Clinical Assessment

Throughout its support in the clinical development of new and existing treatments, InViva seeks to ease the process of clinical trials, helping companies achieve product licensure.

• Phase I clinical trials or safety studies

• Phase II clinical trials

• Phase III clinical trials or pivotal clinical trials

• Phase IV or post-marketing trials 

• Phase V

All new products are required to be registered by regulatory agencies and boards of health before it can be supplied for use. Similarly, a form of registration is required before clinical trials may be conducted. Such registration activities are mandatory before any studies on human subjects can be considered.

Investigational New Drug (IND) application (USA)

An IND application is filed with the US FDA, for either commercial or research purposes, to enable early assessment and evaluation of potential new drugs. Filing an IND application triggers a change in legal status under the Federal Food Drug and Cosmetic Act and the target molecule becomes a new drug that is subject to specific requirements under the drug regulatory system.

Three types of IND currently exist:

• An investigator IND – submitted by a physician who both initiates and investigates, and under whose immediate direction the investigational drug is administered or dispensed.

• Emergency use IND – allowing the FDA to authorise use of an experimental drug in an emergency that does not allow time for submission of a formal IND in accordance with 21 CFR.

• Treatment IND – submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions.

All types of IND application must contain information in three broad areas:

• Pharmacology and toxicology Studies – from the pre-clinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans

• Manufacturing information – detailing the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product to ensure that the company can adequately produce and supply consistent batches of the drug.

• Clinical protocols and investigator information – for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. Commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.

Once IND application has been submitted there is a 30-cal day wait period whilst the FDA performs a safety evaluation before clinical studies may be initiated. 

Clinical Trials Authorisation (CTA) (EU and UK)

An Investigational Medicinal Product Application (IMPD) and / or Clinical Trials Authorisation (CTA) application is required to be filed with the EMA / UK’s MHRA. The Clinical Trials Directive states that clinical trials of medicinal products in human subjects require authorisation by the competent authority and a favourable opinion by an ethics committee before a study may commence. Clinical studies may only commence following the receipt of an approval from the licensing authority.

How InViva can help with IND application and CTA

InViva supports clients conducting, and planning to conduct, clinical trials in Europe and the USA, from the collation of information, agency meetings and negotiations through to the compilation and submission of IND / CTA / IMPD applications. InViva prides itself on providing the highest quality strategic advice and project planning and management.

Current Good Manufacturing Practice (cGMP) is the rigorous system and process that is legally required for the manufacture of all pharmaceutical products, including biopharmaceuticals and over-the-counter medicines.

cGMP requirements cover the manufacture and testing of pharmaceuticals or drugs, active pharmaceutical ingredients, diagnostics, foods, and medical devices.

Whilst there is no formal requirement to comply with cGMP during early clinical development in phase I and phase II clinical trials, cGMP must be fully implemented by phase III clinical trials and for all subsequent manufacturing activities.  

cGMP Regulations

cGMP regulations are extensively covered in many resources and therefore only summarised here. GMP regulations provide a detailed guide to the activities that must be performed to ensure pharmaceutical products are manufactured consistently.

Some specific areas covered include:

• Manufacture using quality systems managed by quality assurance

• Process validation

• Analytical validation

• Cleaning validation (equipment, facilities, etc.)

• Facilities and utilities validation

• Training and Documentation

Standard guidance on cGMPs covering the EU, Japan and the US is covered under ICH (International Conference on Harmonisation) regulations. Local guidance is also available, in the UK Orange Guide by the MHRA and in the US by FDA-21 CFR 210 Code of Federal Regulations.

 

cGMP applies to countries that are signatories to ICH, as well as countries that have adopted ICH guidelines, e.g. Australia, Canada, and Singapore.

The World Health Organisation (WHO) also has a mandated version of GMPs used by pharmaceutical regulators in over 100 countries worldwide. These cover the key elements of ICH, FDA, and MHRA GMPs but generally are less rigorous.

How InViva can help with cGMP implementation and management

InViva has extensive practical expertise of supporting pharmaceutical,  biopharmaceutical, and healthcare manufacturers develop and implement cGMP systems globally.

This has included review and remediation of existing GMP standards, development and implementation of quality systems including Validation Master Plans, GMP training, GMP auditing including Pre-approval Inspection (PIA) and preparation of GMP standard documents such as SOPs, validation documents, and submission ready components.