The industry’s pledge to improve the clinical trial experience for participants and investigative sites is taking center stage in 2019. Greenphire’s CEO, Jim Murphy, spoke with World Pharma Today about current trends that will gain momentum this year, and how they will revolutionize the global clinical trials sector.
Definitions of in vitro-in vivo correlations is defined by FDA as “a predictive mathematical model describing the relationship between an in vitro property of an extended release dosage form and a relevant in vivo response.”
Innovation and collaboration are the lifeblood of the life sciences. Without them, both research and business come to a standstill.
Imagine the Possibilities: What if innovations in the life sciences supply chain kept up with innovations in medicines and treatments?
With many serialization and track & trace regulations in the compliance period, and others (e.g., EU FMD, US DSCSA) on the horizon, life sciences companies need to think beyond serialization as a core capability and prepare for the next generation of supply chain. Verifying the provenance of a medicine—from where its ingredients were made and where the drug was manufactured, to how the medicine was handled through the end-to-end supply chain and all the way to the patient in a trusted manner, is becoming an increasingly mandatory supply chain capability.
That scenario is now possible using blockchain technology.
Blockchain (sometimes referred to as Distributed Ledger Technology, or DLT) is protected by cryptography, that allows a network of nodes to collectively maintain a shared ledger of information without the need for complete trust between the nodes. Blockchain is essentially a time-sequenced chain of events based on an agreed upon consensus mechanism. The mechanism guarantees that, as long as the majority of the network validates the entries (i.e., the “blocks”) posted to the ledger (i.e., the “chain) as per stated governance rules, information stored on the blockchain can be trusted as reliable.
Investors and enterprises across multiple industries and functions have taken notice of blockchain’s potential. Recently, investment and spending on blockchain-based technology have each topped more than $1 billion and continues to accelerate. Accenture’s current projections for the blockchain services market alone estimates a CAGR of more than 60 percent, hitting close to $7 billion by 2021. Within life sciences alone, blockchain technology could provide a $3 billion opportunity by 2025.2
THE CASE FOR BLOCKCHAIN IN LIFE SCIENCES
While significant investment has gone into serialization capabilities over the past decade, life sciences companies are restricted by traditional technology limitations where information is captured in a database, transmitted to another database (owned by a separate internal or external partner) and then reconciled.
Blockchain is becoming increasingly relevant to address the perennial challenges of trust and speed in the life sciences supply chain. For example, enabling data driven business decisions in forecasting the flow of goods and having visibility into the origin of materials and inputs has always been difficult, partly due to the technologies involved and partly because suppliers are mistrustful about sharing data they fear will be abused by downstream customers, impacting their ability to price products effectively.
Blockchain’s ability to generate trust and create the right permissions around the sharing of data allows life sciences companies to break through some of those commercial challenges, enabling better traceability. Companies can access the information they want without revealing commercially sensitive data. For example, complications associated with the recall process are dramatically streamlined through concurrent notification within the supply chain.
There are several types of blockchains that can drive value for the life sciences supply chain, depending on the need and types of permissions among those sharing information.
Different types of blockchains include:
One important attribute of blockchain technology is smart contracts. Smart contracts are event-driven programs which run on a distributed ledger and can take custody over an asset on that ledger. The embedded “IF, THEN” statements allow for automatic transactions based on pre-defined terms. For example, a payment can be remitted when certain criteria are achieved in a transaction on the blockchain.
PRACTICAL APPLICATIONS ACROSS THE LIFE SCIENCES SUPPLY CHAIN
Blockchain has applicability across all supply chain functions. However, it can particularly address certain unique aspects of the life sciences supply chain as there requirements of the supply chain evolve with the product and therapy mix.
