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Understanding Pharmaceutical Research

Understanding Pharmaceutical Research Studies

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Medical researchers are constantly on the lookout for new or improved methods of treating illness or disease. However, it cannot be widely used until years of careful testing have been completed if they discover something valuable. Medical research studies are what connect medical research to the availability of a drug to physicians and patients. Clinical trials, drug trials, and drug studies are other names for research studies.

What exactly are pharmaceutic research studies?

  • Research studies are designed to test the effect of a medication or treatment on a group of volunteers, assess a drug’s ability to treat a medical condition, monitor the drug’s safety, and look for potential side effects.
  • Research studies are carried out by trained doctors, nurses, and researchers. The study coordinator is in charge of the study’s day-to-day operations. The protocol is carried out under the supervision of the principal investigator (usually a physician).
  • Pharmaceutical companies or other health organizations may fund research studies and design the protocol, a detailed set of guidelines—multi-center research conducted at several locations.

What Are the Various Kinds of Pharmaceutical Research Studies?

  • In conducting research studies, there are three phases or steps. Before a new drug can be approved for public use, complete all three of these steps.
  • Successfully, and all results must be known.
  • Phase I studies are conducted on healthy volunteers who agree to take the study drug to assist doctors in determining the drug’s safety and the presence of any side effects. In addition, studies are conducted to determine how the drug is absorbed, metabolized, and excreted. Phase I studies typically involve a small number of subjects (20-100). Approximately 70% of new drugs will make it through this stage.
  • Phase II studies assess the new drug’s efficacy in patients suffering from the disease or disorder being treated. The primary goal is to determine the new drug’s safety and effectiveness. Hundreds of patients usually take part. These studies are typically “dual-blind, randomized, and controlled.” The effect of the active drug compared to the effect of a placebo (inactive or “sugar” pill) in controlled studies. In a double-blind study, neither the investigator nor the study subjects know who is receiving the active drug and receiving a placebo. One-third of the medicines studied thoroughly in both Phase I and Phase II.
  • Patients with the disorder being treated by the new drug are also used in phase III studies. These studies are carried out to understand better the effectiveness, benefits, and side effects of the study drug. These studies involve many subjects, ranging from hundreds to thousands—seventy to ninety percent of new medicines that enter Phase III studies complete this phase. If the results show a positive effect and safety profile, the company will submit the data and request FDA approval to market the drug.

What Exactly Is Involved in Taking Part in a Research Study?pharmaceutic research studies

  • Participating in a research study is similar to going to a clinic or doctor’s office but with more personal attention. The subject of the study may have been referred by their doctor or may have learned about it elsewhere.
  • Typically, preliminary screening for the study is done over the phone. The study’s actual age, symptoms, and medical history are reviewed, and the study’s details are discussed. If the caller appears to be eligible for the research and is interested in participating, they are invited to come in for the initial, or screening, visit.
  • The screening is performed in a clinic, office, or hospital. The subject and the supervising physician sign the informed consent form after reviewing the information gathered over the phone. The subject receives a copy. May perform a physical examination, blood tests, and other tests. Following this, most studies have a period, usually a few weeks, where baseline information, such as the severity and frequency of symptoms, is collected.
  • The patient returns to the clinic for the randomization visit at the end of the screening period. If the patient’s baseline data indicate that they are eligible for the study, they then randomized (usually by computer) to receive either a placebo or an active drug.
  • During the treatment period, the subjects take the study medication regularly and keep track of their symptoms. Throughout the treatment period, the study coordinator makes regular visits. Medication use and symptoms are reviewed at the end of the treatment period. The study medication’s potential side effects are documented. Many studies include a follow-up period after the treatment period to assess how symptoms and possible side effects have changed. There may be one more visit or phone call to see how the subject is doing since stopping the study drug.

What is a Pharmaceutical Consultation?

Consultation is a formal process for gathering input from our stakeholders. Stakeholders include all individuals and organizations who influence or are influenced by our work, such as:

  • patients, carers, users of pharmacy services and members of the public
  • pharmacists and pharmacy technicians
  • pharmacy owners
  • professional bodies and organizations
  • other regulators
  • governments
  • educators
  • employers

Why do we consult?

We believe people who are impacted by our work must have a say in how we operate. Effective consultation is critical to assist us in improving our work. It informs us and helps us achieve our purpose of protecting, promoting and maintaining the health, safety and wellbeing of patients and public members by upholding standards and public trust in pharmacy.

Pharmaceutical Consulting The Smart Way

Pharmaceutical Consulting The Smart Way

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The Intelligent Approach to Pharmaceutical Consulting

Expenses for research and development, manufacturing, regulatory compliance, marketing, and product distribution continue to rise. Medication and other types of specialist health services continue to increase in price. Furthermore, the number of blockbuster medicines is decreasing, safety concerns are growing, and further government involvement is on the horizon. All of this implies that the value and ROI of pharmaceutical consulting services are rising.

Staying competitive and profitable is becoming more difficult for pharmaceutical businesses, notably smaller enterprises and health care institutions. The challenge then becomes determining which of the many possible solutions will allow businesses to remain competitive and continue in the market. Add to that the tough job of choosing which pharmaceutical consulting business is the greatest match and can offer the finest answers for a particular organization.

