advanced therapies guide from complex to controlled - vineti | cell … · 2019-09-04 · advanced...

ADVANCED THERAPIES GUIDE

From Complex To Controlled Proven data management strategies for greater speed and simplicity in operaCons and filings

Heidi Hagen - Chief Strategy Officer and Co-Founder Christophe Suchet - Chief Product and Compliance Officer

TABLE OF CONTENTS Overview 3 Introduc0on 4 Data volume, data quality, and good data management 5 Unique data management challenges 7

Living “raw material” 7 GMP outside the “four walls” 8 Traceability requirements 9 Mul0ple, variable data sources 9 Increased risks 10

Six essen0al strategies for data management success 11 Strategy 1 - Automate 11 Strategy 2 - Adopt technology early 11 Strategy 3 - Employ ecosystem exper0se 12 Strategy 4 - Standardize 12 Strategy 5 - Make collabora0on manageable 13 Strategy 6 - Op0mize analysis and repor0ng 14

Six benefits of a modern data management approach 15 Benefit 1 - Improved pa0ent safety, pa0ent care, and compliance 15 Benefit 2 - Product and process understanding 15 Benefit 3 - Collabora0on with regulatory agencies 16 Benefit 4 - Reduced 0me to filing 16 Benefit 5 - Reduced cost 16 Benefit 6 - Scalability 17

Conclusion 18 About the Authors 20

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FROM COMPLEX TO CONTROLLED: Proven data management strategies for greater speed and simplicity in opera0ons and filings © Vine0 2019V I N E T I . C O M / C O N TA C T

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O V E R V I E W

•The personalized nature of many advanced therapies profoundly changes the nature of clinical development and regulatory filings, requiring a modern data management paradigm.

•Personalized therapeu0cs bring greatly increased data volume and data complexity to clinical trials, regulatory submissions, and commercializa0on, especially in the area of chemistry, manufacturing, and controls (CMC).

•Six designed-for-purpose data management strategies, outlined in this white paper, can provide an effec0ve solu0on, especially in the cri0cal area of CMC.

•These data management strategies will deliver a range of benefits that support more efficient, effec0ve regulatory submissions for advanced therapies.

•Biopharmaceu0cal sponsors who adopt modern data management will be more in sync with recent regulatory guidances, and well-posi0oned to benefit from the next wave of innova0on.

V I N E T I . C O M / C O N TA C T �FROM COMPLEX TO CONTROLLED: Proven data management strategies for greater speed and simplicity in opera0ons and filings. © Vine0 2019

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I N T R O D U C T I O N

Advanced therapies — cell therapies, gene therapies, personalized cancer vaccines, and gene0cally tailored therapies — are a rela0vely new category of drug products genera0ng widespread excitement. Almost $37 billion in global investment has poured into advanced therapies since 2015. 1

Funding, however, is only one of many requirements to reach pa0ent popula0ons in need. Other hurdles, including R&D, regulatory submissions, and infrastructure development must also be overcome. This is demanding, as evidenced by the mere 14% success rate typically seen for drug development programs. These challenges are amplified 2

in advanced therapies. According to one recent study, clinical trials have seen an 86% increase in the total number of endpoints per trial in a recent ten-year period, much of which can be akributed to the growing volume of advanced therapy trials. 3

To address these challenges, new data management prac0ces have emerged as a solu0on, especially in advanced therapy products. A key factor in filing success for personalized therapeu0cs will be the ability to capture, manage, analyze, and report on the large quan0ty of pa0ent-specific data generated to support the chemistry, manufacturing, and controls (CMC) sec0on of a license applica0on.

The first half of this paper, wriken by industry experts involved in mul0ple, successful cell therapy filings, discusses the new challenges of data management for advanced therapies — why and how data management has become much more complex. The second half outlines the essen0als of implemen0ng a successful data management strategy and the benefits of doing so.

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REGULATORY FILING COMPONENTS

Regulatory filing applica0ons require sponsors to submit documenta0on demonstra0ng the safety and efficacy of a product. For a commercial marke0ng license, this typically includes:

• Preclinical and clinical data that includes safety and efficacy informa0on

• Product labeling samples • Informa0on on the chemistry, manufacturing

and controls of the product • A valida0on summary • A descrip0on of the manufacturing facility • Reports on clinical experience • Serious event narra0ves


D A T A V O L U M E , D A T A Q U A L I T Y, A N D G O O D D A T A M A N A G E M E N T

Many of the unique data challenges in advanced therapies arise from their pa0ent- and donor-centric supply chains. The amount of data in a typical Biologics License Applica0on (BLA) filed with the U.S. FDA or Marke0ng Authoriza0on Applica0on (MAA) filed with the E.U. EMA is already large, olen in the range of several thousand pages. Advanced therapies generate significantly more data because of the need to connect the individual pa0ent supply chain data for each pa0ent product with the individual pa0ent clinical data. A typical BLA will have pooled data from three to five conformance lots for manufacturing, plus the development data from all the GMP lots used in clinical trials. Personalized therapies also require data for each batch — but each pa0ent may be a batch of one. Sponsors then need to connect each individual lot with each pa0ent and pool data for overall manufacturing consistency and robustness. If an advanced therapy trial enrolls several hundred pa0ents, the data pool thus expands drama0cally.


