Welcome to the October 2016 issue of FREYRFOREWORD!

A monthly round-up of the latest happenings and updates from Freyr.
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Freyr receives Frost & Sullivan’s 2016 Best Practices Award

Just into the third quarter, nothing more we could ask for. It’s time for celebrations at Freyr. The joy, the pride and most importantly the delighted feeling of being recognized for our commitment towards addressing the time-critical Regulatory challenges the global life sciences industry is facing today. We are pleased to share with you that Frost & Sullivan, a leading global strategy consulting company, headquartered in the US, recognized Freyr for its best practices in the Life Sciences Regulatory domain and presented us the “2016 India Knowledge Process Services for Life Sciences Growth Excellence Award.”

The background

Frost & Sullivan recognizes outstanding industry achievements by presenting Best Practices Awards to companies that have demonstrated exemplary performance across various industries, commending the diligence, commitment, and innovative business strategies required to advance in the global marketplace. The award program acknowledges the companies that excel in their respective business segments and their efforts to improve the industry as a whole. Frost & Sullivan’s Knowledge Process Services for Pharmaceutical Life Sciences Growth Excellence award identifies companies that exhibit exemplary growth, attributed to enhanced solutions and superior service capabilities.

Why Freyr?

Presenting the award, the consulting firm expressed their views on why they have selected Freyr as:
Freyr is a leading Global Regulatory Services and Solutions provider with an exclusive focus on Regulatory domain for Global Life Sciences industry. Freyr displays a strong expertise in providing end-to-end Regulatory services and solutions to address the time-critical Regulatory challenges the life sciences industry is facing today across diverse Regulatory segments such as Regulatory Affairs and Operations, Submissions and Publishing, Regulatory Intelligence, Labeling and Artwork, Authority Directives, Regulatory Strategy and Business Consulting and Regulatory Information Management.
Freyr has been successfully providing hi-end, next-generation Regulatory Solutions and Services to 6 of the global top 10 Pharma companies, 8 of Top 20 global Generic companies, and 3 of the global top 7 Consumer Healthcare companies, 3 of the global top 6 Biotech companies and 40+ small & medium fast growing global Life Sciences companies.

Freyr has grown exceptionally in 2015, which reflects its capability to offer unique and customized solutions designed to address the regulatory domains such as generics, consumer healthcare, Drugs, Devices, Nutritional Supplements, Biologics, innovative, and therapeutic areas. The company’s performance is driven by the right blend of customer focus, intense competitive technology positioning, and its strategic partnership with top pharma and consumer healthcare companies.

“Given its strategic intent to provide end-to-end regulatory services across the entire value chain, supported by regulatory bodies, Freyr demonstrates a high growth rate in the pharma and life sciences industry. The company, with de-risked Centers of Excellences (CoEs) and with in-house specialized regulatory framework streamlines Regulatory procedures across the lifecycle and ensures the quality of the processes from an operational, subject-matter and technology perspectives.” - Shruti Jadhav, Manager - Best Practice Research, MENASA, Frost & Sullivan.

Aiming at Radically Redefining Global Regulatory Solutions and Services going forth, entire Freyr team is delighted to receive this award at the right time, which keeps us more rooted to our deliverables. Nothing more we could ask for than keeping our clients compliant enough.

Global Labeling Management Roadblocks Disquieting the Efficiency of Pharma Companies

The accelerated introduction of new regulations and guidelines for pharmaceutical labeling industry during past few decades, demands companies to be pro-active in terms of the implementation lifecycles. The dire consequences associated with the erroneous label on a drug or a medical device accounts for severe health risks for the patients. Physicians rely on the label instructions and integrity of the information on the label while prescribing to patients, which further makes it unavoidable for companies to roll out their products with inaccurate labels. However, with the changing landscape of labeling guidelines, released by major health authorities around the globe, the execution challenges emerge as major obstacles in the lifecycle. It further becomes a rigorous task when companies carry out their expansion plans and new geographies are involved. Let’s discuss some major challenges that companies generally stumble upon when it comes to global labeling management.

Collaboration between Global and Regional Teams

Business expansions are obvious in the pharmaceutical industry which in turn demands cross-functional coordination among the teams established across borders. Every geography demands distinct regulations to be followed by the manufacturers in order to make it easy for the regional end-users to understand the label instructions easily. In order to manage the language complexities, pertinent harmonization amid regional and global teams becomes fundamental.