Pharmaceutical consulting is a newer kind of consultation. While most consulting companies provide a fairly typical set of services, there is a considerable specialization within the sector. For example, Rondaxe Consulting is one of the world’s biggest and most experienced worldwide CMC consulting firms. Rondaxe works with both virtual pharma/biotech startups and multi-national pharmaceutical customers from concept to commercialization. Comprehensive CMC solutions, medication development, manufacturing, and worldwide regulatory strategies are among the services provided. “Re]sourceTM is a unique pharmaceutical process software designed to help customers with data management, cost of goods, productivity analysis, and other features.

The Benefits of Hiring a Pharmaceutical Consultancy FirmHiring a Pharmaceutical Consultancy Firm

The pharmaceutical business is highly competitive since new medicines are created every week, and each firm wants to be the first to market with theirs. A consultant may assist your firm in this area, but there is more to having a successful pharmaceutical company than just putting your goods on the market. Your brands and products need support from physicians, insurers, and community pharmacists to be prescribed at all, which may be difficult to accomplish. 

How would physicians know to prescribe your goods if they are unaware of them and you fail to advertise them to them adequately? 

A GP will only prescribe a medication that has been marketed to them, and pharmaceutical consultants may assist you with this.

In truth, pharmaceutical consulting is intended to advise businesses on all aspects of their operations, ensuring their success and keeping them up to speed with the rules and legislation regulating the pharmaceutical sector. Consultants will work with you to ensure that you get the most profit out of the money you spend, from creating a product to making sure it lasts on the market.

Licensing, brand management, business development, clinical research, medical affairs, sales and trade, and product distribution are some areas in which pharmaceutical consultants specialize. While you may have expertise in any or all of these areas, the consultants will have specialized in one and will therefore be able to provide you with the finest information in the industry. They make it their mission to stay one step ahead of product releases and new laws to advise their customers on the best approach to earn money while complying with the law.

Clinical development is particularly essential in today’s pharmaceutical business since resources are static while the size and complexity of clinical procedures grow. Pharmaceutical experts will evaluate your clinical practices and develop new, more cost-effective, and efficient processes to make the most of what you have. Their goal is to help your company and products reach their maximum potential in all areas of consulting.

A pharmaceutical business cannot keep up with every new product on the market, the laws that go with it, conducting clinical studies, marketing their brand, and selling goods. That is why pharmaceutical consulting is an excellent option—keeping you up to date on industry changes and helping you maximize your company potential.

Drugs Designed and Developed

How are Drugs Designed and Developed?

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Table of Contents

Producing a new medication is a costly and time-consuming procedure that is heavily regulated.

What is a drug?

  • Drugs are chemical or biological compounds that have an impact on our bodies’ physiological or biochemical functions.
  • They may be single compounds or a combination of several chemicals.
  • Their effects are meant to be helpful. However, some individuals may have negative side effects.
  • All medicines interact with particular ‘targets’ in the body to alter their activity and, in many cases, result in a therapeutic? Impact. As an example, consider pain alleviation.
  • Are drug targets often proteins? However, in other instances, they are tiny segments of DNA or RNA.
  • Drugs either stimulate or inhibit the action of their targets.

How is a Drug Developed? How is a Drug Developed

  • The creation of a novel medicinal medication is a complicated, time-consuming, and costly process.
  • It could take 10-15 years and more than $500 million to develop a medication from an original idea, test its safety and efficacy in humans, and then bring it to the hospital market.
  • 2-4 years of pre-clinical development
  • 3-6 years of clinical development, additional
  • time for dealing with the regulatory authorities.

The first stage in drug discovery.

  • The first stage in the drug development process is drug discovery.
  • In the past, certain medications, such as penicillin, were discovered by mistake.
  • More systematic methods are now utilized, such as:
  • High-throughput screening: a technique that enables scientists to test thousands of possible targets with thousands of different chemical compounds to discover a novel drug-target combination.
  • Developing and synthesizing compounds based on a particular target molecule’s known structure is rational drug design.
  • While high-throughput screening may discover hundreds of possible lead components, many will be discarded during the first round of testing. Compounds are examined in cultured cells or animals during this phase to see how efficient they are and if they are harmful.
  • When compared to high-throughput screening, rational drug design generates fewer molecules. On the other hand, these chemicals are particular to the target and attain this specificity via computer-based modelling.

Stage 2: Preclinical Development

  • Pre-clinical testing is performed to identify how the medication should be developed for its intended purpose.
  • It seeks to determine how medicines are absorbed and distributed in the body and how they are broken down and eliminated.
  • If necessary, promising medicines may be changed to subtly enhance their characteristics, a process known as lead optimization.
  • Pre-clinical testing findings are also used to identify how to best manufacture the medication for its intended clinical usages, such as whether it is more effective as a cream, tablet, injection, or spray.
  • The goal of the pre-clinical trials is to narrow down hundreds of molecules to a few promising potential medicines.
  • These few medicines will then be submitted to the relevant regulatory authorities for approval, and if approved, the compound will be moved forward to clinical development.

