Facial Cream Containing Small Molecule Inhibitor for Hair Loss

• Executive Summary

The smoothened molecule inhibitor is known as PEZ2020D or “SmoothSkin.” Smoothskin is a synthetic molecule that is involved in the stem cells of mammals inhibiting the effects of stem cells, thereby leading to loss of hair (Elvira, 2015). This potent molecule can be successfully used to get rid of unwanted hair, thereby proving to be a viable beauty and skincare product.

This paper looks into the five-step regulatory strategy that PharmaEZ will use to get US FDA approval in order to put the product into the market. Their latest product is PE2020D (Smooth Skin). Smoothskin is a signaling molecule that was covered by PharmaEZ.

The company is currently interested in marketing PEZ2020D as a facial cream for removing facial hair. Once PEZ2020D is approved by the FDA and out on the market, this drug will help many patients who are dealing with mild to severe skin disorders and generate a big revenue that could offset the declining sales due to patent expiration.

• Goal – a step by step strategy for obtaining US regulatory approval for PEZ2020D (Smooth Skin).

1. Objectives
2. A regulatory strategy for US approval

• Preclinical trials

Preclinical trials allow scientists to vet the safety and effectiveness of drugs and other substances prior to testing them on human subjects. The reason this process is necessary for PharmEZ is directly linked with the need for the FDA to prove that the SmoothSkin molecule is safe to be tested on real human subjects (Maguire & Davenport 2014). These studies are often undertaken in the lab.

• Clinical Trials

Clinical trial evidence may be requested during the certification process, but otherwise, the procedure is really similar to the US 510(k) process (Elvira, 2015). It is possible during the review process that a clinical trial could be requested in order to provide additional support to the application in cases where there have been changes made to the product that could affect the intended use, or the material or composition of the product, or major changes to the design of the product that may affect its safety and effectiveness (Maguire & Davenport 2014).

• NDA application for FDA approval for marketing in the US

At the point when a substance is prepared for clinical investigation, yet before any testing in human subjects, the drug engineer is obligated to embrace the FDA. This procedure starts when the drug’s support (typically the drug producer or wholesaler) applies for the new drug (NDA) with the office. Government law necessitates that a drug is the subject of an endorsed promotional application for it to be lawfully dispatched across state lines. An affirmed NDA application furnishes the engineer with a specialized exclusion to this government regulation so clinical agents can disseminate a drug to various investigation habitats over the US.

• Description of the meetings that will be scheduled with the FDA and when in the process, they will occur.

A 510(k)-premarket notice ought to be submitted to exhibit generous identicalness, and our organization must stick to the general controls, including yearly foundation enlistment, product posting, and legitimate product naming, great assembling practices.

• Design post-marketing surveillance for potential adverse events.

SmoothSkin is a product for indications that are common and would not be classifiable as a HUD, as it would be a treatment option for more than 6,513 individuals in the US annually. Therefore, there will be no orphan device application routes available for SmoothSkin (Elvira, 2015).

1. Potential Side Effects

• Types of side effects predicted for Smoothskin

There two types of side effects, namely irritation of the skin and lack of appetite.

• Conditions inhibitors and agonists of Smoothened signaling are currently being tested. Inhibitors include penicillin, aspirin, and protease.
• Types of side effects have been reported.

Two types of side effects have been reported namely irritation of the skin and lack of appetite

• Types of side effects have been reported for naturally occurring inhibitors and agonists of Smoothened signaling.

Two types of side effects for naturally occurring inhibitors include irritation of the skin and lack of appetite

• Types of preclinical and clinical tests would be possible and appropriate to rule out serious potential side effects. The lab attendant will check how the drug is metabolized, distributed, absorbed, and then disregarded in the body.

