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Vaccination has transformed global health and is one of modern medicine's greatest success stories. From eradicating smallpox, preventing lifelong disabilities, and slashing child mortality to now holding down COVID-19, vaccines have helped to save millions of patients over the years. Indian pharmaceutical industry has played a major role in making high-quality and affordable vaccines available for all. The country meets 60 percent of the global vaccine demand and contributes 90 percent of the World Health Organisation's demand for the measles vaccine.
Indian companies have contributed significantly by bringing vaccines/medicines at a scale and affordable price to patients in India and across the world. For instance, licensing arrangement between Indian companies and Gilead even before the pandemic has helped the generic companies to expand access to chronic hepatitis C medicines. Voluntary licensing for COVID 19 vaccine is also working well for example Astra Zeneca with Serum Institute, J&J with Biological Evans and Sputnik with Dr Reddys and Panacea. All the companies are ramping up production facilities to meet increased requirements.
In treatment category, Gilead's licensing agreements with generic pharmaceutical manufacturers based in India to further expand supply of remdesivir is vital. The agreement has allowed the companies – Cipla, Dr. Reddy's Laboratories; Eva Pharma; Ferozsons Laboratories Hetero Labs, Jubilant Lifesciences, Mylan; Syngene, a Biocon company and Zydus Cadila Healthcare, to manufacture remdesivir for distribution in 127 countries.
Importantly, Cadila Healthcare and Bharat Biotech are the leading Indian companies that have indigenously produced COVID 19 vaccines. Cadila Healthcare has produced the first DNA based vaccine ZyCov-D, which was approved for Emergency Use Authorization for adult population including the age group of 12 years and above.
Covishield produced by Serum Institute in collaboration with AstraZeneca is used widely across the country. Sputnik is also available in the market while others like Moderna Pfizer vaccine wanting to venture in India after due approvals.
India flagged off its vaccination drive in January and so far, over 15 percent Indians have been fully inoculated, and 46 percent have received at least one dose.1 However, despite a promising start, many Indians are reluctant to get inoculated, especially in rural areas where 65 percent of India's population resides. This brings focus on 'vaccine hesitancy' and the need to understand what it means. The reluctance or refusal to receive a recommended and available vaccine is known as 'vaccine hesitancy'.
The Covid Symptom Survey (CSS) conducted by Facebook in partnership with the University of Maryland, in 200 countries, revealed that a significant proportion of the Indian population is vaccine hesitant.2 As the vaccination drive continues, it is often hear individuals say that they want to 'wait and see' the effectiveness of the vaccine on others.
Key Factors for Vaccine Hesitancy
Multiple factors have emerged as the common reasons for the COVID-19 vaccine hesitancy in India
• Overarching concerns about potential side effects
• Ongoing narratives such as 'Vaccines won't work' or 'Don't believe in vaccines'
• Fear that the vaccine contains virus that will cause the disease
• Doubts regarding clinical trials
• Low risk perception from COVID-19
• Fake information about infertility and death after receiving the vaccine
As per the Centre for Economic Data & Analysis at Ashoka University, only 90 women received the dose for every 100 men inoculated during this period. Half-baked information about the vaccine causing infertility is the major cause of the hesitancy in women across India.
In order to fight COVID 19 and to overcome its spread, vaccination is key. It is crucial to address vaccine hesitancy among people.
Addressing the Vaccine Hesitancy Challenge
To develop vaccine confidence among the vocal vaccine deniers, India requires
• A target-based approach that focuses on the needs of individual groups and communities
• Discussions among friends and family about their positive experiences of getting the jab
• Educating people about how the vaccine was developed and awareness generation on importance of vaccine
• Involving local influencers, NGOs, doctors, and panchayat heads may aid in vaccine uptake
• The daily wagers should be given one-day wage for taking the shot given India's large rural population works as daily wagers who fear losing a day's income due to vaccine
• Vaccination rate can also be boosted in rural India by announcing certain incentives such as distribution of free cooking oil or rice and lucky draws
• Amplify available content to debunk myths and misinformation about vaccination online
• Highlighting the number of vaccinated people and support research to understand the consumer perception about the vaccine
• Partner with women health providers to address misinformation about adverse impact of COVID-19 vaccines on fertility and reproductive health may help to convince women to get vaccinated
Tackling Vaccine Hesitancy: Measures Taken by Indian states
An analysis by Facebook's Covid-19 Symptom Survey (CSS) in India shows India's vaccine hesitancy rate at around 28.7% with variations across states and union territories (UTs).5 Some of the measures Indian states are taking include prompting people about appointments for vaccination through social chat groups, digital media and newspaper ads.
