Customized Solutions for Complex Challenges
R&D Idea to Registration Framework
Situation
A rapidly expanding global biological solutions company aspired to develop an ideation to registration framework to accelerate product development from R&D to registration and commercialization.
Commercial and technical resources were being added in multiple countries with minimal awareness of other products being developed outside their specific country/region.
Solution
Our NGT principal led an international team to define an end-to-end process to integrate R&D, regulatory, operations, manufacturing, marketing, sales, and intellectual property protection activities.
Market and customer feedback loops were established at each development stage gate to address changes within regulatory and other external factors.
Tools were designed to capture key technical, market, and financial information essential to the success of new product development and commercialization in strategic market segments. A reward and recognition system was developed to build engagement, acknowledge achievements, stage gate advancements and first sales, and create awareness amongst colleagues and leaders globally.
Impact
Development and deployment of the end-to-end process:
Improved lab to marketplace connection and well-defined product concepts with customer-validated key competitive advantages,
Improved cycle times from one stage gate to the next, and
Transformed individual country/regional silos into efficient global network recognizing that common country-specific product concepts could be more efficiently developed under a globally integrated framework.
Candidate to Clinic Acceleration
Situation
A pharmaceutical company’s promising lead compound unexpectedly failed in a Phase 1 trial due to insufficient exposure. Despite the trial failure, the company had confidence that the knowledge and experience gained from previous pre-clinical pharmacokinetic (PK) testing and the Phase 1 trial would allow them to quickly and efficiently advance structurally similar compounds.
Solution
NGT’s consultants identified structurally similar compounds from the company’s candidate drug library that met the desired in vitro criteria and had profiled well in a non-human primate PK study. Two of these compounds were selected for testing in healthy human volunteers.
Impact
Focusing on molecules structurally similar to the first asset enabled the company to leverage the lead's preclinical safety package and profile multiple compounds in a new Phase 0/1 study at sub-therapeutic doses. Ultimately, the company selected a new progression compound more quickly and at a lowered cost compared to the original lead compound's development.
Leveraging Early-Stage Clinical Data, Enabling the Start of Phase 3
Situation
After completing Phase 2 clinical trials for a small molecule cardiovascular asset, a pharmaceutical company wished to advance a new salt form of the active moiety, possessing superior physiochemical properties, into Phase 3. The company hoped to leverage data from a Phase 1 PK/PD comparator study with the FDA to mitigate the need for larger Phase 2 clinical studies.
Solution
NGT subject matter experts reviewed the data in the clinical study report (CSR), researched public-domain literature, and consulted with Key Opinion Leader’s. A report was written outlining approaches that would hold up to regulatory scrutiny.
Impact
The client accepted NGT’s recommendations, commencing dialogue with the FDA, and laying the groundwork for entry into Phase 3.
Late-Stage Development Report
Situation
A start-up company with an asset ready to enter Phase 3 enlisted the support of NGT’s consultants to prepare an end of Phase 2 product development report, which was to include an assessment of the company’s CMC strategy and an articulation of the steps necessary to achieve the commercial cost of goods target. The start-up company executives indicated that the report was also to be presented to a potential commercial partner.
Solution
NGT’s consultants created a regulatory and technology development report that included levers to reduce the cost of goods and a framework for finalizing the API and DP commercial processes. NGT’s consultants also performed an eCTD submission gap assessment (e.g., evaluation of critical process parameters, critical quality attributes, and material attributes) and provided a regulatory starting material strategy. In addition, a digital validation lifecycle management solution was introduced to fulfill validation requirements, including customized risk and knowledge management processes.
Impact
The commercial partner endorsed the cost of goods reduction proposal and other CMC recommendations enabling the start-up company to secure the finances necessary to proceed into Phase 3.
Acceleration Through Manufacturing Technology Innovation
Situation
A large pharmaceutical company sought to accelerate product launch timelines for several small molecule drugs in clinical development by transitioning from a batch to a powder-to-coated tablet continuous manufacturing platform. The company wished to accommodate smaller production volumes without compromising its ability to rapidly scale-up for anticipated variable supply demands.
Solution
Conceptual design of a modular, small footprint continuous tablet manufacturing platform inside of an autonomous shell that allowed for parallel workstreams at different locations was developed. Equipment platforms and factory shells were to be pre-fabricated and pre-qualified at different off-site locations concomitant to on-site facility preparation. A business case was prepared and presented to company governance bodies to align key stakeholders and secure project financing. Upon endorsement, we provided design and fabrication oversight in close collaboration with internal and external partners.
Impact
The new facility was fabricated according to plan and successfully deployed, commissioned, and validated in time for the commercial manufacture of a recently approved drug. The company planned to launch several small molecule drugs from this new facility.
Rare Disease Regulatory Strategy
Situation
A pharmaceutical client acquired an asset with considerable Phase 2b data supporting a cardiovascular indication. The company wished to repurpose the chemical entity to treat a rare disease and required regulatory and clinical support to submit a type B meeting request to the FDA.
Solution
NGT consultants analyzed the cardiovascular clinical study reports, disease history, public domain literature, and other related internal documents. NGT consultants subsequently developed a Product Development Plan that included a 505(b)(2) roadmap and a financially viable clinical program for the rare disease indication.
Impact
The proposed strategies provided the client with the most expeditious registration and market access pathways enabling compressed timelines and manageable budgetary options.
Quality Management System Design & Implementation
Situation
A start-up pharmaceutical company with a promising pre-clinical development drug candidate wanted to utilize an existing non-GMP facility to manufacture clinical, and potentially commercial, supplies of the compound.
Solution
An extensive evaluation of the company’s existing facility, processes and procedures was conducted. To ensure compliance with current Good Manufacturing Practices (cGMP), a fully cGMP compliant Quality Management System (QMS) was designed and implemented for the existing facility.
Impact
Implementation of the QMS system ensured that the existing facility was cGMP compliant for both clinical and commercial drug manufacturing. With a cGMP compliant facility, the client could proceed to manufacture their promising drug candidate for clinical development. Overall, converting the existing facility to a cGMP compliant facility resulted in substantial cost savings and an accelerated clinical development timeline.
GMP Quality Remediation After FDA 483/Warning Letter
Situation
A pharmaceutical company received numerous FDA 483’s and a Warning Letter related to continual non-conformance of the company’s Quality Management System with respect to current Good Manufacturing Practices (cGMP). Continued non-conformance and/or unsatisfactory responses could have resulted in the company entering into a Consent Decree with the FDA that would have caused delays and exposed the firm to significant financial risk.
Solution
An extensive audit of the company’s Quality Management System (QMS) was completed and a corrective and preventive action plan (CAPA) was developed and implemented.
Impact
A high-quality, robust cGMP compliant Quality Management System (QMS) was deployed, and all FDA 483 and Warning Letter observations and deficiencies were satisfactorily addressed. Overall, the new QMS system reduced the likelihood of further regulatory action, which could be time-consuming and expensive.
GMP Quality Remediation After Consent Decree
Situation
A pharmaceutical company entered into a Consent Decree with the FDA related to continual non-conformance of the company’s Quality Management System (QMS) with current Good Manufacturing Practices (cGMP).
Solution
An extensive audit of the company’s QMS was completed, followed by assistance with developing and deploying appropriate corrective and preventive actions (CAPA) and daily support of critical quality systems. Certification of satisfactory CAPA completion against current standards and monitoring of effectiveness through ongoing audits was also provided.
Impact
A robust, cGMP compliant Quality Management System was put in place, all Consent Decree commitments were met and financial impacts to the company were minimized.
