/481947

Rgds…,:cool

Dear Mr. Jogendar Dubey,

I would like to highlight one important point regarding establishment of CV limits for steroids. If you refer to the clause 7.11.3 (Carry-over of product residues) of PIC/S guideline on cleaning validation, you will find this statement:

“(d) For certain allergenic ingredients, penicillins, cephalosporins or potent steroids and cytotoxics, the limit should be below the limit of detection by best available analytical methods. In practice this may mean that dedicated plants are used for these products.”

I hope your reason behind obtaining “minimum therapeutic dose” for corticosteroids is to use the “Dose criterion (i.e. 0.1% of the minimum therapeutic dose)” for the calculation of CV limits. However, the dose criterion cannot be applied to potent steroids (as mentioned above). Before you do lot of search about therapeutic doses, I will recommend you to first check the potency of corticosteroid, you may refer to following websites for the potency:

[LIST=1]

  • http://www.mass.gov/?pageID=eohhs2terminal&L=6&L0=Home&L1=Provider&L2=Insurance+(including+MassHealth)&L3=MassHealth&L4=MassHealth+Drug+List&L5=Therapeutic+Class+Tables&sid=Eeohhs2&b=terminalcontent&f=masshealth_provider_pharmacy_therapeutic_table_16&csid=Eeohhs2
  • http://www.lichensclerosus.net/docs/TopicalSteroidsPOTENCY.pdf
  • http://www.psoriasis.org/netcommunity/sublearn03_mild_potency

    For mild to less potent steroids you may use the dose criterion but for potent and superpotent steroids you might have to use “analytical limit” as the acceptance criteria. You may refer to Martindale and/or Goodman & Gilman textbooks on pharmacology to find the lowest therapeutic doses. You may also use lowest marketed dose in place of minimum/lowest therapeutic dose. Refer to the article suggested by MAC and use the formulae to determine CV limits.

    Another approach to overcome all these problems (searching of minimum therapeutic doses, development of analytical limits) is to use acceptable daily intake/ acceptable daily exposure (ADI/ADE) values for the corticosteroids and replace the “safety factor * minimum therapeutic dose” with ADI/ADE values. Please refer to new ISPE baseline guideline Volume 7: Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP) for more information on how to derive ADE values.

    Hope this will help.