• In Rajasthan, a reminder message for vaccination date is being sent to beneficiaries on WhatsApp groups, Facebook, and Twitter by health officials
• When India began its vaccination drive, Punjab faced issues with managing anxiety among healthcare workers as there were reports of side-effects. To build confidence in people, the state strengthened its counselling mechanism, ran newspaper ads advocating that the COVID-19 vaccines are safe
• Uttarakhand shared videos of people who received the vaccine and appointed doctors from the state to promote the need of vaccines and their safety. To promote the vaccine at the grassroot level, Uttarakhand involved accredited social health activist (ASHAs) and nurses to promote the vaccine drive
• Assam addressed vaccine hesitancy by disseminating reliable information through social media, digital platforms, print and electronic channels regarding recovery details and adverse events following immunisation
Vaccine hesitancy leads to a reduction in vaccine uptake, compromises herd immunity and undermines the success of immunisation programmes. According to extant science, when herd immunity is compromised, disease outbreak becomes more likely among the unvaccinated population. For instance, when the UK was battling measles in 2017, the sub-optimal uptake of the MMR vaccine due to hesitancy led to an increase in the cases4. In France, a 2018 survey had revealed that close to one in three citizens doubt the safety of vaccines. In terms of COVID-19 vaccines, close to 50% respondents of a survey worried about factors like inadequate testing and long-term side-effects.6
The COVID-19 has highlighted the urgent need of addressing vaccine hesitancy in India, to achieve herd immunity that is one of the ways to address COVID 19 pandemic. To reinforce confidence in COVID-19 vaccine, there is a need for all stakeholders in the country to communicate transparently about the process for approving, authorizing, distributing, monitoring the safety of, and administering COVID-19 vaccine.
3 The Centre for Economic Data & Analysis at Ashoka University
Dr. Navneet Tewatia, Associate Secretary General, Indian Pharmaceutical Alliance
Rising importance of the Indian pharmaceutical industry
The Indian pharmaceutical industry has played a pivotal role in driving better health outcomes across the world through its affordable and high-quality generics medicines. The contribution of the industry has become even more prominent since the last year as India continues to support the global response to the COVID-19 pandemic. The industry stepped up to meet the challenges posed by the pandemic and ensured consistent supply of medicines needed in the management of COVID-19 (e.g., HCQ, Itolizumab, Remdesivir, Favipiravir, Dexamethasone etc.) across the world strengthening India's position as the 'Pharmacy for the World'.
There have been many examples where innovations by Indian companies have improved the quality of healthcare across the world. The Indian industry has pioneered the development of affordable heat-stable fixed-dose combination of Antiretrovirals (ARVs) for paediatric use, alcohol-free and pleasant-tasting granules (combination of four ARVs in the form of granule-filled capsules). This formulation has enabled great advances in the treatment of the children living with HIV in low-and-middle income countries by improving compliance. The Indian industry has also successfully obtained the first-ever WHO approval for rectal artesunate suppositories (RAS) for the pre-referral management of severe malaria in children. The innovations by the Indian industry have also contributed to bring down the treatment costs of life-threatening diseases such as Chronic Myeloid Leukaemia and viral hepatitis C, to less than five percent of the original cost. The prices for Hepatitis B vaccines have also been brought down due to these innovations.
As we look forward, Indian pharmaceutical industry must move up the value chain and build its position in the innovation space to further augment its contribution to Indian and global healthcare.
Favorable Policy Landscape to encourage innovation at scale
Several leading countries such as the US, UK, Israel, Switzerland and China, among others, have built a strong innovation ecosystem for pharma and med-tech. A favorable policy landscape through coherent policies across scientific research, technology scale-up and commercialization, funding, Intellectual Property framework etc. has proven to be a key building block in developing the innovation ecosystem in these countries. Currently, India has innovation and R&D policies for different product groups with each having different goals and outcomes and vastly different timelines. These numerous policies lead to incoherence and make articulation as well as the implementation challenging. We need to have a robust governance framework that provides favorable regulatory environment to nurture innovation.