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Figure 1: Data capture along the advanced therapy supply chain


Advanced therapeu0cs are therefore likely to generate a much greater amount of data than a tradi0onal drug product — with more data to be managed and analyzed for regulatory review. For example, an industry execu0ve recently noted that a single gene therapy BLA consisted of about 60,000 pages. 4

In addi0on to greater data volume, the types of data generated and required differ as well. According to one FDA es0mate, the agency’s review of gene-based therapies is the reverse of that for tradi0onal therapeu0cs. Tradi0onally, about 80% of a review focuses on Clinical, and about 20% on CMC. But in advanced therapies, it is the inverse, with the majority of the focus on CMC, not Clinical. In the case of the above-men0oned BLA, for example, the industry 5

execu0ve stated that most of the 60,000 pages submiked to the FDA focused on CMC.

The purpose of the CMC sec0on in any BLA is to provide enough evidence and assurance of product safety, iden0ty, quality, purity, and strength to support the asser0on that pa0ents will receive a well-understood, consistently produced, safe, and efficacious product. Given the inherently complex and unique biology of pa0ents, the produc0on process, the large volume of data to be managed for advanced therapy submissions, and the CMC-focused nature of that data, it is essen0al to clarify what key data management terms mean, and what successful data management looks like.

High-quality data has five key characteris0cs:

• Validated - the data collected measures what it is intended to measure, and the accuracy and quality of the source data has been confirmed in pre-determined and formal valida0on protocols.

• Complete - all of the required informa0on is collected and there are no gaps.

• Accurate - all of the data captured is factually correct and without error.

• Standardized - the data entries are captured in an expected and consistent format.

• Timely - the data is collected and available in real-0me (or near real-0me).

Data specific to advanced therapies typically includes:

• Pa0ent-specific CMC data from the supply chain and opera0ons (biological collec0ons to finished product).

• An integrated view of the CMC data linked to individual pa0ent Clinical outcomes (in addi0on to the typical aggregated CMC and Clinical summaries).

• Assessments and data compila0ons of product handling prior to, during, and aler manufacturing.

Above all, industry veterans find it essen3al to focus on one guiding principle: the pa3ent and/or donor is the central source of both CMC and Clinical data.

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U N I Q U E D A T A M A N A G E M E N T C H A L L E N G E S

L I V I N G “ R A W M AT E R I A L”

In a pa0ent-specific supply chain and manufacturing process that relies on a living “raw material” — human cells — the pa0ent or donor is the product. Batch sizes are small (olen individual) and tailored, but the amount of data each generates is large. In the case of autologous products, each pa0ent’s cells make a single batch of drug product specific to that pa0ent.

An autologous cell therapy product typically has mul0ple batch records — some0mes as many as 20 per product — that can be hundreds of pages long for each pa0ent. Each individual pa0ent’s supply chain data must be captured and connected with each individual pa0ent’s clinical trial data, in addi0on to being pooled to demonstrate overall manufacturing consistency and robustness. This generates a high volume of data — and a mul0-dimensional complexity to data capture and analysis — not seen in tradi0onal drug products and essen0al for the CMC sec0on of any advanced therapy filing.


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Figure 2: The pa0ent-centric circular supply chain


G M P O U T S I D E T H E “ F O U R W A L L S ”

Associated with the need to procure the raw material from a pa0ent or donor are three addi0onal complica0ng factors that impact data quality:

• The drug product process, from cell collec0on to infusion, will likely take place in mul0ple loca0ons such as hospitals and clinics, some of which are not typical GMP facili0es. However, for advanced therapies, these centers are required to follow regulated GMP procedures and capture data in a compliant manner.

• The distributed nature of the supply chain results in a high number of stakeholders, olen opera0ng in silos with their own processes, systems, and priori0es; all stakeholders generate important data, which must also be captured and integrated in a compliant manner.

