FROM CONCEPT TO CARE: A COMPREHENSIVE NEW THERAPEUTIC (DRUG) DEVELOPMENT & POST-MARKETING SURVEILLANCE PLAN

FROM CONCEPT TO CARE: A COMPREHENSIVE NEW THERAPEUTIC (DRUG) DEVELOPMENT & POST-MARKETING SURVEILLANCE PLAN

DRUG DEVELOPMENT PLAN:

A thorough drug development plan?specifies each process for taking a new drug from the laboratory through every stage of development (Lifecycle Management) to the intended licensed drug product. LCM includes the development of new indications and begins with the initial approval of BLA/NDA (first Marketing Authorization). All the regulatory, nonclinical, clinical, chemistry, manufacturing, and controls (CMC), formulation activities, and commercial plans, along with the target product profile (TPP) of the drug, are included in the drug development plan. The?pre-approval process for an NDA includes steps including facility inspection, CMC approval, labeling approval, and the approval of a bioequivalence report (Rogozinska, 2017) (1).

Sections of Development Plan:

  1. General Product Description
  2. Strategy for Selected Indication(s) & TPP
  3. CMC plan
  4. Non-Clinical data
  5. Preclinical pharmacology and data collection
  6. Clinical Development Plan
  7. Summary Benefit / Risk Assessment
  8. Project Management Resource Plan & Development Timeline
  9. Product Commercial Value & Competitive Environment
  10. Intellectual Property and Exclusivity Strategies
  11. Pricing, Product?Market Access, and Evidence Generation Strategy
  12. Overall Regulatory Development Strategy
  13. Critical Risks and Contingency Plan
  14. Communication Strategy

?General Product Description:

In this section, reasons for why the product should be developed and its value are mainly described by using medical and scientific reasons which in turn reflects the commercial success of the drugs. Magic dust #1, #2 and #3 have unique characteristics with respect to their pharmacodynamic mechanism of action and there are high chances of benefits from using these types of magic dust in the US to cure certain disease conditions.

Strategy for Selected Indication(s) and TPP:

Based on the information gathered, a probability estimates for achieving the TPP is provided.

Target Product Profile (TPP):

The TPP, which is frequently referred to as the PDP's "backbone," specifies the target product characteristics required to obtain regulatory?authorization and to meet commercial goals. These requirements are crucial in deciding what can be asserted on the product label and also guide the design and scientific proof strategies for other important components.

A destination that includes the essential elements of the finished medicinal product is?clearly defined in developing a strategic roadmap for a drug development program. This plays as a crucial role in drug development. All internal and external specialists work together in describing the required final product attributes. The target indication or disease(s) to be cured, patients' population(s), therapeutic efficiency and?safety, formulations, dosage regimes, and administrations along with drug-drug interactions, contraindications, and cautions are?addressed.

These traits are compiled into a TPP, which serves as a foundation for planning all program activities (such as non-clinical and clinical trials) to ensure that?necessary data is?determined in order to identify?whether the drug has the desirable properties. This helps the clinical and non-clinical trials to focus on the answers to the typical questions that arise during the early stages of clinical development.

The TPP is updated with fresh data from clinical trials, nonclinical studies, and the external regulatory and business environment to ensure that continuing development stays on course. The updated?TPP?ultimately serves as the foundation for creating the final, approved product label.

Clinicians used TPP to evaluate how the proposed drug product would address a medical need while commercial professionals start to strategize where the medicine should be sold, how the drug might fill a market niche, and how it would obtain reimbursement. Along with these, the pattern of new drug evolution by health authorities, and the type of non-clinical and clinical trial data are assessed with the command of the regulatory experts (Creating a comprehensive drug development plan) (2).

Isolation and Refinement of the indications and APIs of drugs:

Isolation and refinement of each indication of the drug having multiple indications or therapeutic benefits is the best way to avoid certain difficulties. For instance, magic dust #1, drug exhibits multiple indications such as it is capable of curing headache, nausea, fever and mild pain (systemic); not every patient may require all of the therapeutic advantages offered by the medicine, which has several therapeutic indications.

