Regulatory Affairs in the Pharmaceutical industry is a profession that acts as the interface
between the pharmaceutical industry and Drug Regulatory authorities worldwide. It is mainly
involved in the registration of the drug products in respective countries before their
marketing.
∙Protection of human health
∙Ensuring the safety, efficacy, and quality of drugs
∙Ensuring appropriateness and accuracy of product information.
It is an application which is filed with the FDA to get approval for legally testing an
experimental drug on human subjects in the USA.
Act as a liaison with regulatory agencies
∙Preparation of organized and scientifically valid NDA, ANDA, INDA, MAA, and DMF
submissions
∙Ensure adherence and compliance with all the applicable cGMP, ICH, GCP, and GLP
guidelines, regulations, and laws
∙Providing expertise and regulatory intelligence in translating regulatory requirements into
practical workable plans
∙Advising the companies on regulatory aspects and climate that would affect their
proposed activities
∙Apart from the above leading roles, there are various other roles which Regulatory Affairs
professionals play.
The NDA is the vehicle through which drug sponsors formally propose that the FDA approve
a new pharmaceutical for sale and marketing in the U.S. The data gathered during the animal
studies and human clinical trials of an Investigational new drug become part of the NDA.
In simple words, “It is an application which is filed with the FDA to market a new
Pharmaceutical for sale in the USA.”
It is an application filed with the FDA for a U.S. generic drug approval for an existing
licensed medication or approved drug.
Simply put, “It is an application for the approval of Generic Drugs.”
A generic drug product is comparable to an innovator drug product in dosage form, strength,
route of administration, quality, performance characteristics and intended use.
It is an application filed with the relevant European authority (typically, the UK's MHRA or
the EMA’s Committee for Medicinal Products for Human Use (CHMP)) to market a drug or
medicine.
As per UK’s MHRA-
Applications for new active substances are described as 'full applications'.
Applications for medicines containing existing active substances are described as
'abbreviated’ or ‘abridged applications.’
A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that
may be used to provide confidential detailed information about facilities, processes, or
articles used in the manufacturing, processing, packaging, and storing of one or more human
drugs.
Important facts regarding DMFs
∙It is submitted to the FDA to provide confidential information
∙Its submission is not required by law or regulations
∙It is neither approved nor disapproved
∙It is filed with the FDA to support NDA, IND, ANDA, another DMF or amendments and
supplements to any of these
∙It is provided for in the 21 CFR (Code of Federal Regulations) 314. 420
∙It is not required when the applicant references their own information.
505 (b)(2) application is a type of NDA for which one or more investigations relied on by the
applicant for approval were not conducted by/for the applicant and for which the applicant
has not obtained a right of reference.
Type I: Manufacturing Site, Facilities, Operating Procedures, and Personnel (No longer
accepted by FDA).
Type II: Drug Substance, Drug Substance Intermediate, and Material Used in Their
Preparation, or Drug Product.
Type III: Packaging Material.
Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation.
Type V: FDA Accepted Reference Information (FDA discourages its use).
∙New chemical entity (NCE)/new molecular entity (NME)
∙Changes to previously approved drugs.
∙Change in dosage form.
∙Change in strength
Change in route of administration
∙Substitution of an active ingredient in a formulation product
∙Change in formulation
∙Change in dosing regimen
∙Change in active ingredient
∙New combination Product
∙New indication
∙Change from prescription indication to OTC indication
∙Naturally derived or recombinant active ingredient
∙Bioequivalence
An active substance master file is a submission which is made to EMA, MHRA or any other
Drug Regulatory Authority in Europe to provide confidential intellectual property or 'know-
how' of the manufacturer of the active substance.
In simple words, “It is a submission made to European Drug regulatory agencies on the
confidential information of Active Substance or Active Pharmaceutical Ingredient (API).”