BENEFITS OF BLOCKCHAIN TECHNOLOGY
Immutability/indisputability: Single source of truth, replicated across all nodes; data on the ledger is encrypted, pervasive and persistent
Automation: Network self-validates all ledger entries; smart contracts automatically enforce business rules; near real-time data and transaction processing
Cost reduction: Reduction in operational costs related to exceptions and reconciliation
Auditability: Provides a real-time track-and-trace audit trail;improves business, operational and regulatory reporting
Decentralization: Assets are tied and controlled by their owners rather than institutional custodians; exchange of information with pre-agreed consensus validation instead of third-party
Security: Encryption provides record-level security of data; no single point of failure—network is resilient against attacks on individual nodes
One of the most complex life sciences supply chain challenges has been the ability to effectively track the origin of a product (or therapy) from raw materials to the finished product. Despite the various efforts of full chain of custody systems that exist today, the fragmentation of systems between trading partners opens the risk for fraud. Blockchain technology is an ideal solution, given that no single organization is responsible for provenance. Organizations across the life sciences ecosystem benefit from having authentic product in the supply chain, ensuring brand integrity and improved patient outcomes by delivering authentic product to the patient. Blockchain enables the idea of a “digital passport” for a product, containing all relevant information for each component or ingredient, including instructions and patient adherence information from the packaging.
SERIALIZATION TRACK AND TRACE
For the last two decades, regulators across the globe have been implementing requirements for unique product identification to deliver greater security of finished products through the supply chain. These requirements have the aspiration to eliminate counterfeit and diverted products, ultimately contributing to increased patient safety.
Like provenance, one of the major challenges with track and trace is the effective exchange of data across the ecosystem of partners - from the pharmaceutical manufacturers, to wholesale distributors, to dispensers. With the use of blockchain,supply chain partners can more effectively and securely share data across the supply chain and, eventually, with the end patient.
A significant business opportunity exists in using blockchain with serialization capabilities for the recall process. Recall notification, once injected into the blockchain, can initiate communication and alert messages to all affected parties (manufacturers, distributors, dispensers and eventually patients). All parties can track and verify the recalled product, minimizing the time it takes to dispose of the recalled products, reducing risk and costs.
In one aspect of the life sciences supply chain, pressure is mounting on pharmas to optimize their cold chain logistics. This series of uninterrupted temperature-controlled, refrigeration, production, storage and distribution of products is complicated and expensive. The pharmaceutical industry expects to spend nearly $17 billion by 2020on cold chain management.4
When applied to the cold chain, blockchain combined with technologies like IIoT (Industrial Internet of Things) can create secure documentation of storage temperatures at every point in a product’s journey. This enables supply chain managers and executives to identify potential temperature excursions and other efficiencies across the end-to-end supply chain, and also presents an opportunity to the challenges posed by CAR-T, as previously mentioned. Additional opportunities exist to complement blockchains with artificial intelligence (e.g., machine learning) to detect potential specialty logistics issues.
BEYOND THE SUPPLY CHAIN:LAST MILE TO THE PATIENT
Only 38 percent of patients feel knowledgeable about new products coming to market that may benefit their health and less than half of patients feel that their doctors discuss the entire spectrum of therapies, which often leads to treatment decisions being made without the ‘big picture’ being understood. Once all the product data in the supply chain is stored in the blockchain, life sciences organizations will be able to target patients with far more relevant information—such as product availability, detailed product information, and specific product history. The ability to tie the patient to the product will not only increase patient satisfaction, but ultimately their ability to manage their own health for better outcomes. Inevitably, blockchain will more effectively deliver personalized medicines to patients in the right setting at the right times, with the right dose.
Compared to the financial markets (which themselves have yet to achieve blockchain maturity), the life sciences industry’s participation with the technology remains in its infancy. The following represent the key barriers the technology must overcome to gain a legitimate place in life sciences:
NETWORK EFFECT. To reap full value from blockchain, the majority of partners in the ecosystem must participate. Interoperability between blockchains and other technology solutions need to be addressed to get full ecosystem participation.
GOVERNANCE. Smart contracts require agreement on allowed transactions among the ecosystem partners and is an ongoing exercise—this requires strong ecosystem participation and buy in.
REGULATORY AND LEGAL. Because blockchain technologies offer a new socio-political paradigm for doing business, few legal and regulatory frameworks are in place to govern their use. From a life sciences perspective, strong regulatory frameworks can ensure the integration of blockchain technology to avoid challenges in terms of regulatory reporting, HIPAA compliance, etc. Regulators also need an in-depth understanding of how to operate in a blockchain environment.
PERFORMANCE. As the blockchain in data and number of nodes, the time to verify transaction may increase causing potential delay to standard business actions.