1. Timeline for the entire process – 7 years

• Some anticipated problems

1. Agreement on one regulatory approach
2. Defining the focus of each objective
3. Finding the appropriate literature
4. Introduction & Background

• Background Information on Company

PharmEZ is a global pharmaceutical company headquartered in New York, New York. The company was founded by Charles Pfizer in 1849. The company strives to be one of the top pharmaceutical companies in the world and focuses on developing, manufacturing, and commercializing best-in-class medicines for better patient care. Our company has a portfolio of top medical products in a variety of categories, including pharmaceutical, medical devices, biologics, and consumer health fields.

• How this project fits into the overall research/business strategy

With the help from the latest acquisition and continuous developing plans for the pipeline, PharmEZ recently designed a new synthetic small molecule that is a potent Smoothen Inhibitor (PEZ2020D or SmoothSkin) (Andi, Liz, Ann,  Anneke,  Louise & Anne, 2014). The company is currently interested in marketing PEZ2020D as a facial cream for removing facial hair. Once PEZ2020D is approved by the FDA and out on the market, this drug will help many patients who are dealing with mild to severe skin disorders and generate a big revenue that could offset the declining sales due to patent expiration (Andi et al., 2014).

III.       Regulatory Strategy

1. Target product profile

PharmEZ requires target product profile during its drug development of PEZ2020D. It is the facilitator of discussions with regulatory agencies. They ensure that the end product is safe for the end-user.

1. Development of bioavailability bridge

Two tests are conducted with application of crossover designs. Principles of bioavailability are used when determining bioavailability of drugs submitted under NDA (Maguire & Davenport 2014). During this development, the new drug is important in establishing and evaluating the effectiveness or safety of the product.

1. Preclinical trials

This is done in the laboratory. It allows the scientists to evaluate the effectiveness and safety of drugs and other substances before testing them on human after the products are applied on animals or any other thing. This strategy is important to PharmEZ because it is directly linked with the need for the FDA to ascertain that molecule is safe to be tested on real human.

1. Clinical Trial

It is an integral part of drug discovery process. It evaluates the safety and effectiveness of the SmoothSkin molecule (Maguire & Davenport 2014). It is conducted in phases. Clinical trial is done on real human. The literature of clinical analysis will give information to prove the safety and efficiency of the product.

1. Outsourcing

It is done to prove effectiveness of PharmEZ. This helps to save money as it makes them to shift their attention to improve overall efficiency.

1. Manufacturing

After everything is worked and proven to be safe and effective, the products are then manufactured.

1. Patent protection

A written record of SmoothSkin molecule is written and it should meet requirements to obtain a patent. A patent search is then done and the attorney is hired to finish up the process.

1. Life cycle of the product

For a biotech company to market an innovative and quality product, the company has to manage the following sub-stages; market research, formulation and, management of regulations and information about the product.

1. Marketing exclusivity

Before a product of PharmaEZ is released into the US market, the must be approved by FDA. Once PEZ2020D is approved, the drug will help many patients who are struggling with skin disorder issues. FDA takes a look at the company’s name, the name and type of the product, the use of the product as well as the technology applied in making the product (Maguire & Davenport 2014).

1. Post-Marketing Trial

Studies are conducted by a sponsor after the PEZ2020D has been approved by FDA, so as to gather more information about the efficacy, safety and, use of the product.

1. Safety concerns

They are based on cases such as; pregnant women, nursing women, pre-existing skin conditions, psoriasis and, eczema. The ingredients of PEZ2020D are evaluated to see if they have side effects on the above cases.

1. Product Overview
2. Chemical structure

Elflornithine Hydrochloride is a chemical component that is included while making PEZ2020D. It helps in treating excessive growth of facial hair especially among females. Potassium Thioglycolate is a chemical component that destroys hair follicles preventing growth of facial hairs. Propylene glycol, sodium hydroxide, calcium hydroxide and thioglycolic acid are among the chemicals used in making PEZ2020D.

