11.9 Summary and conclusions – • Safety pharmacology is concerned with the safety margin for a new drug (i.e., nature of the dose-limiting adverse event, the therapeutic indication, and the intended patient population), whether the toxicity is reversible and has a biomarker and its mechanism.

The liver is a primary site for observing safety issues from two points of view: compromise of the liver as a metabolizing organ for drugs with resulting drug–drug interactions and also direct hepatic cytotoxicity. • The reversibility of hepatic enzyme inhibition is important for assessing progress of candidate drug molecules.

• There are numerous in vitro cellular markers for cell viability that can indicate cytotoxicity. • Mutagenicity can be predicted in many cases with the Ames test, and hERG channel inhibition can predict serious lethal cardiotoxicity. • Activity on autonomic receptors should be carried out in functional receptor assays where possible.

What is the definition of drug safety?

ESTIMATION OF INITIAL SAFETY AND TOLERABILITY – Drug safety refers to the frequency of adverse drug effects (i.e., physical or laboratory toxicity that could possibly be related to the drug) that are treatment emergent—that is, they emerge during treatment and were not present before treatment, or they become worse during treatment compared with the pretreatment state.

An adverse drug effect is distinguished from an adverse event (or experience), which refers to any untoward experience that occurs while a patient is receiving the medication, whether or not it is attributable to the drug. The seriousness of an adverse event dictates how quickly it must be reported to regulatory agencies and to others who may have ongoing experimental protocols.

A serious adverse event is defined as one that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect.

• Investigators conducting pharmaceutical industry–sponsored studies should be aware that companies may have their own, more strict definition of serious adverse events.
• The term severity is distinguished from serious in that severity refers to the intensity of a specific event, whereas serious refers to the outcome or consequences of the event.

Drug tolerability refers to how well subjects are able to tolerate overt adverse drug effects. Read full chapter URL: https://www.sciencedirect.com/science/article/pii/B978141606581410007X

What determines the safety of a drug?

Therapeutic Index The Therapeutic Index (TI) is used to compare the therapeutically effective dose to the toxic dose of a pharmaceutical agent. The TI is a statement of relative safety of a drug. It is the ratio of the dose that produces toxicity to the dose needed to produce the desired therapeutic response. For example, if the TD50 is 200 and the ED50 is 20 mg, the TI would be 10. A clinician would consider a drug safer if it had a TI of 10 than if it had a TI of 3 (Figure 1). Figure 1. A higher value on the Therapeutic Index indicates a more favorable safety profile (Image Source: ORAU, ©) However, the use of the ED50 and TD50 doses to derive the TI may be misleading about a drug’s safety, depending on the slope of the dose-response curves for therapeutic and toxic effects. The graph in Figure 2 shows the relationship between effective dose response and toxic dose response. The shaded area represents the doses at which the substance produces an effective dose response while the toxic dose response remains below the TD50. The slope of a curve shows how dose increases result in responses to the effective or toxic dose. Figure 2. Relationship between effective dose response and toxic dose response (Image Source: NLM) Because of differences in slopes and threshold doses, low doses may be effective without producing toxicity. Although more patients may benefit from higher doses, that is offset by the probability that toxicity will occur. Figure 3. Comparison of the toxicity of two substances (Image Source: NLM) For some substances, a small increase in dose causes a large increase in response, which is seen in Toxicant A’s steep slope. For other substances, a much larger increase in dose is required to cause the same increase in response, as indicated in Toxicant B’s shallow slope.

What is the difference between safety and efficacy?

Obviously, a drug (or any medical treatment) should be used only when it will benefit a patient. Benefit takes into account both the drug’s ability to produce the desired result (efficacy) and the type and likelihood of adverse effects (safety).

What is the 2 difference between drug safety and pharmacovigilance?

Difference between Drug Safety and Pharmacovigilance Drug Safety & Pharmacovigilance are receiving more attention than any these days. “Drug Safety and Pharmacovigilance” is not a single term. There is a slight difference between “Drug Safety” and In short, we can say one is reactive, and the other is proactive.

