Challenges in Implementation of Green Chemistry in Indian Pharmaceutical Sector

The alarming environmental pollution caused by pharmaceutical Industries has led to the growing importance of Green Chemistry in India. It is high time that the pharmaceutical industry that is considered as a red category by the environment ministry, adopts green chemistry & green technology to address this issue. This study aims to find out the major barriers to implementing green technology in the pharmaceutical sector. Integrated Structural Modelling method & MICMAC Analysis has been adopted to identify a structure by which the pharmaceutical industries can implement green technology. An extensive literature review & discussions with industry experts led to identifying ten major challenges to the adoption of green technology in the pharmaceuticals. Economic &financial barriers & regulatory barriers have been identified as the major barriers. This study brought out a lack of consolidation of knowledge in this field as a challenge to the implementation of green practices, which has been largely ignored in previous studies and needs to be addressed.


INTRODUCTION
The global pharmaceutical industry is expanding at an accelerating rate, with the United States as the leader, followed by Russia, Brazil, China, and India [1]. The pharmaceutical sector is one of the fastest-growing sectors of the Indian Economy, with the potential to grow to USD 100 billion by 2025 [2]. India has captured the global market with its innovation in generic drugs and active pharmaceutical ingredients engineering. The development of the pharmaceutical industry in India and across the globe has led to many environmental degradation instances. The report of the presence of pharmaceuticals in the environment was first filed in the 1970s, but it was only in the 1990s that it became a matter of concern when its traces were found in drinking water [3].
The Indian pharmaceutical sector is categorized as a "Red Category" by the environment ministry about the pollution caused by it over several years. India, a global manufacturing hub, generates highly acidic & alkaline waste due to large-scale chemical processing, including nitration, chlorosulphonation, sulphonation, etc. Groundwater near pharmaceutical units contains toxins like lead, cadmium, arsenic, etc. thousand times more than what is permissible in drinking water by WHO & Bureau of Indian Standards [4].
Green Chemistry in India commenced some 20 years back with a few conferences and began to gain recognition in the 2000s through industry initiatives like Industrial Green Chemistry World. In the past few years, Green Chemistry has gained importance in India for the government, industries, consumers, and media. India is moving towards the implementation of  Chemistry & sustainability, the pharmaceutical industry is reluctant to adopt it. Study in this domain has been inclined towards the economic aspect, ignoring other aspects that can affect its adoption in the pharmaceutical industry [6].
This study addresses this gap by looking at the existing challenges and constructing a model to help pharmaceutical companies understand the hierarchical nature of the issue and the interrelationships of the challenges identified to adopt green chemistry [6] in India. Finally, these challenges have been classified using MICMAC analysis based on driving and depending on power [7]. The paper starts with a detailed literature review highlighting the ten major challenges identified. Further, an interrelation is found out between the disablers after discussion with industry experts. The paper concludes with a summary & implications for the pharmaceutical organizations.

Economic and Financial Barrier
According to [8], a green chemistry product should be both economic & environmentally friendly. A product should focus on improving the environment & health making profits as well. According to [9], business focuses primarily on economic stability rather than social and economic stability as a measurement for success. A small decrease in the cost of waste, implementation of less harmful processes, and marginal efficiency improvements are not enough to outweigh the cost of large investments when the amount of savings is uncertain or difficult to quantify.
According to [10], the GC process can be brought in only if it can pay back the investment within few years to attract the investors. Highlight basic economic and financial barriers: the high cost of capital, uncertainty to future benefits, and unwillingness to abandon sunken capital [11]. It is not feasible for firms to abandon their old capital-intensive technology and invest in new green technology [12]. Difference between traditional unsustainable methods and modern green methods is made to shed light on the economic and environmental benefits of greener methods [13]. It is found that the government scientists were using patented techniques extensively without knowing effects of green methodologies in some cases or don't know whether not caring about it.

Regulatory Barrier
Regulatory risk has been reported as one of the two top challenges for the adoption & implementation of Green Chemistry in pharmaceuticals for both Generic & API industries. Increased environmental rules and regulations over time have an important impact on pharmaceutical industries. In 2005 in the United States of America, Chemical Industries spent more on pollution reduction than any other sector [14].
Suppose any industry needs to change a process or method. In that case, it has to go through many time-consuming and costly legal procedures that are mandatory and may vary from a few months to a few years worldwide, posing a great barrier [15]. Going through legal processes, documentation, and filling and approval from internal affairs teams and external agencies like the FDA also acts as a major barrier [16].
Financial regulations like write off old infrastructure, accounting details, etc., also add to the barriers. Further, no quick approval process for green drugs makes the process more cumbersome [11]. The lack of funding for R and D are major reasons for regulatory barriers.

Leadership and Management
Top management plays a major role in taking all major decisions. Limited support from top management makes green chemistry adoption a less priority. The absence of common organizational goals and power struggles within an organization also acts as a major challenge 12. Further lack of clear vision & mission of top management for green chemistry application makes it difficult for it to be adopted by the entire organization. Management is responsible for training the employees & making them ready with knowledge and skills to implement green chemistry technology.

Lack of Expertise
Green Chemistry has some disciplines that act as a barrier. The chemists and engineers have limited knowledge about the adoption of green engineering [8]. Lack of expertise is a major barrier to the adoption of GC in the case of API industries. There are different branches in Green Chemistry [14]. Expert in one branch does not know another very essential branch. Nanotechnology also faces the problem of lack of expertise. The chemists' greatest challenge is to eliminate the environmentally harmful chemical products from the drugs [10]. Lack of expertise also includes lack of technical knowledge of chemists who deal with the end customer [17].

