I am working in a company specialised in drug develivery systems.Back to the Top
We have developped a subcutaneous formulation essentially simiilar to
a reference product with the only difference of the substitution of
acid lactic and sodium bicarbonate by glycine and hydrochloric acid in
aqueous solution, the pH of the our product being slightly lower than
the reference one.
A publication from the reference product laboratory shows
bioequivalence between the active substance by sc and by iv route.
The question is whether a bioequivalence study would be necessary.
Kind regards
Elisabeth Lopez
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Hi, I think IF you have bioequivalence between the Sub-Q and IV routes,
the experiment may be faulty in some manner. You cannot have
instantaneous system availability from a sub-Q injection. So, I think
you should re-check everything, e.g., sampling times, etc. With
respect to your question, in general, you will require a bioequivalence
study. Harold
Harold Boxenbaum
Pharmacokinetic Consultant
Arishel Inc.
14621 Settlers Landing Way
North Potomac, MD 20878-4305
(P) 301-424-2806
(F) 301-424-8563
harold.-at-.arishel.com
www.arishel.com
dear harold,Back to the Top
thanks for your info. In fact what I said was not totally true since
the rate of absorption was not essentailly similar.
Do you think that a bioequivalence study would be also necessary
between im and sc with the same change in excipients?.
Elisabeth
ELM
Barcelona Spain
HaroldBack to the Top
Are you right about this. Surely the availability (or area under the
curve) is independent of the input rate into the measuring
compartment. Indeed if the drug is not removed from the injection site
by another route or by degradation then wouldn't you expect 100 per
cent bioavailability?
Joe Chamberlain
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Yes, you must demonstrate bioequivalence of Cmax, per FDA regulations.
Harold.
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If your formulation, as it sounds from your mail, is pharmaceutically
equivalent ( essentially similarity) to the reference product except
for the permitted Q1/Q2 changes like antioxidants , preservative and
buffers ( as is your case), you may request for a biowaiver provided
your generic product is intended to have same route of administration
as labelled for the reference product. ( See section 21 CFR 314.94
(a)(9). )
If you are looking for any other route of administation not labelled
as targetted route ( I.V. to S.C. to I.M.) on reference product then
probably you have to demontrate the Bioequivalence and infact you may
be asked to demontrate the suitability of route exchange by limited
clinical trials and a meeting with FDA would be imperative.
Kind regards,
Pradeep s. Bhaduria
RANBAXY RESERACH LABORATORIES
INDIA.
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Great point. Are you looking for Cmax bioequivalence of active drug or
excipients? Harold.
Back to the Top
Dr. Clerk,
The agency considers two factors very close while evaluating the ANDA
dossiers of injectable products.
1. Pharmaceutical equivalence: Interms of Active drug/its
salt/polymorphic form (esp. for suspension injectables) and purity
/quantity thereof. The agency gives flexibility to have minor
deviations like quantitative/quanlitative changes in
antioxidant/preservatives/Buffers etc.But the changed excipients should
be previously appoved by the same route in the concentration
employed.The final physical form of the formulation and injectable
volume (pH and tonicity) and packdress should be same as that of the
innovator otherwise the generic doesn't qualify with the requirements
of injectable ANDA filing under section 505(j).
In case applicant fails to meet the any of criteria of Pharmaceutical
equivalence as listed above, one has to adopt the suitability petition
filing and failing to get petition approved applicant has to go for
505(b)2 approval route.
2.Bioequivalence:Equivalence in terms of Cmax and AUC.As per agency's
current requirements if the injectable product is clear aqueous
solution intened for IV/SC administration & meeting the criteria of
Pharmaceutical equivalence a bioequivalnce study can be waived.For
suspension or anhydrous "solubilized products" (like Taxol inj)
bioequivalence is required.
A change in the route of administration even from IV to IM( or SC) will
render the dossier unsuitable for filing under 505(j) and applicant is
advised to either file a suitability petition or else has to go for
505(b)2 application.
I hope this makes sense.
Regards,
Pradeep S. Bhadauria
RANBAXY REASEARCH LABORATORIES.
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