The two words Drug Safety and Pharmacovigilance can be used conversely – the same primary role is being performed. But Pharmacovigilance is more encompassing and more strategic. Feel free to share this article with your colleagues. This not only shows that you have the expertise needed for the job or the project, but certifications also showcases your dedication towards what you do, giving credible proof that you have full fledged knowledge on the topic.

What is another word for Drug Safety?

Pharmacovigilance (PV, or PhV), also known as drug safety, is the pharmaceutical science relating to the ‘collection, detection, assessment, monitoring, and prevention’ of adverse effects with pharmaceutical products.

What is Drug Safety and effectiveness?

Obviously, a drug (or any medical treatment) should be used only when it will benefit a patient. Benefit takes into account both the drug’s ability to produce the desired result (efficacy) and the type and likelihood of adverse effects (safety).

What is the difference between toxicity and safety?

Clinical Benefit, Safety, and Toxicity In deciding whether or not to approve a new drug, is primarily concerned with the drug’s effectiveness and safety. A successful drug will benefit patients without causing disproportionate harm. In order to be considered effective by the FDA and physicians, a new drug must demonstrate the ability to improve at least one of the following: the way a patient feels, functions, or survives.

If a new drug can demonstrate that it produces at least one of these three outcomes, it can be said to provide clinical benefit, FDA reviewers weigh a drug’s clinical benefits against its in order to determine whether or not it should be approved. The type of clinical benefit that drug developers expect an experimental drug to provide plays a major role in guiding and the selection of,

An endpoint measures clinical benefit. Toxicity refers to a drug’s potential to cause harm to a patient. While extremely toxic drugs are rarely approved for use, analyzing a drug’s safety is more complicated than determining whether or not it has any harmful side effects.

1. Regulators must decide whether a drug’s benefits outweigh its potential harms.
2. If a mild painkiller has the potential to cause liver damage, for example, that would likely be deemed an unreasonable risk.
3. On the other hand, a cancer drug with the same potential side effect might be considered reasonably safe, due to the severity of the condition being treated.

: Clinical Benefit, Safety, and Toxicity

What is safety monitoring of drugs?

Drug safety monitoring is a risk mitigation exercise in which the ADRs caused by therapeutic drugs, biologicals or devices can explored, prevented or minimized.

How does the FDA determine if a drug is safe?

Developing New Drugs – American consumers benefit from having access to the safest and most advanced pharmaceutical system in the world. The main consumer watchdog in this system is FDA’s Center for Drug Evaluation and Research (CDER). The center’s best-known job is to evaluate new drugs before they can be sold.

1. CDER’s evaluation not only prevents quackery, but also provides doctors and patients the information they need to use medicines wisely.
2. The center ensures that drugs, both brand-name and generic, work correctly and that their health benefits outweigh their known risks.
3. Drug companies seeking to sell a drug in the United States must first test it.

The company then sends CDER the evidence from these tests to prove the drug is safe and effective for its intended use. A team of CDER physicians, statisticians, chemists, pharmacologists, and other scientists reviews the company’s data and proposed labeling.

If this independent and unbiased review establishes that a drug’s health benefits outweigh its known risks, the drug is approved for sale. The center doesn’t actually test drugs itself, although it does conduct limited research in the areas of drug quality, safety, and effectiveness standards. Before a drug can be tested in people, the drug company or sponsor performs laboratory and animal tests to discover how the drug works and whether it’s likely to be safe and work well in humans.

Next, a series of tests in people is begun to determine whether the drug is safe when used to treat a disease and whether it provides a real health benefit. For more information about the drug development and approval process, see How Drugs Are Developed and Approved,

What is safety in clinical trials?

2.2. Communicating Safety Information among Stakeholders – Timely communication among the various stakeholders is critical to ensure subject safety in clinical trials. Sponsors of clinical trials are accountable for monitoring the subjects appropriately, including the requirement of long-term follow up as appropriate.

The protocol (including the ICF) specifies the details of the assessments, the frequency and the length of follow-up. In addition, most pharmaceutical sponsors have Standard Operating Procedures (SOPs) in place to collect, process, review, evaluate, report and communicate accumulating safety data to ensure a systematic approach for safety surveillance and monitoring.