Lack of Standardization Regarding Definition and Metrics
GC is governed by "The Twelve Principles of Green Chemistry." People often consider green chemistry the same as sustainable development or chemical sustainability. There is ambiguity in deciding whether a process or a product can be categorized under Green Chemistry or not. There is no recognized certificate or standard set to mark a product under green chemistry. According to [8], lack of metrics and loose definition makes it hard to declare a product green. This ambiguity in the definition & metrics to decide what green chemistry is and what it is not is a major barrier [18].

Lack of Awareness and Knowledge among Stakeholders
According to [10]

Organizational Barrier
An organization's structure also acts as a major barrier to green chemistry implementation 5. Even if the implementation is beneficial for the organization, a particular division may be unwilling to adapt if it affects its profits. According to [17], industries face a lack of adaptability & flexibility while adopting green chemistry. Many times, a product made through green chemistry hinders the sales of another product of the same industry. This lack of flexibility & interdepartmental is chaos while implementing a green process acts as a major organizational barrier.
According to [10], the pharmaceutical industry has shifted from internal manufacturing to external manufacturing, where the degree of unsustainable manufacturing is higher.

Time Pressure
The pressure to deliver drugs fast is a major barrier to adopting the pharmaceutical industry to green chemistry. Time pressure is an important barrier to the implementation of GC in generic industries [14]. Usually, researchers need approximately two years to develop a synthesis, but the average is just half a year for the entire industry. Further redesigning an existing product according to green chemistry is burdensome and costly. Even if the drug is ready, regulatory approval time differs from few months to few years, varying in different countries. It further creates financial and operational problems for the pharmaceutical industry [15].

Technological Barrier
We do not have adequate green technologies for many processes like sulphonation and nitration. In the absence of these technologies, the pharmaceutical industries have to stick to using conventional processes that involve high usage of acids, alkalis, and other chemicals is a major barrier [16].
According to [10], one of the major barriers is that green chemistry technologies are not easily procurable, and old technologies are easier to implement than green technologies. The cost of operating green technology & of the solvents also acts as a disabler [19]. The difficulties in sharing information across industries and lack of available substitutes for solvents and chemical reactions also hinder barriers.

Lack of Consolidation of Knowledge
According to [16], many Green Chemistry solutions are proven by scientists, researchers, and startups. Still, the industry does not know of it because of the researchers' lack of marketing or lack of initiatives taken by the industry. According to [11], there is no formal database or repository for green chemistry developments for major reasons like trade secrets. This lack of consolidation of knowledge or a consolidated database also acts as a barrier.

METHODS AND MATERIALS
Interpretive Structural Modeling (ISM) follows a procedure starting with identifying the most relevant variables through literature review followed by a brainstorming session conducted with a group of experts where a relationship is derived between various variables. This method helps the manager assess the priorities & and understand the relationship between various variables.

Structural Self-Interaction Matrix
A structural self-interaction matrix has been formulated after determining ten major challengers for determining the relation between them. Industry specialists were brainstormed & to identify, as shows in Table 1.
This rating system is used to identify the relation between 10 disablers that is showcased in Table  1.

Reachability Matrix
Initial Reachability Matrix has been formed with the help of SSIM. IRM symbolizes binary relations between various challengers. Here the symbols V, A, X, O are interchanged by binary numbers 0 & 1. The given parameters are observed for the formation of the Initial Reachability Matrix, which is shown in Table 2:  If the (i, j) is V, then the (i, j) in the IRM is changed to 1, and the (j, i) is changed to 0  If the (i, j) is A, then the (i, j) in the IRM is changed to 0, and the (j, i) is changed to 1  If the (i, j) is X, then the (i, j) in the IRM is changed to 1, and the (j, i) is also changed to 1  If the (i, j) is O, then the (i, j) in the IRM is changed to 0, and the (j, i) is also changed to 0

Now, after the Initial Reach ability Matrix, the Final Reach ability Matrix is formed by integrating transitivity. Transitivity indicates that disabler X is affected by disabler Y & disabler Y affected by disabler Z; then disabler X will also be affected by disabler Z. This transitivity is incorporated in Final Reach ability Matrix & is represented by
one* in the matrix. The matrix is given in Table 3 3

.4 Partition of Final Reach ability Matrix
Final Reach ability Matrix is partitioned to identify the level of the hierarchy of all the disablers. This hierarchy is necessarily used in the formation of a conical matrix. Reach ability& Antecedent sets have been obtained from the Final Reach ability Matrix & Intersection Sets are identified from the two [20]. The Reach ability set includes the variables affected by it & the Antecedent set includes the variables that affect that particular variable or have control over it. Intersection sets are variables that are common in both the Reach ability& Antecedent set. The elements for which antecedent & reachable variables are common are topmost level variables in the ISM model pyramid. After they are determined, they are detached from other elements where the procedure is repeated till the level of every variable is found, as shown in Table 4. This is used for the formation of the conical matrix & the diagram.

Conical Matrix
After the partition on the Final Reach ability Matrix, the disablers are arranged according to their level vertically & horizontally in the Conical Matrix. Level 1 includes variables 5, 6,7,10 & level 2 includes variables 3,4,8,9, and all are arranged accordingly in the conical matrix as shown in Table 5.
Adopting green technology involves a high capital investment that small industries cannot make & large industries are reluctant to lock their funds when they are not sure of the return. These two major factors restrict top management from making the desired decisions. Economic & regulatory barriers lead to uncertainty where the industry is reluctant to take major decisions that lead to all the eight barriers, as shown in the diagram above. The first and the foremost step need to be taken by the government & regulatory authorities to ease legal formalities and give industries an incentive to embrace green chemistry.

CONSENT
It is not applicable.

ACKNOWLEDGMENT
The authors wish to acknowledge Symbiosis Institute of Management Studies for assisting & providing access to resources for this study.