Need a New Drug Exam 2

Does a generic drug need to have the identical stability/shelf life as the brand name product?

Must demonstrate the same stability Does not have to have identical shelf life

Compare and contrast the NDA approval process and the OTC monograph process with regard to review and approval of drug products.

NDA: Pre market approval Confidential Drug product specific User fee Exclusivity Clinical Studies OTC Monograph: No pre market approval Public process Active ingredient specific No fee No exclusivity Manufacturer responsible for ensuring product complies

Who approved Wichita layers

No approval

Which dose (relative to the doses tested in Phase I) are typically tested in Phase II human clinical trials?

No effect dose

In order to shorten the time needed to develop new drugs, describe which types of toxicology trials need to be completed before an IND is filed and which can be conducted concurrently with ongoing human clinical trials.

No effect dose Minimum lethal dose Medial lethal dose

Describe the accessibility differences between "prescription" medications and "over the counter" medications.

Over the counter: do not need physician to obtain Prescription: Only safe for use under physician because of its toxicity

. Phase II clinical trials (when conducted in volunteers with disease of interest) are often "double-blind". What are the characteristics of a double blind study?

Patient nor researcher knows if they're receiving the drug

How are clinical trials typically funded?

Pharmaceutical companies, medical centers, voluntary groups

. If a non-China-based sponsor wants to conduct clinical trials in China, at what investigational stage must the product be in other countries?

Phase II

Describe the "safety" differences between prescription drug products and OTCs.

Possible toxicity in prescription

Who typically conducts clinical studies (principal investigator and scientific team).

Principal investigator: doctor Research team: doctors, nurses, social workers

Describe the types of human clinical trials conducted by a generic drug company for an ANDA submission. What is the goal of these studies? How many volunteers are typically included in these studies?

Product acts the same as original. Conducted using fewer than 100 patients.

Identify the 6 required components of a clinical study protocol

Reason for conducting study Eligibility criteria Number of participants needed Schedule of tests, procedures, drugs and their doses Length of study What info will be gathered about participants

Where are Phase I human clinical trials typically conducted? What is the background of the principal investigators?

Research centers by specially trained clinical pharmacologists

Phase I trials are typically "open label". What does this term mean?

Researchers and participants now what treatment is being administered

What quality standards do generic drug products need to meet?

Same as brand name

Where are Phase III trials typically performed?

Settings similar to those anticipated for the ultimate use of the drug

The product development and validation investigations conducted by a generic drug manufacturer are equivalent to what steps at what stage in the development of a brand name drug product?

Similar to preclinical IND filings. Some additional human testing to make sure it works

What dose is administered during Phase I trials (relative to estimated therapeutic dose)?

Single dose, or multiple doses over weeks

What are the typical doses used in Phase 0 trials?

Small, very low doses

Where are phase II trials performed?

Special clinical centers (university hospitals)

What is the background of the principal investigators typically involved in Phase III human clinical trials?

Specialists in the disease being treated

What information about a human clinical study is included on ClinicalTrials.gov

Study protocol, study locations, contact information

What is the "Belmont Report" and how are its content currently used and applied?

Summarizes the basic principles which underlie research Respect for persons, maximizing possible benefits, justice in sharing research with people, informed consent

What are the concerns about different regulatory standards in China for domestic (in country) drug products versus those produced for export?

That they can meet the demands of both exports and their citizens

What is the name of the drug regulatory agency in China?

The Chinese FDA

How are generic drugs able to enter the marketplace at a lower price than the brand name drug?

The discovery, preclinical and clinical studies do not need to be repeated. They do not have to participate in advertising and promotion.

What was the "Nuremburg Code" and what did it accomplish?

The first internationally recognized code of medical research ethics; increase protection of rights and welfare of human subjects

How many volunteers are typically involved in Phase 0 trials

10-25

What is the minimum number of years of patent protection for new drugs resulting from the Patient Protection and Affordable Care Act?

12 years

Which phase of human clinical testing has the highest drug failure rate?

2

. How many volunteers are typically included in Phase I clinical trials?

20-100

Describe the Tuskegee Study and identify the breaches in "ethical conduct" based on the current (2017) definitions of human subjects research.

300 black men with syphilis were followed to watch the disease and how it worked. They didn't know they had the disease and they weren't offered treatment

What is the typical review time period needed for marketing approval in Canada?

355 days

. What is the typical review time (NDA equivalent) for drug approval in Japan?

6 months to 2 years

What is the typical drug review (NDA equivalent) time in India?