In general, safety information, including adverse events and laboratory findings are reported to a sponsor by investigators conducting the clinical trial. However, safety information may come from sources outside the immediate clinical trial. The sponsor is required to promptly review all information relevant to the safety of the drug and to update subjects, investigators, IRBs and regulatory authorities of any new risks associated with the use of the investigational drug that arise from the clinical trial or from other sources.

Amending the clinical trial protocol is one way to implement procedural changes that are necessary given the updated safety information. Another way to communicate the evolving safety information is through the periodic update of the Investigator’s Brochure (IB). The IB is a compilation of the clinical and non-clinical data on the investigational drug that are relevant to the study of the drug in human subjects.

Its purpose is to provide the investigators and others involved in the trial with the information to facilitate their understanding of the rationale for and their compliance with many key features of the protocol, such as the dose, dose frequency/interval, methods of administration and safety monitoring procedures,

The IB should be reviewed at least annually and revised as necessary in compliance with the sponsor’s written procedures and the local requirements. A new safety finding that represents a significant risk to study subjects should be communicated to the investigators immediately, along with an update to the IB and possibly to the protocol and the ICF.

For trials where DSMBs are in place, sponsors should also communicate significant safety findings to the DSMBs employed to oversee clinical trials of the same or similar investigational drug(s). In other situations, DSMBs may be in possession of critical safety information and they will need to follow the DSMB charter and the protocol to make recommendations to the sponsor with regard to its safety findings and whether the trial should continue as planned.

1. The goal of safety monitoring in clinical trials is to identify, evaluate, minimize and appropriately manage risks.
2. In Europe, Risk Management Plans (RMPs) are required by the EMA as part of the drug approval process.
3. An RMP includes a summary of important identified risks of the drug, potential risks and missing information, which serves as the basis for an action plan for pharmacovigilance and risk minimization activities.

The CIOMS VI working group recommended establishing a multidisciplinary Safety Management Team (SMT) within the sponsor organization to be in charge of safety surveillance and decision making on risk management and minimization activities. The SMT is responsible for coordinating all safety-related activities involving quantitative assessment of risks, signal detection and identification of adverse events of special interest (AESIs).

For trials in earlier stages without DSMBs, sponsors may choose to appoint an internal multi-functional data review team removed from the direct day-to-day trial operations related to the investigational drug to perform ongoing review of the safety data. This independent data review team is empowered to perform similar functions as the DSMB on later stage trials.

The CIOMS VI working group endorsed the use of the Development Core Safety Information (DCSI) as the summary of the identified safety issues for an investigational drug. DCSI was recommended to be a part of the IB that defines the list of suspected adverse reactions.

Safety issues or adverse drug reactions contained in this document should be considered “expected” for regulatory reporting purposes. Only suspected adverse drug reactions that are both serious and unexpected are subject to expedited case reporting to regulatory authorities in either seven (fatal or life-threatening) or 15 calendar days.

Slightly different terminologies exist, including Suspected Unexpected Serious Drug Reaction (SUSAR) or Serious Unexpected Suspected Drug Reaction, Contrary to the routine expedited case reporting to regulatory authorities, the CIOMS VI working group recommended sponsors provide periodic updates of the evolving benefit/risk profile and highlight important new safety information to the participating investigators and IRBs.

However, in some regions, expedited case reporting to investigators and IRBs are still required by local regulations. Regulatory authorities also require reporting of safety information in the aggregate rather than the individual cases. In the US, the FDA IND regulations require annual IND reports, which include aggregate safety information across the entire development program of an investigational drug.

CIOMS VI working group recommended defining a single Development Safety Update Report (DSUR) for submission to regulators on an annual basis. For submission of New Drug Applications (NDAs), sponsors aggregate safety information from all relevant trials of the drug to perform integrated safety analyses in support of the filing for marketing authorization.

The common data structure using SDTM (Standard Data Tabulation Model) defined by Clinical Data Interchange Standards Consortium (CDISC) has greatly facilitated the safety data integration and analyses. It also enables sponsors to build a safety data warehouse to better respond to safety related queries across the entire drug program.

Proactive early planning of safety analyses in a Program Safety Analysis Plan (PSAP) and periodic aggregate safety analyses have been recommended as standard industry practices, The PSAP is a living document that will form the basis for integrated safety analyses in an NDA.

