Regulatory requirements for drug approval – Industrial Pharmacy II B. Pharma 7th semester PDF Notes

Regulatory Requirements for Drug Approval

Regulatory Requirements for Drug Approval

Regulatory Requirements for Drug Approval

Regulatory requirements for drug approval are stringent standards and processes established by regulatory agencies to ensure the safety, efficacy, and quality of pharmaceutical products before they are allowed on the market. They are necessary to protect public health.

The development and approval of new drugs are crucial for addressing medical needs, improving patient care, and advancing medical science. However, ensuring the safety and effectiveness of these drugs is paramount.

Non-clinical/pre-clinical drug development

  • This phase primarily aims to identify which candidate therapy has the greatest probability of success, assess its safety, and build solid scientific foundations before transitioning to the clinical development phase.
  • The drug candidate should meet non-medical objectives, including defining the intellectual property rights and making enough medicinal product available for clinical trials.
  • The non-clinical development of a medicine is complex and regulatory-driven.

Studies in non-clinical development are performed:

  • In silico: ‘performed on computer or via computer simulation’, e.g. predicting the toxicology profile of a product using its chemical structure from data-based approaches.
  • In vitro (Latin for ‘within the glass’): performing a procedure in a controlled environment outside of a living organism, e.g. use of hepatocyte (cells from the liver) cultures for metabolism studies.
  • In vivo (Latin for ’within the living’): experimentation using a whole, living organism as opposed to tissues or cells, i.e. animals, humans or plants.


  • Once a candidate compound is identified, the non-clinical development should start answering the following questions, and answers will come from specific assessments/studies:
  • Does it work? → Efficacy assessment
  • How will it be delivered and how will the body react? →profiling
  • Is it safe? → toxicology/safety
  • Is the manufacture viable and controllable?

Non-clinical development activities can continue throughout the life-cycle of the product, although the earlier these questions are answered, the easier it is to identify the profile of the patient who will benefit most.

  • Provide individual study reports, including pharmacology, toxicology, ADME studies.
  • Effects related to the therapeutic indication, such as the pharmacodynamics ED50 in dose-ranging studies and the mechanism of action (if known)
  • Interactions with other drugs (or cross-reference the location of the information in any of the above subsection

Human Pharmacokinetics and bioavailability

  • Data from Phase I safety and tolerance studies in healthy volunteers
  • Summary of analytical method used in the in-vivo bio-pharmaceutic study
  • Pilot or background studies
  • Bio-availibility or bioequivalence studies
  • Pharmacokinetic studies
  • In vitro studies


Includes for the anti-infective drug product. It requires the following technical information and data:-

  • A complete description of the biochemical basis of the drug action on microbial physiology
  • The drugs antimicrobial spectrum
  • Describe any known mechanism of resistance to the drug and provide information/data of any known epidemiologic studies demonstrating the prevalence to resistance factor
  • Clinical microbiology laboratory methods

Assure the sterility of the product through the manufacturing process – especially important with injectable drug products.

Safety Data

  • Statements in draft labeling
  • Contraindications
  • Warnings
  • Precautions
  • Adverse events

Statistical Data

  • All controlled clinical trial reports
  • Integrated efficacy and safety summaries
  • Integrated summary of risks and benefits
  • CASE REPORT TABULATION:- Includes complete tabulation for each patient from every adequate well-controlled phase II and Phase III efficacy, clinical pharmacology study. It also tabulation of safety data from all clinical studies.
  • CASEREPORT  FORMS:-  Includes the complete CRF for each patient who died during a clinical study or adverse event, regardless of whether the AE is considered to be related to the study drug, even if the patient was receiving a placebo or comparative drug.


 Assure manufacturing facilities are in compliance with current good manufacturing practices (cGMPs)

 Assure bioequivalence sites are in compliance with current good clinical practices (cGCPs)

 Conducted primarily by Field/Office of Regulatory Affairs with support from Center (Office of Compliance) and assigned geographically

 Labs are in the Office of Regulatory Affairs and the Center


  • A generic drug is considered to be bioequivalent to the brandname drug if:
  • The rate and extent of absorption do not show a significant difference from listed drug, or
  • The extent of absorption does not show a significant difference and any difference in rate is intentional or not medically significant.