It is beneficial to isolate every indication or merge a few indications. For example, ?since some symptoms, like fever and headache, are related to one another, they can be merged as a drug with multiple indications. The isolation of different APIs results in the isolation of the indications of the drugs. For a number of reasons, the separation and purification of these therapeutic substances were crucial. The drugs?contained unknown and unpredictable levels of the active substance, making it impossible to provide precise doses of the medications. Second, if just the pure active substances were employed, adverse effects brought on by impurities in raw forms of drugs?might be removed. Last but not least, understanding the chemical composition of pure pharmaceuticals enables?the laboratory synthesis of numerous structurally related molecules and the creation of useful drugs (Dailey, 2015) (3).

To avoid issues in handling pricing for drugs with multiple indications, isolation of each therapeutic indication of the drug is the best option.

Chemistry, Manufacturing and Controls (CMC):

All procedures involved in developing the final dosage form, such as sourcing?the active pharmacological component (API) that includes adequate drug supplies for each phase of the program, creating a viable formulation with a formulation suitable for the intended route of administration that meets all nonclinical and clinical trial needs, assessing and maintaining quality, packaging, and shipping as well as all regulatory requirements are included in CMC plan.

The manufacturing/quality group sometimes makes costly mistakes because of failing to integrate all the domains in drug development from the onset. CMC plan is established to supply to fulfill the clinical and commercial projection and to assist clinical testing quality TPP.

CMC Plan:

By detailing the key components of drug supplies and formulating a strategy in addition to any supply requirements for placebo or comparator drugs, the CMC plan serves as an essential part of a fully integrated development approach. The anticipated cost of goods (COGs) for the drug material and the finished product is evaluated as part of a CMC strategy, which is an important step in the development of novel drugs.

Components of a CMC Plan:

? Analyze all current drug formulation, production, or scale-up processes and costs.

? Strategies for packaging, shipment, or quality assurance

? Suggestions for future medication manufacturing procedures on the basis of the anticipated clinical trials (consideration of their time, size, and locations)

? Predicted demand when the medicine is available on the market

? Liabilities specific to a drug that could endanger its approval or success on the market, such as chemical instability or expensive synthesis expenses

? Suggestions to avoid or lessen potential dangers

A detailed technical, scientific, and regulatory study of all available data on the drug substance or API is frequently the first step in developing a CMC approach. The study additionally looks at any current pilot drug formulations to determine whether the intended nonclinical research and clinical trials can be supported by the available CMC data and also meet the necessary Good Manufacturing Practices (GMP) regulatory standards.

In the?study, any extra CMC work needed to assure drug supply accessibility, consistency, and purity, including analytical procedures for quality control that match specified criteria,?are outlined (2).

Non-Clinical Data:

Nonclinical laboratory studies refer to in vivo or in vitro tests where test objects are prospectively examined in test environments under controlled laboratory circumstances to ascertain their safety. These studies do not contain any experiments involving human participants, clinical trials, or animal field studies.

Studies on pharmacology, safety pharmacology, toxicology and carcinogenicity, genetic toxicology, metabolism of the drugs, pharmacokinetic analyses, and bioanalytical investigations are conducted on the drugs as per the regulatory guidelines outlined in GCP.

In the non-clinical studies conducted on magic dusts, the safety of the medications was evaluated using biomarkers, and the findings indicated that the drugs are safe and met all the regulatory requirements to employ in clinical trials (Rogozinska, 2017) (1).

Important Aspects of a Nonclinical Strategy:

??????????? A thorough plan is maintained to provide all the data regarding the non-clinical studies. The crucial aspects include

? Selection of doses and animal species in toxicological studies

? Opinions, justifications for study plans, and the significance of nonclinical research

? The function of regulatory agency input and its timing.

Preclinical Pharmacology and Data Collection:

Preclinical pharmacology and toxicology are crucial aspects of drug development to effectively translate research from the lab to the clinic. Compound identification, lead optimization, pharmaceutical profiling using animal models are carried out to determine the effectiveness and safety, and toxicity screening of all the magic dusts with respect to certain indications.

The studies have shown positive results with respect to the safety profile of all magic dusts and these results exhibit the Proof of Concept as these correspond to the regulatory standards for Phase I trial start-up (McGonigle & M, 2017) (4).

IND Submission: ?After obtaining the beneficial results in preclinical trials, an investigational New Drug Application is submitted to Food and Drug Administration (FDA) in order to perform clinical trials on human beings.