Disparate Data

Global labeling management is set on the foundation of huge volumes of drug and medical devices data scattered over a wide range of sources. Many times this information is distributed in unstructured files and formats which make it difficult for companies to pull out all the relevant information and consolidate it. Information stored at multiple sources further accounts to duplicate records mainly because of different regional versions available across different geographies. In other words, the “single source of truth” is missing here. Since the compilation process is an arduous activity mostly undertaken manually; the possibility of landing on error-prone end-results are quite high.

Incompetent Tracking Process

This activity commonly involves a robust technology in order to monitor the labeling lifecycle progress by tracking and maintaining the repository of products. Failing to deploy a robust global labeling management software solution, companies can witness ineffective tracking that could result in high risk of mislabeling and counterfeit drugs leading to product recalls, affecting overall finances of the organization.

Knock Over these Challenges with Freyr GLX Framework
Freyr is a strategic global partner for labeling change management and helps its clients navigate through the complex labeling processes with an end-to-end labeling Center of Excellence. Freyr has established Freyr Global Labeling Xcellence (GLX) Framework that has enabled organizations uncover potential for managing highly complex, global labeling documents and processes for creating and managing the changes worldwide under well-defined, proactively-intelligent and metrics-driven and technology-enabled environment.

The innovative 360 degree framework ensures quality of end-to-end labeling processes from operational, subject-matter and technology perspectives. The components of this framework broadly includes:

  • Labeling Process Design and Framework
  • Labeling Functional Support
  • Label Management Technology Implementation

A deep dive into the above mentioned segments include:

  • A well-defined process for creating and managing global label documents
  • Managing the changes and deviations in a centralized and streamlined manner
  • Defined SOPs for labeling for Consumer Healthcare and Generic industry to suit the fast-paced environment and low margin product portfolio
  • Technology solution, Freyr LABEL (Freyr’s in-house technology) for global label creation, management and change management
  • Creating a centralized repository of institutional knowledge to assist teams with relevant information in real-time
  • Intelligence driven regulatory services to ensure market specific nuances are available as well as ensure access to ever changing guidelines
  • The Freyr’s GLX has been proven in the industry with Freyr consistently serving labeling clients and their internal procedures using a part or all of the aspects of the framework. The framework has solved key scientific and process-related problems with technology intervention where applicable and availing well-defined processes and KPIs. As a result, Freyr’s clients have been able to realize value upwards of 30% in cost savings in their ongoing programs. Freyr, with its GLX Framework, has been consistently winning all the competitive bids it has participated in the past two years requesting labeling services.

Freyr LABEL, an in-house centralized labeling lifecycle management solution, and as part of Freyr GLX Framework, streamlines end-to-end Regulatory labeling practice in a company of any size. Right from creation, tracking and managing Company Core Data Sheet (CCDS) deviations, CCDS updates, and developments to creating, implementing, and inspecting multi-lingual regional labels as well as custom reporting. Freyr LABEL puts companies in total control of all their regulatory labeling compliance needs to manage the complexity of Regulatory labeling (Core and regional) with a centralized label lifecycle management platform.

Freyr GLX Framework enables organizations to overcome many challenges (Business, Functional and Technical/Operational), that are expected to be faced within the organization both from scientific and operational perspectives.

Get in touch with our experts to overcome the ever-evolving regulatory labeling environment to manage the complexity of process (Core and Regional) with a centralized label lifecycle management platform.

eCTD Submissions  A quick look over the FDA & HC deadlines

Do you know? The United States Food and Drug Administration (US FDA) has mandated that certain Regulatory submission types (NDA, BLA, and ANDA) should be filed in electronic Common Technical Document (eCTD) format beginning May 5, 2017. Also, Health Canada (HC) is considering to make eCTD format mandatory by 1st January 2018. As the drug makers across the world are waking up to the fact that they should do away with the legacy paper document submissions adhering to the HA regulations, let us give you a quick roadmap towards successful eCTD submissions.

eCTD – the definition and the purpose.

According to ICH, eCTD is an interface for industry to transfer  regulatory information while facilitating creation, review, life cycle management and archiving of the electronic submissions. eCTD provides a harmonized technical solution to implement the Common Technical Document (CTD).

The main purpose of this technical solution is to make the Regulatory submissions easier with a common global standard enabled for all drug makers which indeed can streamline the Regulatory submissions to health authorities.

Countries accepting eCTD format

Now eCTD has become a global submissions format. The countries which are accepting eCTD submissions are:

  • US
  • Europe
  • Canada
  • Japan
  • Switzerland
  • Australia
  • Saudi Arabia
  • Oman
  • Thailand

Which applications should be in eCTD format?

