NorthWest Biotherapeutics Inc (NWBO)

[hyperopia]

I suspect that Northwest Bio will first take advantage of a more favorable route in the UK, and may have applied for the Innovation Passport, which is the entry point for the Innovative Licensing and Access Pathway (ILAP). Nineteen applications were filed in only the first few months of the year, yet to date, only about a half dozen have been publicly announced. (some may have been denied)

Les has stated privately to a number of investors of their intention to apply for approval first in the UK, and Dave Innes talked enthusiastically about the various new regulatory pathways in the UK, and continues to state that getting DCVax to market is the primary goal. Compared to the FDA, the MHRA (post-Brexit) seems far more eager to bring new and innovative treatments to patients as rapidly as possible, and is also very willing to assist companies through the regulatory process.

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MHRA Innovation Office
The MHRA Innovation Office is open to ideas for innovative medicines, medical devices and manufacturing processes. It provides free and confidential expert regulatory information, advice and guidance to organisations of all backgrounds and sizes based nationally or internationally. Call our customer services team on 0203 080 6000.

https://www.gov.uk/government/groups/mhra-innovation-office


Innovative Licensing and Access Pathway
A new pathway supporting innovative approaches to the safe, timely and efficient development of medicines to improve patient access.

https://www.gov.uk/guidance/innovative-licensing-and-access-pathway


The Target Development Profile Toolkit
This toolkit is for Innovation Passport holders following the Innovative Licensing and Access Pathway (ILAP) and provides activities to support the design and development of medicines.

SOME HIGHLIGHTS:

Certifications
Building on the Agency’s scientific advice approach, the Certification tool provides developers with an enhanced official regulatory review of packages of Common Technical Document (CTD) data (including Module 1). The process will provide applicants with specific and actionable feedback on the expectations for marketing authorisation and the regulatory requirements, highlighting potential deficiencies and where there are key issues to address.

This tool is not part of a formal marketing authorisation application but provides expert advice on how ‘regulatory ready’ a particular part of the development is.

How it works
You must confirm in the TDP which aspects of the CTD you are interested in having certified. We would expect this to be within Module 1, Module 3, Module 4 or Module 5, not necessarily a full module.

You can apply to have packages of CTD data assessed by an MHRA multi-disciplinary team including licensing, pharmacovigilance and inspectorate colleagues who will review the submission against marketing authorisation requirements and expectations for regulatory compliance.

Packages of CTD data might include quality, non-clinical or clinical and pharmacovigilance aspects. Early engagement on the acceptability of the submission will provide the developer with the opportunity to make timely changes to their programme in advance of a formal marketing authorisation application.

For biological medicines, such as vaccines, blood products and other immunological biotherapeutics, you will be able to engage early on with the National Institute for Biological Standards and Control (NIBSC) scientists. Interactions will facilitate the rapid establishment of the relevant tests and make sure that, where possible, legally mandated batch testing can be performed in parallel to manufacturer’s in-house testing, ensuring no delays in access to these medicines.

Certification may be considered for the whole of one module or a subsection or across modules if agreed. You can request more than one certification over time for different modules.
Following the submission, the team will assess the modules against the regulatory framework and standards. The outcome of the certification will be a letter summarising the regulatory view of the data, the parts that are satisfactory and the major deficiencies if they exist and opportunities for further scientific advice as needed.

Delivery partners
If you use the Certifications tool you will work with experts from the MHRA divisions and centres.

Related tools
The Certification tool could be used alongside rolling review in the Innovative and Flexible Licensing tool and Adaptive Inspections tool.


Innovative and Flexible Licensing Routes
The tool is intended to provide support and guidance in the choice of routes for products in the ILAP. Some of these routes may be available as options to companies with products outside of ILAP.

The Innovative and Flexible Licensing Routes tool can provide expedited timelines for review, pragmatic approaches to evidence requirements and international options where appropriate and available.

Regulatory licensing flexibilities can be used to expedite the approval process once a product or new indication has sufficient data for regulatory review. Independent laboratory testing can also support authorisations based on reduced data packages through the generation, post-licensure, of data supporting batch-to-batch consistency.

The routes are:
* Accelerated assessment

* Rolling review

* Approval with conditions

* Conditional Marketing Authorisations

* Approval under exceptional circumstances

* Project Orbis

* Access Consortium

Accelerated Assessment
An accelerated assessment procedure will reach opinion on approvability of a marketing authorisation application within 150 days of submission of a valid application. This option is available for good quality marketing authorisation applications for both new and existing active substances.

Eligibility will also include those applications seeking an orphan MA approval in Great Britain and those submitted for conditional and full marketing authorisations as well as those submitted for approval under exceptional circumstances.

Rolling Review
The Rolling Review is a new route for marketing authorisation application intended to enhance development of novel medicines. It does this by offering ongoing regulatory input and feedback. The process is envisaged as a phased, modular, iterative approach to evaluation of marketing authorisation applications.