A year

The regulatory application that is submitted for the approval of a generic drug is referred to as:

Abbreviated New Drug Application

What are the concerns regarding differing regulatory standards in India for domestically-produced and marketed drug products versus those produced for export?

Approval process: government organization responsible, be conducted in Indian population

Why is the IND review time in China longer than in the US?

Based in application back log and lack of personnel

Are Phase 0 trials conducted before or after the approval of the IND?

Before IND approval

What were the issues at the core of case in Wichita layers

Behaviors would change with knowledge if there was consent

What is the difference in naming between an "innovator/brand" drug and a generic drug?

Brand name drugs are supplied by one drug company and sold under a trademarked name Generic drugs may be supplied by multiple companies and sold under the name of the active ingredient

Studies of Brand and Generic drugs

Brand: bioavailability Generic: bioequivalence

Which South American country has the most developed drug regulatory and drug manufacturing sector?

Brazil

How is a "clinical trial" defined?

By phase

Which section of an IND is also required for an ANDA

CNC

What is the name of the drug regulatory agency in Mexico?

COFEPRIS: Federal commission for protection against sanitary risks

What effects do generic drugs have on drug process.

Causes drug prices to go down, when they lose the patent

What is the name of the drug regulatory agency in India?

Central Drug Standard Control Organization (CDSCO) and Drug Controller General of India (DCGI)

. Define the term "Clinical Study". What 2 types of research does this term include?

Clinical study involves using human volunteers to aid medical knowledge. Two types: clinical trials (interventional) and observational studies

What is an IRB - Institutional Review Board?

Committee of scientists and nonscientists at the local level that reviews protocol and consent forms to make sure that the rights of research subjects are protected

What are the characteristics of an OTC drug that assure its safety when used by the consumer?

Consumer can read label and figure out how to use Good safety margin, low potential for abuse Adequate labeling

. In December, 1946 a group of German scientists was on trial in Nuremburg for the unethical use of humans in experiments conducted during World War II. These trials stimulated what activities?

Creating ethical standards

What role does the Jurisdictional Formulary /Regional Review process play in the approval of drug products in Canada? Which type of drug product most frequently uses this process?

Decides whether a drug will be available in certain regions, used for generics or decides if brand will be evaulated

What is a unique requirement regarding the clinical trial populations when seeking drug approval in Japan?

Demand that clinical trials be conducted in Japanese volunteers only.

What components must be present in an OTC label? Are OTC labels reviewed by the FDA in the same way as for NDAs?

Desciption of active ingredients and purpose, uses, warnings, directions, other information, and inactive ingredients No, Isn't approved individually

How is the process of clinical trial evaluation different between Koseisho and the trial sponsor compared to the FDA and the trial sponsor?

Difference in Clinical trials are conducted and results evaluated. As soon as the trial starts, there is continuous feedback to regulatory body.

Are the volunteers in Phase II trials healthy or do they have the disease?

Disease

Describe the decentralized approval process that allows each country within the European Union to continue to approve drug products specifically for marketing in an individual country.

Each country works under ICH guidelines. Can each issue an approval without recognition from each of EU.

What are the primary goals/outcomes of Phase II clinical trials?

Effectiveness of treating disease

What is the EMA (including its full name)? When was it established?

European Medicine Agency, Established in 1995 in London

What are the goals/milestones of the Phase 0 trials? (What do the sponsors want to know about the drug?)

Evaluate potential differences in results from animals and cells and to confirm or reject the preclinical results before testing in larger populations

What are the primary goals/outcomes of Phase I trials?

Evaluate safety in humans

Why is it unethical to conduct human clinical trials to demonstrate the effectiveness of a generic drug product?

Exposing people to experimentation if you already know the answer is unethical

Key characteristics of Phase 0 trials

FDA allows testing in humans, evaluation of safety from animals to humans

What changes were made regarding informed consent as the result of the negative effects of thalidomide, an investigational drug in the US in the early 1960's?

FDA: investigators must inform potential subjects of the experimental status of the drug and obtain consent

How are Phase IV clinical trials different from Phase I-III trials?

Follow up studies for long term safety; post approval, ongoing

Describe how "Fast-track", "priority approval" and "accelerated approval", and the identification of "breakthrough" products contribute the accessibility of important new drug products before full clinical evaluation and FDA review has been completed.

For serious diseases, these can contribute to the accessibility to cures.

Describe the issues associated with India's state-controlled regulatory bodies in addition to the national regulatory agency.

