Current and Future Outlook of Pharmacogenomics in Paediatric Asthmatic Medications

Ensuring Efficiency in Packaging Process should be a top Priority for Pharma Packaging Companies

Covid-19 drastically impacted the way pharma packaging functioned. The overnight entire supply chain was heavily fractured across the globe and at the same time demand for healthcare products skyrocketed due to panic amongst the public. There is no scope of mistake when it comes to packaging critical drugs, especially rubber stoppers. It is a test of all our compliances, quality and proficiency in producing critical components to protect drugs and maintain their safety and efficacy. We are now witnessing a robust change in the working environment with demand planning, Quality, Innovation, Supply chain as well as storage. India is the new powerhouse of pharmaceutical packaging. It is time to increase capacity for quantity and quality production.

Siddharth Shah, Director, Bharat Rubber Works

The pharmaceutical industry is one where decades of innovation lead to one new product, like a drug or vaccine. It’s common knowledge that the development of a critically vital drug or vaccine is a difficult process that requires years of development time and millions of dollars in research funds to complete. Pharmaceutical manufacturers are faced with many obstacles once they've formulated a new drug or vaccine. One of the obstacles is the packaging of these newly developed drugs. When it comes to packaging, there are several critical steps that go into ensuring that a product reaches the end-user in very good condition. Pharmaceutical manufacturers often have many options when it comes down to picking the correct type of packaging solutions that can protect their product to ensure uncompromised quality along with maximum safety and efficacy. A lot of the time, the success or failure is usually determined right at this stage. There are many factors that can be taken into account such as shelf life, homogeneity of drug formulations and composition, as well as patient safety and delivery control considering it may require controlled temperatures for efficacy.

The Repercussions of COVID-19 on the Pharmaceutical Packaging Industry

Starting with the outbreak of the COVID19 pandemic, the pharmaceutical packaging sector suffered a significant setback. The supply chain was severely disrupted, and the rapid increase in demand posed difficulties for both manufacturers and packaging solution providers alike. An important problem was the inability to dispatch supplies during this period due to a lack of available global logistical facilities. Aside from that, supplementary industries to the pharmaceutical industry, such as the manufacture of packaging materials for pharmaceuticals, had not yet been placed under the purview of vital services. Slowly, but steadily, the

industry was able to adapt and restore normalcy throughout the supply chain as a result of government policies and actions designed to transform these services into vital services. However, there were some important shifts during this period. COVID-19 paved the way for a more prominent localisation approach, which had a significant impact on pharmaceutical packaging. As a result of the COVID-19 pandemic, Indian pharmaceutical packaging contractors got an opportunity to actively enter and compete in a growing global packaging market.

The Pharmaceutical Packaging Industry Has Undergone Significant Changes

Indian pharmaceutical manufacturing is third in volume, leading to an industry nickname of "The Pharmacy of the World." Supply chain constraints during the pandemic forced pharmaceutical manufacturers to seek out solutions with quicker turnaround times. Localisation worked as a big push towards this change, transforming India into a world pharma packaging center. Domestic producers were also forced to seek effective pharmaceutical packaging solutions due to the pandemic, and they rapidly learned that the local pharma packaging industry was more than capable of satisfying local and global requirements for pharmaceutical packaging. The production and packaging of COVID-19 vaccine was a product that received significant attention from both Indian and international manufacturers, serving as validation for Indian pharmaceutical packaging companies at large. Thus, the fortunes of India's pharmaceutical packaging business changed substantially, for the better, in the last 24 months.

The Indian pharmaceutical packaging businesses provide solutions for a broader range of pharmaceutical products than merely the COVID-19 vaccines. In fact, what has been observed over the last few years is that the demand for non-COVIDrelated drugs has surged by a factor of per cent. This has ensured that the pharmaceutical packaging industry has seen significant growth and demand, not just for COVID-19 related drug packaging but also for the other essential medications in constant demand. Given this reality, it's common to find an alliance between pharmaceutical producers and pharmaceutical packaging companies during all phases of development. Aside from that, the sector has gained a great deal of knowledge about operational strategy, particularly in the area of raw material procurement since it is vital for them to stay profitable and maintain the price point advantage. Through the use of smart supply chain management and realistic market forecasting, the sector is on track to grow at previously unheard-of rates.