The quality, non-clinical and clinical parts may be submitted singly or in combinations depending on the individual circumstances as data becomes available. It is expected that each module will be near completion to avoid multiple iterations of assessment of the same module. Each assessment phase will progress independently permitting early identification of issues.

Each assessment cycle with points of clarification raised will offer the applicant the opportunity and time for a comprehensive update of the modules prior to final submission. The final phase will involve submission of a complete application including the remaining module together with updated versions of the modules evaluated previously.

Approval with Conditions
Conditions are obligations that are imposed at the time that the marketing authorisation is granted. Conditions include PASS/ PAES that can be used to provide reassurance that gaps in the evidence generation will be filled appropriately.

Conditional Marketing Authorisation
In order to meet unmet medical needs of patients and in the interest of public health, it may be possible to grant marketing authorisations on the basis of less complete data than is normally required. In such cases, the granting of a marketing authorisation is subject to certain specific obligations to be reviewed annually.

These medicines are for the treatment, the prevention or the medical diagnosis of seriously debilitating diseases or life-threatening diseases, medicinal products to be used in emergency situations, in response to public threats and medicinal products for rare diseases. Conditional marketing authorisation will allow medicines to reach patients with unmet medical needs earlier than might otherwise be the case and will ensure that additional data on a product are generated, submitted, assessed and acted upon.

Approval under exceptional circumstances
For licensing under exceptional circumstances, the applicant must demonstrate that they are unable to provide comprehensive data on the efficacy and safety under normal conditions of use. This may be because:

* the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence or

* in the present state of scientific knowledge, comprehensive information cannot be provided or

* it would be contrary to generally accepted principles of medical ethics to collect such information

Under these circumstances an authorisation may be granted with a reduced clinical data package than would ordinarily be required.

Project Orbis
Project Orbis is an initiative of the Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) that provides a framework for concurrent submission and review of oncology products among international partners including the UK.

Access Consortium
The Access Consortium is a collaborative initiative of medium-sized regulatory authorities between Australia’s Therapeutic Goods Administration (TGA), Health Canada (HC), Singapore’s Health Sciences Authority (HSA), the Swiss Agency for Therapeutic Products (Swissmedic) of Switzerland and MHRA. The purpose of the consortium is to build synergies and share knowledge amongst the regulatory authorities thereby enhancing the efficiency of regulatory systems.

How it works
The TDP will recommend the most suitable routes to market based on the product and patient population to treat in the context of the ongoing development programme.

Regulatory licensing flexibilities can be used to expedite the approval process once a product or new indication has sufficient data for regulatory review. Independent laboratory testing can also support authorisations based on reduced data packages through the generation, post-licensure, of data supporting batch-to-batch consistency.

Early engagement with NIBSC will enable the rapid establishment of the relevant tests to make sure that, where possible, legally mandated batch testing can be performed in parallel to manufacturer’s in-house testing, ensuring no delays in access to these medicines.



Novel methodology and innovative clinical trial design
The Novel Methodology and Innovative Clinical Trial Design tool, co-developed by MHRA, NICE and SMC, is designed to establish a system and culture that is receptive and supportive of novel methodologies in both the clinical and pre-clinical space to develop new medicines or new indications. This includes innovative clinical trial designs, manufacturing, and endpoint development. We will also demonstrate that innovative methodologies are acceptable to all stakeholders, for example by issuing an opinion on the proposed methodology or technology.

The tool has the potential to significantly accelerate development and bring safe, effective medicines to patients faster, balancing the risks and benefits of any novel approaches, with a strong patient focus.

Novel trial designs with virtual and decentralised elements will increase patient-centricity in trials and reduce the burden of taking part, improving recruitment and retention. Qualification and multi-stakeholder regulatory acceptance of novel methodologies will de-risk and reduce the costs of development. The tool will encourage and facilitate the proactive use of novel trial designs for evidence generation – including master protocols – to ensure a flexible regulatory approach that can react to emerging data with a focussed, efficient use of resources.

How it works
According to the individual requirements of the applicant, key outputs from the tool include:

* securing multi-stakeholder agreement for novel and innovative approaches to evidence generation

* qualification of the new methodologies and support via (joint) scientific advice procedures (e.g. with NICE) offered during the ILAP, including targeted inspections of novel technologies

* guideline documents on topics of interest

* encouragement and facilitation of the use of novel trial designs, including master protocols, to ensure a flexible regulatory approach that can react to emerging data with a focussed use of resources

* regulatory assurance on the requirements and acceptability of virtual, AI and decentralised elements in trial conduct

* regulatory assurance on new e-systems technologies that may be used to support any such novel trial designs

You should expect regulatory assurance on the requirements and acceptability of, for example, use of Artificial Intelligence (AI), virtual and decentralised elements in trial conduct, and e-systems technologies used to support such novel trial designs. Developers will also see use of new approaches for qualification of new methodologies, technologies, use of modelling and simulation, and novel endpoints.

https://www.gov.uk/guidance/the-target-development-profile-toolkit