Clinical Development Stage 3

  • This is split into four phases: 0 (zero), I, II, III, and IV.
  • Clinical development, often known as clinical trials, tests medication on human volunteers to learn more about its safety and efficacy.
  • Most experimental novel medicines will have been removed before the clinical development phase due to safety and efficacy concerns.
  • A new drug application will only be filed for one or two substances. 
  • After the relevant regulatory authorities authorize a medication, pharmaceutical firms have a limited time to have exclusive rights to sell the drug (exclusivity) before other businesses may market the same drug.
  • This exclusivity term is intended to recoup the enormous expenditure needed to develop and market the new medication.
  • Following complete approval, pharma firms must continue to test their medication and monitor input from healthcare experts to guarantee the drug’s safety and efficacy.
  • Following the release of medication, additional side effects or risk factors that were not previously documented may be discovered. This is Phase IV clinical development, and it is part of the ongoing monitoring of the drug’s efficacy in its target patients adverse.
FAQs about Pharmaceutical Manufacturing

FAQs about Pharmaceutical Manufacturing for Production of Medicines

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Steps in Pharmaceutical Manufacturing for the Production of Medicines

To manufacture effective medications, the pharmaceutical manufacturing unit goes through several processes. Design conception, withdrawal, dispensation, production, modification, liberation, packing, and storage are all stages in the manufacturing process. These elements are critical, and the whole manufacturing process will be complete only when all of these production stages are properly finished. All pharmaceutical manufacturing departments must follow these procedures to create effective medications and various other pharmaceutical products. This article outlines the critical procedures that all pharmaceutical factories must take to produce effective medications.

There are two stages in the pharmaceutical production process. The first unit is the main processing level, while the second is the secondary processing level. The first processing stage is primarily concerned with the enhancement of an effective medication component. This stage also includes some research centers run by pharmaceutical graduates that provide essential pharmaceutical components.

The second portion of this secondary process consists mostly of transforming pharmaceutically active components into effective medications. So, we can say that this is the last stage in drug processing, which is the most essential in creating goods that can be utilized as pharmaceutical products in many healthcare organizations and are used by patients for various health problems.

The finished pharmaceutical goods come in a variety of forms, including liquid, semi-solid, and solid. Capsules, pills, lotions, ointments, and other solid forms are available. Liquid pharmaceutical products include solutions, gels, suspensions, emulsions, and injectables. Several items for external use only, such as inhalers and aerosols, primarily include butane and chlorofluorocarbons. We may conclude that pharmaceutical manufacturing units have contributed significantly to the medical sector and assisted humanity in the battle against various health problems. They are constantly striving to contribute more and more to the medical field.

Pharmaceutical Manufacturing’s Development of Efficient MedicinesPharmaceutical Manufacturing's Development

To create functional medicines, pharmaceutical manufacturing companies go through design conception, manufacture, extraction, dispensation, sanitization, packing, release, and storage of chemical agents. As a result, pharmaceutical production is the foundation of pharmaceutical engineering. The pharmaceutical companies‘ creation of efficient and cost-effective medications is the focus of this essay.

Two main units are engaged in pharmaceutical manufacturing production processes. These are the main processing unit (PPU) and secondary processing unit (SPU) (SPU). The primary function of PPU is to manufacture active pharmaceutical components. It also comprises research efforts carried out by professional and experienced Pharmaceutical engineers. SPU is a set of procedures for converting active pharmaceutical substances into essential medications. As a result, SPU is the second component of the manufacturing process that fully creates essential medications that are very promising and capable of combating many terrible illnesses.

All pharmacological products are primarily offered in three varieties (solid, partially solid, and liquid). Creams, ointments, capsules, and tablets are the most common types of solid and partly solid medicinal medicines. Liquid pharmaceutical products come in various forms, including suspensions, solutions, gels, and emulsions. 

Pharmaceutical manufacturing facilities create finished medications such as synthetic pharmaceuticals, hormones, vaccines, glandular products, antibiotics, vitamins, and pharmaceutical compounds. Some important medicines are derived from plants and are extremely powerful and devoid of any adverse effects. These pharmaceutical companies have created a plethora of essential medications that can combat both common and critical illnesses.

Development Of Pharmaceutical Industry

The Importance Of Research And Development Of Pharmaceutical Industry

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What function does research play in development?

Many organizations rely heavily on research and development (R&D). When properly planned and implemented, it allows a company to create additional money from time to time. The majority of people connect a company’s research and development role with the creation of new goods. While innovations are essential, improving current goods is also crucial since customer tastes are always changing. As a result, we may state that R&D refers to a particular set of operations inside a company. R&D varies from one business to the next based on the operations of that company.

Objective of R&D

R&D is a process that aims to develop new or better technology that may offer a competitive edge at the corporate, industry, or national levels. While the benefits may be enormous, the process of the technical invention is complicated and dangerous. The majority of R&D initiatives do not provide the anticipated financial results, and successful programs may pay for those that are failed or canceled early by management. An R&D project must achieve the following goals:

1 acquire new ideas or information 

2 put it to practical use

3 boost the company’s sales and profits

Types of R&D

The National Science Foundation(NSF) defines three types of R&D:

1 Basic Research

2 Applied Research

3 Development

Rather than a practical application, basic research goals are to gain a deeper knowledge or understanding of the topic under study. Basic research is defined as a study that increases scientific understanding without a particular commercial goal in mind.