Packaging of Critical Drugs: How Rubber Stoppers Play a Huge Role

Pharmaceutical packaging solutions in this field have a greater obligation to produce high-quality solutions because vaccines and other critical drugs have the potential to save millions of lives. Having said that, preserving these critical drugs and vaccine integrity across the supply chain can be difficult without the proper packaging solutions. There are two crucial components to consider when it comes to packaging these: the first is glass vials, which are all designed to have a very low moisture vapor transmission rate, and the second is rubber stoppers. During the pandemic, the producers of these vials and stoppers were under enormous pressure to manufacture items in a timely and high-quality manner while adhering to strict quality standards. Stakes were high as there was no COVID-19 vaccine without the right packaging. The fact that Indian pharmaceutical packaging industry could ensure adequate and high-quality packaging solutions during the pandemic has further catapulted their image and importance in the global pharmaceutical space. This has helped them garner a good reputation, not just as the largest producers of pharmaceuticals but also as one of the largest providers of high-quality packaging solutions to the pharmaceutical industry worldwide.

Pharmaceutical Packaging as a Solution to Combat Counterfeiting

As a result of the pandemic, there were acute shortages of some important pharmaceuticals. As a result of the high demand for these drugs, many people were forced to purchase medicines from black market dealers who sold counterfeits that came in significantly lower quality than what they were substituting. Several counterfeits entered the market to fill this resulting supply gap and take undue advantage of the situation. This was a major source of concern for producers, merchants, end-users, and all other players in the ecosystem. Fortunately, modern communication methods, increased reliance on digital verification, as well as a

swift action by influential opinion leaders assisted in the fight against counterfeits.

There are many ways that a packaging solution provider can be proactive when it comes to tackling counterfeiting drugs or medication. By actively fighting against counterfeit drugs, manufacturers and suppliers of medicine will experience a much-needed reduction in black market trade and positively impact consumers' health and safety. In turn, fighting counterfeit drugs directly helps foster the pharmaceutical industry's growth.

Packaging is an essential part of fighting counterfeit drugs in the pharmaceutical industry because it can serve as both a way to identify and authenticate medications and a way to protect the medication itself. This problem of counterfeit medicines can be easily avoided by including pharmaceutical packaging solutions in the manufacturing process as early as possible. Packaging companies worldwide, including India, are actively developing trace and track technology solutions, which incorporate advanced blockchain technology to create an atmosphere of assurance, security, and trust for all stakeholders at all stages of the manufacturing and distribution processes.

Packaging That is Centered on the Customer is Essential.

India is gaining the much-needed recognition for its pharmaceutical packaging supplies capabilities and is growing considerably at the global level. Less than 40 percent of the country's businesses in this industry have reached a point where they are able to offer their customers products that are highly customizable. In today's world, customer-centricity is one of the most difficult aspects of any business to execute. Some companies emphasize giving their customers what they want, when they want it, and even how they want it. The same is true for pharmaceutical packaging businesses in India.

Building best-in-class customer experiences is vital since it is a discipline that has the potential to revolutionize entire sectors. Customers' needs are becoming increasingly important to the best-in-class organizations, which is allowing them to organize their businesses around them. By providing customers with simple, differentiated, safe and effective experiences, a company may unleash great value by increasing client loyalty while simultaneously lowering leakage and churn. Having said that, the Indian pharmaceutical packaging business is still in its growing phase when it comes to developing solutions. A significant amount of emphasis is still placed on the fact that the majority of packaging companies in the domain are striving to make every packaging collateral as customer-centric as possible. It is fair to say that customer-centric packaging will be critical to the future success of the pharmaceutical sector, and as time goes on, more and more companies will begin to take this into consideration when designing their goods.

