Tag Archives: Guidlines

FDA guidance – Submission of Bioequivalence data for ANDA’s

Posted on May 18, 2009 by admin| 3 Comments

The FDA published this guidance back in April but we have just now had the time to review it.

This guidance is intended to assist applicants who are submitting abbreviated new drug applications (ANDAs) in complying with FDA’s new requirements for the submission of bioequivalence (BE) data.

FDA’s final rule on “Requirements for Submission of Bioequivalence Data” (the BE data rule) requires ANDA applicants to submit data from all BE studies the applicant conducts on a drug product formulation submitted for approval, including studies that do not demonstrate that the generic product meets the current bioequivalence criteria.

This guidance provides information on the following subjects:

  • The types of ANDA submissions covered by the BE data rule
  • A recommended format for summary reports of BE studies
  • The types of formulations FDA considers to be the same drug product formulation for
  • Different dosage forms based on differences in composition.

The important points of this guidance is that all studies must be submitted for ANDA applications and a format for those submissions is advised:

“For a suggested format for summary reports, please refer to the Office of Generic Drugs (OGD) Web page.6 The Division of Bioequivalence has developed model data summary tables in a concise format consistent with the ICH Common Technical Document (CTD). The tables, under the heading “Model Bioequivalence Data Summary Tables,” are available in Word and PDF formats. The FDA recommends that these table formats be used to organize the data for summary reports required by the BE data rule”

Drug Formulation

FDA amended the regulations to require an applicant to submit data from all BE studies conducted on the same formulation of the drug product submitted for approval.

“Same drug product formulation means the formulation of the drug product submitted for approval and any formulations that have minor differences in composition or method of manufacture from the formulation submitted for approval, but are similar enough to be relevant to the FDA’s determination of bioequivalence”

The guidance goes into greater detail on this point, this forms the bulk of the guidelines.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

ida consultants freestrategyconsultation 515x64 FDA guidance Submission of Bioequivalence data for ANDAs

As you know this website is a great resourse for keeping up to date with developments and regulations, why not get our FREE monthly regulatory and market round up. You can un-subscribe at any time and we do not share your details with anybody.

→ 3 Comments

Posted in clinical, formulation, regulatory

Tagged , , ,

EMEA puts out a new concept paper – developing a guidline for the use of Pharmcogenomic Methodologies in the Pharmacokinetic Evaluation of Medicinal Products

Posted on May 15, 2009 by admin| Leave a comment

EMEA put out a concept paper on “The development of a guidline on the use of pharmacogenomic methodologies in the pharmacokinetic evaluation of medicinal products”

Background

In recent years there has been a rapid development regarding our understanding of the genetics behind interindividual differences in drug response, pharmacogenomics forms a major part of this research area, where interindividual variability in genes encoding drug transporters, and drug metabolising enzymes affects the systemic and target organ exposure of pharmacologically active substances, thereby affecting the efficacy obtained of drug treatment as well as the occurrence of adverse drug reactions. The highest abundance of genetic polymorphism is registered at the level of drug metabolism where approximately 40 % of phase I metabolism of clinically used drugs is catalysed by enzymes with polymorphisms known to have a marked impact on their function in vivo.

In light of the evolution and broad acceptance of genotyping methods, as well as increased experience in the use of such pharmacogenomic methodologies during drug development, the EMEA considered it appropriate to update and align this progress in a Guideline on this topic.

What the guideline hopes to achieve

The fundamental issues to be discussed in a proposed CHMP Guideline is how to implement pharmacogenetics affecting PK in drug development, how the pharmacokinetic variability arising from pharmacogenetic differences may best be determined, how to assess clinical relevance of the pharmacokinetic differences and recommendations on how to reflect these data in the labelling.

So if you have any interest in the topic you need to be getting in touch with the EMEA and register your interest.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

ida consultants freestrategyconsultation 515x64 EMEA puts out a new concept paper developing a guidline for the use of Pharmcogenomic Methodologies in the Pharmacokinetic Evaluation of Medicinal Products

As you know this website is a great resourse for keeping up to date with developments and regulations, why not get our FREE monthly regulatory and market round up. You can un-subscribe at any time and we do not share your details with anybody.

→ Leave a comment

Posted in clinical, pre-clinical, regulatory

Tagged , , ,

New EMEA Draft Concept Paper – Immunogenicity Assessment of Manoclonal Antibodies for In-vivo clinical use

Posted on May 3, 2009 by admin| 1 Comment

The EMEA release for review a draft concept paper today (24th March) on immunogenicity assessment of monoclonal antibodies for in-vivo clinical use. the consultation period lasts until June 2009.

Backgound to the concept paper

Unwanted immunogenicity is a significant problem with therapeutic biologicals. The clinical problems associated with unwanted immunogenicity vary in nature and incidence. The importance of the unwanted immunogenicity problem has led to the preparation and adoption of the ‘Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins’ by the CHMP (adopted April 2008).
Monoclonal Antibodies (mAbs) comprise a large important class of therapeutic biologicals. Different mAb products share some properties, but may differ in other aspects. Many mAb products are known to be associated with unwanted immunogenicity. Some issues pertaining to unwanted immunogenicity of mAbs differ in important aspects from those generally associated with therapeutic biologicals.