There is a scope for strengthening policy framework for pharma innovation and R&D. The framework of the innovation and R&D policy should focus on a common vision to offer universal access to healthcare with equity promoting self-reliance and being responsive to the healthcare needs of the citizens of India. The common goal of the policy should be to promote indigenous drug discovery which would significantly improve India's position in the pharma value chain. The policy should aim to promote R&D to reduce the burden of neglected diseases in India which would pay for itself in the form of improved social and health outcomes and reduced morbidity.
The innovation and R&D policy should identify and drive synergies between all stakeholders in the drug research and development. Developing these synergies in scientific research, technology commercialization, IT investments, education and skills development, tax, trade, IP, in an integrated manner is essential to drive a sustainable innovation ecosystem.
Vision for a sustainable innovation ecosystem in India
Creating an interconnected network of industry, academia, start-ups, business schools, clinical settings, funding agencies (including VCs) to deliver solutions will help shape the innovation ecosystem in India. While few innovation clusters exist in India, the current infrastructure is limited and concentrated in a nascent innovation hubs in the country, emphasizing the need for more high-quality infrastructure. To support innovation and for pharmaceutical industry to flourish, the government needs to enhance quality of infrastructure which can be achieved by scaling up 'innovation hubs' in the country. This would provide industries, academia, incubators a co-location and create a valuable innovation ecosystem. Incentives such as tax exemptions and plug and play facilities, and local regulatory support for speedy approvals should be offered to companies in these parks. Public Hospitals should be provided IT and data management systems to create adequate support for clinical trials and encouraged to participate in clinical trials.
Impact of building a strong innovation ecosystem
Innovation will drive the next wave of growth for the industry with potential to propel projected growth rate from the current 7-8% to 11-12%. This will lead to a substantial increase in the global market share by value enhancing Indian pharma's significance beyond generics, to biologics, new drug development and incremental innovation thus positioning India as the true "Pharmacy of the World". It will also mean the Indian pharmaceutical market will feature into top 5 markets by value globally, from its current rank of 11th and become world's largest supplier of drugs by volume.
Creating a stable and supportive policy environment for the pharmaceutical industry is a critical step towards building a sustainable innovation ecosystem. The government has a crucial role to play in the growth of the pharmaceutical industry. Building presence in the innovation space is now a high priority for India in order to both address the needs of the healthcare system in the country, as well as maintain relevance in the global pharma and med-tech space. India has several strengths to leverage, and a strong starting position to build on, as it looks to evolve beyond its successful journey of "Make in India" towards the vision of "Discover in India".
The Indian pharmaceutical industry has achieved tremendous growth over the years and has made a massive impact on the global market. 2020-21 has been a challenging year, but the industry rose up to the occasion and demonstrated great resilience. Since the outset of pandemic, the industry focused on ensuring continuous supply of medicines in the country and abroad , at a time when manufacturing operations faced severe challenges as a result of the lockdown imposed across the nation in COVID 1.0. It emerged as reliable partner to the world through its dedicated efforts in 2020 ensuring that essential medicines were supplied to all the partner countries, quick turnaround time in manufacturing repurposed drugs – Remdesivir, Favipiravir and hydroxychloroquine, commitment to manufacturing COVID-19 vaccines, and its R&D investments in the screening, treatment, and prevention of COVID-19 through the launch of indigenous testing kits, treatments, and vaccines. The momentum gained during these trying times last year have sent positive signals across the world with regards to Indian pharma industry’s commitment, resilience, adaptability, and its untapped potential.
While the COVID-19 pandemic has provided impetus to the Indian pharmaceutical industry on some fronts, the industry’s global presence has been growing at a steady rate over the past few years. Indian pharma accounts for 60 percent of global vaccine production and contributes to 40 to 70 percent of the World Health Organisation (WHO) demand for Tetanus and Pertussis (DPT), Diphtheria and Bacillus Calmette–Guerin vaccines. India’s per person disease burden measured as Disability Adjusted Life Years (DALYs) dropped by 36 percent between 1990 and 2016 and during the same period drug penetration increased by 50 percent in the country. The lowering of disease burden is attributed to the increased accessibility to affordable drugs. India also meets 90 percent of the WHO demand for the measles vaccine. Furthermore, as a result of strong collaboration between vaccine manufacturers, the government, and healthcare providers, India has now been declared Polio-free.