So, what is the future of the Indian Pharmaceutical Packaging Industry?

As previously said, pharmaceutical packaging is vital in ensuring access to pharmaceuticals and medicine, and in a country known as "The Pharmacy of the World," the local pharmaceutical packaging business plays an even more critical role than it did prior to the current crisis. As more pharmaceutical businesses rely on medications and medication produced in India, this presents a new set of constraints as well as opportunities for innovation. When developing devices for new pharmaceuticals, the pharmaceutical packaging industry must first satisfy a specified benchmark before moving on to the next step. This step is carried out to ensure the safety and preservation of the medication under various circumstances. This test should also be specific to the drug's identity and conform to worldwide and regional regulatory standards. Additional requirements include: Regular quality control inspections are required to guarantee that this system is not tampered with.

Additionally, the Consumer Product Safety Commission (CPSC) has established a set of guidelines that must be rigorously adhered to at all times. Today, there are very few things available on the market that are not packaged in a way that is child-resistant. This is particularly true in the case of medications. Product and packaging teams are also concentrating on ergonomic solutions that are efficient at the logistics end while also being more consumer-centric in their design. All things considered, pharmaceutical packaging is an essential component of pharmaceutical supplies throughout the world. With more localisation and manufacturing taking place within the country, the scope and quality of local pharmaceutical packaging are becoming increasingly important for sustained growth across the pharmaceutical industry.

No matter the type of medication, it’s crucial to make sure an appropriate pharmaceutical packaging is used to seal and maintain the safety, efficacy and quality of the medicines at all times. This is exactly why global pharmaceutical companies are eager to work with India's most reliable pharmaceutical packaging manufacturers and see what they offer as appropriate solutions to their pharmaceutical packaging conundrums.

AUTHOR BIO

A young stalwart of Bharat Rubber Works, Siddharth Shah has been the Director of the company since 2018. Mr. Shah joined Bharat Rubber Works after completing his bachelor’s in Banking and Wealth Management from the University College of Dublin in 2018. He has also completed his Diploma in Marketing from Kaplan. As the director of the company, Mr. Shah is responsible for overall growth and company operations. Since his arrival at the family-owned business, Mr. Shah has taken the company to another level, allowing Bharat Rubber Works to become a leading manufacturing solutions provider to the healthcare industry.

Current and Future Outlook of Pharmacogenomics in Paediatric Asthmatic Medications

Current treatment options for asthma, a respiratory condition often stemming from childhood, include beta-2 agonists, inhaled corticosteroids, and leukotriene modifiers. Despite recommendations by the Global Initiative for Asthma, a substantial number of patients are unresponsive to treatment. Paediatric pharmacogenomics could allow for potential preemptive screening, thus improving patient outcomes.

Christy Lim, Massachusetts College of Pharmacy and Health Sciences University Ronny Priefer, Massachusetts College of Pharmacy and Health Sciences University treatment and highlights the importance of optimising a patient’s response to drug therapy while minimising adverse reactions. Although most studies have looked more closely at children, there have been no clinically relevant findings that have warranted specific therapeutic recommendations.Commonly researched medications include beta-2 agonists, inhaled corticosteroids (ICS), and leukotriene modifiers (LTM).

