Case Studies Archive - Alacrita

Pharmaceutical Regulatory Affairs Case Studies

Written by Cort | Jun 28, 2022 4:35:37 PM

Alacrita's regulatory affairs consultants provide support to biotech, pharmaceutical and medtech clients, as well as companies and investors conducting regulatory due diligence. Our regulatory team has extensive experience in a range of modalities and therapeutic areas. All of our regulatory specialists are seasoned industry leaders who have spent their careers either working within regulatory agencies or shepherding life science products through regulatory processes. The below selection of regulatory case studies outlines the typical support we provide. 

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Regulatory strategy and preparation for pre-IND meeting with the FDA

Challenge: A biotech company working in the microbiome space engaged Alacrita to provide advice about regulatory strategy and to prepare for and conduct a pre-IND meeting with the FDA. The product in question was a massively multiplex composition that presented complex CMC and assay issues.

Solution: Alacrita's regulatory specialists with experience in the microbiome arena worked closely with the client's management team to develop a regulatory approach to the FDA. Alacrita guided the client team, which took primary responsibility for drafting the pre-IND briefing document, providing critical review and direction along the way. We worked closely with the client to develop a series of key questions for FDA and the pre-IND request was submitted. Due to COVID-19 restrictions, the FDA provided written responses only, but nevertheless the FDA views were very informative and were used to initiate an IND process.

Supporting regulatory affairs due diligence

Challenge: A clinical stage biopharmaceutical specialist needed support with its regulatory due diligence activities for products in the respiratory field.

Solution: Alacrita assembled an expert team comprising an ex-quality assessor who had previously worked in the biologicals unit at the MHRA (primarily on EMA-centralized procedures), and an ex-Senior Director and ex-Medical Advisor for a biotechnology company. The team reviewed all correspondence with regulatory authorities to identify any red flags that needed to be addressed.

This included the following activities:

  • Reviewing proposed validation plans for a new manufacturing process and assessing suitability for MAA using a centralized procedure.
  • Reviewing the packaging used to support two of their products.
  • Reviewing clinical data for one of their vaccines to assess suitability for a new centralized procedure using a well-established use dossier.
  • Identifying any other major deficiencies in the dossier that may prevent an MAA using the centralized procedure.

BLA Submission Regulatory Support

Challenge: Our client was nearing the completion of a pivotal Phase III with a novel antibody-based therapeutic. The product was designed to delay recurrence in cancer patients with minimum residual disease following debulking surgery and standard chemotherapy.

The Phase III trial design had been agreed with FDA under the SPA procedure and the client had gained fast-track status from FDA. In addition, the client had received EMA Scientific Advice and intended to file for Conditional MAA approval subject to satisfactory Phase III results.

Although the client was a fully integrated pharmaceutical company and had significant regulatory experience with small molecules, this was the company’s first biological product candidate to reach the registration stage. The company was therefore seeking to supplement its existing in-house capabilities with the appropriate external biologics regulatory expertise.  Specifically, the company needed to gain a better understanding of the BLA process, clarify the level of detail needed for the various sections of the license application and obtain high-level review and sign-off of the regulatory dossier.

Team Lead: Alacrita’s biologics regulatory affairs consultant spent eight years at FDA/CBER acting as a BLA reviewer before moving into industry where she spent 20 years implementing innovative regulatory and quality strategies for timely product approvals.

Solution: Alacrita prepared and presented an overview of the BLA process to the Client’s BLA Project Team. After the presentation Alacrita held a Q&A session on specific areas of the chemistry, manufacturing and controls, non-clinical, and clinical parts of the Common Technical Document.

Alacrita performed a high-level review and sign-off of each section of the BLA, as it became available, to  ensure consistency of message and highlight any areas that could be improved to enhance the licensure process

Alacrita helped the client prepare for, and participate in, a pre-BLA meeting with the FDA. This included drafting of key questions to pose to the Agency, assistance with preparation of the meeting presentation materials, presentation rehearsal and participation in the meeting itself.

CMC and regulatory support for AAV in vivo trans-differentiation

Challenge: A biotech company developing novel gene therapy approaches for in vivo cell trans-differentiation had lead programs in IND-enabling studies for two indications. The client requested regulatory affairs assistance from CMC and regulatory experts with experience in gene therapies and working with CDMOs, including oversight.