• Live cells create an urgency, or “real-0me,” aspect to the supply chain. They require special handling and tracking at every step to ensure appropriate viability and biological ac0vity and link to the correct pa0ent, including while holding and processing cells aler collec0on and during manufacturing.

As an example, immune cells, such as T-cells, are commonly collected through apheresis. This procedure may be done at a community blood center or at a medical center, neither of which typically operates under GMP and may not have digital supply chain management plarorms of their own. Data are generated at every point in the process, for every batch, and every pa0ent or donor.

Olen, these procedures and documenta0on are recorded on paper. A recent study indicates that as many as 26% of trial sponsors and 52% of contract research organiza0ons (CROs) con0nue to use paper case report forms. Paper-based processes, however, have a higher risk 6

of error and delay. Before digital systems were available, manual data processes required numerous personnel, including clinical, quality, manufacturing, and supply chain. The pa0ent focus would be paramount to make sure the therapy would be delivered. But paper processes cannot be scaled for higher volumes of pa0ents. In addi0on, lack of integra0on across various stakeholders was a challenge.

According to one manufacturing study, automa3on would yield a projected 25% reduc3on in material rejects and reviews, which, in turn, would free up significant staff hours that would be otherwise spent reviewing manual data entry and re-entering faulty informa3on. Automa3on also reduces field ac3ons generated by

manufacturing sites, and generates a $2 million savings, at minimum. 7

These factors affect the volume and quality of data that must be monitored, analyzed, and summarized to ensure pa0ent safety and support a robust CMC sec0on that can be integrated with the Clinical data sec0ons. They also lead to increased risk for the product and filing by complica0ng traceability and increasing the poten0al 0me and cost of comple0ng a filing if high-quality data is not readily available and easy to analyze.

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T R A C E A B I L I T Y R E Q U I R E M E N T S

Chain of Iden0ty (COI) and Chain of Custody (COC) are essen0al data sets for both ongoing pa0ent safety and regulatory filings. COI is the fundamental method for ensuring pa0ent safety on each advanced therapy product journey from order through treatment. It provides an overarching method for linking key iden0fiers and data to a par0cular pa0ent or donor throughout the process and ensures that the pa0ent is treated with the correct cells (in the form of drug product). Traceability is so important that regulators (both the FDA and EMA) require robust traceability systems be in place for most advanced therapies , and a detailed 8 9

systems and methods descrip0on must be in license applica0ons.

Traceability informa0on — data and repor0ng — also plays an indispensable role in day-to-day opera0ons, rou0ne compliance, and regulatory inspec0ons. It is important to have this informa0on available on demand. There are many points in the process, for instance, where it is crucial to verify that the correct pa0ent’s cells are in the right place and undergoing the appropriate procedures. Addi0onally, Quality and other stakeholder groups will rely on COI and COC reports and data points to inves0gate devia0ons, isolate root cause, and iden0fy trends. Ready access to traceability reports will also be vital for inspec0ons by regulatory agencies as this is a key pa0ent safety aspect.

And in advanced therapies, traceability olen does not end with treatment. Long-term monitoring requirements need ongoing COI and associated data tracking for a significant 0me period aler the pa0ent is treated — in some cases for the life0me of the pa0ent.

M U LT I P L E , V A R I A B L E D ATA S O U R C E S

Mul0ple sources of data across the supply chain drive high variability in data quality and create accessibility issues. Sources of pa0ent-related supply chain data can typically include:

• Healthcare providers complete a cell collec0on report which may include data on pa0ent or donor health status, processing 0me/custody, cell collec0on data, and cell condi0on data.


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COI AND COC DEFINED

Chain of IdenCty: COI is the permanent and transparent associa0on of a donor’s unique iden0fiers to their 0ssue or cells, and the resul0ng drug product, for the en0re process from order through manufacturing to treatment and post-treatment monitoring. For example, an autologous donor’s pa0ent number should be linked to their unique dona0on number and manufacturing batch number as part of the COI.

Chain of Custody: COC is a core component of the COI which captures the “who, what, when, and where” related to the raw material and drug product star0ng from 0ssue/cell collec0on to product administra0on. This includes iden0fying the staff that handled the raw materials or drug product, what ac0ons were performed, and the loca0on, date, and 0me of any ac0ons.


• Couriers and transporta0on systems provide pick-up and drop-off dates/0mes, custody data, and packaging and environmental data.

• Manufacturing produces unit opera0on data, custody and 0ming data, and product quality control data.

• Pa0ent treatment data may include opera0onal data on infusion, concomitant medica0ons, and pa0ent health data.

I N C R E A S E D R I S K S

With so much data and complexity involved, there is addi0onal risk to:

• PaCent safety - each pa0ent must receive the correct drug product handled with appropriate and defined procedures.