As US FDA mandates drug makers who are willing to file the below applications should follow eCTD format:

  • New Drug Applications (NDAs) – 5th May 2017
  • Biologics License Application (BLAs) – 5th May 2017
  • Abbreviated New Drug Applications (ANDAs) 5th May 2017
  • Investigational New Drug Applications (INDs) – 5th May 2018

For Health Canada, the following applications are considered to be mandatory for filing in eCTD format:

  • New Drug Submission (NDS) – 1st Jan 2018
  • Supplement to a New Drug Submission (SNDS) – 1st Jan 2018
  • Abreviated New Drug Submission (ANDS) – 1st Jan 2018
  • Supplement to an Abreviated New Drug Submission (SANDS) – 1st Jan 2018
  • Additional information or subsequent regulatory activities viz. NC, PSUR, RMP, etc. must also be filed in eCTD format – 1st Jan 2018

Why should you adopt eCTD?

  • For reviewers, it saves a lot of time in order to search and edit the submissions with automated functionalities
  • For sponsors, the cost would be reduced as they will not be required to physically ship the documents and create new documents, if any amendments needed
  • With its global standardized format, eCTD can be repurposed for Regulatory submissions to different agencies thus, the enables cost savings

To conclude, electronic submissions are the order of the day. However, Drug makers are not on the verge of deadlines. With a little time in hand, chalk out your region-wise eCTD submissions plan for faster drug approvals. Consult an exclusive Regulatory Submissions & Publishing partner.

Type IV DMF  Drug Master File

Drug Master File (DMF) holds great importance in terms of information associated with several medical products regarding their chemical specifications, and manufacturing. The type IV DMF is associated with the material used in their preparation or as we call them excipients. Excipient DMF is submitted to FDA to support IND, NDA, ANDA, BLA, and other DMF.  Let’s take a tour of the general guidance to prepare Excipient DMF as stated by “The International Pharmaceutical Excipient Council (IPEC) of the Americas”

  • Excipients should follow ICH CTD format
  • Excipient: Other than API which are tested for safety, functionality and included in the formulation
  • There can be a single DMF for single ingredient excipient  / for mixtures formulated to one excipient
  • Excipient DMF submission is not a law, it is up to the DMF holder
  • Excipient DMF will not be approved/rejected
  • The main purpose of filing excipient DMF is to maintain confidentiality of the information containing manufacturing, controls and technical data to support safety and quality
  • DMF should be in English / translated to English (if in other language)
  • DMF should contain
  • US Agent appointment letter (If agent appointed)
  • Statement of commitment (stating that DMF is current)

Maintaining the DMF

  • If DMF holder adds/deletes/changes any significant information from the DMF, then he/she should intimate changes to authorized persons to use DMF in writing
  • Two types of submissions may occur once DMF is filed
  • Significant change reports to FDA (refer IPEC significant change guide for the classification of the changes like Level 1 changes and Level 2 changes)
  • Annual reports to FDA
  • Both the submissions should contain transmittal letter regarding the submission type and complete Letter Of Authorization (LOA) list
  • If no annual report is filed for 2 consecutive years then the FDA will consider DMF as Inactive .

DMF - New Submission

  • Transmittal Letter
  • Contains Type of DMF, US agent address, manufacturer name, manufacturing facility address, holder
  • Statement of Commitment
  • To ensure that the DMF is current and will comply with the statements made, conditions and procedures described herein shall be strictly followed
  • Content according to ICH CTD - Explained

Amendment to Original Submission

  • Transmittal Letter
  • Must contain, type of DMF, US agent address, manufacturer name, manufacturing facility address and holder
  • Statement of Commitment
  • To ensure that DMF is current and will comply with the statement made. Conditions and procedures described herein shall be strictly followed
  • US Agent Appointment Letter
  • Changes Description

Annual Report

  • Transmittal Letter
  • Contains type of DMF, US agent address, manufacturer name, manufacturing facility address and holder
  • Statement of Commitment
  • To ensure that DMF is current and will comply with the statement made. Conditions and procedures described herein shall be strictly followed
  • US Agent Appointment Letter
  • List of changes during one year period, with dates
  • List of authorized parties to refer the DMF, dates of LOAs
  • List of parties whose authorization has been withdrawn to use the DMF

Technical content of the DMF

Recommendations from FDA

  • A4 size
  • 8.5×11 size paper
  • Times new roman font 12 size

Is recommended and any required binders should be used as per the DMF specified by FDA.
Description & Characterization
Physicochemical characterization of the excipient (if it is a mixture – composition of the mixture)
Intended Use
Maximum daily dose, functionality, human/veterinary use etc.