The journey of the industry to this critical point has been a long one beginning in 1970 with the introduction of the Indian Patents Act 1970 and Drug Policy 1978. A new generation of scientists and entrepreneurs in the country leveraged the opportunities provided by these new regulations in order to set into motion what today is one of the world’s largest pharmaceutical industries. Prior to 1970, India relied mostly on imports for many drugs consumed in the country. In the 1950s, foreign companies held the patent for nearly 99 percent of all pharmaceutical products under patent in India. India had some of the highest drug prices in the world. The 1960s saw a push towards self-reliance with the government setting up five state-owned pharmaceutical companies in order to meet domestic demand. These in turn led to the reforms seen in the 70s, which allowed Indian companies to grow into international markets in the 1980s. This period saw a large growth in the number of pharmaceutical companies from 2,000 in 1970 to 24,000 in 1995.
Year 2005 saw the emergence of a new era in Indian pharma with the introduction of the 2005 Patents (Amendment) Act which introduced product patents in the country. This move encouraged foreign pharmaceutical companies to venture in India, thus promoting healthy competition in the market. This also encouraged Indian pharmaceutical companies to invest in innovation and R&D with some companies developing their own new molecules, while others entered into R&D joint ventures with foreign pharma companies.
Today the Indian pharmaceutical industry is truly global in its nature with Indian companies responsible for approximately 40 percent of all generics consumed in the United States and 25 percent of all medicines dispensed in the United Kingdom are manufactured in India. India supplies two-third of antiretroviral drugs globally, contributing to the international fight against AIDS. Indian pharma’s affordable generic alternative led to an 18-fold increase in the number of AIDS patients being treated between 2003 and 2009. North America buys 34 percent of India’s total pharmaceutical exports, which is the country’s largest export market followed by Africa at 19 percent.
The Indian pharmaceutical industry is on the path to steady growth, certain factors and incentives will enable it to achieve its ambitious target of reaching USD 130 billion by 2030. These factors include increased investments in R&D which can be boosted through incentivization by the introduction of tax incentives as well as adoption of more flexible regulatory norms around clinical trials. The introduction of the new PLI scheme aimed at boosting the domestic Active Pharmaceutical Ingredients (API) industry is a positive move towards this long-term goal. Identification of new export markets or assessing ways to make greater inroads into existing export markets are strategies that will be adopted by all companies. COVID-19 has forced countries to re-think global drug supply chain models and there is an increased focus on diversification of supply chains. Indian pharmaceutical industry is in a favorable position to capitalize on this opportunity due to its affordable, quality manufacturing and because of the dependability it has shown during the pandemic.
Contributions of Indian pharma industry to economic and health outcomes
The Indian pharmaceutical industry has played a key role in improving the world health outcomes through its affordable and high-quality generic drugs. It has helped many countries in their fight against life-threatening diseases and has provided countless people with an improved quality of life. Indian pharma presently fulfills over 50% of the global vaccine demand, 40% of the US's generic medicine demand and 25% of all the UK's medicine demand1. India has also played a vital role in supplying lifesaving anti-retroviral (ARV) medicines-critical for controlling and preventing the transmission of HIV/AIDS - to southern and western African regions2.
India's pharmaceutical industry has also been instrumental in achieving the goal of a polio-free country. The accessibility and availability of affordable drugs has played a vital role in India's progress on the reduction of national disease burden. This was driven by a decrease in infectious and associated diseases from a 61 percent disease burden in 1990 to 33 percent in 20163.In the coming years, India has the potential to become the global leader in the pharmaceutical sector.
Aspirations of Indian pharma industry
As we move towards the future, the healthcare and pharma industry in India will have to move up the value chain and expand its presence in the innovation space which continues to account for 2/3rd of the global pharmaceutical market value1. The Indian Pharmaceutical Industry in 2020 is at an inflection point like the Indian IT industry which blossomed in the 1990s-2000s. The pharma sector has the potential to grow to a value of USD 120-130 Bn by 20302 from its current value of USD 43 Billion The key drivers in achieving this growth will be building a strong, innovation-based pipeline with potential breakthroughs in next-generation products (non-generics) coupled with a strong growth in international markets such as USA and Europe and large, under-penetrated markets such as China and Japan.