Governmental structure isn't as nationalized; less power. Regional drug agencies operate under their own rules

What is the name of the drug regulatory approval agency in Canada?

Health Products and Food Branch of Health Canada

How many volunteers are typically involved in phase II clinical trials?

Hundreds

What is unique about a Phase IIIb clinical trial?

It is additional studies conducted to increase patient exposure, for additional questions after NDA filing

What is the name of the drug regulatory agency in Japan?

Koseisho

What are the primary goals/outcomes of Phase III clinical trials?

Larger scale safety and effectiveness

Describe how the incidents associated with the Wichita layers and their studies of jury behaviors were also impacted by the Nuremburg code and human research ethics, even if their activities did not involve research in the biomedical sciences.

Lawyers argue before juries Wanted to know how they come to conclusions Recorded six jurors without their consent, behavior would've been altered

In order for a disease to be classified as an "Orphan Disease", how many individuals in the US can be affected?

Less than 200,000

What is the typical review time (NDA equivalent) for drug approval in China?

Longer than six months

Which type of drug-induced effects are most likely to be first identified in Phase IV testing?

Low incidence drug effects

National Research Act

Make IRBs and explore ethics

Describe how ICH membership accomplishes global drug product importation

Many are manufactured in US. Switzerland has quality standards and location that make it a good source to import to.

What are the characteristics of the volunteers in Phase III trials?

Many patients with any disease

Briefly describe the goals of Phase IV human clinical testing. When does Phase IV commence?

Monitoring the safety of the new drug under actual conditions of use in large numbers of patients Starts when approval to market a drug has been obtained

What is an OTC monograph? How is the monograph developed?

Monograph has all clinical info for drug, standard for manufacturing, dosing and forms If has all, they can market it as OTC. GRASE: Generally recognized as safe and effective

What is the maximum number of days the EMA can take to review an "NDA" for marketing approval? When delay time is incorporated for additional information requests, what is the average time for drug product approval by the EMA?

Must be issued within 210 days Typical max product approval time is less than 358 days

Why is Puerto Rico the largest exporter of pharmaceutical products in the Central/Southern American region?

Their status as a territory of the US US provide tax incentives for Puerto Rico based exports

How many volunteers are typically included in Phase III clinical trials?

Thousands

How is bioequivalence demonstrated (experimentally measured) to demonstrate equivalence to the FDA.

Time it takes drug to travel to the highest plasma concentration

Why were independent committees of researchers originally formed to review research involving humans?

To review formed research from an ethical perspective

What does a "bioequivalence" test demonstrate to the FDA?

Two drug products provide same biological effects of user

What are 2 common reasons for drugs to fail in Phase I clinical trials?

Unexpected toxicity and ineffectiveness in humans

What are the characteristics of the volunteers who typically participate in Phase I trials?

Usually healthy, exception of cancer patients or chronically ill

What are 3 confounding factors known to contribute to variability in human clinical trials? Be able to provide a brief definition of each and how various types of trial designs can limit/overcome/address these variabilities.

Variable natural history of disease: crossover design Presence of other diseases and risk factors: crossover design Subject and observer bias: single blind studies

What types of materials can be included to provide "informed consent"?

Verbal instructions, question and answer sessions, activities

. What types of volunteers are usually used in bioequivalence studies?

Very small amounts

Briefly describe the major principles outlined in the Nuremburg Code.

Voluntary informed consent Experiments shouldn't be unnecessary or for no reason Should be tested on animals first Unnecessary pain should be avoided Licensed medical professionals Subjects should be permitted to withdrawal at any time Investigator should stop it if it endangers subject

Describe the pricing review process utilized in Canada. Note that pricing discussions take place during the review process and are finalized immediately prior to the final drug approval. Why do these pricing discussions take place?

What the government wants to make vs what the producer wants to make is negotiated. How much the government will pay for medication No similar treatment, it is set higher Cost effectiveness

When can a generic drug manufacturer bring a generic drug product into the commercial marketplace to compete against a brand name drug?

When a patent expires

What is an "observational study" in the context of human clinical research? Can interventions be involved in these studies?

Where an investigator assesses health outcomes in participants according to a research plan, participants can receive interventions or procedures as part of medical care, but are not assigned to specific interventions by investigator

Can a drug product be covered by more than 1 patent?

Yes, some have multiple

For OTCs, which products are exempt from these packaging requirements?

dermatologicals, dentifrices, insulin, lozenges