Nearly 300 million people worldwide are affected by asthma, which, left untreated or uncontrolled, decreases quality of life and increases the risk of developing chronic obstructive pulmonary disease (COPD). More than half of these asthma cases originate from childhood. Shortness of breath, tightness, and wheezing are just a few of the symptoms caused by asthma. Although robust evidence supports the efficacy of current treatment options, approximately 100 million additional asthma cases are expected by 2025. Despite recommendations by the Global Initiative for Asthma (GINA) guidelines, up to 70 per cent of patients are still unable to find proper symptom relief. While the lack of adherence and improper diagnosis have been implicated, genetics may also play a role. With widespread intra-variability among medication responses, pharmacogenomics has an emerging place in asthmatic

Beta-2 agonists

Classified as bronchodilators, beta-2 agonists are categorised into two groups:

short-acting beta agonists (SABAs) and long-acting beta agonists (LABAs). Examples of these include albuterol and formoterol, respectively. Commonly utilised in respiratory distress, these agonists induce bronchodilation and relax smooth muscles by binding to the adrenergic receptor located in the lungs. The activation of G-protein coupled receptors (GPCR) causes an increase in cAMP concentration, decreases intracellular calcium and in turn, relieves asthma symptoms (Figure 1).

SABA and ADRB2 Variations

The adrenergic receptor is encoded by the ADRB2 gene and is found on chromosome 5q31-32, an area highly associated with asthma. Position 16 and 27 are two amino acid locations thought to modulate down regulation and airway responsiveness. Choudhry et al. discovered that the presence of Arg at position 16 produced the greatest bronchodilation compared to Gly16Gly when administered albuterol in the Puerto Ricans. Although the study included both Puerto Rican and Mexican children, no genetic association was found among Mexican children. Martinez et al. reported that Arg16Arg and Arg16Gly were more likely to produce greater bronchodilation compared to Gly16Gly when given albuterol. Similar studies by Salah on Egyptian children and Finkelstein on multiethnic children also found favourable results with Arg16Arg in response to albuterol. Both studies found reduced responses in those with Arg16Gly and Gly16Gly genotypes. In contrast, a study conducted by Carroll et al. found that children with the Gly16Gly variation showed a better response, to albuterol, compared to those with the Arg variants. Similarly, Giubergia observed changes in desensitisation over four weeks among some Argentinian children treated with albuterol and reported those with the Arg16Arg genotype displayed a decline in responsiveness to long-term treatment.

Unlike amino acid position 16, conflicting reports in response to SABA therapy at amino acidposition 27 on the receptor have limitedany significant associations. Alghoshaby measured bronchodilator response by FEV1/ forced vital capacity (FVC) and FEV1 whereas Giubergia utilized change in FEV1 over thirty days. While the former found greater improvements with the Gln27Glu variants, the latter found a decrease in responsiveness. A study conducted by Elbahlawanon 31 African American children found that those with the Glu27Glu treated with albuterol needed additional medication for symptom control. These contradictory results provide no clear association at position 27 and bronchodilation in response to SABA.

1, Billington, C.K.; Penn, R.B.; Hall, I.P. Agonists. Handb. Exp.Pharmacol.2017, 237, 23–40

Figure 2: ICS Mechanism of Action. Adapted from2 .

Inhaled Corticosteroids (ICS)

GINA guidelines currently recommend using as needed SABA or ICS -formoterol for children who only require rescue therapy. A low dose of ICS in conjunction with a SABA is recommended as controller therapy for children ages 6-11.ICS work to improve asthma symptoms by decreasing mast cells, cytokines, COX-2, etc thereby decreasing inflammation (Figure 2). FDA indicated to reduce asthma attacks, ICS not only reduce respiratory swelling but also reduce morbidity in both children and adults. Although the risk of systemic exposure is minimal due to their route of administration, side effects such as osteoporosis, glaucoma, and metabolic disturbances are not negligible, especially when used for an extended period (Figure 2).

Tantisira conducted a genome-wide association study (GWAS) and identified the glucocorticoid-induced transcript 1 (GLCCI1) gene and the SNPs, rs37972 and rs37973. Although little is known about GLCCI1, those homozygote for the mutant T allele at SNP, rs37972, yielded a poorer response to ICS compared to those who were heterozygote (CT) or homozygote (CC). Conversely, Vijverberg saw no association with individuals having SNP, rs37972 and ICS response in Northern European children. It was concluded that