Regulation by government agencies

  • Concerns related to the efficacy and safety of drugs have caused most governments to develop regulatory agencies to oversee the development and marketing of drug products and medical devices.
  • Use of any drug carries with it some degree of risk of an adverse event. For most drugs the risk-to-benefit ratio is favorable; that is, the benefit derived from using the drug far outweighs the risk incurred from its use. However, there have been unfortunate circumstances in which drugs have caused considerable harm.
  • The harm has come from drug products containing toxic impurities, from drugs with unrecognized severe adverse reactions, from adulterated drug products, and from fake or counterfeit drugs.
  • Because of these issues, effective drug regulation is required to ensure the safety and efficacy of drugs for the general public.
  • The process of drug regulation has evolved over time.
  • Laws regulating drug marketing and development, government regulatory agencies with oversight of drug development and use, drug evaluation boards, drug information centres, and quality control laboratories have become part of the cooperative venture that produces and develops drugs.
  • In some countries drug laws omit or exempt certain areas of pharmaceutical activity from regulation. For example, some countries exempt herbal or homeopathic products from regulation.
  • In other countries, there is very little regulation imposed on drug importation. Over time, the scope of drug laws and the authority vested in regulatory agencies have gradually expanded.
  • In some instances, the strengthening of drug laws has been the result of a drug-related catastrophe that prompted public demand for more restrictive legislation to provide more protection for the public. One such example occurred in the 1960s with thalidomide that was prescribed to treat morning sickness in pregnant women.
  • At other times the public has perceived that drug regulation and regulatory authorities have been too restrictive or too cautious in approving drugs for the market.
  • This concern typically has been related to individuals with serious or life-threatening illnesses who might benefit from drugs that have been denied market approval or whose approval has been inordinately delayed because regulations are too strict.
  • At times, governments have responded to these concerns by streamlining drug laws and regulations. Examples of types of drugs given expedited approval are cancer drugs and AIDS drugs.
  • Regulatory measures that make rapid approval of new drugs paramount sometimes have led to the marketing of drugs with more toxicity than the public finds acceptable. Thus, drug regulations can and probably will remain in a state of flux, becoming more lax when the public perceives a need for new drugs and more strict following a drug catastrophe.
  • Current Federal law requires that a drug be the subject of an approved marketing application before


  • Current Federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines.
  • Because a sponsor will probably want to ship the investigational drug to clinical investigators in many states, it must seek an exemption from that legal requirement.
  • The IND is the means through which the sponsor technically obtains this exemption from the FDA.
  • During a new drug’s early preclinical development, the sponsor’s primary goal is to determine if the product is reasonably safe for initial use in humans, and if the compound exhibits pharmacological activity that justifies commercial development.
  • When a product is identified as a viable candidate for further development, the sponsor then focuses on collecting the data and information necessary to establish that the product will not expose humans to unreasonable risks when used in limited, early-stage clinical studies.
  • FDA’s role in the development of a new drug begins when the drug’s sponsor (usually the manufacturer or potential marketer), having screened the new molecule for pharmacological activity and acute toxicity potential in animals, wants to test its diagnostic or therapeutic potential in humans.
  • At that point, the molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system.

Types of IND

There are three IND types:

  • An Investigator IND is submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed.A physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population.
  • Emergency Use IND allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with 21CFR, Sec. 312.23 or Sec.312.20. It is also used for patients who do not meet the criteria of an existing study protocol, or if an approved study protocol does not exist.
  • Treatment IND is submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place.

There are two IND categories:

  • Commercial
  • Research (non-commercial)

The IND application contain information in three areas:

  • Animal Pharmacology and Toxicology Studies – Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans. Also included are any previous experience with the drug in humans (foreign use).
  • Manufacturing Information – Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product. This information is assessed to ensure that the company can adequately produce and supply consistent batches of the drug.
  • Once the IND is submitted, the sponsor must wait 30 calendar days before initiating any clinical trials.
  • During this time, FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk.

Regulatory Requirements for Drug Approval FAQ

What are the regulatory requirements for drug approval, and why are they necessary?

Regulatory requirements for drug approval are stringent standards and processes established by regulatory agencies to ensure the safety, efficacy, and quality of pharmaceutical products before they are allowed on the market. They are necessary to protect public health.

What are the fundamental principles of drug approval?

As per Regulatory Requirements for Drug Approval The fundamental principles include safety, efficacy, and quality. Regulatory agencies demand extensive data to assess and mitigate potential risks, establish therapeutic effectiveness, and ensure manufacturing quality.

What are the key stages of drug development?

Drug development typically involves discovery and pre-clinical testing, followed by clinical trials in three phases (I, II, III), and post-approval Phase IV trials for post-market surveillance.

What is the role of clinical trials in drug approval?

Clinical trials are meticulously designed studies involving human volunteers or patients to provide critical data on a drug’s safety and efficacy, helping regulators make informed decisions.

Which regulatory agencies oversee drug approval?

Regulatory agencies vary by country. In the United States, the FDA (U.S. Food and Drug Administration) is responsible. In Europe, it’s the EMA (European Medicines Agency). Each country often has its regulatory agency.

What is the submission and review process for drug approval?

Drug manufacturers submit a New Drug Application (NDA) or equivalent to regulatory agencies. The review process involves a thorough assessment of data, clinical trial results, manufacturing practices, and labeling.

What happens after a drug is approved?

After approval, drugs continue to be monitored through post-marketing surveillance. Adverse events are reported, and regulatory agencies take necessary actions to ensure continued safety and efficacy.

Why are regulatory requirements for drug approval essential for the pharmaceutical industry?

Regulatory requirements are essential because they establish a rigorous framework to safeguard patient health, ensure drug effectiveness, and maintain high manufacturing and quality standards. Compliance with these requirements is necessary for drug development and market access.

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