What is safety and clinical effectiveness?

Dorset HealthCare is committed to ensuring that the care we provide is evidence-based, effective and founded on the principles of good practice. Clinical effectiveness includes monitoring and improving the outcomes of patients and service users, and also involves:

ensuring health professionals are up-to-date in their practices and properly supervised where necessary implementation of best practice including National Institute for Health and Care Excellence (NICE) guidance and quality standards and implementation of care pathways involvement in local and national clinical audits.

The Trust has also implemented projects to capture patient reported outcomes or goals to ensure that services are working in partnership with service users/patients in working towards their own goals.

Which is better efficiency or efficacy?

Efficacy is getting things done. It is the ability to produce a desired amount of the desired effect, or success in achieving a given goal. Efficiency is doing things in the most economical way. It is the ratio of the output to the inputs of any system (good input to output ratio).

Is pharmacovigilance and drug safety the same thing?

Pharmacovigilance is also known as drug safety and is defined by the World Health Organization as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems,.

What are the 3 major components of pharmacovigilance?

The major components of a pharmacovigilance system are data collection, which can be passive, active, or man- datory, and data analysis and reporting.

What is drug in one word?

A. : a substance used as a medication or in the preparation of medication. b according to the Food, Drug, and Cosmetic Act. (1) : a substance recognized in an official pharmacopoeia or formulary (see formulary sense 3)

What is one word for drug addict?

synonyms for drug addict –

addict drug user junkie user burnout dopehead doper drug abuser drug fiend druggie freak hophead narcotics addict space cadet

On this page you’ll find 17 synonyms, antonyms, and words related to drug addict, such as: addict, drug user, junkie, user, burnout, and dopehead.

What is another word for clean off drugs?

What is another word for off drugs?

What is the margin of safety of drugs?

The difference between the usual effective dose and the dose that causes severe or life-threatening side effects is called the margin of safety.

Why is drug safety evaluation important?

Drug safety evaluation – Expert Collection Drug Safety Evaluations focus on providing an independent perspective on the safety of a specific drug. The purpose of the Drug Safety Evaluation is to promote best practice in use of the drug and should therefore be limited to approved indications and avoid off-label discussion.

• The word limit for Drug Safety Evaluations is 3,000 words.
• Titles should be concise but informative, and contain no brand names.
• They should also be impartial and non-promotional.
• Including address, academic qualifications and job titles of all authors, as well as telephone number, fax number and email address of the author for correspondence on a separate cover sheet as the peer reviewers will be blinded to the authors’ identity.

Please note that only the address of the first author of the article will appear on Medline/PubMed, not necessarily the corresponding author. Maximum 200 words.The aim of the abstract is to draw in the interested reader and provide an accurate reflection of the content of the paper.

• Introduction: Authors are required to describe the significance of the topic under discussion.
• Areas covered: Authors are required to describe the research discussed and the literature search undertaken.
• Expert Opinion: Authors are required to summarize briefly their Expert Opinion section.
• References must not be included in the abstract.

A brief list of keywords, in alphabetical order, is required to assist indexers in cross-referencing. The keywords will encompass the therapeutic area, mechanism(s) of action, key compounds etc. Incorporating basic information on disease incidence and prevalence, unmet medical need and present treatment guidelines (highlighting regional variations where appropriate).

1. Body of review:
2. Safety evaluation (note, this section should form the main part of the review):
3. Comparison with safety of other drugs:
4. Conclusion:

– Mechanism of action, including key PK/PD data – Clinical applications, including key efficacy data– Safety in clinical studies– Postmarketing data– Safety in special populations, including pharmacogenomic data if availableInclude a table comparing data if appropriateAn analysis of the data presented in the review To distinguish reviews published in the series of journals, authors must provide an additional section entitled Expert Opinion.

1. This section affords authors the opportunity to go beyond the conclusion and provide their interpretation of the data presented in the article.
2. Authors should answer the following: 1.
3. What, if any, improvement does the drug hold over other therapies? 2.
4. What, if any, impact is this drug likely to have on current treatment strategies? 3.