1. Mechanism of Action
2. Literature on stem cells

When PEZ2020D is applied on the skin, it removes facial hair. The chemical component works deep in the skin to correct skin disorders. The stem cells keep on dividing in adults. There

2. Delivery system

Apply a thin layer of PEZ2020D twice daily on the affected part, rub until you can’t see the cream on your face and wash after several hours have elapsed.

1. Indications
2. Patients with unwanted hair
3. Patients dealing with mild to severe skin disorders
4. Target patient population
5. Women and men. The potential market exist between women and men aged between 18 to 45 years.
6. All ethnic group. All ethnic groups are a target market for PEZ2020D, but more especially Caucasians because they have more facial hair (Popescu, & Vlad, 2016). Africans and Asians have less facial hair.
7. Timeline for obtaining US regulatory approval for PEZ2020D
8. Key regulatory milestones
9. Pre-IND submission. It takes 30 days to file a submission to facilitate early communications.
10. Duration of preclinical trials. It will take a period of 1 year for PEZ2020D to move from the laboratory to medicine cabinet.
11. Patient Registries for Patient Enrollment
12. IRB Submission/Informed Consent. It is a basic ethical obligation and legal requirement to obtain it.
13. IND Submission. It takes up to a maximum of 30 days. They are submitted immediately after studies of clinical research have commenced (Popescu, & Vlad, 2016).
14. Duration of Clinical trials. It takes 3 years to complete clinical trial for PEZ2020D.
15. NDA Submission. It takes a maximum of 60 days for FDA to file a review or reject.
16. USA Market Approval. Approval of a product (PEZ2020D) into the market is done by FDA.
17. Post Marketing Surveillance/Reporting. Report of the surveillance is done after 10 years.
18. Pre-IND Submission
19. Pre-IND Formal Meetings with FDA

It is conducted within 60 days of request. For planning purposes the pre-IND meeting request is submitted 2 months early (Andi, 2014).

1. Justification of Literature for Preclinical Trial
2. Preparation for GLP/GMP for preclinical trial

VII.     Design of Preclinical Testing Based on literature

Preclinical testing is done in the laboratory. The following is what takes place;

1. Rodent drug testing.
2. Non rodent drug testing.

Pigs are used in place of human because there is similarity on their skin.

1. API
2. Absorption, Distribution, metabolism, and excretion (ADME)
3. Toxicity of the drug
4. Pharmacodynamics (PD)
5. Dosage of product
6. Good Laboratory Practices
7. Adverse events of skin irritations and loss of appetite if any.

VIII.    Manufacturing

            The following are determinants essential for manufacturing of PEZ2020D;

1. Facility to manufacture the drug is determined.
2. Equipment necessary in the process of manufacturing are assembled.
3. Materials to be used especially the chemical components.
4. Production process to be followed.
5. Packaging and Labeling of PEZ2020D
6. Validation of the drug making it authentic for human use.
7. Laboratory

Quality control testing is done in the laboratory. All the factors involved in production of PEZ2020D are reviewed to identify need for correction of errors in product preparation.

1. QA System

It ensures that customers of the products are retained because the goods produced are of high-quality. This system evaluates the quality of the drug before it is released into the market (Popescu, & Vlad, 2016).

1. IND submission

The following are necessary during IND submission;

1. 21 CFR 312
2. 1571 form
3. Nonclinical data
4. Clinical trial protocol
5. CMC data
6. Investigator
7. Design of Clinical testing Based on Literature Research
8. Good Clinical Procedures. The procedures are good and meant to ensure safety and effectiveness of PEZ2020D.
9. IRB. The forms are needed to obtain consent.
10. Study Design. Participants are assigned to two or more groups randomly. Classification is by chance.
11. Enrollment of subjects
12. Contract Research Organization (CRO). It has provided support on research to PharmEZ. It operates on contract. They also provide clinical trial and support for drugs.
13. Phase 1
14. The trial length is determined
15. Number of healthy subject are enrolled in the study
16. Site of clinical trial is determined. Clinical trial is done in the laboratory on real human.
17. Dosage regimen. The drug is used twice a day where the first time. Then it is applied in the morning. It is then applied in the evening after cleaning the skin
18. Adverse events that are likely to occur after using the PEZ2020D is skin irritation and loss of appetite (Popescu, & Vlad, 2016).
19. Safety of product. This determines whether the product is harmful to human beings.PEZ2020D is safe for human beings with mild skin disorders.
20. Phase 2