STARTING THE BLOCKCHAIN JOURNEY
Within the next three years, approximately 30 percent of life sciences companies plan to utilize blockchain (if they aren’t already), opening new business opportunities and addressing challenges of the past.5 Supply chain applications of blockchain are endless for life sciences companies given the requirements for specialized medicines and therapies. Those that start now—who are willing to experiment, fail fast and innovate based on that experience—will be the organizations to achieve competitive advantage and improve patient outcomes.
Set vision for how Blockchain can support the business challenges or opportunities
2. DEVELOP & PLAN
Define the specific business areas for blockchain value Develop plan to execute PoC(s)on high value areas and opportunities
3. PROOF OF CONCEPT
Controlled learning of Blockchain Technology with a focus on select use case Incorporate learnings from PoC phase into pilot
Continued learning of the Blockchain based use case Complete high-level assessment and roadmap to transition
End-to-end implementation of Blockchain based solution for targeted business challenge, aligned to strategy
6. EXPAND & MANAGE
Expand platform to additional business units and deploy on going improvements
1 Accenture Research
2 Accenture projection
3 Accenture Research
4 2017 Biopharma Cold Chain Sourcebook, Pharmaceutical Commerce (www.PharmaceuticalCommerce.com), Brooklyn, NY
5 Accenture Research
ABOUT ACCENTURE LIFE SCIENCES
Accenture’s Life Sciences group is committed to helping our clients make a meaningful impact on patients’ lives by combining new science with leading edge technology to revolutionize how medical treatments are discovered, developed and delivered to people around the world. We provide end-to-end business services as well as individual strategy, consulting, digital, technology and operations projects around the globe in all strategic and functional areas— with a strong focus on R&D, Sales & Marketing, Patient Services and the Supply Chain.
We have decades of experiences working with the world’s most successful companies to innovate and improve their performance across the entire Life Sciences value chain. Accenture’s Life Sciences group connects more than 15,000 skilled professionals in over 50 countries who are personally committed to helping our clients achieve their business objectives and deliver better health and economic outcomes.
Clinical oncology research is unique when compared to other therapeutic areas. Cancer patients experience substantial physical and psychosocial consequences of the disease and its treatment and much of the symptom burden occurs outside the clinical environment.
The 3 Ways Johnson & Johnson Is Capitalizing on Digital Innovation to Better Deliver Medicine to You?
In recent years, the pharmaceutical industry has seen tremendous changes in the way it is expected to deliver new drugs to market: being under increasing pressure to expedite the development of new therapies,to decrease clinical study duration, and to drive new treatments through their clinical phases as quickly, safely and cost-efficiently as possible.
Reducing the costs associated with clinical trials is one of the pharmaceutical industry’s core challenges. Running a clinical trial is incredibly expensive and if a compound fails in the late phases, it can be catastrophic for its sponsor company.
The world of drug development and manufacturing is undergoing a change. Nowhere is this more evident than in the rapid increase in complex compounds such as biologics.
2018 has seen some of the most fundamental changes to the pharmaceutical industry– driven by serialisation requirements in the US and EU, as there has been a seismic shift towards a more digitalised supply chain.
For a number of years now, immunotherapy has been seen as the dawn of a new era, and is the most promising approach to cancer treatment since the use of targeted therapies, making headlines as results for successive novel immunotherapeutic drugs and combination therapies are released.
Adherence generally refers to taking a medication as prescribed which includes maintaining the proper dosing schedule throughout the medication cycle as well as continuing to take a medication for as long as the treatment is necessary.
Not only is adherence critical for patients who are prescribed medications, but non-adherence has caused significant financial hardship on the overall healthcare system. Today, adherence is closely monitored, with pharmacies and doctors bearing responsibility for ensuring patient adherence.
Pharmacies influence patient behavior, improve adherence, and reduce costs across the spectrum. In order to do this,pharmacists must know their patients and use best practices to achieve results.
Improvements to adherence practices are constantly being developed and put into effect; however, reports as recent as 2017 find that approximately 50% of patients are still non-adherent, costing approximately $300 billion in avoidable U.S. healthcare spending.
So, what can we do about it? To answer this question, we must first understand what causes patients to become non-adherent to begin with.
What Causes Non-adherence?
Adherence is complicated because there are many factors that contribute to why a patient may fail to take a medication. Cost, side effects, complexity of the treatment regimen, forgetfulness, and finally, lack of motivation and faith are all reasons why a patient may miss a dose or neglect taking medications altogether.