Building Blocks of Innovation
Innovation is a long-term commitment requiring strong industry academia interactions and steady financial support. Sustained advancements in Innovation can be achieved by recognizing and boosting the essential drivers of growth in the ecosystem. Furthermore, it is essential to engage academia and industry in understanding existing challenges in promoting innovation. At its essence, pharmaceutical innovation in India requires the following:
Favorable Policy Landscape: Policy makers should draft coherent policies and laws supporting and boosting scientific research and technology to promote an ecosystem of innovation. This will help facilitate the scaling up of the effectiveness of innovation1.
Enabling Regulatory Landscape: The regulatory landscape should be streamlined with robust guidelines, high predictability, increased capacity, and strong governance. Adequate and well-defined approval timelines, complete procedural transparency, and seamless processes should create a regulatory landscape conducive to innovation1.
Robust Funding: It is imperative to encourage industry-related R&D and studies, backed by governmental monetary sanctions, funds, investments, policies, and subsidies along with significant VC / PE investments. Government organizations should help sustain the momentum on funding by increasing the public spend on R&D and promote innovation focused research in areas such as genetics, biochemistry, molecular biology etc1.
Strong Linkage Between Academia and Industry: Interactions with academic institutions to incorporate accurate syllabus, strong policy framework for Academia-Industry collaboration, increased support for outcome-oriented research and a greater focus on industry-oriented research. can help drive innovation talent in the pharma industry1.
High Quality Infrastructure: Setting up of innovation hubs across the nation will help accelerate the innovation in the pharma industry. The innovation hubs should facilitate co-location of industry, academia, VCs, and incubators to create a vibrant innovation ecosystem. Incentives like tax exemptions and plug-and-play infrastructure will further fortify the infrastructure set-up1.
Innovation as a key to achieving Vision 2030
With an increase in global market share to ~7.0% by 2030, the Indian pharma market is expected to break into the top 5 markets by value globally, taking it from its current rank of 10th to become the world's largest supplier of generic drugs2. This will enable the industry to push the net foreign exchange earnings to around USD 30-40 billion annually by 2030 from current levels of ~USD 10 billion2.
Moving up the value chain in Innovation can drive significant health and economic benefits for India. Development of drugs for India-specific ailments that do not get adequate global attention (e.g., Tuberculosis, Leprosy, Drug-resistant infections like NDM-1, Elephantiasis, Kala Azar) will help reduce India's disease burden. Innovation will not only help in improving health conditions but also contributes to the nation's GDP. R&D and Innovation will enable the creation of high skilled white collar jobs enabling differentiation vis-à-vis other developing economies apart from contributing an additional USD 10-12 Bn of exports every year for the economy from 2030.
Collective efforts from industry experts, academic institutions and government authorities can address the challenges in the ecosystem which are hindering India's ability to unleash its innovation potential. If the Indian pharma industry continues to build in the innovative space and bridge the gap in the healthcare sector, it can dominate the international pharma market. These initiatives can also help augment the Indian Prime Minister's 'Make in India' vision to "Discover and Make in India".
India pharma industry, Innovation, Pharmaceutical, Healthcare, Accessibility, Affordability, Funding, Regulatory Landscape, Academia, Health care index, Make in India, Aatmanirbhar, R&D, GDP, Employment, Infrastructure, Policy
By Mr. Sudarshan Jain, Secretary General, IPA and Ms. Archana Jatkar, Associate Secretary General, IPA
The Covid-19 pandemic has catapulted the world into a humanitarian crisis of immense magnitude. It has presented an unprecedented challenge to public health, with healthcare being fundamental. The coronavirus spread rapidly through China and around the world with the WHO declaring COVID-19 a global pandemic in March 2020. As the world took emergency measures to address the crisis, the pandemic has had a profound impact on life and businesses across the world leading to lockdowns in many countries, restrictions on movement, travel, social gatherings, among others. In these unprecedented times, the Indian pharmaceutical industry emerged as a dependable partner by supplying uninterruptedly the life-saving medicines not only in India but across the world and demonstrated tremendous commitment towards patient welfare.