How likely are physicians to prescribe the drug? 4. What data is still needed? 5. Where is the drug likely to be in five years’ time? Please note that ‘opinions’ are encouraged in the Expert Opinion section, and as such, referees are asked to keep this in mind when peer reviewing the manuscript. A maximum of 100 references is suggested. Ensure that all key work relevant to the topic under discussion is cited in the text and listed in the bibliography. Reference to unpublished data should be kept to a minimum and authors must obtain a signed letter of permission from cited persons to use unpublished results or personal communications in the manuscript.

What is the goal of medication safety?

Reduce harm to people from medications through safe and effective medication management. What is the problem that needs to be addressed? Adverse medicines events can affect a consumer’s health in a range of ways, from a mild allergic reaction to death.

What is drug safety or pharmacovigilance?

Pharmacovigilance vs. Drug Safety Identifying key differences between PV and drug safety. Often the question, “what is the difference between pharmacovigilance and drug safety?” comes up around both our Pharmaceutical Executive and Applied Clinical Trials content.

• Here, I offer a comparison definition taken from a slide deck from our friends at PhysIQ: Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other medicine/vaccine related problem.
• It is proactive, and focused on signal interpretation.

Drug safety refers to the frequency of adverse drug effects (ie., physical or laboratory toxicity that could possibly be related to the drug) that are treatment-emergent. That is, they emerge during treatment and were not present before it, or they become worse during treatment compared with the pre-treatment state.

It is reactive and focused on compliance reporting. In this recent Applied Clinical Trials, Beth MacEntee Pileggi, head of global case and safety data management with Janssen Pharmaceuticals, and co-lead of TransCelerate BioPharma’s Pharmacovigilance Agreements Optimization Initiative, explained that 20 to 30 years ago, the role was called drug safety.

But the therapeutic landscape has changed drastically; increasing regulatory requirements and new novel medicinal products—and not just the compounds, but also with delivery systems and multiple combination products. “All of this adds layers of complexity,” said Pileggi.

Pharmacovigilance brings in other aspects of managing a drug’s risk profile, so it’s not just about the benefits, but also about the risks.” Drug safety in clinical trials, however, remains its own regulatory segment, though both clinical and commercial teams may work together, depending on the pharma company.

At the same time, there is a computing/analytics movement within the PV space to create opportunities within the actual PV function or externally. For example, Pileggi notes that internally is a better way to receive, process, manage, evaluate, and monitor the multitude of incoming PV data to evaluate and aggregate insights.

• Externally, many are looking at the trove of PV data to inform real-world evidence, clinical trial design, drug discovery, and improve clinical care or interventions of same, plus many more.
• Drug safety is not just a regulatory obligation; it now has the potential to change the world of therapeutics and clinical care for more positive patient outcomes.

: Pharmacovigilance vs. Drug Safety

What is the standard definition of drug?

In pharmacology, a drug is a chemical substance, typically of known structure, which, when administered to a living organism, produces a biological effect. A pharmaceutical drug, also called a medication or medicine, is a chemical substance used to treat, cure, prevent, or diagnose a disease or to promote well-being.

What is definition drug in simple words?

Any substance (other than food) that is used to prevent, diagnose, treat, or relieve symptoms of a disease or abnormal condition. Drugs can also affect how the brain and the rest of the body work and cause changes in mood, awareness, thoughts, feelings, or behavior.

What is drug definition 21 CFR?

CFR – Code of Federal Regulations Title 21 (a) The definitions and interpretations contained in section 201 of the Federal Food, Drug, and Cosmetic Act apply to those terms when used in this part and part 320 of this chapter. (b) The following definitions of terms apply to this part and part 320 of this chapter: 180-day exclusivity period is the 180-day period beginning on the date of the first commercial marketing of the drug (including the commercial marketing of the reference listed drug) by any first applicant.

The 180-day period ends on the day before the date on which an ANDA submitted by an applicant other than a first applicant could be approved.505(b)(2) application is an NDA submitted under section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act for a drug for which at least some of the investigations described in section 505(b)(1)(A) of the Federal Food, Drug, and Cosmetic Act and relied upon by the applicant for approval of the NDA were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.