Cost & Financial Hardship
Cost is one of the most unfortunate factors affecting adherence. We all know stories of patients rationing medications or skipping treatments entirely because of the high cost of acquisition. For common drugs such as insulin, antibiotics, and anti-psychotics, adherence can mean the difference between life and death. Pharmacists must communicate with patients and their providers about all their available options that can have an impact on cost.One of the first things a pharmacist can do is ensure that providers are prescribing the most cost-effective treatment. In many cases, switching therapies from brand names to generics or recommending a titration schedule when warranted can bring costs down for both the patient and the doctor.
When expensive medications are required, advising on cash discounts, co-pay assistance programs, manufacturer rebates, and government programs for high cost medications can provide support to those in need.Utilization of these programs can increase the likelihood of adherence if costs can be brought down to affordable levels. Of course, advocacy is always beneficial to create systems where such strenuous measures are not necessary to bring treatment to disadvantaged patients.
Treatment Side Effects
Side effects and treatment complexity is the easiest of the factors to influence simply because Medication Therapy Management (MTM) fits so soundly within the scope of a pharmacist’s role in the healthcare system.
In many instances, risks to adherence is abundantly apparent when pharmacists evaluate patient medication profiles. We can see duplications of therapies prescribed by multiple doctors, harmful drug interactions, or a dosing schedule that is difficult to comprehend, let alone adhere to. In these cases, it is the pharmacy’s job to work with a physician and the patient to streamline the process. This includes making sure that the patient only has the medications they need and that they will provide the healthcare results sought out by the physician.
In these interactions, we can ascertain from the patient whether side effects are playing a role in non-adherence. In most cases, the solution is simply a new dosing schedule or switch from one manufacture to another of the same medication. When a medication is not well-tolerated, a pharmacist can speak to a physician about alternative drugs of the same type or side effect mitigation treatment that will alleviate discomfort and increase adherence.
Out of Sight, Out of Mind
Forgetfulness is probably the trickiest of the factors to influence, although there are many tools at a pharmacy’s disposal that can help. We all live busy lives, even the best patient can be prone to miss a dose here and there or simply forget to pick up medications from the pharmacy when refills are ready. In this area, technology can be its most useful.
Today, there are packaging machines specifically designed to improve adherence. They pre-sort and pre-package a patient’s medications into easy-to-use pouches, each containing the prescribed medications in the correct doses for every time of the day treatment is needed. This is particularly helpful for patients with stable multi-drug medication regimens because it eliminates guesswork and allows a patient to clearly see when a medication should be taken. Missed doses are also easy to spot, as each pouch is labeled with the date and time the medication was directed to be taken. The pouches are convenient for active lifestyles because patients can just take the pouches they need for the day or week and are compact enough to fit in travel bags or even small purses.
Pharmacies are increasingly turning to application developers to provide patients with medication information, current lists, medication reminders, and refill notifications to prevent forgetfulness. These applications are currently available from a number of providers that track everything from weight and blood sugar, to anxiety triggers and sleep. These applications can gather valuable data on adherence, as well as whether a prescribed treatment is providing the desired results.
At time of refills, many pharmacies are implementing the home delivery model to improve adherence. In this way, pharmacists can provide immense assistance by making sure that medication arrives at the patient’s home or a location of convenience. Pharmacies can also monitor when refills are due and ensure that medications arrive prior to an occurrence of a gap in therapy.
Time, mobility, or transportation should not be a deterrent - being proactive is key to improving adherence at every step of the process.
Lastly, and arguably the most difficult factor to mitigate in non-adherence is the lack of motivation and/or faith. The reason this is so hard is because these factors have more to do with how a patient feels about healthcare and less about the healthcare itself. Upbringing, worldview, and trust impact the way people access healthcare and even the effect a treatment has on a person. If a person does not believe in medicine or believes in it too much, then they are not only less likely to take it properly, but also less likely to recognize or achieve results. To help guide patients to the right understanding of what medicine can do for them, we must reach them on an emotional level. This cannot be done in quick soundbite interactions, but actual meaningful conversations about life and health.
Pharmacists have more opportunities to encounter patients than their providers. They are a unifying source of information for patients and are a valuable resource when discussing medication options. When a patient is non-adherent, the evidence presents itself early and often in the form of excess medication, running out of medication early, or failing to access refills appropriately. When pharmacists en-counter these symptoms of non-adherence, it is incumbent upon them to act and engage. Pharmacists can initiate their own MTM cases through which they can document their patient interactions. During this process, pharmacists can get to the root of the problem and address it.