Applied research involves acquiring the information or understanding required to determine the methods to fulfill a recognized and particular demand.

It comprises studies to discover new information with particular business goals regarding products, methods, or services.

Research generates information and development designs, as well as prototypes to demonstrate viability.

Engineering then transforms these prototypes into marketable goods or services or processes to create commercial products and services.

Government Promotes Research and Development

The government’s strategy already encourages research and development in a variety of ways. In 1996, the government supported about 32% of gross national spending on R&D. The government also encourages business innovation via direct expenditure on education and training, patent protection, regulation, and competition policy. The government implements various measures that influence companies’ incentives to spend in R&D. Direct financing of government R&D laboratories, universities, or businesses, investment in human capital creation, patent protection legislation, and R&D tax credits are examples of policies that directly target research and development. Other policies that are not directly aimed at R&D but may have a major effect on R&D expenditure include competition policy and regulation.

R&D Tax Credits

The government may stimulate business research and development through tax incentives like

  1. allowance
  2. exemptions
  3. deductions
  4. tax credits

Each of which can be designed with differing criteria for eligibility, allowable expenses, and baselines.

The Advantages of Research And Development Of Pharmaceutical Industry

The pharmaceutical industry includes pharmaceutical production,Promotes Research and Development preparation, and marketing services, and it is heavily reliant on R&D&I for growth.

This industry is continuously pushed to rethink its business models to maximize the revenue from existing patents and optimize the development of new medicines, making R&D&I investments critical to avoid becoming outdated in a highly competitive market.

Investment in innovation in this field enables the development of new medicines, a rise in life expectancy, and the treatment of a wide variety of illnesses, allowing for a substantial improvement in available therapies.

Similarly, investment in R&D in pharmaceutical manufacturing benefits population health. In the long term, other features are identified, such as savings in health expenditure (by decreasing hospitalizations) and lower operational costs in the health sector.

Based on innovation, the pharmaceutical industry has positioned itself at the forefront of the manufacturing model in many nations. It is one of the most significant industrial sectors, with the pharmaceutical industry ranking fourth in sales and employment. From an economic and social standpoint, the contribution of this sector is noteworthy, emphasizing the positive outcomes in employment creation resulting from significant expenditures in R&D&I.

Phases of Drug Development

What are the Phases of Drug Development?

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Stages of Drug Development

To create a safe, effective, and meets all regulatory criteria, every drug development process must go through several phases.

Rondaxe can help you in every step of drug development. Our scientists can assist you in determining your testing requirements, and our professional team can conduct the necessary tests and studies required for FDA approval.

To get you started, we’ve given an in-depth description of several phases in the drug development process, as well as the required research, below.

Discovery

Target identification – selecting a biochemical process implicated in a medical state – is a common starting point for discovery. Drug candidates developed in academic and pharmaceutical/biotech research laboratories are evaluated for interactions with the drug target. For each prospective therapeutic candidate, up to 5,000 to 10,000 molecules are exposed to a rigorous screening procedure that may involve functional genomics and proteomics, as well as other screening techniques. Once scientists have confirmed interaction with the drug target, they usually verify that target by looking for activity against the medical condition for which the medication is being produced. After careful consideration, one or more lead compounds are selected.

Product Characterization

During drug discovery, a promising candidate molecule is identified it can be used in clinical trials. First, the molecule must be described, which includes determining the molecule’s size, shape, strengths, weaknesses, the environment where it functions well, toxicity, bioactivity, and bioavailability. Analytical method development and validation will occur during characterization investigations—early-stage pharmacology research aids in characterizing the compound’s underlying mechanism of action.

Formulation, Delivery, Packaging Development

Medication designers must create a formulation that guarantees appropriate drug delivery parameters. At this stage of the medication development process, it is essential to start thinking about clinical trials. Medication formulation and delivery may be continually improved until, and even beyond, the ultimate approval of the drug. Scientists test the drug’s stability in the formulation and storage and shipping conditions such as heat, light, and time. The formulation must stay potent and sterile, as well as safe (nontoxic). Extractables and leachables research on containers or packaging may also be required.

Pharmacokinetics And Drug Disposition

Pharmacokinetic (PK) and ADME (Absorption/Distribution/Metabolism/Excretion) studies offer valuable information for formulation experts. AUC (area under the curve), Cmax (the highest concentration of the medication in the blood), and Tmax (the time to maximum concentration) (time at which Cmax is reached). Animal PK research will be used in tandem with early-stage clinical trials to see whether animal models predict real-world outcomes.

Preclinical Toxicology Testing and IND Application

Preclinical testing evaluates the developed drug product’s bioactivity, safety, and effectiveness. This testing is crucial to a drug’s ultimate success and is thus examined by several regulatory bodies. Plans for clinical tests and an Investigative New Drug (IND) application are developed throughout the preclinical stage of the research process. Tests conducted during the preclinical phase should be intended to assist subsequent clinical studies.