Abbreviated application, abbreviated new drug application, or ANDA is the application described under § 314.94, including all amendments and supplements to the application. Acknowledgment letter is a written, postmarked communication from FDA to an applicant stating that the Agency has determined that an ANDA is sufficiently complete to permit a substantive review.

1. An acknowledgment letter indicates that the ANDA is regarded as received.
2. Act is the Federal Food, Drug, and Cosmetic Act (section 201 et seq.
3. 21 U.S.C.301 et seq.)).
4. Active ingredient is any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals.

The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.

• Active moiety is the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance.
• ANDA holder is the applicant that owns an approved ANDA.
• Applicant is any person who submits an NDA (including a 505(b)(2) application) or ANDA or an amendment or supplement to an NDA or ANDA under this part to obtain FDA approval of a new drug and any person who owns an approved NDA (including a 505(b)(2) application) or ANDA.

Application, new drug application, or NDA is the application described under § 314.50, including all amendments and supplements to the application. An NDA refers to “stand-alone” applications submitted under section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act and to 505(b)(2) applications.

1. Approval letter is a written communication to an applicant from FDA approving an NDA or an ANDA.
2. Assess the effects of the change is to evaluate the effects of a manufacturing change on the identity, strength, quality, purity, and potency of a drug product as these factors may relate to the safety or effectiveness of the drug product.
3. Authorized generic drug is a listed drug, as defined in this section, that has been approved under section 505(c) of the Federal Food, Drug, and Cosmetic Act and is marketed, sold, or distributed directly or indirectly to the retail class of trade with labeling, packaging (other than repackaging as the listed drug in blister packs, unit doses, or similar packaging for use in institutions), product code, labeler code, trade name, or trademark that differs from that of the listed drug.

Bioavailability is the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of drug action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by scientifically valid measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of drug action.

Bioequivalence is the absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study.

Where there is an intentional difference in rate (e.g., in certain extended-release dosage forms), certain pharmaceutical equivalents or alternatives may be considered bioequivalent if there is no significant difference in the extent to which the active ingredient or moiety from each product becomes available at the site of drug action.

This applies only if the difference in the rate at which the active ingredient or moiety becomes available at the site of drug action is intentional and is reflected in the proposed labeling, is not essential to the attainment of effective body drug concentrations on chronic use, and is considered medically insignificant for the drug.

For drug products that are not intended to be absorbed into the bloodstream, bioequivalence may be assessed by scientifically valid measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of drug action.

• Bioequivalence requirement is a requirement imposed by FDA for in vitro and/or in vivo testing of specified drug products that must be satisfied as a condition of marketing.
• Class 1 resubmission is the resubmission of an NDA or efficacy supplement, following receipt of a complete response letter, that contains one or more of the following: Final printed labeling, draft labeling, certain safety updates, stability updates to support provisional or final dating periods, commitments to perform postmarketing studies (including proposals for such studies), assay validation data, final release testing on the last lots used to support approval, minor reanalyses of previously submitted data, and other comparatively minor information.
• Class 2 resubmission is the resubmission of an NDA or efficacy supplement, following receipt of a complete response letter, that includes any item not specified in the definition of “Class 1 resubmission,” including any item that would require presentation to an advisory committee.

Commercial marketing is the introduction or delivery for introduction into interstate commerce of a drug product described in an ANDA, outside the control of the ANDA applicant, except that the term does not include transfer of the drug product for investigational use under part 312 of this chapter or transfer of the drug product to parties identified in the ANDA for reasons other than sale.

Commercial marketing includes the introduction or delivery for introduction into interstate commerce of the reference listed drug by the ANDA applicant. Complete response letter is a written communication to an applicant from FDA usually describing all of the deficiencies that the Agency has identified in an NDA or ANDA that must be satisfactorily addressed before it can be approved.

Component is any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product. Date of approval is the date on the approval letter from FDA stating that the NDA or ANDA is approved, except that the date of approval for an NDA described in section 505(x)(1) of the Federal Food, Drug, and Cosmetic Act is determined as described in section 505(x)(2) of the Federal Food, Drug, and Cosmetic Act.