Characterization of the Excipient

  • Physical characters: Color, MP, BP, Refractive index, Pk, Optical rotation
  • Chemical structure: proof of structure (IR, NMR, UV, optical rotation, MS etc.,)
  • If the excipient is USP/NF grade then no need to further characterize the excipient. If not, detailed methodology and validation data should be provided
  • If the excipient is not official
  • Qualitative and quantitative description, proof of structure (IR, NMR, UV, optical rotation, MS etc.,), chemical attributes like – M.P, structural formula, empirical formula, molecular formula etc.,
  • Any recordings like chromatograms / graphs etc.,
  • Purity tests like HPLC/GC/TLC/appropriate analytical procedures

Facilities Description
Address and contact details of the manufacturing site

Manufacturing
Origin of materials, flow chart of manufacturing process, identify critical steps, key equipments, controls and packaging

Process Controls during Manufacturing and Packaging

  • Controls during manufacturing and packaging
  • Acceptance criteria and results

Specifications

  • Based on the developmental data, manufacturer should propose specifications
  • If any monograph controls the excipient, and reference to monograph should be provided and all the tests in the monograph should be included and additional test methods should be validated.
  • If the excipient is of non-compendia excipient then minimum specification should include description, identification assay, impurities, water content (if applicable), physicochemical characters (pH, viscosity, particle size etc.,) of the excipient

Reference Standards for Materials
Details regarding used reference material

Batch Analysis

  • Size, date, batch number
  • Minimum of 1 COA should be provided

Stability

  • Most of the excipients are stable but some excipients which are liable to change with respect to time – manufacturer should conduct stability studies on 3 batches (minimum of pilot scale)
  • Refer IPEC guideline for further information.

In Conclusion

In order to ensure quality, safety, and efficacy of the medicines it is critical to maintain quality of the excipients. The drug formulations are influenced by excipients to a great extent due to which the API (active product ingredient) and drug products falling under categories of cosmetics also get impacted. For that reason, implementing GMP (Good Manufacturing Practice) standards and maintaining smooth CMC operations for the excipients becomes necessary.

eTMF Implementation: An Electronic Arrangement to Handle Clinical Trial Documents

Background

For any Pharma or Life Sciences company involved in conducting clinical trials, maintaining / managing a Trial Master File (TMF) is inevitable. A decade ago, the master file enclosed heavy volumes of paper-based documents for majority of the clinical trials carried out. The only central location for these documents, supporting compliance requirements and good clinical practices, was a physical repository piled up with stacks of files. Such arrangement of documents led to discrepancies and inconsistencies in TMF in terms of file name, structure classification and information distribution among various stakeholders. Although there were companies that adopted an internal TMF structure that covers a better classification outline and content model for existing TMFs, it did not align with that of the TMF arrangement carried out by other clinical trial stakeholders in the industry.

To address the inconsistency in TMF structure, a source model was announced in 2010 that represented as a reference point for all clinical trial stakeholders in the industry. The new TMF model standardized document names, classification and descriptions that could be used commonly by majority of the stakeholders. It has been observed that companies utilizing electronic document management system for clinical trials witnessed higher degree of quality in clinical study, improved cost effectiveness and reduced timelines. Subsequently several pharma companies involved in clinical trials are eager to shift from huge volumes of paper-based CT documents to a centralized online mode of document management system.

Advantages for Pharma Companies Implementing eTMF Models

In the era that is evolving constantly, organizations tend to move faster and expect the exchange of documents in a snap of finger and the accessibility of information from anywhere, anytime. In this context, eTMF delivers advanced features of document management with high data security to manage clinical trial information. From a business value standpoint, companies using eTMF solutions can be benefited in following aspects:

High Quality of Documents

eTMF is an automated document management system. Thus it offers very minimal scope of errors in document management as compared to paper-based processes, handled manually.

Abridged Overall Cost

Implementation of eTMF helps reducing overall compliance overheads since the extra costs incurred in manual auditing and report generation are saved.

Improved Accessibility

One of the major drawbacks with paper-based TMF management system is the difficulty in accessing a specific file remotely. eTMF eliminates these shortcomings and offers an easy and secured access for viewing, sharing, and retrieving any file from anywhere, anytime with customizable access levels.

What features should an effective eTMF solution entail?