The main stages of preclinical toxicology testing are:Preclinical Toxicology Testing

  • Acute Studies – Acute tox studies focus on the effects of one or more doses given during 24 hours. The aim is to identify hazardous dosage levels and to look for clinical signs of toxicity. At least two mammalian species are usually examined. Acute toxicity data is used to help establish dosages for repeated dose studies in animals and Phase I human trials.
  • Repeated Dose Studies – Repeated dosage studies may be classified as subacute, sub chronic, or chronic, depending on their length. The exact duration should anticipate the length of the clinical study for the new medication. Once again, two species are usually needed.
  • Genetic Toxicity Studies – These investigations determine if a medication compound is mutagenic or carcinogenic. Genetic alterations may be detected using procedures such as the Ames test (conducted in bacteria). The Mouse Micronucleus Test, which uses mammalian cells to evaluate DNA damage, is one example. In addition, the Chromosomal Aberration Test and related methods identify chromosomal damage.
  • Reproductive Toxicity Studies – The effects of the medication on fertility are investigated in a segment I reproductive tox investigations. Segment II and III research look for impacts on embryonic and postnatal development. In general, reproductive tox studies must be performed before medication may be given to women of childbearing age.
  • Carcinogenicity Studies – Carcinogenicity studies are often required only for medicines used to treat chronic or recurrent diseases. They take time and money and must be prepared for early in the preclinical testing phase.
  • Toxicokinetic Studies – These are usually designed like PK/ADME experiments, except that considerably larger dosage levels are used. They investigate the effects of hazardous medication dosages and aid in estimating the clinical margin of safety. Many FDA and ICH recommendations provide extensive information on the various kinds of preclinical toxicology studies and the proper scheduling for them with IND, NDA, or BLA submissions.

Bioanalytical Testing 

The majority of the other activities in the drug development process are supported by bioanalytical laboratory work and the development of bioanalytical methods. The bioanalytical work is critical for appropriate molecular characterization, assay creation, establishing optimum cell culture or fermentation techniques, calculating process yields, and providing quality assurance and quality control throughout the development process. It is also essential for preclinical toxicology/pharmacology testing and clinical trials.

Clinical Trials

Clinical trials are classified into three kinds of phases based on their objective:

  1. Phase I Clinical Development (Human Pharmacology) – Unless the FDA puts a hold on the research, a biopharmaceutical company may commence a small-scale Phase I clinical trial thirty days after filing an IND. Phase I studies are performed to assess pharmacokinetic parameters and tolerance in healthy individuals. These investigations include initial single-dose trials, dosage escalation, and short-term repeated-dose studies.
  2. Phase II Clinical Development (Therapeutic Exploratory) – Phase II clinical trials are small-scale trials in which 100 to 250 individuals are evaluated for a drug’s preliminary effectiveness and side-effect profile. This category also includes additional safety and clinical pharmacology research.
  3. Phase III Clinical Development (Therapeutic Confirmatory) – Broad-scale clinical trials evaluating safety and effectiveness in large patient groups are known as phase III investigations. While phase III studies are being conducted, preparations are being made to submit the Biologics License Application (BLA) or the New Drug Application (NDA). The FDA’s Center for Biologics Evaluation and Research is presently reviewing BLAs (CBER). In addition, the Center for Drug Evaluation and Research evaluates NDAs (CDER).
Research And Development Of Pharmaceutical Industry

Research And Development Of Pharmaceutical Industry

By | Pharmaceutical Development | No Comments

Why are research and development essential in the pharmaceutical industry?

R&D plays a vital role in the pharmaceutical industry in enhancing company capability by stimulating innovative production methods, lowering drug costs, and improving product quality. In addition, R&D can encourage highly skilled, creative, and innovative individuals to join the company and plays a vital role in the innovation process, particularly in the pharmaceutical industry. The R&D process is a critical stage in the drug development process in the pharmaceutical industry. The process begins with identifying an initial candidate drug and includes the rigorous research tests that determine the drug’s therapeutic suitability.

The pharmaceutical industry involves human lives because it manufactures and produces medicines that are miracle tablets for humans. Therefore, it is India’s most critical sector.

Diseases are becoming more prevalent these days as a result of pollution and people’s eating habits. Today, everyone has at least one condition, whether it is an infection or a viral infection. Furthermore, due to pollution, people are facing many skin problems also. All these situations drag them to the category of patients. Therefore, medicines are becoming regular meals for many peoples.

This makes the Pharmaceutical industry growing and, most important.

Research Development

In all industries, research and development are critical. And, when it comes to the Biopharmaceutical research industry, R&D services generate revenue for the companies involved in the study lives or improve results frequently in saving lives or improving patients’ lives. The development of many businesses necessitates the perfect Pharmaceutical research and development. Doctors and scientists from all over the world have invested heavily in research and development in this industry. Reliable Pharmaceutical R&D services enable businesses to adhere to manufacturing procedures, quality control measures, production scope, and technical know-how.

Digital Solutions in Drug Development

Digital technology has been driving a revolution in healthcare, from mobile medical apps and fitness trackers to software that supports clinical decisions made by doctors every day. As we adjust to the new normal brought on by the COVID pandemic, the adoption of digital solutions has accelerated.