The COVID-19 Challenge
While the pandemic posed several new challenges, it also provided the pharma industry an opportunity to emerge as a reliable supplier of high-quality, affordable medicines. At the same time, this has been a period of significant learning for the Indian industry. When a national lockdown was announced in early 2020, the government, pharmaceutical associations and industry leaders in India worked in a coordinated manner to address the potential challenges.
Collaboration is Key
After the first week of the first lockdown in March 2020, manufacturing capacity across plants dropped to less than 20% due to various disruptions including the exodus of workers returning to their villages, shutting down of ancillary and related operations, prevention of workers from being able to reach their places of work and large-scale supply disruptions from China. In these trying times, supply of medicines is fundamental need of the hour for which smooth functioning of manufacturing operations is critical. This was recognised early on by the industry and the government. As a result, the Government of India classified pharmaceutical manufacturing, distribution, ancillary and support operations as essential goods and services and exempted it from lockdown. Effective collaboration among the government, pharma industry, trade associations, ancillary industry and others, enabled capacity utilisation to reach 70-80 percent by end of May 2020. Regular feedback, integrated efforts, sharing and consistent dialogue between industry stakeholders and government authorities has worked well during COVID 19 pandemic.
Need for Resilience in Supply Chains
The Active Pharmaceutical Ingredient (API)/Key Starting Material (KSM) supply disruptions from China in February 2020, had highlighted the dependence of the Indian pharma industry on imports. Given this, the Indian pharmaceutical industry needed to secure its supply of APIs and KSMs in the wake of the Coronavirus. The Government of India recognized the need to revive the domestic API manufacturing industry and announced an API policy incentivizing the domestic production of APIs/KSMs in March 2020. The core focus of creating scale and long-term survivability of the industry was developed through constant engagements between the API and formulation manufacturers and the Government.
Importantly, no drug shortages were reported domestically, and Indian pharma companies were able to meet global demand as well. The lockdown highlighted the importance of a diverse and resilient supply chain and the potential challenges of heavy reliance on one country for APIs.
Best Practices Protocols
In the initial period of lockdown/pandemic, the pharma companies worked onto share the best practices for the safety of employees engaged in the manufacturing of pharmaceutical products. Safety protocol documents were prepared and provided a comprehensive set of practices that have been deployed across pharmaceutical manufacturing companies in response to the COVID-19 crisis. The Indian companies came together to prepare a protocol for pharmaceutical manufacturing facilities in India in case any personnel is reported COVID positive. The objective of preparing this protocol was three-pronged –
The protocols were also shared with Indian Government authorities including the Indian Council of Medical Research (ICMR). The ICMR found the protocol useful and endorsed it. The sharing of protocol along with other safety measures taken by companies helped in strengthening the implementation of the safety measures underlining the importance of safety.
Vaccines and Re purpose Medicines
The disruptive role of the COVID-19 pandemic on the pharmaceutical industry has been varied and has challenged the industry to deliver solutions at a pace and efficiency. The industry responded promptly by evaluating possible utilisation of available drugs (repurpose drugs) and exploring more innovative approaches. Indian companies are engaged in developing indigenous vaccines that are currently undergoing testing for efficacy & safety. The momentum gained in R&D in India is positive and should continue beyond the pandemic. Innovation will act as a key catalyst in Indian pharma realising its Vision 2030.
The Way Forward
Indian pharmaceutical industry has been playing a key role in improving access to affordable medicines in India and abroad. As the race for a vaccine intensifies, the role of Indian pharma industry will increasingly become vital. This is an opportune time to move beyond firefighting and to address challenges facing the industry from a long-term perspective across the value chain. The need is to resolve bottlenecks and bring in simplified regulatory system that will boost competition, keep the quality enhanced and a market that fosters innovations.
In crisis lies an opportunity for India, to be truly the “Pharmacy of the World” and to realise its aspiration of reaching 120-130 Bn USD, becoming the largest volume producer in the world. Robust policy changes and additions implemented during the last nine months enabled pharmaceutical companies in the country to maintain production and increase efforts during the peak months of the pandemic. In the post-pandemic world, these collaborations with significant investments in R&D and innovations will define the course of our future.