• PaCent and HCP experience - lack of real-0me visibility into the status of any part of the value chain affects the level of trust and service for key stakeholders, such as the pa0ent and health care providers, who need to be apprised of delays and other product success issues.

• Product and process knowledge - incomplete data or data that is difficult to access and analyze may prevent the most complete understanding of the product and process possible.

• Regulatory filing Cmelines - high volumes of data in mul0ple loca0ons and formats requires more resources and 0me to compile, harmonize, analyze, and summarize.

• OperaConal efficiency - manual and disconnected systems and data create opera0onal inefficiency, including higher error rates.

• Cost - inefficient opera0onal, trial, and filing prepara0on ac0vi0es require more 0me and resources.

• Compliance - regulatory agencies have clearly ar0culated the requirements around traceability and data capture for advanced therapies, both in guidance documents and approval summaries.

• Security - a variety of patched together informa0on repositories — paper and/or electronic — make it difficult for sponsors to ensure that all applicable laws and standards are met.

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AUTOMATION IN ACTION

Within the manufacturing process, cell therapies can have variability from one pa0ent product to another for process

intermediates, such as the number of cell culture bags required for incuba0on. To address the risks that this variability presented for one cell therapy product, the decision was made to create a scan-in and scan-in out verifica0on process that ensured COI/COC and made it much easier on the different manufacturing

personnel in different manufacturing sites.


S I X E S S E N T I A L S T R A T E G I E S F O R D A T A M A N A G E M E N T S U C C E S S

Based on decades of collec0ve experience in advanced therapies, Vine0 has iden0fied six fundamental strategies that will help provide more successful data management, meet opera0onal objec0ves, and streamline the process for regulatory license applica0on submission.

S T R AT E G Y 1 - A U T O M AT E

Using automa0on will help deliver data completeness, improve efficiency and quality, and reduce resource needs, Consider:

• Leveraging cloud technologies to maintain compliance across the supply chain and to accelerate and enable ongoing standardiza0on.

• Building intelligent algorithms to op0mize regional scenarios, capacity management, and scheduling across all ac0vi0es: collec0on, manufacturing, transporta0on, and treatment.

S T R AT E G Y 2 - A D O P T T E C H N O L O G Y E A R LY

A digital plarorm has become more essen0al for effec0ve data management in early phases, with the right 0ming varying from product to product. Implemen0ng standardized, automated processes early will make consistent data capture and filing prepara0ons far easier as data volume increases.

• Earlier is generally beker — the right 0ming will be a func0on of scale, complexity and stage.

• The threshold for a digital plarorm could be a low as 10 to 20 pa0ents if the process is quite complex and batches are being processed with regularity. Any system implemented, especially those implemented early, should be capable of adap0ng to process refinements and growth. Balance the cost-benefit issue by considering the cost of not achieving pa0ent safety and regulatory success.


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- Expert Tip -

Focus on automa0ng cri0cal process steps and data

elements for the end-to-end process that protect pa0ent

safety, support efficient opera0ons, and streamline

the path to filing.

- Expert Tip -

Implemen0ng a digital plarorm at the start of a trial or trial phase (instead of mid-trial or mid-phase) saves 0me

and money by avoiding re-training, conversion of

exis0ng data, and change management.


S T R AT E G Y 3 - E M P L O Y E C O S Y S T E M E X P E R T I S E

The value of experience is heightened in a space that is s0ll evolving. Sponsors can look to their ecosystem partners for exper0se in cri0cal areas, such as technology. Implemen0ng digital plarorms that enhance compliance and have passed the hurdles for regulatory approval provides proven support.

• In addi0on to the system itself, consider the experience of the vendor team. It is important that they have both opera0ons and regulatory experience in real-0me biological supply chains and deep knowledge of solware prac0ces in a regulated environment.

• Leverage proven off-the-shelf configurable solware (versus custom-developed) to take advantage of regulatory authori0es’ familiarity with the plarorm, industry standards, and simpler updates that support ongoing regulatory compliance.

S T R AT E G Y 4 - S TA N D A R D I Z E

Data standards do not yet exist broadly in many areas of the industry. Standardizing data and processes provides a 10

significant step toward crea0ng a data set that is complete and easily analyzed. Some of the key areas to standardize for support of the CMC sec0on include pa0ent iden0fica0on, COI, pa0ent material data collec0on, and labeling.

• Data variability olen stems from disparate data collec0on and repor0ng systems, including paper-based systems, digital systems, and a mix of both — especially when the systems of record are owned and managed by individual stakeholder organiza0ons.