In order to be effective, we must speak the healthcare language our patient understands. We have to be compelling in a way that leads to patient action. Staff diversity can help with this,as patients are more likely to trust a pharmacy they feel understands where they are coming from and how they might feel. Encouraging diversity of thought amongst technicians, delivery staff, cashiers, and pharmacists will not only increase patient loyalty, but increase patient adherence as well.
Patients often lack the tools and skills necessary to achieve the healthcare results they want. Medication regimens are increasingly more complex, requiring patients to devote significant time and effort just to manage a day’s dosing schedule. Even though the world is moving toward a patient-driven healthcare system, pharmacies can - and must - play a vital role in helping patients.We must move beyond the statistics and metrics and reach the heart of patient adherence.
Shital Mars is the Chief Executive Officer of Progressive Care, a personalized healthcare services and technology company based in South Florida. Shital’s passion for creating an ethical pro-active pharmacy model led her to her current position in January 2016. Under her direction, Shital has guided Progressive Care and its wholly-owned subsidiary PharmCo LLC on a rapid growth trajectory with the signing of an investment deal with The Benchmark Company in June 2018 and the acquisition of Touchpoint pharmacy.
Shital has continued to focus on creating and implementing systems that help to improve patient adherence and provide risk management practices for physicians and providers. She is also responsible for spearheading Progressive Care’s efforts to combat the nationwide opioid epidemic through a campaign designed to educate patients, physicians and providers on pain management alternatives offered by PharmCo.
Prior to becoming the CEO of Progressive Care, Shital was the company’s Chief Operating Officer from 2012-2016. Shital also served as a vital consultant to Progressive Care from 2010-2012 where she provided business development consulting services and advised the company on human resources, financial reporting and transactions, operations, compliance, investor relations, among other areas.
About Progressive Care Inc
Progressive Care Inc. , through its PharmCo, LLC, is a South Florida health services organization and provider of prescription pharmaceuticals, compounded medications, provider of tele-pharmacy services, the sale of anti-retroviral medications, medication therapy management (MTM), the supply of prescription medications to long term care facilities, and health practice risk management. Visit Progressive Care online at: https://progressivecareus.com/
The WHO estimates that roughly 10% of drugs in the global marketplace are counterfeit, with levels being much higher in developing countries (30-40%).
In November 2017, the pharma industry was granted an extension of the Drug Supply Chain Security Act (DSCSA) enforcement date to November 2018. Regulators told the market that they would not actively enforce the new serialization requirements until this date.
Standfirst:There is growing awareness of the valuable role that diagnostics can play, both in the early identification and treatment of dangerous or infectious diseases as well as genetic disorders.
Compliance is a serious issue for India’s pharmaceutical manufacturers, distributors, and retailers; due to the complicated nature of the pharmaceutical supply chain. Serialization requires pharmaceutical manufacturers to invest in new technology and adapt their current processes and systems.
What is a biosimilar?
Whereas generic drugs are identical copycats of small-molecule chemical products, biosimilars are only similar to biologic products; innately more complex than chemical products, biologics are large-molecule, organic drugs, subject to natural variability and vulnerability due to climate changes during the manufacturing process, and as such, it is impossible to produce an exact replica of a biologic—hence the adoption of the nomenclature, “biosimilar.”
Every day, the United States loses 116 lives to the opioid epidemic.(1) Pharmacists are asking what can be done to combat the opioid epidemic and treat pain effectively.
CRM, CLM, KAM, Big Data, customer focus, patient centricity… for the last 20 years,buzzwords and concepts have been raining down on the Pharmaceutical Industry, generating a flurry of projects, proof of concepts, pilots and even some successful implementations.
The emergence of regenerative medicine as a viable therapy class has created an urgency to review and improve upon the current quality systems distribution standards that are employed in support of these therapies.
Automation has expanded its base in various sectors of the manufacturing industry and the application of robotics is gaining wide acceptance in well – defined processes like the FMCG industry, automotive, healthcare industry, pharma industry, etc. Even with the inclusion of latest technological advancements, the pharmaceutical industry faces a few issues.