The IND application form containing

? Data from animal studies and information on toxicity (side effects that cause significant risk).

? Data from?previous human studies

? Clinical procedures (research protocols) for research to be executed

? Manufacturing details

? Details about the investigators, are submitted for FDA approval of clinical trials in humans. (Center for Drug Evaluation and Research, 2022) (5).

Preclinical Requirements addressed in the clinical trials plan:

Preclinical testing consists of laboratory and animal investigations that assess the drug's pharmacologic and toxic effects. The FDA guidelines known as Good Laboratory Practices (GLP) for Nonclinical Laboratory Studies, 21 CFR 58, also apply to preclinical studies. The GLP laws outline minimum requirements for persons, facilities, tools, and operations. Pharmacokinetics, the study of how a medication flows through living things, is a component of preclinical testing. To make sure the medication reaches its objective and moves through the body effectively, researchers look at absorption, distribution, metabolism, and excretion (commonly known as ADME).

In addition to biological studies, chemical studies are carried out to determine the purity, stability, and shelf life of the medicine. To evaluate whether it is feasible to manufacture the drug on a wide scale and to investigate dosage, packing, and formulations, manufacturing studies are carried out. Sponsors in accordance with FDA regulations create?the drug's pharmacological profile?at the preclinical stage,?ascertain the drug's acute toxicity in a minimum of two species of animals and carry out short-term toxicological?studies.

All the adequate safety data, traditional knowledge, animal data and pre-clinical information, bioavailability, pharmacology, toxicology, formulation, and dosing schedule are taken into consideration while designing a clinical development plan (6).

Clinical Development Plan:

A key component of a thorough development plan is a carefully designed series of clinical trials, ranging from first-in-human Phase I to Phase II "proof of concept" and crucial Phase III trials for registration.

Clinical Trial Designing: Designing clinical trials that are both essential and adequate for regulatory approval and market success takes a lot of effort as they are frequently the most expensive and rate-limiting component of a plan. Physician-scientists evaluate the pre-clinical description of the new drug (such as its pharmacology, mechanism of action, and toxicology) before developing a design for the?clinical trial plan.

The final data?after that?will be?summarized by analyzing?how these properties may affect clinical trial design as well as proposed therapeutic use in patients. The scientific and medical basis for the drug product is examined to see whether it has a good chance of being accepted by patients, healthcare professionals, and professional health organizations.

In Clinical Development, drug research is carried out on humans in phase I, II and phase III clinical studies. ?The FDA examines the IND within 30 days of submission to ensure that the study participants won't be exposed to unreasonably high risk.? After getting the approval from FDA, the clinical trials are started and carried out as per GCP and ICH guidelines (Commissioner, 2018) (7).

Randomized Controlled Trial:

In a Randomized Controlled Trial (RCT), subjects are randomly assigned to two or more groups, each of which is given a different course of treatment, before being compared in terms of a measured response. The goal of an RCT is to minimize potential sources of bias when evaluating the efficacy of new therapeutics. One of the experiment's groups receives the intervention, whereas the other, known as the control group, typically gets a different course of therapy, such as a placebo or no treatment at all.

Generally, RCTs are conducted in two types such as well-blended and Blinded RCTs. ?Based on the allocation, any one of the randomization methods such as simple, Block, Stratified and Unequal randomization is carried out by the researchers. The blinded studies such as Single, Double, or Triple Blind, are employed based on the requirements.

Adaptive Clinical Trials:

Clinical trials known as "adaptive" are ones that monitor participant outcomes and maybe other metrics, such as side effects, on a predetermined timetable in order to evaluate a drug or medical equipment. The trial protocol is then modified based on the observations made.

There are certain advantages associated with these trials: An adaptive trial tries to pinpoint patient populations for which the drug is suited and to more quickly find pharmaceuticals or technologies that have a therapeutic effect. This study design may result in fewer participants participating in studies and fewer clinical trials overall. Clinical effectiveness and safety trials that are well managed can benefit greatly from adaptive design. Early-phase studies, exploration trials, and subsequent trials to fulfill post-marketing requirements can all benefit greatly from adaptive design. However, there is a chance of bias during trials, and sometimes the experiment could overlook important findings that were discovered during exploratory research during a quick interim analysis. These drawbacks make this trial not a suitable option for every type of clinical trial.