• Standardized formats are not common from organiza0on to organiza0on and it may be difficult to access informa0on quickly, or at all.

• A complete data set is essen0al for correct interpreta0on of product safety and efficacy, and for op0mizing the pa0ent experience, the process, and the product. These issues must also be resolved in order to prepare a quality CMC sec0on.

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- Expert Tip -

Choose digital plarorms that demonstrate prior regulatory

authority acceptance and performance with full-scale

opera0ons.

- Expert Tip -

Work with all stakeholders (internal and external) on

standardized data collec0on, and u0lize systems that make

standardiza0on as easy as possible. Early data

standardiza0on ensures that data are readily available,

accurate, easily analyzed, and interpreted appropriately.


S T R AT E G Y 5 - M A K E C O L L A B O R AT I O N M A N A G E A B L E

Orchestra0ng the many partners, func0ons, process steps, and geographical loca0ons of the value chain requires 0mely and effec0ve collabora0on. These “many-to-many” requirements are best supported digitally, reducing the 0me and effort required to gather and synthesize the mul0-stakeholder data needed for a successful CMC data package. An integrated supply chain also provides:

• Real-0me visibility, ac0onable data, and alerts (couriers, cold chain, equipment) signal adjustments needed to manufacturing, capacity, and delivery, improving order fulfillment rates and access to treatment.

• The ability to easily scale opera0ons up and out with con0nued data quality, completeness, and accessibility.

• Ongoing, real-0me compliance and pa0ent safety. First, COI/COC can easily be tracked and verified at every step along the way. Secondly, the necessary informa0on for devia0on inves0ga0ons and regulatory inspec0ons is readily available when needed. And thirdly, changes in protocols, procedures, regulatory standards, or the product can easily be disseminated resul0ng in a constant state of compliance.


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- Expert Tip -

Implemen0ng digital collabora0on early delivers

benefits upon implementa0on, enables easy and low-cost scaling up and out, and lowers the barriers

to adop0on of new technologies such as

blockchain and machine learning.

Figure 3b: Standardized and controlled data flowsFigure 3a: Complex, decentralized, error-prone data flows


S T R AT E G Y 6 - O P T I M I Z E A N A LY S I S A N D R E P O R T I N G

A high-quality data set makes informa0on readily available for analysis, compliance, inspec0ons, filings, and decision-making. It is an invaluable component in building a robust CMC sec0on, as well as to ongoing opera0ons and pa0ent follow-up. Advanced data analysis and repor0ng:

• Provide insights into the product, process, and performance.

• Should be available in real 0me to support pre- and post-approval regulatory inspec0ons and help with answering follow-up ques0ons during filing review. Analysis and reports also enable stakeholders to ensure pa0ent safety, manage opera0ons, and support Quality ac0vi0es.

• Can be enhanced by machine learning and ar0ficial intelligence (AI) leading to valuable addi0onal discoveries.

• Enable the long term follow-up that is a requirement of many advanced therapy clinical trials and applica0on approvals (because of safety profiles and inherent product unknowns).

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- Expert Tip -

Stay ahead of regulatory requirements for long-term pa0ent monitoring by laying the groundwork now. Start

with asking relevant, focused ques0ons and begin gathering intelligence. Prepare now for ongoing and future repor0ng and monitoring requirements.

DATA TO CAPTURE IN LONG TERM FOLLOW-UP (LTFU)

“For the first five years or more (as applicable to your product), we recommend that you… : • Assure that inves0gators maintain, in the case history, a detailed record of exposures to

mutagenic agents and other medicinal products, and have ready access to informa0on about their adverse event profiles.

• Establish a method for inves0gators to record the emergence of new clinical condi0ons, including, but not limited to:

• New malignancy(ies) • New incidence or exacerba0on of a pre-exis0ng neurologic disorder • New incidence or exacerba0on of a prior rheumatologic or other autoimmune

disorder • New incidence of a hematologic disorder

• Design a plan for scheduled visits with an HCP to elicit and record new findings for each study subject, including history, physical examina0on, or laboratory tes0ng.

• Such a plan needs to facilitate repor0ng of delayed adverse events, including unexpected illness and hospitaliza0on by study subjects and HCPs.”

Long Term Follow-Up ALer Administra3on of Human Gene Therapy Products — DraL Guidance for Industry. (2018.) U.S. FDA. hYps://www.fda.gov/media/113768/download

https://www.fda.gov/media/113768/download


https://www.fda.gov/media/113768/download

S I X B E N E F I T S O F A M O D E R N D A T A M A N A G E M E N T A P P R O A C H

Even amid all the other demands of a clinical trial, automa0ng data management early will improve pa0ent safety, service level, regulatory processes, and save 0me and money.