The Main problem being addressed

The incidence of immunogenicity associated with mAbs differs greatly between products, patients and even in different studies with the same product and patient type. The complexity of structure of mAbs possibly explains at least some of this variation. In some cases, especially with humanised or human sequence mAbs the immune response is predominantly anti-idiotypic, which clearly can compromise clinical responses to the mAb. In some cases the induced antibodies reduce clinical responses to the mAb to such an extent that further therapy has to be terminated.
The very large number of mAbs in clinical development and undergoing regulatory scrutiny emphasises the critical need for provision of appropriate guidance on the unwanted immunogenicity of this large class of biologicals. Questions on immunogenicity are often asked during assessments of marketing authorizations for mAbs. The development of biosimilar mAbs is prevalent in various parts of the world, which again stresses the importance of having good guidance available, as unwanted immunogenicity is well known to also be a concern with biosimilars.

The main recommendation from this concept paper are, the drafting of a guideline on immunogenicity assessments of monoclonal antibodies intended for in vivo clinical use. The EMEA are looking for expert input and opinion into this subject from the pharmaceutical industry.

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug  development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

ida consultants freestrategyconsultation 515x64 New EMEA Draft Concept Paper Immunogenicity Assessment of Manoclonal Antibodies for In vivo clinical use

→ 1 Comment

Posted in biotechnology, clinical, pre-clinical, regulatory

Tagged , , , , , ,

New FDA Draft Guidance – Non Clinical evaluation for Anticancer Pharmaceuticals

Posted on April 2, 2009 by admin| 1 Comment

The FDA has produced some draft guidance aimed at establishing an internationally accepted objectives and / or recommendations on the design and conduct of nonclinical studies to support the development of anticancer pharmaceuticals in patients with advanced disease and limited therapeutic options.

Because malignant tumours are life-threatening, the death rate from these diseases is high, and existing therapies have limited effectiveness, it is desired to provide new effective anticancer drugs to patients more expeditiously. Nonclinical evaluations are intended to 1)identify the pharmacological properties of a pharmaceutical, 2) establish a safe initial dose and 3) understand the toxicological profile.

These new guidlines only apply to pharmaceuticals intended to treat cancer in patients with late stage or advanced disease regardless of the route of administration, including both small molecule and biotechnology-derived pharmaceuticals.

Studies to support nonclinical evaluation

Pharmacology – prior to phase I studies, preliminary characterization of the mechanism(s) of action, resistance, and schedule dependencies as well as anti-tumour activity should have been made. appropriate models should be selected based on the target and mechanism of action but need not be studied using the same tumour types intended for clinical evaluation. these studies can provide proof of principle, guide schedules and dose escalation schemes, provide information for selected test species, and aid starting dose selection.

Safety Pharmacology – as assessment of vital organ function should be available before initiation of clinical studies. Stand alone safety pharmacology studies need not be conducted to support studies in pateiutne with late stage cancer or advanced disease.

Pharmacokinetics – the evaluation of limited kinetic parameters, e.g. peak plasma levels, AUC and half life in the animal species used for non-clinical studies can facilitate dose escalation during phase I.

General Toxicology – The primary objective of Phase I clinical trials in patients with cancer is to assess the safety of the pharmaceutical. This can include dosing to a maximum tolerated dose (MTD) and dose limiting toxicity (DLT). Therefore, determination of a no observed adverse effect level (NOAEL) or no effect level (NOEL) in the toxicology studies is not considered essential to support clinical use of an anticancer pharmaceutical. To support Phase I clinical trials at least one nonclinical study should incorporate a recovery period at the end of the study to assess for reversibility of toxicity findings or the potential that toxicity continues to progress after cessation of drug treatment. Toxicokinetic evaluation should be conducted as appropriate.

Reproduction Toxicology – These studies are not considered essential to support clinical trials intended for the treatment of patients with late stage or advanced cancer. These studies are also not considered essential for pharmaceuticals which target rapidly dividing cells in general toxicity studies or belong to a class which has been well characterized in causing developmental toxicity. Generally no fertility study is warranted to support the treatment of patients with late stage or advanced cancer. A peri- and postnatal toxicology study is generally not warranted to support the treatment of patients with late stage or advanced cancer.

Genotoxicity – Genotoxicity studies are not considered essential to support clinical trials for therapeutics intended to treat patients with late stage or advanced cancer.

Immunotoxcity – For anticancer pharmaceuticals the design components of the general toxicology studies are considered sufficient to evaluate immunotoxic potential and support marketing.

The guidelines go on to describe how you can use the pre-clinical data in designing you clinical trial: start dose for first administration in man, dose escalation and the highest dose in clinical trials. the guidelines also provide guidance on duration and schedule of toxicology studies to support initial clinical trials, the duration of toxicology studies to support continued clinical development and marketing, how to manage combination pharmaceuticals and Finlay the non clinical studies to support trials in pediatric populations. Other considerations addressed in the guidelines include conjugated agents, liposomal products, evaluation of drug metabolites, and evaluation of impurities.

Table – Example schedules for anticancer pharmaceuticals to support initial clinical trials. (reproduced from FDA guidelines S9)

moz screenshot 1 New FDA Draft Guidance Non Clinical evaluation for Anticancer Pharmaceuticals

table1 300x182 New FDA Draft Guidance Non Clinical evaluation for Anticancer Pharmaceuticals

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch


e5 New FDA Draft Guidance Non Clinical evaluation for Anticancer Pharmaceuticals


ea featured 4 New FDA Draft Guidance Non Clinical evaluation for Anticancer Pharmaceuticals

→ 1 Comment

Posted in clinical, pre-clinical, regulatory

Tagged , , , , , ,