Bio-waiver : Recent Developments

Dr. V. Venkateswarlu Managing Director Neuheit Pharma Technologies Pvt Ltd HYDERABAD – INDIA www.neuheitpharma.com

BioAsia 2016 : Hyderabad

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Role of Regulatory Agency

Safety: One time assessment with dossier mainly BE

Efficacy: One time assessment with dossier mainly BE

Quality: Continuous monitoring to the end of the life of the product

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BIOEQUIVALENCE METHODS

In-Vitro BE

In-Vivo BE

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In-Vitro BE

Cholestyramine powder: Bile acids salts binding studies by in-vitro methods

Sevelamer carbonate: Phosphate binding studies by in-vitro methods

In-vitro equivalence as a pre-requisite for in-vivo BE studies: Mesalamine, inhalation products, DPI etc.,

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In-Vivo BE

Pharmacokinetic Study

Pharmacodynamic Study

Clinical Study

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US FDA

• Guidance for Industry: “Waiver of in vivo bio-equivalence studies for immediate release solid oral dosage forms containing certain active moieties/active ingredients based on a Biopharmaceutics Classification System” (2000)

EU

• “Note for Guidance on the Investigation of Bioavailability andBioequivalence” CPMP/EWP/QWP/1401/98; paragraph 5.1

WHO

• Technical Report Series No. 937, May 2006

• Annex 7: Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability

• Annex 8: Proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate release, solid oral dosage forms

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Dosage form based

• Aqueous solutions, Dispersible tablets, miscellar injections etc.

Lower strengths

• Biowaiver for lower strengths that meet defined criteria

BCS Class based IR products

• BCS class 1 drug products in USA and BCS class 1 &3 products in EU

• WHO provided a list of drug products that are eligible for bio-waiver

DIFFERENT BIO-WAIVERS AVAILABLE

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Ciproflaxacin in solution and dexamethasone in suspension

• US FDA issued a BE guidance involving clinical in Patients

• Complete in-vitro characterization of test and RLD convinced FDA to change BE guidance to in-vitro characterization

Reconstitution of vial with 4 ml of WFI forms suspension hence BE requirement

• Initial guidance was issued a PK study in MDS patients which is very difficult

• Q1, Q2 & Q3 concept was used to convince US FDA to change to characterization

Entry of generics into market is blocked by complex BE studies

• Innovative thinking in designing appropriate in-vitro surrogates is required

• Regulatory Agencies are helpless unless scientists come with alternative approaches for bio-waiver