1. Dosage form is the physical manifestation containing the active and inactive ingredients that delivers a dose of the drug product. This includes such factors as:
2. (1) The physical appearance of the drug product;
3. (2) The physical form of the drug product prior to dispensing to the patient;
4. (3) The way the product is administered; and
5. (4) The design features that affect frequency of dosing.

Drug product is a finished dosage form, e.g., tablet, capsule, or solution, that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients.

• Drug substance is an active ingredient that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the human body, but does not include intermediates used in the synthesis of such ingredient.
• Efficacy supplement is a supplement to an approved NDA proposing to make one or more related changes from among the following changes to product labeling:
• (1) Add or modify an indication or claim;
• (2) Revise the dose or dose regimen;
• (3) Provide for a new route of administration;
• (4) Make a comparative efficacy claim naming another drug product;
• (5) Significantly alter the intended patient population;
• (6) Change the marketing status from prescription to over-the-counter use;
• (7) Provide for, or provide evidence of effectiveness necessary for, the traditional approval of a product originally approved under subpart H of this part; or
• (8) Incorporate other information based on at least one adequate and well-controlled clinical study.
• FDA or Agency is the Food and Drug Administration.
• First applicant is an ANDA applicant that, on the first day on which a substantially complete application containing a paragraph IV certification is submitted for approval of a drug, submits a substantially complete application that contains, and for which the applicant lawfully maintains, a paragraph IV certification for the drug.
• Inactive ingredient is any component other than an active ingredient.

Listed drug is a new drug product that has been approved under section 505(c) of the Federal Food, Drug, and Cosmetic Act for safety and effectiveness or under section 505(j) of the Federal Food, Drug, and Cosmetic Act, which has not been withdrawn or suspended under section 505(e)(1) through (5) or section 505(j)(6) of the Federal Food, Drug, and Cosmetic Act, and which has not been withdrawn from sale for what FDA has determined are reasons of safety or effectiveness.

Listed drug status is evidenced by the drug product’s identification in the current edition of FDA’s “Approved Drug Products With Therapeutic Equivalence Evaluations” (the list) as an approved drug. A drug product is deemed to be a listed drug on the date of approval for the NDA or ANDA for that drug product.

NDA holder is the applicant that owns an approved NDA. Newly acquired information is data, analyses, or other information not previously submitted to the Agency, which may include (but is not limited to) data derived from new clinical studies, reports of adverse events, or new analyses of previously submitted data (e.g., meta-analyses) if the studies, events, or analyses reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA.

Original application or original NDA is a pending NDA for which FDA has never issued a complete response letter or approval letter, or an NDA that was submitted again after FDA had refused to file it or after it was withdrawn without being approved. Paragraph IV acknowledgment letter is a written, postmarked communication from FDA to an applicant stating that the Agency has determined that a 505(b)(2) application or ANDA containing a paragraph IV certification is sufficiently complete to permit a substantive review.

A paragraph IV acknowledgment letter indicates that the 505(b)(2) application is regarded as filed or the ANDA is regarded as received. Paragraph IV certification is a patent certification of invalidity, unenforceability, or noninfringement described in § 314.50(i)(1)(i)(A)( 4 ) or § 314.94(a)(12)(i)(A)( 4 ).

Patent owner is the owner of the patent for which information is submitted for an NDA. Pharmaceutical alternatives are drug products that contain the identical therapeutic moiety, or its precursor, but not necessarily in the same amount or dosage form or as the same salt or ester. Each such drug product individually meets either the identical or its own respective compendial or other applicable standard of identity, strength, quality, and purity, including potency and, where applicable, content uniformity, disintegration times, and/or dissolution rates.

Pharmaceutical equivalents are drug products in identical dosage forms and route(s) of administration that contain identical amounts of the identical active drug ingredient, i.e., the same salt or ester of the same therapeutic moiety, or, in the case of modified-release dosage forms that require a reservoir or overage or such forms as prefilled syringes where residual volume may vary, that deliver identical amounts of the active drug ingredient over the identical dosing period; do not necessarily contain the same inactive ingredients; and meet the identical compendial or other applicable standard of identity, strength, quality, and purity, including potency and, where applicable, content uniformity, disintegration times, and/or dissolution rates.