Process development in the pharmaceutical industry

Process development is the process of establishing, implementing, or improving an existing manufacturing process. It ensures that a product can be routinely made aseptically and meet specifications before mass production. At Akron, we create and optimize processes that create commercially viable products that prioritize quality, affordability, and reproducibility. We develop a minimal industrial strategy by converting methods developed on the bench in a research lab to industrial-scale study lives processes that consider the necessary upgrades in a controlled environment, equipment, and ancillary materials.

In every project, we assess manufacturability and determine the quality and testing required for production-process controls and released products. From the early stages of development, we can create new processes, transfer existing processes, or optimize existing processes. Whether we develop an end-to-end process or optimize specific phases, our goal is to reduce the risk of producing a final advanced therapy medicinal product.

Pharmaceutical Development Company

Demand-side research and development

Drug prices would be determined by supply and demand in a market economy. The government is acting solely to provide patent protection and exclusivity to allow for viable innovation because much of the cost of producing drugs involves research and development instead of manufacturing pills. Can obtain this price influences the amount invested in the development of new medicines. Higher prices, on the other hand, result in fewer units of the drug being sold. Because of this demand constraint, investment is sensitive to value—what a drug accomplishes medically for patients compared to how much it will cost. Manufacturers can charge higher prices and will likely invest more in developing new drugs if health insurance pays for a significant portion of the cost of drugs.

However, three significant developments in recent years have shifted the demand constraint. First, due to the implementation of Medicare Part D and the expansion of insurance coverage under the Affordable Care Act, more people have drug coverage. Second, drug insurance has become significantly more comprehensive due to the proliferation of benefit designs that limit the amount of out-of-pocket spending that the enrollee is required to pay.

Third, some newer drugs, particularly specialty drugs used to treat complex, chronic conditions such as cancer, rheumatoid arthritis, and multiple sclerosis, have incredibly high prices. This factor influences demand via interactions with various elements of insurance benefit design. For example, suppose a patient is taking a $50 drug, and a new, possibly better medication becomes available for $100. In that case, insurance benefit designs usually allow the patient (with the support of a prescribing physician) to use the newer drug at an additional cost. While the difference in cost to the patient is less than the price difference between the drugs, only patients who believe they will benefit from switching will do so.

However, when prices are $100,000 or $200,000 per year, everything changes. Most patients who must pay a significant portion of the cost for these drugs will not afford the medication at all. On the other hand, out-of-pocket maximums make the drugs affordable and, as a result, make the patient insensitive to price differences. As a result, the patient pays the same amount for the $100,000 and $200,000 drugs—their out-of-pocket maximum. This means that raising prices at this level does not result in patient demand restraint.

As a result of the current benefit designs and costly drugs, raising prices even higher may not result in fewer units. On the contrary, because new drugs promise to be profitable, the result will likely be higher revenues and more investment in their development.

Consulting For Pharma

Mitochondrial Uncoupling: If You Want to Live Longer, Look to the Skies

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Over the years an enormous amount of both scientific and pseudo-scientific speculation has been aimed at explaining prevailing trends in the lifespan of animals,and how we might apply those lessons to humans.

Since clear, observable trends exist with respect to various groups of animals and lifespan, if we can understand the underlying processes behind those trends, we might be able to extend and maximize our own lifespans.  The most obvious trend is body size versus lifespan, which is robust and repeatable, yet has some outliers that offer tantalizing grounds for speculation.

Figure 1 shows the trend between size and lifespan.  The trend lines, both of which have significant scatter, clearly show two trends, with the data broken down to illustrate the difference between flying and non-flying species.  The striking difference between species who can and cannot fly will be immediately available to anyone who has ever kept a parrot – some species can reliably outlive their human owners.

sizeA number of theories exist to explain the differences between these groupings – and why bats and birds live so much longer.  The authors of the study behind Figure 1 [1] point to the differences in predation vulnerability and argue that flying reduces predation and vulnerability to food shortages.  In that respect, flight offers some of the same advantages as large body size, resulting in the anomalously longer lifespans enjoyed by bats and birds.  The only problem with this hypothesis is that a Malthusian distribution should ensue, and when these populations explode to the very limits of their ecological carrying capacity, one would expect that these advantages would be nullified.  Yet the differences persist.

An alternative view is that animals adapted for flight have a chemical advantage related to flying.  Their tissues express larger quantities of mitochondrial uncoupling proteins, which allow the “leak” of H+ without producing ATP in the mitochondria.  This means that they can “throw away” excess energy produced when they are at rest, necessary because their cellular machinery is designed to process huge amounts of energy during periods of flight.  Tossing the protons made by oxidative respiration has the side benefit that reactive oxygen species (ROS) are destroyed, preventing cellular damage that accumulates over time and causes aging.  Birds therefore age slowly and maintain their youthful function throughout the vast majority of their years.