Multiple stages make up an adaptive design, and to increase the success chances of the trial, the researcher analyzes data at each stage and modifies it depending on newly available information.

? Modifications could affect the dosage, sample size, the drug being tested, patient selection standards, and "cocktail" mixture.

? Prior to the trial, the researcher establishes the protocol.

? The adaption procedure and schedule were outlined in advance by the protocol (8).

RCT for magic dusts:

The traditional method of clinical trials– Randomized Clinical Trial is the suitable option for conducting clinical research on all the magic dusts in humans. This method of the clinical trial is beneficial in terms of assessing the safety and efficacy parameters of the drugs.

RCT provides more advantages by reducing bias and spurious causality though it is expensive. It also provides more reliable scientific evidence and the possibility of combining the RCTs results in a systemic way is high.

These trials are more in use when performing evidence-based practice.


Phase I: (1-2 years)

The 1st in human trials are performed on 12-40 healthy volunteers or subjects. Drug profile and dosage regimens, safety & tolerability are established in this phase.

The data is collected during phase I trials?on the?drug's interactions with the human body under close observation in order to determine what amount of a drug the body can handle and what its severe side effects are.? The required dosage regimen modifications by researchers are generally carried out during this phase.

All the questions regarding the magic dusts related to the drug metabolism, its function in the body, its side effects related to increased dose levels, early evidence on how effective the drug is, how to administer it to minimize the dangers and improve the potential benefits, etc. are answered in this phase by the research teams. The questions answered in this phase play a crucial role in planning phase II trials.?

The results reveal that magic dust #1, #2, and #3 have more advantages than disadvantages. The maximal dose quantity is connected with no serious side effects (only moderate ones), and the metabolism in the body is efficient. Overdosing should be avoided in order to maximize the drug's potency while lowering the risks and?the medications have demonstrated greater than 50% efficacy.


Phase II: (2-3 years)

The second phase trials are conducted in 20-400 subjects having the target disease. Test safety, Proof-of-concept and preliminary efficacy in disease-affected patients are established in this phase. Further safety data regarding the drugs are provided in Phase 2 studies. The safety data is utilized to answer all the questions regarding the research, to develop research methodologies, and to design and plan the phase III trials.

??????????? The results have shown that the magic dusts are safe with the data provided with respect to safety and are capable of entering the next phase of clinical trials.

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Phase III: (3-4 years)

This phase is performed in between 300-1,500 subjects having the target disease. In this phase, the safety and effectiveness of the drug are proved with the results obtained and the long-term safety of the tested drug is established.

Phase III studies are designed by the research team to demonstrate the treatment benefits of the drug with respect to a specific population. More data on safety is provided in this phase in order to counteract any potential side effects that may have gone undetected during phase II. The results are more likely to show long-term or rare side effects related to the drugs in this phase (Commissioner, 2018) (9).

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Proof of Concept:

A Phase I or II trial can frequently be planned so that results permit a well-founded conclusion when an early "Go/No-Go" milestone decision is necessary to determine if the medicine can satisfy the TPP (e.g., as could be needed for further investment or to influence partnering/licensing decisions). Specific "Go/No-Go" decision criteria might also be included in the clinical development plan (2).

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Summary Benefit / Risk Assessment:

Each study subject may frequently encounter any of a number of different outcomes during the course of a normal randomized clinical study to evaluate a new treatment with a control, which together comprise the "risk-benefit" profile. It is ideal to make use of all of this outcome data while evaluating the treatment's impact.

Risk-benefit profile:

In a randomized, prospective clinical trial, the risk-benefit ratios of therapy and control are compared. ?A complete view of whether the risks exceed the benefits is provided by the risk-benefit profile. Details about trial participants and their reactions to the medications are included in this profile. Regulatory bodies seek a favorable risk-benefit profile that balances risks and rewards in accordance with the standards.

All treatment decisions entail some sort of therapeutic benefit-risk trade-off; a new medication may be linked to improved efficacy but also a higher chance of adverse effects. Clinical evidence about risk and benefit magnitudes and the accuracy of the estimates must be considered by clinicians when making treatment decisions (Claggett et al., 2014) (10).