By Mr. Ganadhish Kamat, Global Head of Quality, Dr Reddy'sPharmaceutical industry is facing lot of challenges. These include - pricing pressure due to various initiatives by governments to control healthcare cost in the respective countries & consolidation of buyers in US, a large number of generic approvals even for complex generics on day 1 in the US, thereby not giving huge dividends for being first to market the generic version, high cost of development, high investments and long gestation period for complex generics, increased regulatory expectations & scrutiny, increasing costs due to increasing cost of materials, transportation, energy cost, rising wages etc. The industry can overcome these issues by adopting the philosophy of continuous improvement to improve efficiency, productivity, yields, resource utilization etc. It will also help in driving down the cost and making the processes robust there by reducing the failure rates, improving compliance, and reducing COPQ (Cost of poor quality). One of the important levers to drive continuous improvement is adopting new age technologies including digital. Pharma companies today are at different levels of digitization and automation. At the base there are business process automations like ERP, LIMS, MES etc. Then there are linkages of these base systems with manufacturing and testing equipment for recipe based process controls and data acquisitions. Many companies use mechanizations and robotics for eliminating human efforts and improving reliability and consistency of the process. Most pharmaceutical manufacturing equipment today are capable to run with recipes and have data acquisition systems. They capture lot more data than those controlled through batch records as Critical Process Parameters (CPPs). The Power of Analytical Dashboards Simple way of using data is creating Analytical dashboards which can give useful information without having to go through piles of data scattered over various systems. Analytical dashboards can be designed to provide meaningful information about Key Performance indicators, health of the processes and quality systems etc. using all the available data across various systems mentioned earlier. These dashboards can help managers in daily management, to take necessary course corrections when required. The dashboards can also help in identifying improvement opportunities. AI tools can be used to perform multivariate analysis and establish relationships between, Critical Material Attributes (CMAs), CPPs and Critical Quality Attributes (CQAs) which were not established during product and process development. These tools can be designed to identify the golden tunnel to run the processes to give best performance with respect to quality attributes as well as yields. Information gathered from manufacturing operations like that mentioned earlier can be leveraged by R&D for optimal process development for new products. Other information available in R&D related to past products including drug- excipient interactions, degradation pathways, structure activity relationships, stability data, bioavailability data, dissolution profiles etc can be mined using AI tools to get first time right development there by reducing the development cycle time. Investigation of non-conformities It is yet another area in the Pharmaceuticals which often takes a long time and huge resources due to difficulty in gathering relevant data from the batch records and its analysis. Also, sometimes analysis of the data available in the batch records do not lead to identification of the root cause because many time the failures could be due to multivariate effect and sometimes even those parameters have impact which have not been earlier identified as CPPs. Having huge amount of data of CMAs, process parameters, machine parameters, environmental parameters etc and ability to do meaningful analysis of such data in short time can help in establishing correlations which might have not been understood in the past. Out of Specification results especially those due to laboratory failures is another pain point in the industry. Data analysis of system suitability parameters and other parameters of chromatography analysis on continual basis can be used to predict the systems or column failures in advance, so that OOS or OOT results which can be caused by these can be avoided by taking appropriate measures. Use of other new technologies in operations Process analytical Technology has been talked about for long time but is still not being widely deployed in the industry. There are lot of sensor available today which can give us important information about the process. PAT tools along with continuous manufacturing technologies can bring significant efficiency in Pharma operations by way of reduced footprint, less material handling, lower storage space and energy consumption. Many IoT sensors are now available for continuously monitoring parameters like temperature, vibrations etc. This data can be analysed using AI tools for predictive maintenance of the equipment thereby minimising breakdowns and improving OEE. Rapid analytical techniques like NIR, Raman spectrophotometry, rapid microbiology etc can bring in significant change in the way we control the quality of products. Establishing appropriate on line or at line controls in the process using these technologies can help us to move towards parametric releases there by eliminating