Other animals, including humans, might be able to benefit from research that targets these proteins.  A growing body of research aimed at treating obesity has a similar goal, and gene therapies that are aimed at stimulating “brown fat” promise to kill two birds with one stone.   Brown fat, a vascular active form of adipose tissue, burns fats rapidly in the presence of oxygen and uncoupling proteins to generate heat.  This is the fat that allows long-lived walruses and cetaceans to keep warm even with wet skin in freezing climates by using fat as nothing more than fuel for the furnace.  Through gene regulation to stimulate brown fat we might be able to reduce obesity and inflammation caused by ROS.

Current research is promising, with the side benefits that gene therapies that increase the activity of the brown fat also cause marked increase in muscle mass and strength, at least in lab mice[2][3].  Scientists at Virginia Tech have recently identified a small mitochondrial uncoupler, named BAM15, that decreases the body fat mass of mice without affecting food intake and muscle mass or increasing body temperature. The research of Santos and colleagues, published in Nature Communications on May 14, 2020, are especially promising for the treatment of obesity and diseases characterized by inflammation.

Although research on mitochondrial decoupling proteins is ongoing, recent progress is promising, and the implications for medicine are sky-high.

[1] Healy, et. al.  2014  Ecology and mode-of-life explain lifespan variation in birds and mammals.  Proc. Royal Soc. B.  DOI: https://doi.org/10.1098/rspb.2014.0298 or visit https://royalsocietypublishing.org/doi/10.1098/rspb.2014.0298.

[2] Weintraub, Arlene.  2020 Gene therapy cuts fat and builds muscle in sedentary mice on unhealthy diets.  Fierce Biotech. May 11. https://www.fiercebiotech.com/research/gene-therapy-cuts-fat-and-builds-muscle-sedentary-mice-unhealthy-diets.

[3] Tang et. al. 2020  Gene therapy for follistatin mitigates systemic metabolic inflammation and post-traumatic arthritis in high-fat diet–induced obesity.   Science Adv. 08 May 2020:Vol. 6, no. 19. DOI: 10.1126/sciadv.aaz7492 or https://advances.sciencemag.org/content/6/19/eaaz7492.

[4]  https://www.sciencedaily.com/releases/2020/06/200608132539.htm?utm_content=131524119&utm_medium=social&utm_source=twitter&hss_channel=tw-463200485

Will Big Pharma Sabotage its’ Own Re-Shoring?

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globe

The need to reshore American products has been recognized on a federal level for many decades, with legislation such as the original Buy American Act, dated to 1933.

The urgency has grown in recent years, with the burgeoning dependence of the United States on foreign medicines and medical equipment now constituting a huge strategic burden.  The issue has recently come to forefront because of  renewed distrust in supply chain stability thanks to Covid-19, however, and current legislation is upping the ante by including Big Pharma among the list of key players that need to be reformed.

The imperative to return American products home is primarily being addressed through legislation offering incentives aimed at making American businesses more competitive, imposing tariffs on foreign goods and offering tax benefits for American manufacturers.  Although 28% of registered worldwide pharmaceutical API manufacturing sites are located within the US, according to government statistics when we consider the sourcing of raw materials, various estimates suggest that the true foreign dependence is even higher.  Indeed, it is surprisingly difficult for consumers to determine the origin of their drugs and medicines, and many pharmaceutical companies are reticent about their suppliers given the proprietary nature of the information.

Figure2-2

President Trump’s proposed “Buy America” Executive Order, spearheaded by White House trade adviser Peter Navarro, was sidelined by the National Security Council before it could be signed last Friday.  Although the exact details of the order are under negotiation, it is clear that the future of the pharmaceutical industry is at a major crossroads: what happens when the order is signed will shape the manufacturing of pharmaceuticals worldwide.

While this situation underscores the necessity for re-shoring American manufacturing of pharmaceuticals, the biggest opposition to the movement is coming from pharmaceutical lobbyists on Capitol Hill.  Perhaps this is unsurprising, given the enormous disruptions that changing the system would cause, and the fact that many of the losers would be large, powerful corporations with pronounced sourcing from overseas.  Nevertheless, the Pharmaceutical Research and Manufacturers of America (PhRMA), which is the largest pharma lobbying group present, has proffered an argument that re-shoring proposals will “… not only overestimate the potential feasibility and underestimate the time and effort it would take to make such changes, but also misunderstand that a diverse pharmaceutical supply chain is precisely what enables the industry to respond quickly and make adjustments in its supply chain sourcing during natural emergencies and global public health crises.”

Some of this rhetoric is true:  the process will definitely be expensive and difficult.  Some of this is false: parallel supply chains increases the robustness of the worldwide supply.  In fact, redundancy is a key element to airplane safety, and by analogy, it’s plain to see that parallel sources are far more secure than relying on a potentially distant source in an emergency.  This resistance is troubling, since the truth is staring us in the face:  global supply chains are not always reliable.  Imports from China for critical medicines and pharmaceuticals are being cut off entirely due to Covid-19.  This dependence has placed lives at risk since 90 percent of the generic medications that Americans use daily are imported.

The reluctance of  Big Pharma to reduce an unhealthy and greedy dependence on cheap labor and materials will have serious consequences for American healthcare as well as national security.  China’s dominance of the pharma supply chain is highly dangerous to the United States.  Pharmaceutical production must be reshored and even expanded in order to develop secure and safe supply chains for medications, vaccines and medical devices. This crossroads brings us to a critical question: will the United States commit its financial might to developing American pharmaceutical manufacturing capabilities, or will pharma itself stand in the way?

