Drug Development Consultant & Regulatory Consultant » Regulations

Drug Regulators, MHRA, Publish Consultation, Intention to Amend the Medicines for Human Use Regulations 2008 (SI2008/1692)

admin — Fri, 12 Feb 2010 10:41:28 +0000

Drug Regulators, MHRA, Publish Consultation, Intention to Amend the Medicines for Human Use Regulations 2008 (SI2008/1692)

full text here

This consultation notifies interested parties that further amendments will be made to the Medicines For Human Use (Prescribing By EEA Practitioners) Regulations 2008
(2008 Regulations). This consultation seeks views on how current guidance can be expanded to provide additional support for community pharmacists following forthcoming legislative changes.

This consultation abides by the seven consultation criteria as set out in the revised Code of Practice on Consultation and which are summarised at Annex A. As the further
amendments to legislation are required for the purpose of complying with the views of the European Commission, a period of consultation of 4 weeks, although shorter than usually expected, is appropriate. Also, as those most affected by the further amendments to the 2008 Regulations will be members of the pharmacy profession, the consultation is being directed primarily to representatives of that profession, in addition to similar bodies representing medical, dental and other interests. However replies from other parties are welcome..

Damien Bové is THE Drug Development and Regulatory Consultant (pharmaceutical or biotechnology), I work with my 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.

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FDA introduces new Rules of IRB Registration

admin — Thu, 23 Jul 2009 08:34:14 +0000

Drug Regulators, FDA, Introduce New IRB registration Rules

Clinical Trials Regulations have been changed following on from the Coast scandal reported in this site (article). I have just received this update from the ICR

The FDA IRB Registration Rule is effective Tuesday, July 14, 2009. All IRBs reviewing FDA-regulated research must register between July 14 and September 14, 2009. IRBs that review FDA-regulated studies and that are not already in the OHRP IRB registration system must submit an initial registration. If your IRB is already registered in the OHRP system, the registration information must be updated to include all of the information required by the FDA IRB Registration Rule. Please see the guidance referenced below for more information.

This registration will be accomplished through a modified version of the database used by the Office for Human Research Protections (OHRP).Please note: the database for electronic submission of IRB registrations will not be available until July 14, 2009.

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.

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This guideline ap

recombinant vaccines for the prevention and treatment of infectious disease, and provides guidance on quality, non-clinical and clinical aspects.

Non GMP stock allowable for Human Radiolabled PK studies

admin — Thu, 25 Jun 2009 08:26:09 +0000

I have just received an interesting letter from Charles Rivers Edinburgh and there are a few interesting points I wanted to share with you.

“Since 2004, there has been a clear requirement to manufacture the IP (drug product) to Good Manufacturing Practice (GMP), however the quality standard required for the radiolabeled Active Pharmaceutical Ingredient (API) was open to interpretation. Following the implementation of GMP Annex 20 on Quality Risk Management in March 2008, and with the amendment to GMP Part II (Basic Requirements for APIs used as Starting Materials) in draft, a risk management approach to the assessment of the quality of the API has been adopted”

So if you wish to use radiolabeled products for human PK it does not necessary need to be GMP stock, this is a great and important point and can be truly valuable to companies planning risk management microdosing studies, but it does need to be assessed for potential risks. its an important point that needs considering.

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

Grow your Expertise for Free

This guideline ap

recombinant vaccines for the prevention and treatment of infectious disease, and provides guidance on quality, non-clinical and clinical aspects.

MHRA guidance on the vigilance systems for medical devices- Intraocular lenses

admin — Mon, 22 Jun 2009 08:22:59 +0000

This guidance document gives advice to manufacturers on the notification of adverse incidents involving intra-ocular lenses under medical devices vigilance system. It includes, but is not limited to, the following types of intraocular lenses: posterior chamber; phakic; anterior chamber; multifocal; and accommodated. It is intended to facilitate uniform application implementation of the medical devices directive.