need for end product testing and significantly bringing down process cycle times. AR & VR technologies can be used to guide operators in flawless execution and also for training of new employees. The last century has seen a steady improvement in the quality of life for people across the world. While several factors have contributed to this development, advances in medical technology have played a significant role. The discovery of new drugs, development of vaccines and therapeutics have transformed the healthcare industry, making previously fatal ailments curable and in some cases, preventable;. Having said that, novel infections such as SARS-CoV-2 continue to present new challenges and opportunities. This makes maintaining the quality of pharmaceutical products paramount in order to ensure safety of the patient. A pharmaceutical product that does not meet the required standards can pose a serious threat to public health and safety. However, what does pharmaceutical quality mean? Before we delve into the meaning of pharmaceutical quality, it may be beneficial to explore the meaning of the word 'quality' itself. Herein lies the first hurdle, as there is no consensus on the definition of quality for any product or service. This, however, has not deterred the presentation of unique perspectives. J.M. Juran defines quality as 'fitness for purpose' while Phillips Corby defines it as 'conformance to requirement'. Some theorists argue that quality means different things when considered from the perspectives of a manufacturer and a consumer. To complicate things further, some suggest that quality could mean different things to different consumers based on their specific needs. The quality of a pharmaceutical product is determined by the quality of the raw materials, equipment, and the technical knowledge required to process, package, and distribute the product. Unlike most other goods, pharmaceutical products are dynamic/versatile in nature. The weight, colour, consistency, and even chemical composition can change between production and consumption. The quality of a pharmaceutical product is grounded in the efficacy and safety of the Active Pharmaceutical Ingredients (API), formulation, manufacturing, and supply chain functions. The potential effects of a sub-par quality product being consumed could be highly damaging to the health of a patient and may have long-term implications on public trust in pharmaceuticals. In the case of the USFDA, the understanding of drug quality is linked to the consistent delivery of the label performance and lack of contamination. This definition is operationalized by a predefined set of quality attributes (e.g., specifications, limits) and through the Current Good Manufacturing Practices (CGMP) regulations.[ Woodcock, Janet. (2004). The concept of pharmaceutical quality. American Pharmaceutical Review. 7. 10-15. ] The Federal Food, Drug, and Cosmetic Act (the Act) states that drugs that do not adhere to the CGMP regulations are deemed 'adulterated'. A different perspective suggests that pharmaceutical quality should be defined as 'fitness of use'. The 'fitness of use' of a product can be defined by whether it meets its designed attributes and meets the standards set out by a regulatory authority. The concept of pharmaceutical quality is dynamic and ever evolving. Is pharmaceutical quality - The answer is likely to be a combination of all the above. Quality forms the basis of ensuring the availability of safe and effective treatments and therapies to patients. There have been several questions raised regarding the overall quality of drugs available in the US, particularly in relation to generic drugs and internationally manufactured drugs. Surveys have indicated that a majority of healthcare practitioners are uncertain of the quality of drugs manufactured outside the US.[ Duke Margolis Center for Health Policy. Understanding how the public perceives and values pharmaceutical quality. https://www.youtube.com/watch?v=dYrVIxVN0ZA] A recent study set out to assess whether there are substantive differences in the major quality attributes of difficult-to-make pharmaceutical products manufactured throughout the world and marketed in the US. The study found that all the drug product samples met the US market standards for the major quality attributes of dosage unit uniformity and dissolution. The findings from the study indicated that drugs were of standard quality irrespective of the country of manufacturing or manufacturing company. This also demonstrated that generic drugs were of standard quality3.
1Woodcock, Janet. (2004). The concept of pharmaceutical quality. American Pharmaceutical Review. 7. 10-15.
2Duke Margolis Center for Health Policy. Understanding how the public perceives and values pharmaceutical quality. https://www.youtube.com/watch?v=dYrVIxVN0ZA
3Fisher AC, Viehmann A, Ashtiani M, et al. Quality Testing of Difficult-to-Make Prescription Pharmaceutical Products Marketed in the US. JAMA Network Open. 2020;3(8):e2013920. doi:10.1001/jamanetworkopen.2020.13920Under this series on 'Quality', we will discuss various factors that can influence the quality of pharmaceutical products. Next blog post will be published in the month of November 2020. Stay Tuned!
-Mr. Shirish Belapure, Senior Technical Advisor, IPA
Tags: Vaccines, USFDA, SARS-coV-2, Active Pharmaceutical Ingredients (API), pharmaceutical, CGMP, MHRA, API, CDSCO, Quality