B E N E F I T 1 - I M P R O V E D P AT I E N T S A F E T Y, P AT I E N T C A R E , A N D C O M P L I A N C E

Regulators require solid, unbreakable COI/COC systems to be in place and fully func0onal from the earliest stages. Addi0onally, readily-accessible, quality data supports efficient, high-success-rate opera0ons, which means that pa0ents who complete collec0on are more likely to receive a treatment with minimal delays and/or rescheduling. Along with real-0me progress tracking, this improves the level of service provided and builds trust with pa0ents and health care providers.

Automa0on also supports improved informa0on security. All par0cipants in the value chain must adhere to applicable laws and standards such as the Health Insurance Portability and Accountability Act (HIPAA), Good Automated Manufacturing Prac0ce® 5 (GAMP 5), and General European Data Protec0on Regula0on (GDPR). Establishing and maintaining appropriate security standards for data can be more easily accomplished with a proven digital plarorm.

B E N E F I T 2 - P R O D U C T A N D P R O C E S S U N D E R S TA N D I N G

More data points means poten0ally more insights into the product and process, providing opportuni0es for improvement — and a solid CMC package. Determining the range of variability during processing and iden0fying root cause for trending devia0ons are just two of the ways that proac0ve data management can benefit product and process understanding. However, for the data to be useful, it must be captured in the first place, and then made readily available in a format that can be consolidated and analyzed.


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A FREQUENT MISCONCEPTION

It’s common to believe that small pa0ent numbers in early phase trials can easily be managed

through manual processes without examining: the specific therapy, the number of touch points, the

number of stakeholders involved, and geographical diversity. Some0mes, small pa0ent numbers in a

complex product will exceed the threshold where manual systems can ensure proper data

collec0on and management.


B E N E F I T 3 - C O L L A B O R AT I O N W I T H R E G U L AT O R Y A G E N C I E S

A key to successfully naviga0ng the clinical trial and applica0on submissions process is ongoing discussion and collabora0on with regulatory agencies. The beker they understand a product and processes, the more feedback that can be incorporated along the way, ul0mately improving submission quality. Ready access to comprehensive, clear data on the product and process will be invaluable in preparing for these discussions.

B E N E F I T 4 - R E D U C E D T I M E T O F I L I N G

One of the biggest challenges for any trial is the massive amount of effort involved in gathering, standardizing, and analyzing all the data generated during clinical trials to prepare a cohesive and convincing narra0ve for the regulatory authori0es. Typically, data may be spread between chart notes, spreadsheets, lab reports, and/or digital plarorms such as EMRs, CTMS, and ERP/MES. The addi0ve piece for advanced therapies is the complex, data-intensive nature of the supply chain related to live human cells and the individual, tailored batches. Automa0ng and standardizing data capture at the right 0me in the clinical trial process will significantly reduce the 0me and resources needed to complete the CMC data package.

B E N E F I T 5 - R E D U C E D C O S T

Foregoing technology may seem cost-effec0ve early on, but prove very costly down the road. It will take considerable, expensive resources to prepare an applica0on package from mul0ple, disconnected, non-standardized data sources (and the cost goes up the faster this effort needs to be completed). Addi0onally, labor intensive manual processes are inefficient, and error prone, driving up the costs of compliance, pa0ent safety, and producing a complex, high-touch product. This could be true with only 20 pa0ents, and will certainly be true as the volume of pa0ents increases, and the number of sites in the supply chain increases. Based on industry experience, automa0ng the end-to-end value chain will reduce overall opera0ng costs by 30 percent or more over 0me, especially as pa0ent volumes increase, and provide high-quality, accessible data for filing prepara0ons.

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CORE REGULATORY FOCUS

Pa0ent safety is at the core. In the cell and gene therapy industry, pa0ent material is the source for the therapy and, as such, the therapy is extremely

personalized. Accuracy, safety, and traceability over the en0re pa0ent journey is the main focus.


B E N E F I T 6 - S C A L A B I L I T Y

As a product advances through the clinical trial phases and approaches commercializa0on, the infrastructure and processes to produce the product and treat pa0ents must naturally scale. The need to scale “up” is driven by the volume of pa0ents receiving treatment. This will increase as more advanced trial phases require higher enrollment and, eventually, more pa0ents have access on the commercial market. Scaling “out” will happen as the supply chain expands to mul0ple suppliers - collec0on sites, transporta0on providers, manufacturing sites, storage facili0es, and treatment prac00oners. This may ini0ally happen in one country or region, but can easily expand globally fairly early on due to the difficulty in enrolling pa0ents for rare condi0ons.