Solution:

Alacrita provided assistance in the below areas on an as needed basis:

  • CDMO site audits
  • Routine meetings with CDMO
  • Analytical review of CMC reports and batch record review
  • CMC plan and process development review
  • QA/QC oversight/review
  • IND preparation and submission
  • FDA INTERACT and/or pre-IND meeting preparation and execution
  • Expedited program designation (e.g. orphan status) applications
  • EMA engagement and submission preparations
  • Environmental risk assessments
  • Establishment of a quality management system

Wound Care Regulatory Support

Challenge: A leading manufacturer of wound care products was assessing opportunities in advanced wound care, and had mapped regulatory pathways that pertained to various classes of product. Having identified various paradigms for currently marketed products in the US including 510K, Class III-PMA, Banked Human Tissue, Biologics License Application;,and New Drug Application, Alacrita was asked to set out the corresponding regulatory pathways in Europe, and to describe the regulatory requirements for bringing three of the client’s products to market.

Solution: For this project, Alacrita drew a regulatory wound care specialist consultant from its Expert Network, who was an MHRA assessor. The final output included descriptions of the considerations used to classify each product into the appropriate regulatory class; risks and uncertainties in such classification and how these may evolve over time; as well as data and documentation requirements likely to be needed for licensure.

Regulatory affairs guidance on expanding capabilities of ancestral DNA device

Challenge: Our client offered a genetic ancestry test in the form of a home kit that contained a buccal swab to collect customer DNA and an analysis service using a SNP array-based chip. Results were then returned to customers through an online interactive website.

The company wished to further develop its service into providing nutritional, fitness and pharmacogenomics information to customers. Alacrita was asked to assess the feasibility of extending the platform and to identify any regulatory hurdles.

Solution:

Alacrita's medical devices consultant assessed the regulatory hurdles of the proposed applications and provided ongoing, ad hoc, advice and assistance with implementing the regulatory processes.

Key analysis points covered:

  • Where the product fell within the regulatory frameworks of the US, UK and Australia;
  • What the simplest route was to ensure compliance with regulations;
  • What was specifically required from the client in order to expand the product offering in these territories;
  • What documentation was needed, who needed to produce this and how long would it take.

After analysis of the above points our regulatory affairs consultant advised the client that the proposed platform development would not be a viable option due to high competition and regulatory hurdles owed to its likely classification as an IVD. As a result the company deprioritized the project.

Regulatory roadmap for a biotech with proprietary nanotechnology

Challenge: Our client was a biotechnology company with proprietary nanotechnology invented to allow different combinations of drugs to be encapsulated in a single nanomedicine and delivered selectively to the tumor microenvironment, thus potentially minimizing systemic side-effects. The client requested our regulatory consulting team A hold a single-day workshop on the data and subsequently develop a regulatory roadmap in collaboration with the company's internal regulatory affairs group.

Solution:

The points discussed in the workshop with the client team included:

  • Understanding regulatory requirements along the development pathway.
  • Determining where the client had immediate needs for regulatory feedback and optimal ways to obtain feedback.
  • Specifying activities/data to be gathered by the client for FDA feedback.
  • A data check: CMC, product characterization, preclinical data, data collected to support dosing and therapeutic indication, safety data, clinical indication(s) considerations, unmet need, exploratory trials.

Based on the workshop, a regulatory roadmap was developed with key actions and timings set out clearly.

Providing regulatory strategy for T-cell therapy

Challenge: Our client, a leading T Cell Receptor (TCR) biotechnology company, with a focus on delivering first-in-class biological therapies. The client wanted to understand whether it had the capabilities to launch its lead product if it were to receive accelerated approval without partnering with a larger company and asked Alacrita for regulatory affairs assistance. The overall objective of the project was to ensure the client was adequately prepared from a regulatory affairs perspective for the possibility of an early commercialization event for the product, which included an assessment of the regulatory pathway for the product and any obstacles that had to be considered.

Solution:

Our assessment comprised three categories:

  1. Marketing approval pathway and data requirements: As a prerequisite for commercialization, the marketing approval pathway and data requirements were evaluated based on the sponsor’s interactions with relevant regulatory authorities and development plans. Having a preferred marketing approval pathway agreed with the agency(ies) and well-defined data requirements and desired labelling for the application reduces risk to achieving a timely approval and, in turn, market launch, for a commercially viable product.
  2. Regulatory strategy plans and execution: The second group of criteria evaluated organizational capabilities to analyze and mitigate development risks and to adequately resource, plan and execute a regulatory strategy leading to marketing approval.
  3. Processes for post approval compliance: Lastly, the regulatory assessment examined the organization’s preparedness to support post-approval compliance requirements to maintain a product license.

A written report was provided to the client summarizing the findings from each analyses and highlighting areas for focus as they work towards commercialization.

 

Our Pharmaceutical Regulatory Affairs Capabilities

We bring over a decade of experience in helping our clients de-risk their regulatory interactions, offering deep expertise in navigating US and EU agency regulations, submissions and responses. 

Click here to learn more about our regulatory affairs consulting services