RMP: The RMP is documentation that demonstrates how risk is consistently managed for a drug from the development stage to post-marketing. All the risks formed during each phase of development are monitored and assessed and with effective risk management, it is possible to lower the likelihood of an incident occurring and the severity of its impact by being proactive rather than reactive.

The administration of pharmaceutical drug development initiatives, programs, and portfolios all heavily rely on risk management. Making better decisions, developing scenarios for risk management, and fostering better teamwork are all made possible by risk assessment at the project, program, and portfolio levels. It is important to apply the RMP in drug development, this involves the

? Identification of the risks associated with drug development,

? Assessment of the risk

? Development of the responses to the risks

? Creation of a contingency plan and preventive measurements

? Communication of the risks

? Mitigation plans tasks and tracking of the risks

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REMS: A known, or prospective major medication risk is managed using the REMS method. It is used to keep patients' access to specific medications when there are safety issues that can be handled by proper use. In some cases, the U.S. Food and Drug Administration (FDA) might demand a Risk Evaluation and Mitigation Strategy (REMS) for specific pharmaceuticals that have significant safety concerns in order to help ensure the benefits of the prescription outweigh its dangers (Rogozinska, 2017) (11).

Project Management Resource Plan and Development Timeline:

The entire program schedule, including all functional tasks, milestones, and important events, the duration of reaching preclinical and clinical proof of concept (POC), submissions, approvals, and launches in the major markets, stage-gate decision timelines, the company's governance framework, and project resource planning plan for each indication (FTEs and budgets) are all included.

Intellectual Property and Exclusivity Strategies:

Drug development is expensive for pharmaceutical corporations, so without?protecting?intellectual property laws, the drug's formula may be simply copied and produced at a lower cost. To ensure that "the first to invent" has the sole right to patents, American intellectual property laws protect the interests of both small and large enterprises. Medication patents are being treated differently from other discoveries to deal with the rising prices of U.S. drugs. Following FDA approval, new medications would be offered at generic costs. The Medical Innovation Prize Fund, which awards money to the developers of new products based on the actual effect on health consequences over ten years, will now be used to reward innovative pharmaceuticals instead of the net profit from sales, at a level of 0.5 percent of the GDP. ?A summary of the intellectual property protection plan, including copyrights, legislative exclusivity, orphan drug status, and any concerns for specific markets, is required in order to obtain drug approval. IP plays a critical role in preserving a competitive edge, guaranteeing protection in important markets, and promptly reacting to any modifications in the IP landscape (Sathwara & Bhandari, 2016) (12).

Pricing, Product Market Access, and Evidence Generation Strategy:

Pricing and reimbursement:

Medicine supply chain complexity has a significant impact on drug pricing. In order to make sure that drug products are readily accessible to patients, reimbursable by patients' public or private insurance, and suitably valued to assure favorable treatment, successful market access entails negotiating the complicated pricing and reimbursement system (Desai et al.) (13).

Generic discussions about fair product pricing offer some insightful cues, which include the transaction, market, and product inherent at a particular time, as well as consumer and supplier attitudes—integrating the buyer and seller-side fairness criteria into a structure that places a reasonable pricing region between a price ceiling and a price floor. The lowest viable fair at which manufacturers can market the medicine is known as the price floor. It may also include other expenses, a reasonable profit, and the price of R&D, production, and distribution. The pricing floor should maintain competition and encourage innovation. The highest that the consumer can afford is the price ceiling. Prices that are higher than the ceiling are considered excessive and would require regulation (Moon et al., 2020) (14). Overall, the cost of a drug or vaccine should be reasonable to the buyer and profitable to the seller as well.

NDA APPROVAL PROCEDURE:

All the test results after the clinical and preclinical trials are provided in the submitted NDA to FDA for the approval process.

About NDA:

The NDA/BLA?is the legal method by which a sponsor requests the FDA for authorization to sell and promote a novel biological or a new pharmaceutical product?in the United States (21 CFR 601.2). The utilization of the product for a certain clinical scenario and the complete lifecycle history of the product are provided in the NDA. The IND is actually a component of the BLA / NDA and?comes prior to the BLA / NDA application, and because it is a dynamic document that is constantly updated all through the clinical assessment procedure.