1. Postmark is an independently verifiable evidentiary record of the date on which a document is transmitted, in an unmodifiable format, to another party.
2. For postmarks made by the U.S.
3. Postal Service or a designated delivery service, the date of transmission is the date on which the document is received by the domestic mail service of the U.S.

Postal Service or by a designated delivery service. For postmarks documenting an electronic event, the date of transmission is the date (in a particular time zone) that FDA sends the electronic transmission on its host system as evidenced by a verifiable record.

If the sender and the intended recipient are located in different time zones, it is the sender’s time zone that provides the controlling date of electronic transmission. Reference listed drug is the listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its ANDA.

Reference standard is the drug product selected by FDA that an applicant seeking approval of an ANDA must use in conducting an in vivo bioequivalence study required for approval. Resubmission, in the context of a complete response letter, is submission by the applicant of all materials needed to fully address all deficiencies identified in the complete response letter.

1. An NDA or ANDA for which FDA issued a complete response letter, but which was withdrawn before approval and later submitted again, is not a resubmission.
2. Right of reference or use is the authority to rely upon, and otherwise use, an investigation for the purpose of obtaining approval of an NDA, including the ability to make available the underlying raw data from the investigation for FDA audit, if necessary.

Same drug product formulation is the formulation of the drug product submitted for approval and any formulations that have minor differences in composition or method of manufacture from the formulation submitted for approval, but are similar enough to be relevant to the Agency’s determination of bioequivalence.

Specification is the quality standard ( i.e., tests, analytical procedures, and acceptance criteria) provided in an approved NDA or ANDA to confirm the quality of drug substances, drug products, intermediates, raw materials, reagents, components, in-process materials, container closure systems, and other materials used in the production of a drug substance or drug product.

For the purpose of this definition, acceptance criteria means numerical limits, ranges, or other criteria for the tests described. Strength is the amount of drug substance contained in, delivered, or deliverable from a drug product, which includes: (1)(i) The total quantity of drug substance in mass or units of activity in a dosage unit or container closure (e.g., weight/unit dose, weight/volume or weight/weight in a container closure, or units/volume or units/weight in a container closure); and/or, as applicable.

Ii) The concentration of the drug substance in mass or units of activity per unit volume or mass (e.g., weight/weight, weight/volume, or units/volume); or (2) Such other criteria the Agency establishes for determining the amount of drug substance contained in, delivered, or deliverable from a drug product if the weights and measures described in paragraph (i) of this definition do not apply (e.g., certain drug-device combination products for which the amount of drug substance is emitted per use or unit time).

Substantially complete application is an ANDA that on its face is sufficiently complete to permit a substantive review. Sufficiently complete means that the ANDA contains all the information required under section 505(j)(2)(A) of the Federal Food, Drug, and Cosmetic Act and does not contain a deficiency described in § 314.101(d) and (e).

Tentative approval is notification that an NDA or ANDA otherwise meets the requirements for approval under the Federal Food, Drug, and Cosmetic Act, but cannot be approved because there is a 7-year period of orphan exclusivity for a listed drug under section 527 of the Federal Food, Drug, and Cosmetic Act and § 316.31 of this chapter, or that a 505(b)(2) application or ANDA otherwise meets the requirements for approval under the Federal Food, Drug, and Cosmetic Act, but cannot be approved until the conditions in § 314.107(b)(1)(iii), (b)(3), or (c) are met; because there is a period of exclusivity for the listed drug under § 314.108; because there is a period of pediatric exclusivity for the listed drug under section 505A of the Federal Food, Drug, and Cosmetic Act; because there is a period of exclusivity for the listed drug under section 505E of the Federal Food, Drug, and Cosmetic Act; or because a court order pursuant to 35 U.S.C.271(e)(4)(A) orders that the NDA or ANDA may be approved no earlier than the date specified.

A drug product that is granted tentative approval is not an approved drug and will not be approved until FDA issues an approval letter after any necessary additional review of the NDA or ANDA. The list is the list of approved drug products published in FDA’s current “Approved Drug Products With Therapeutic Equivalence Evaluations,” available electronically on FDA’s Web site at http://www.fda.gov/cder,

Jack Gloop