∙New active substances
∙Existing active substances not included in the European Pharmacopoeia (Ph. Eur.) or the
pharmacopoeia of an EU Member State
∙Pharmacopeial active substances included in the Ph. Eur. or the pharmacopoeia of an EU
Member State.
ASMF is submitted as Applicant’s Part (Open Part) and Restricted Part (Closed Part)
There isn’t any differentiation of DMF’s into parts.
International Conference on Harmonization of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH): is a project that brings together the regulatory
authorities of Europe, Japan and the United States and experts from the pharmaceutical
industry in the three regions to discuss scientific and technical aspects of pharmaceutical
product registration.
The Common Technical Document (CTD) is a set of specifications for an application dossier.
for the registration of Medicines. It is designed to be used across Europe, Japan, and the
United States.
Quality, Safety and Efficacy information is assembled in a standard format through CTD. The
International Conference on Harmonization of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) maintains the CTD.
Regulatory authorities in other countries like Canada, Australia, etc, widely accept the CTD
format for submitting drug registration applications/dossiers.
M4 Guideline
M4Q Guideline
M4S Guideline
M4E Guideline.
The Common Technical Document is divided into five modules:
Module 1. Administrative information and prescribing information
Module 2. Common Technical Document summaries (Overview and summary of modules 3
to 5)
Module 3. Quality
Module 4. Nonclinical Study Reports (toxicology studies)
Module 5. Clinical Study Reports (clinical studies).
It is the commonly used name for the book “Approved Drug Products with
Therapeutic Equivalence Evaluations” published by USFDA.
∙It contains the list of drug products approved based on safety and effectiveness by the
Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act.
It is the popular name for Drug Price Competition and Patent Term Restoration Act, 1984.
It is considered the landmark legislation that established the modern system of generic drugs
in the USA.
Hatch-Waxman amendment of the federal Food, Drug and Cosmetics Act established the
process by which marketers of generic drugs can file Abbreviated New Drug Applications
(ANDA) to seek FDA approval of generic drugs. Paragraph IV of the act allows 180-day
exclusivity to companies that are the "first-to-file “ an ANDA against holders of patents for
branded counterparts.
In simple words, “Hatch-Waxman Act is the amendment to Federal, Food, Drug and
Cosmetics Act which established the modern system of approval of generics.”
As per the Hatch and Waxman Act, generic drug and 505 (b) (2) applicants should include
certifications in their applications for each patent listed in the “Orange Book” for the
innovator drug. This certification must state one of the following:
(I) that the required patent information relating to such patent has not been filed (Para I
certification);
(II) that such patent has expired (Para II certification);
(III) that the patent will expire on a particular date (Para III certification) or
(IV) that such patent is invalid or will not be infringed by the drug for which approval is
being sought (Para IV certification).
A certification under paragraph I or II permits the ANDA to be approved immediately if it is
otherwise eligible. A certification under paragraph III indicates that the ANDA may be
approved when the patent expires.
The Hatch-Waxman Amendments provide an incentive of 180 days of market exclusivity to
the “first” generic applicant who challenges a listed patent by filing a paragraph IV
certification and thereby runs the risk of having to defend a patent infringement suit.
180 Day Exclusivity could be granted to more than one applicant. A recent example is that
180-day exclusivity was granted to Ranbaxy and Watson Laboratories for marketing a
generic version of Lipitor (Atorvastatin calcium).
Centralised Procedure (CP)
Decentralised Procedure (DCP)
Mutual Recognition Procedure (MRP)
National Procedure (NP)
Certificate of Suitability to the Monographs of the European Pharmacopoeia (or) Certificate
of suitability of monographs of the European Pharmacopoeia (or) Certification of suitability
of European Pharmacopoeia monographs. It is also informally referred to as Certificate of
Suitability (COS).
It is the certificate issued by the Certification of Substances Division of the European
Directorate for the Quality of Medicines (EDQM) when the manufacturer of a substance
provides proof that the relevant monographs of the European Pharmacopoeia suitably control
the quality of the substance.