In addi0on to the infrastructure expansion, there may be mul0ple regulatory authori0es and standard sezng bodies to sa0sfy. The need to scale both up and out has an exponen0al effect on complexity and data. Implemen0ng the right systems early will provide a key factor for successful, compliant expansion by ensuring the ability to capture and u0lize the high volume of data generated as scaling occurs. Automated data management can also make it easier to comply with the varying requirements of different regulatory agencies from region to region.


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Figure 4: Scale requires modern data management


C O N C L U S I O N

The data complexi0es and data management requirements of advanced therapies have prompted regulatory authori0es to recommend a modern approach. Both U.S. and E.U. regulators have issued regulatory guidances calling for a new focus on data management.8,9

“To… protect pa0ents,” one recent FDA dral guidance states, “it is impera0ve that sponsors establish an infrastructure to streamline trial logis0cs, facilitate data collec0on and incorporate plans to rapidly assess emerging data in real 0me and to disseminate interim results to inves0gators, ins0tu0onal review boards (IRBs), and regulators.” 11

A modern approach to data management also lays the founda0on for further innova0on. New op0ons for data connec0vity, such as integra0on of electronic health records with the rest of the value chain, will provide a more complete view of both individual pa0ents and pa0ent popula0ons. This holis0c end-to-end view of the en0re treatment landscape will provide more data intelligence, improved pa0ent care, and even more simplified, robust filing prepara0on for advanced therapeu0cs.

Collec3vely, the Vine3 team has decades of leadership experience in clinical and commercial advanced therapies. Vine3’s digital pla_orm supports

several companies with approved cell and gene therapies, as well as others working in clinical trials. We ac3vely collaborate with regulators and our industry to promote standards that support growth and pa3ent access.

Please contact us with ques3ons about data management and related opera3onal or filing challenges. We are honored to provide support for

advanced therapy data management and transforma3ve treatment op3ons for pa3ents worldwide.

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R E F E R E N C E S

Alliance for Regenera0ve Medicine, Annual Data Report 2018, 2017, 2016, 2015. hkps://alliancerm.org/1

publica0ons-presenta0ons/

Chi Heem Wong, Kien Wei Siah, Andrew W Lo, Es0ma0on of clinical trial success rates and related 2

parameters, Biosta0s0cs, Volume 20, Issue 2, April 2019, Pages 273â€“286. hkps://doi.org/10.1093/biosta0s0cs/kxx069

Tuls Center for the Study of Drug Development. (2018). Rising protocol complexity is hindering study 3

performance, cost, and efficiency. Impact Report, 20(4). hkps://sta0c1.squarespace.com/sta0c/5a9eb0c8e2ccd1158288d8dc/t/5b4de76e352f53bd7a416e1b/1531832174796/julaug-summary.pdf

“Spark looks at scale, manufacturing as gene therapy matures,” BioPharma Dive; January 10, 2019. hkps://4

www.biopharmadive.com/news/spark-gene-therapy-manufacturing-scale-cmc/545723/

“Unblinded: Scok Goklieb on biosimilars' precarious moment and the gene therapy boom,” BioPharma Dive; 5

March 12, 2019. hkps://www.biopharmadive.com/news/unblinded-fda-scok-goklieb-biosimilars-gene-therapy/549997/

Tuls Center for the Study of Drug Development. (2018). eClinical data volume and diversity pose increasing 6

challenges and delays. Impact Report, 20(1). hkps://www.veeva.com/wp-content/uploads/2018/03/Tuls-Impact-Report-2017-eClinical-Landscape-Study.pdf

Jacobson, Simon F. “Extend the Value of MES Beyond the Plant,” 14 March 2014, Page 4, ID:G00260891. 7

hkp://www.crossroadsrmc.com/Portals/0/Documents/MGG%20Library%20Docs/MES%20and%20Dashboards/Extend%20the%20Value%20of%20MES%20Beyond%20the%20Plant.pdf

U. S. Department of Health and Human Services. (2018). Chemistry, Manufacturing, and Control (CMC) 8

Informa0on for Human Gene Therapy Inves0ga0onal New Drug Applica0ons (INDs) (Dral Guidance for Industry). Rockville, MD: Dockets Management Staff (HFA-305), Food and Drug Administra0on. hkps://www.fda.gov/regulatory-informa0on/search-fda-guidance-documents/chemistry-manufacturing-and-control-cmc-informa0on-human-gene-therapy-inves0ga0onal-new-drug

European Commission. (2018). Good Manufacturing Prac0ce Guidelines on Good Manufacturing Prac0ce 9

specific to Advanced Therapy Medicinal Products (EudraLex, The Rules Governing Medicinal Products in the European Union, Volume 4). Brussels, Belgium. hkps://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf

Standards Coordina0ng Body. (2019.) Community Perspec0ves — Needed Standards in Regenera0ve 10

Medicine. hkps://www.standardscoordina0ngbody.org/standards

U.S. Food and Drug Administra0on, Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite 11

Development of Oncology Drugs and Biologics Guidance for Industry, August 2018. hkps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma0on/Guidances/UCM616325.pdf


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https://www.biopharmadive.com/news/unblinded-fda-scott-gottlieb-biosimilars-gene-therapy/549997/

https://www.biopharmadive.com/news/unblinded-fda-scott-gottlieb-biosimilars-gene-therapy/549997/

https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf

https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf

https://www.biopharmadive.com/news/spark-gene-therapy-manufacturing-scale-cmc/545723/

https://www.biopharmadive.com/news/spark-gene-therapy-manufacturing-scale-cmc/545723/

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chemistry-manufacturing-and-control-cmc-information-human-gene-therapy-investigational-new-drug



https://static1.squarespace.com/static/5a9eb0c8e2ccd1158288d8dc/t/5b4de76e352f53bd7a416e1b/1531832174796/julaug-summary.pdf

https://static1.squarespace.com/static/5a9eb0c8e2ccd1158288d8dc/t/5b4de76e352f53bd7a416e1b/1531832174796/julaug-summary.pdf

http://www.crossroadsrmc.com/Portals/0/Documents/MGG%20Library%20Docs/MES%20and%20Dashboards/Extend%20the%20Value%20of%20MES%20Beyond%20the%20Plant.pdf

http://www.crossroadsrmc.com/Portals/0/Documents/MGG%20Library%20Docs/MES%20and%20Dashboards/Extend%20the%20Value%20of%20MES%20Beyond%20the%20Plant.pdf


https://doi.org/10.1093/biostatistics/kxx069

https://doi.org/10.1093/biostatistics/kxx069

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM616325.pdf

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM616325.pdf

https://www.veeva.com/wp-content/uploads/2018/03/Tufts-Impact-Report-2017-eClinical-Landscape-Study.pdf

https://www.veeva.com/wp-content/uploads/2018/03/Tufts-Impact-Report-2017-eClinical-Landscape-Study.pdf

https://alliancerm.org/publications-presentations/

https://alliancerm.org/publications-presentations/

https://www.standardscoordinatingbody.org/standards

A B O U T T H E A U T H O R S

HEIDI HAGENChief Strategy Officer and Co-Founder, Vine8 Inc.

Heidi has been an Opera0ons Execu0ve in the Biotechnology industry for over 25 years and is a Co-founder of Vine0. She has overseen the delivery of more than 100,000 doses of personalized cell therapy, and has guided numerous therapies through clinical development on to commercializa0on. She has an extensive and proven track record in leading opera0ons and commercializing innova0ve technologies ranging from recombinant protein/device combina0ons to the first ac0ve immune cell therapy, Provenge. Heidi is on the Board of Directors for Vericel Inc, Ziopharm Inc, and Lykan Biosciences. Previously, Heidi was the Global COO for SOTIO, in Prague, Czech Republic with a U.S. office in Boston, MA. Before joining SOTIO, she worked for Dendreon for ten years as Senior Vice President of Opera0ons, and ten years with Immunex Corpora0on in a range of roles in drug development and opera0ons management. Heidi has a BS in Cell and Molecular Biology, an MS in Bioengineering, and an MBA from the University of Washington.

CHRISTOPHE SUCHET Chief Product and Compliance Officer, Vine8 Inc.

Christophe brings more than 20 years of informa0on technology and senior biopharmaceu0cal IT experience to Vine0. Most recently, he served as Vice President of IT for Kite Pharma, Inc., where he developed the essen0al technology systems that helped Kite’s first cell therapy receive FDA approval, scale rapidly, and secure the landmark sale of the business to Gilead Sciences, Inc. Prior to Kite Pharma, Christophe served as Vice President of IT at Pharmacyclics Inc., a clinical stage and commercial biopharmaceu0cal company that grew in two years from no product revenue, to $1 billion revenue, to acquisi0on by AbbVie for $21 billion. Christophe has served as Genentech’s Director, IT Pharma Development Applica0ons, and as IT Director, SAP Center of Excellence & Enterprise Applica0ons. He received his MS in Biology and Economy from AgroParisTech.

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Advanced therapies require advanced solware.

Thank you!


Headquarters

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Tel: (415) 704-8730 [email protected]

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© VineC 2019

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