All the details?and data regarding the medication as learned from clinical and non-clinical research, also an overview of procedures for manufacturing and formulation development and suggested details of labeling to be incorporated on the drug's package are included in NDA.

NDA application is further assessed by the FDA to check the medicine or biologic is effective and safe for the intended purpose or not, whether the benefits exceed the risks, also whether the medication was created in a way that maintains its identification, potency, quality, and pureness. The medicines are regulated by the FD&C Act's Section 505, which receives approval through an NDA path. The?Center for Biologics Evaluation and Research (CBER) and the Center for Drug Evaluation and Research (CDER)?are two units inside the FDA that are in charge of examining and approving drug commercialization submissions as well as general regulatory monitoring. While CDER regulates all traditional drugs (tiny molecules), biologics are regulated either by CBER or CDER, depending on the scenarios.

All the following premarket prerequisites are submitted:

? IND Registration and maintenance

? Regulations of the Pediatric Research Equity Act (PREA)

? Prescription Drug User Fee Act (PDUFA) fee; and

? Standards for Labeling and Advertising

The full NDA submission containing evidence supporting the following is submitted for approval:

? The medication is suitable for use in patients with the identified disease and is both safe and effective.

? The advantages offered by the drug product outweigh the risks associated with its use.

? The package inserts and labeling that have been suggested for commercialization give the end-user all the information they require.

? The medicine is produced in continuous batches to maintain its quality and qualities.

? Along with the clinical results, intended labeling, safety revisions, data on drug abuse, patent info, data from potential studies carried out outside of the United States, institutional review board compliance data, and usage instructions are also submitted.

The common technical document (CTD) format, which is the technical standard for all agency submissions beginning with the IND phase, organizes the submission of an NDA. The eCTD is regarded to be the quickest way for the submitting party and FDA to move the NDA process along.

After the NDA got approved by the FDA, Post-approval activities began to start. Activities related to drug development that follow the first NDA/BLA approval are regarded as a part of product life cycle management (LCM) (Commissioner, 2018) (15).

POST-MARKET APPROVAL PLAN:

After the drug gets approved, some clinical trials and post-market commitment and requirement studies occur after an FDA-approved medication or biological product is released into the market.

PMR:

Study and clinical trial requirements that sponsors must carry out in accordance with one or more laws or regulations are known as post-marketing requirements (PMRs). FDA has the authority to demand post-market research and clinical trials from producers of specific drug products under several regulatory and statutory provisions. Th

The Food and Drug Administration Amendments Act (FDAAA) of 2007 gives the FDA the ability to require drug producers to perform clinical trials and post-market safety testing in order to evaluate any potential significant risks related to the products. Under?Section?505(o)?of?the?Federal?Food,?Drug,?and?Cosmetic?Act. FDA is permitted to demand specific post-marketing tests and clinical studies at the time of authorization after approval if FDA discovers new safety information.

Post-marketing surveillance (PMS) or Phase IV clinical studies are conducted on the new drugs

? To identify an unanticipated major risk when existing data suggests the possibility of a serious risk,

? To evaluate identified serious risks associated with drug use

? To evaluate indications of serious risks associated with drug use (Center for Drug Evaluation and Research, 2022) (16).

Post-marketing activities:

Submission of the label's final content, electronic drug registration, and listing, and pharmacovigilance operations, including FAR,?ADER,?and PAS for any alterations to the product's authorized formulation, are submitted in order to ensure an uninterrupted and efficient commercial supply of the products.

Pertaining to certain exceptions, in accordance with Section 510 of the Act & 21 CFR part 207, the manufacturers have?to register their facilities and submit listing data for all drugs in commercial sale when they first begin manufacturing, preparing, propagating, compounding, or handling drugs (such as human, veterinary, and biological drug products). Each drug's registration information must be provided by registrants in accordance with the activity-specific listing standards outlined in 21 CFR part 207 that apply to that drug.