Around the world, the pharmaceutical market is rapidly evolving, driven by greater access to medicines, an increased focus on patient needs and the emergence of innovative therapies for chronic conditions such as diabetes, multiple sclerosis and rheumatoid arthritis.
Environmental concerns in China leading to closure of factories that make the basic raw materials and key starting materials required for the API industry to be dearer?
The relationship between pharmaceutical and biopharmaceutical companies and drug delivery system manufacturers has evolved over the past 20 years. In the past, the relationships were purely transactional, but this has changed over the last two decades.
Significant innovation in disease treatment, including the increased focus on complex biologic therapies1, has resulted in important industry trends that have had an impact on many aspects of aseptic processing.
The year 2018 marks a notable milestone in the history of stem cell and regenerative medicine. It was twenty years ago, in 1998, that James Thompson and John Gearhart published methods for the creation of the first human embryonic stem cell (hESC) lines.
Digital technology has been driving change throughout the life science industry for years, however the sector is currently standing on the precipice of revolutionary development – some organizations have already taken the jump towards a more digital future.
The Falsified Medicines Directive 2011/62/EU, which is due for adoption in February 2019, will require pharmaceuticalcompanies to apply serialisation codes to every applicable pack (OTC and some minor exemptions).
While the requirements for serialization in the pharmaceutical supply chain are generally regarded as inevitable counterfeiting is simply too large of a problem to not be addressed there is some uncertainty around the specifics,particularly globally.
When it comes to the manufacturing of drugs, particularly highly sensitive biologics, a high-level of expertise is required. Typically, small and medium-sized pharma and biotech companies lack the knowledge and know-how necessary to cover all the processes independently prior to completion of the entire final product.
“IGNITE is a creative environment that fosters innovative thinking and encourages new ideas and enables users to have their voice heard in overcoming challenges that are faced to find new ways to better deliver quality data, speed up clinical development, lower cost to drug and device developers, and, to improve patient safety.”
Historically, injectable drugs havemostly been packaged aseptically, with pharmaceutical laboratoriescarrying out the sterilization of the primary packaging components internally.
Aurolab, the manufacturing division of Aravind Eye Hospital, at Madurai, Tamil Nadu that supplies high quality ophthalmic consumables at affordable prices to developing countries.
Do you providecompanies with innovative solutions to improve supply chain efficiency?
In addition to our primary packaging for solid doses, unit dose packaging and secondary packaging services, we also provide integrated supply chain services, such as postponement packaging or late-stage customisation to help our customers cope with small-scale market requirements.
In June 2017, the FDA announced that it will delay the active enforcement of the Drug Supply Chain Security Act (DSCSA) for pharmaceutical manufacturers to November 2018 due to industry-wide concerns that many members of the pharmaceutical supply chain are behind in implementing serialization systems and processes.
The market for organs-on-chips (OOCs), the cell culture chips that imitate the activities, mechanisms and responses of organs, will be worth $284 millionby 2021, according to research from The Business Research Company in its report Organ-On-Chip (OOC) Global Market 2011-21.
Rivaroxaban plus aspirin improves survival and reduces stroke and heart attack in patients with stable coronary or peripheral artery disease, according to late-breaking results from the COMPASS trial presented today in a Hot Line – LBCT Session at ESC Congress1 and published in the NEJM.
The numbers are daunting – 15% of the global population suffers from hearing loss, including a significant number of children, teenagers, and the elderly. Hearing loss presents a growing public health problem, due to ageing and an urban way of life that features excessive noise exposure.
The average cost of bringing a new drug to market is $2.6 billion, according to a 2014 report published by Tufts Center for the Study of Drug Development. This is a rise of 145%, adjusted for inflation, compared to just a decade earlier and is driven in part by the increasing complexity of clinical trials.
Biotechnology and pharmaceutical companies within the United States and Europe face an increasing number of hurdles when undertaking clinical trials within their own country or region; problems such as over saturated patient pools, difficulties meeting and maintaining enrollment numbers, increasing costs and lengthy time delays.
Stem cell science has made huge progress since the early 1960s when Canadian researchers James Till and Ernest McCulloch discovered blood stem cells and advanced medical research across the globe.
Despite the wide array of information systems available for biopharmaceutical manufacturing, we need to adopt a “follow-the-workflow” approach to overcome the process inefficiencies generated by quality and production silos.