Cow Hearts: Beefy Benefits for Humans

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heart2According to the CDC, heart disease is the leading cause of death in the U.S., killing more than 600,000 Americans each year.

  • More than five million Americans are diagnosed with heart valve disease annually.
  • Heart valve disease can occur in any single valve or a combination of the four valves, but diseases of the aortic and mitral valves are the most common.
  • Calcific aortic stenosis is the most common form of aortic stenosis (AS).
  • While up to 1.5 million people in the U.S. suffer from AS, approximately 500,000 within this group of patients suffer from severe AS. An estimated 250,000 patients with severe AS are symptomatic.
  • Without an aortic valve replacement (AVR), as many as 50 percent of patients with severe AS will not survive more than two years after the onset of symptoms.

Aortic valve stenosis — or aortic stenosis — occurs when the heart’s aortic valve narrows. This narrowing prevents the valve from opening fully, which reduces or blocks blood flow from your heart into the aorta and onward to the rest of your body.

heart picRecent advances in the treatments for aortic valve stenosis[1] seem to be tipping doctors and patients increasingly towards xenografts for treatment.  Traditional treatment regimes have involved open heart surgery, focused on the replacement of the damaged aortic valve with a mechanical replacement.  The move away from these highly invasive operations has been prompted largely by a single, increasingly attractive development: Transcatheter Aortic Valve Replacement, or TAVR.

The new method of TAVR was only approved as recently as August 2019 for low-risk patients, as new research began to overturn the idea that mechanical heart valves were superior for patients with significant post-operative life expectancy.  The old thinking went like this: since mechanical heart valves do last longer, these valves could provide patients with a lower risk of failure, complications or repeat surgery.  The problem is that some of these assumptions are no longer true, and in many cases, “biologic valves are better even in the young patient.”[2]

The only true representation of the above claims is the fact that mechanical heart valves last longer.  That’s absolutely true; a valve made from titanium or other high-strength, highly impervious material can last for decades.  Unfortunately, these materials increase the risks of blood-clots since platelets have an affinity for collecting on non-biogenic surfaces.  These blood clots can result in thromboses, heart attacks and strokes.

The current treatment regimen is at best an uneasy compromise, because patients are assigned a life-long regimen of anti-coagulants that must balance the risks of clots against the risks of fatal bleeding, hemorrhagic stroke and other complications from the anti-coagulants.  The mortality and morbidity due to surgical complications and failure of the mechanical valves are complicating factors as well.

TAVR addresses some of these problems with short-term mortality by significantly reducing the risks of open heart surgery.  The minimally-invasive procedure begins by inserting a catheter into the femoral artery (or another blood vessel) and threading it up into the aorta.  Once there, in the increasingly common valve-in-valve (VIV) procedure, a collapsible replacement valve can be delivered right inside the aortic valve and then expanded.  Once it’s inside the valve, the new valve holds everything open during systole, meaning output resistance drops and the heart doesn’t have to work as hard.  The new valve will also close more effectively, so blood doesn’t continually wash back and forth, which further eases stress on the heart.

TAVR heart valves are typically made from cow pericardium[3], which also eliminates the platelet adhesion problems seen with mechanical valves.  Some people can go off of blood thinners, and not have to worry about their potential side effects.  The primary disadvantage of TAVR valves is their limited lifespan of 10 to 12 years.  New refinements are addressing this problem: recent studies have shown the chances of having problems with repeat surgeries and TAVR for failed bio-prosthesis valves are either the same, or slightly better for redo TAVR[4].  In another study of approximately 50 patients who had redo TAVR due to failing bio-prosthetic valves, every patient survived to discharge, with only one serious bleed and one minor, non-disabling stroke[5].  In fact, the lower risk of early- and mid-term morbidity associated with TAVR means that for many people, the procedure offers the best chance to live their best lives – living with the highest quality and lowest risk of disability.

[1] Source for stenosis diagram: Michigan Medicine, Frankel Cardiovascular Center.  https://www.umcvc.org/conditions-treatments/aortic-stenosis.

[2] Expert Analysis. 2015 Surgical Aortic Valve Replacement: Biologic Valves Are Better Even in the Young Patient. American College of Cardiology.

[3] Source for TAVR diagram: TCTMD.com

[4] Maxwell, Y.R. 2018.  Valve-in-Valve TAVR: Mortality, Adverse Events Similar to Redo Surgery at 30 Days. TCTMD/the heart beat.  < https://www.tctmd.com/news/valve-valve-tavr-mortality-adverse-events-similar-redo-surgery-30-days>.

[5] Barbanti, et al. 2016. Circ. Cardiovasc. Interv. (9):e003930.  Outcomes of Redo Transcatheter Aortic Valve Replacement for the Treatment of Postprocedural and Late Occurrence of Paravalvular Regurgitation and Transcatheter Valve Failure.  < https://pubmed.ncbi.nlm.nih.gov/27578840/>. DOI: 10.1161/CIRCINTERVENTIONS.116.003930