Based on the requirements, the following needs to be submitted for commercial distribution:

? Labeler code for the registrant,

? Information about the package type and volume that corresponds to the NDC's packaging line of code

? The legal and proprietary names of the mentioned drug,

? Each active pharmaceutical ingredient's name and dosage for each listed medicine,

? Each dormant component's name,

? The dosing method,

? Number of the drug's approved U.S. application

? The form of drug

? The drug's administration route (s)

? The name and Unique Facility Identifier of each additional location that does medication manufacture

? Advertisements,

? All the changes concerning the submitted information after the approval are carried out as per CFR or FDA’s PAS guidance (Dey & Chowdhury, 2018) (17).

The following clinical trials or studies can be required based on the requirements.

? Post-marketing?or clinical studies to show the therapeutic benefit of medications licensed in accordance with 21 CFR 314.510 & 21 CFR 601.41's accelerated approval procedures.

? Postponed pediatric studies (21 CFR 314.55(b) & 601.27(b)), wherever investigations are mandated by the Pediatric Research Equity Act (PREA).

? Human safety and efficacy studies or clinical testing must be carried out before using products that have received approval under the Animal Efficacy Rule (21 CFR 314.610(b)(1) & 601.91(b)(1)) (Center for Drug Evaluation and Research, 2016) (18).

Periodically, all reports of adverse?events are filed. For the first three years, these reports must be filed quarterly; after that, they must be filed annually. A report to the FDA is sent as quickly as possible for side effects that are deemed serious and unexpected (i.e., deadly or life-threatening, permanently impairing, necessitating or extending hospitalization) (a handwritten report must be submitted within fifteen days of receiving the data, and a telephone or faxed report must be sent within Seven calendar days). The MedWatch program of the FDA?encourages individuals and medical professionals to immediately report significant drug side effects to the FDA.

Conclusion:

It is becoming more crucial for pharmaceutical companies to apply appropriate Life Cycle Management (LCM) strategies to maximize profits and the longevity of their assets due to constricting Research and Development (R&D) pathways and rising expenses associated with medication development. LCM includes the development of new indications and also helps in providing safe and effective drugs to the world.

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Note: Check below for the References section.


References

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10.? Claggett, B., Tian, L., Castagno, D., & Wei, L.-J. (2014). Treatment selections using risk-benefit profiles based on data from comparative randomized clinical trials with multiple endpoints. Biostatistics, 16(1), 60–72. https://doi.org/10.1093/biostatistics/kxu037?

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14.? Moon, S., Mariat, S., Kamae, I., & Pedersen, H. B. (2020, January 13). Defining the concept of fair pricing for medicines. The BMJ. Retrieved December 16, 2022, from https://www.bmj.com/content/368/bmj.l4726

15.? Commissioner, O. of the. (2018, January 4). Step 4: FDA Drug Review. U.S. Food and Drug Administration. Retrieved December 16, 2022, from https://www.fda.gov/patients/drug-development-process/step-4-fda-drug-review

16.? Center for Drug Evaluation and Research. (2022, March 1). Postmarketing requirements and commitments: Legislative background. U.S. Food and Drug Administration. Retrieved December 16, 2022, from https://www.fda.gov/drugs/postmarket-requirements-and-commitments/postmarketing-requirements-and-commitments-legislative-background

17.? Dey, R., & Chowdhury, D. R. (2018, June 8). Post-approval activities of Anda: USFDA Regulation and Timeline. crimsonpublishers. Retrieved December 16, 2022, from https://crimsonpublishers.com/abb/fulltext/ABB.000513.php

18.? Center for Drug Evaluation and Research. (2016, January 12). Postmarketing requirements and commitments: Introduction. U.S. Food and Drug Administration. Retrieved December 16, 2022, from https://www.fda.gov/drugs/guidance-compliance-regulatory-information/postmarket-requirements-and-commitments

Looking forward to diving into this insightful piece! ??

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Shravan Kumar Chitimilla

Information Technology Manager | I help Client's Solve Their Problems & Save $$$$ by Providing Solutions Through Technology & Automation.

7 个月

Sounds like a fascinating read! Can't wait to check out your insights on drug development. ???? #ExcitedForKnowledge Swarna Latha Paladugula

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Vivek Amin

Pharmacovigilance/Clinical Research Professional | Passionate About Drug Safety & Clinical Research/Trials

7 个月

great read, amazing Swarna

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Nag D

Senior Specialist- Global Clinical Labeling at Biogen ; Co-op, Pharmacovigilance at Moderna

7 个月

Great efforts, indeed.

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