While planning to integrate eTMF with their on-going practices, companies need to consider few key aspects that an eTMF solution should have.  Following are some of the features /aspects they should look upon:

End-to-end TMF Process

When looking for an eTMF solution, consider a complete package that offers services right from set up to configuration to management to reporting and auditing of clinical trial documents. It should allow to create and index documents as per the agency’s TMF structure. Auditing is an essential element of a complete eTMF system, therefore the solution should also support internal and external audits in all aspects.

Flexibility

This aspect of an eTMF solution accounts for the performance and versatility in order to adapt to any kind of organization. A flexible solution should enable competency for both small and large clinical trials without disturbing the system performance.

Customizable

In order to be suitable for every kind of infrastructure comprising clinical trial documents, the solution must be highly customizable. Features like advanced search options, user management controls, monitoring activities, categorizing of groups, etc. accounts to a customizable eTMF solution.

Cloud Infrastructure

Remote accessibility is one of the prime features that an eTMF solution should have which enables companies to author, review and approve clinical trial documents and update global repository in real-time provided the solution is securely cloud-hosted. If an eTMF solution facilitates the cloud advantage, it will offer companies a comprehensive global access functionality.

Clinical Cosmetic Safety Assessment
Freyr has successfully assessed 40+ products across diverse global brands as part of clinical cosmetic safety assessment for a global top 5 Pharma and Consumer Health company. Know more.
CLIENT

Global Top 5 Pharma & Consumer Health Company

GEOGRAPHY

Asia Pac

FUNCTIONS

Regulatory Affairs

SOLUTIONS

Clinical Cosmetic Safety Assessment

THERAPEUTIC AREA / INDICATION

Skin Care, Baby Care, Wound Care, Oral Care

PRODUCT

OTC

BENEFIT HIGHLIGHTS

  • Assessed 40+ products across diverse global brands
  • Submission of fast track assessment reports within a week
  • Significant cost benefits with strategic advice on claim support for “To-be” marketed products

BUSINESS IMPERATIVES

  • The project required performing a benefit and risk assessment report on the product and regulatory filing strategy
  • The focus was to provide consultation in terms of the clinical safety tests required based on its available data, exposure and intended population.

CHALLENGES

  • Providing rational and scientifically sound clinical safety assessment in a time-bound frame ensuring cost effective solutions
  • Effective communication with the formulators from different countries
  • Helping client to streamline and harmonize clinical safety assessment across all the business regions.
  • No clear information about the safety and efficacy of the product

FREYR SOLUTIONS & SERVICES

  • Provide highly rational and scientifically sound clinical safety assessment to determine the clinical safety of the client products
  • Minimize redundant testing for similar formulations
  • Conduct literature search and compile the scientific data to enable client to design strategy to elevate their efficacy and safety standards of their products

CLIENT BENEFITS

  • Rationale, sound and scientific assessment enabling client to place the products confidently in market
  • Fast-track assessment report delivery timeline within 6 working days
  • Strategic advice on claim support for to-be marketed products
  • Significant cost-reduction by providing technical justification to support the safety of the product
  • Freyr has assessed over 40 products across diverse global brands
Robust Program Management
 
Explore how Freyr established a centralized and robust PMO and streamlined processes across Europe, Middle-East and Africa for a global top 5 Pharma company.
CLIENT

Global Top 5 Pharma Company

GEOGRAPHY

Europe Middle East and Africa

FUNCTION

Regulatory Affairs

SOLUTION

Program Management Office

BENEFIT HIGHLIGHTS

  • Successfully establishing a centralized PMO
  • Defined processes and streamlined metrics
  • Substantial savings on cost of compliance

BUSINESS IMPERATIVES

  • The client needed to set up a robust Program Management Office (PMO) for EMEA
  • The PMO is responsible for defining, planning and scheduling the program goals, milestones and deliverables in consonance with the client’s requirements.
  • Freyr needed to deliver the EMEA centralization program within the agreed quality, costs, resources, and scope and time parameters.

CHALLENGES

  • The PMO was expected to function in a complex environment such as multiple stakeholders, diverse geographically distributed teams and multiple business units
  • No single platform to identify the synergies between the various projects being executed by different teams.

FREYR SOLUTIONS & SERVICES

  • Freyr developed a centralization strategy to provide both strategic and operational oversight to all the projects
  • Delivery of program within the agreed quality, costs, resources, and scope and time parameters
  • Predictive cost tracking to ensure optimal utilization of allocated budgets

CLIENT BENEFITS

  • Substantial savings due to reduction of onsite contractors
  • Cost avoidance on several critical compliance mandates
  • Ongoing compliance to health authority mandates
  • Development of metrics resulted in identification and elimination of inefficiencies