The kinds of things should be reported include:

Any deterioration or malfunction of an intraocular lens or any inadequacy in instructions for use which has led, on might lead to, a serious deterioration in the state of health and vision.
The intraocular lens has been subject to a field safety corrective action
Common faults that require reporting are also listed

The guidance also goes on to give some details about Periodic Summary Reporting and Adverse Incident Trending, its a short guidance but should be look at and considered by those working in the area.

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

Grow your Expertise for Free

This guideline ap

recombinant vaccines for the prevention and treatment of infectious disease, and provides guidance on quality, non-clinical and clinical aspects.

MHRA publishes guidance on the Medical Devices Directives

admin — Mon, 01 Jun 2009 08:55:32 +0000

The MHRA has published Guidance on the EC Medical Devices Directives.

The guidance document is a comprehensive document, and covers the regulations in some detail:

The Medical Devices Regulations 2002
The Active Implantable Medical Devices Directive
Medical Devices Directive
In Vitro Diagnostic Medical Devices Directive

The Guidance provides help interpreting these regulations in a number of Specific Areas:

Clinical Investigtions in the UK
Is a Clinical Investigation Required
Special Clinical Investigations
- Changes in intended use
- Comparative Studies
- Prototype Devices
- Clinical Investigations also submitted to the FDA of other Non-EU Regulatory Authorities
- In-house manufactured medical devices
- “Off-Label” use
Making an Application for Pre-clinical Assessment
Competent authority processing of the clinical investigation
Documentation required for all submissions
Clinical Investigational Plans
Documentation to be kept available
Special features of clinical trials
How your application will be handled by the UK-competent authority
Adverse event handling

The publication is detailed and covers a number of areas in detail, it is recommended reading for anybody developing a medical device.

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

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FDA guidance – Submission of Bioequivalence data for ANDA’s

admin — Mon, 18 May 2009 07:31:04 +0000

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

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FDA Draft Guidance – Label Comprehension Studies for Non-prescription Drug Products

admin — Sun, 03 May 2009 16:20:21 +0000

It has been a busy week for new guidance and draft notices from the regulators, and this latest one is new draft guidance for Label Comprehension Studies for Non-prescription (over the counter) drug products.

The Food and Drug Administration (FDA) often requires sponsors to conduct label comprehension studies that are designed to evaluate proposed nonprescription drug product labeling. This guidance is intended to provide recommendations to industry on conducting label comprehension studies. A label comprehension study is a tool that can be used for assessing the extent to which consumers understand the information conveyed by proposed nonprescription drug product labeling and then apply this information when making hypothetical drug product use decisions.

When designing and conducting a label comprehension study it is important to:

Clearly state the purpose of the study
Identify the communication objectives (the important concepts that need to be understood by the consumer)
Enroll a demographically diverse population with varying levels of literacy
When necessary, enrich the study with subjects who have specific characteristics that are relative or absolute contradiction to the use of the drug product
Specify a study design that meets study objectives and calculate the appropriate sample size
Construct a questionnaire that targets the communication objectives
Use test labeling as close as possible to the final product label
Minimize factors that may contribute to a biased study
Compare different versions of the label to study the effect of variations in working and information location on comprehension.

Study Objectives

Primary Communication Objectives: the information that has the greatest clinical significance, target understanding should be 90% or greater. (indications, dose and dose interval, contraindications, warnings, and drug interactions, and when to stop taking the product)

Secondary Communication Objectives: Address areas of less critical importance and 80% or higher understanding is the target. (general health information)

Self Selection: the decision consumers make to use or not use a drug product based on reading the information and applying their own personal medical history.

Study Populations

The study should include all subjects who could potentially use the drug product, regardless of their age, sex, underlying medical conditions, and use of concomitant medications. The study should test label comprehension in a general population whether or not individuals express interest in using the drug product.

Label comprehension studies also should enroll a low literacy cohort. This low literate population should represent a range of low literacy below an 8th grade reading level.

Statistical Considerations and Data Analysis

The primary endpoints should be the endpoints capable of capturing the most relevant and convincing data on consumer comprehension of the critical label elements.

Based on the clearly defined primary endpoints, the study protocol should also specify what criteria determine success for the study. These success criteria should be related to the predefined target level of comprehension for the primary communication objectives.