We evaluate the efficacy, safety and effectiveness of PEZ2020D to determine if there are side effects (Popescu & Vlad, 2016).The following takes place in phase 2;

1. Length of trial is determined
2. Number of subject with disease (~200) are evaluated
3. Maximum dose regimen is issued
4. Safety and efficacy of product is evaluated
5. End-of-Phase 2 Formal Meeting with FDA
6. Phase 3

The following takes place in phase 3;

1. Length of trial is determined
2. Number of subjects with disease (hundreds to thousands) are determined
3. Safety and efficacy assurance
4. Pre-NDA Formal Meeting with FDA to allow release of the drug.
5. Adverse Events
6. Serious adverse

There is likelihood of the user developing skin irritations and loss of appetite after using PEZ2020D. It can also lead to skin rash, dandruff and skin dryness.

1. Risk to fetus

This is more likely to affect pregnant mothers and nursing mothers causing reduced hormones leading to reduced skin hormonal imbalance.

XII. NDA Submission

The submission takes 60 days for FDA to establish whether the file is going to be reviewed or rejected (Popescu & Vlad, 2016). If the file is reviewed and approved then the product is allowed into the market. The following are essential in NDA file submission;

1. 505(b) (2)
2. 356H form

There is application to market new drugs for human use.

1. Index of application
2. Preclinical data
3. Clinical data. Clinical trial protocols.
4. Clinical pharmacology
5. CMC data
6. Proprietary Name
7. Labeling – carton, container, Patient information leaflet, Medication Guide

XIII.    Post market surveillance

(Phase 4) (To test for the occurrence of these potential adverse events). This surveillance is very costly. It’s about $26 million (Popescu, & Vlad, 2016).

1. Post-Approval Formal Meeting with the FDA. It is held prior to starting of drug manufacturing with FDA.
2. Duration of Trial. There is no specified time for trials; it may take up to a maximum of 0 to 15 years but with PEZ20202D it takes one year.
3. Pharmacovigilance (FAERS). Bears information of adverse events caused by medical errors by health care providers. The reports are submitted to FDA for approval.
4. REMS with ETASU. They are manual guides, packed along with the drug for the patient to go through as a prescription for safe use. It is a communication from health care providers.
5. Pregnancy registry. Contains the name of expectant mothers who used PEZ2020D with the side effects if any.
6. Requirements for adverse-events reporting
7. PADER. Periodic Adverse Drug Experience Report. Its main function is to update and evaluate report on world’s drug data to ensure safety (Carretta, Farina & Schwizer, 2017). It is submitted to the FDA.
8. PSUR. This document captures data of PEZ2020D (Carretta et al., 207). It is a stand-alone type of data document that is designed to ensure assessment of the drug in the market.

XIV.    Recommendations and Conclusion.

Patients who experience any adverse effects like skin irritation and loss of appetite after using PEZ2020D should stop using the drug and seek to see a health care provider to be advised accordingly (Polonsky, Miles & Grau, 2011).

PharmEZ has sought to be the best biopharmaceutical company in the world. It has developed synthetically a small molecule that is helpful in removing skin hair on patients with disorders. This project has designed a step by step regulatory strategy for obtaining US approval by FDA.it has also done a clinical research on the adverse effects on human beings. The pharmaceutical industry has seen a continuous rise of innovative products as well as generics in the market. The rapid rise put pressures on drug manufacturing, R & D and regulatory aspects of product development. As a company standing in the highly saturated U.S market, it is necessary to consider short-term plan options to maximize profit.