Sample Size Considerations

The number of subjects in a label comprehension study should be large enough to provide a reliable answer to the primary communication objectives. Sizing of such a study should be based on the success criteria.

Questionnaire Design

The questionnaire design should: 1) clearly reflect the communication objectives of the study; and 2) optimize the validity and interpretability of the information collected. Wording, question structure, and question sequences significantly affect the validity and interpretability of the data collected.

Questions should assess specific objectives
Simple vocabulary should be used
Questions would be direct, specific and unambiguous
Different types of questions should be used, open, closed etc
Closed questions should be validated with open-ended probing questions (e.g. please explain your answer)
if answers are incorrect, open ended probing questions should be issued to investigate the cause of the error
Leading question should be avoided
Multiple choice should be clear and only one correct answer (include I don’t know)

Guidance is also provided on location, conduct of the study, data analysis and final reporting and interpretation.

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

GMP for phase 1, or not GMP as the case may be.

admin — Tue, 07 Apr 2009 12:58:09 +0000

The FDA has set a trend towards the reduction of Good Manufacturing Practice (GMP) regulation in phase 1 clinical trials with the publication of guidelines “CGMP for Phase 1 investigational drugs”, this was published in July 2008, but we through it worth mentioning again for reasons that will become clear shortly. Not being a GMP specialist my interpretation is based on a read through the guidelines and comment for other experts in the field. In summary the guidance is that you can manufacture to GMP but without all the documentation that accompanies GMP, its not a return to investigators making drugs in an academic laboratory and giving them to patients, but it does significantly reduce the burden and more importantly the cost of preparing drugs for Phsae1 clinical trials.

Drug regulators are a pragmatic bunch and this is just another example of that good sense being applied, but why bring it up again, well as you all know the European Clinical Trials Directive (ECTD) has brought GMP to European phase 1 clinical trials, however word is starting to spread that Belgium and Holland and some other ECTD countries are interpreting GMP requirements for phase 1 clinical trials in a slightly different way, more along the lines of the US guidelines, and this author wonders if we might see a more “official” relaxing of the stance in Europe.

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

Bioequivalence of Therapeutic Proteins

admin — Wed, 25 Mar 2009 09:37:46 +0000

As the first major generation of therapeutic proteins come of age and their patents expire the possibility of “generic versions” has raised. However the regulatory pathway for such “generic” drugs does not fit the complexities of therapeutic proteins. However the EMEA released guidelines on so called biosimilars (follow-on biological product in the USA), and a number of products have made it to market, we ask what are the key learning’s.

The issues to overcome:

Large complex molecules and standard analytical methods do not allow their full physical characterisation
Heterogenicity due to natural processes in the host cells needed for their production
Modification introduced during production, purification, formulation and storage
Impurities introduced during production and purification
Production processes are dynamic and undergo continuous improvement
Changes are accepted if similarity can be established, their is no need to be identical
In house methods and standards are not in the public domain

The Regulations

The EMEA is the only regulator to introduce regulations, these regulations make it clear that biosimilars are not the same and are not regulated in the same was as generic drugs. The regulations hinges on clinical data, and needs to go through the centralised procedure. The regulations provide clear guidance on data requirements and quality standards that need to be established to gain market approval, the requirements include:

Same extensive data on quality and safety as an innovative protein drug
Supplement showing similarity in quality, safety and efficacy between biosimilar and the same reference product
Extensive comparability exercise is required to demonstrate that the similar biological medicinal product in terms of quality, safety and efficacy to the reference medical product
Assessment of biological properties.
Results of biological assays
Non-clinical and clinical focusing on Pharmacokinetic (PK), Pharmacodynamic (PD), efficacy and safety with a focus on immunogenicity

Practicle Experience

A recent product approved as a bio-similar, Retacrit has provided a number of insights into the process and how data is evaluated through the publication of its European Public Assessment Report (EPAR), the issues considered in detail included:

Structural comparability
Purity comparisons
Biological activity
PK profiles
Clinical effect and side effects (over 600 patients were used in the studies)

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 development target, define a 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