A GUIDE TO REGULATORY AFFAIRS
ALL YOU NEED TO KNOW
Regulatory affairs (RA), also known as government affairs, is a profession involved in
monitoring and regulating the development, manufacture, testing and marketing of
products from a range of industries. Regulatory affairs is vital to the proper
functioning of societies and economies.
ORIGIN, IMPORTANCE AND REQUIREMENT
Before we get into the details of Regulatory Affairs as a profession, let us understand
the origin, importance, and requirement of regulatory approvals.
In 1937, Elixir Sulfanilamide which was marketed without any marketing testing caused
deaths of more than 100 people in the USA. The pharmaceutical company added DEG as
a solvent along with raspberry flavor for Sulfanilamide to be used as an elixir. This
created an outrage and finally, led to the Federal Food, Drug and Cosmetic Act in 1938.
However, the tragic incidents did not end there, there were many which led to various
acts and amendments and one of the impactful being the “Thalidomide Tragedy”. The
drug thalidomide was given to pregnant women to control morning sickness; however,
it was late until it was realized that children were born with phocomelia because of the
drug intake, and a major amendment was made to the Federal Food, Drug, and
Cosmetic Act in 1962.
With this comes the need of Regulatory Affairs Consultants who are responsible for
the protection and safety of human health; ensure the safety, efficacy, and quality of
drugs; and ensure that the product is intended for use only where it is appropriate. To
fulfill these goals:
Regulatory Affairs Consulting Services work as per the guidelines of regulatory
agencies, prepare and compile documents like NDA, ANDA, INDA, MAA, and DMP
that are required by regulatory authorities.
Make sure that all the processes involved comply and adhere to the applicable
guidelines and regulations like cGMP, ICH, GCP, GLP, etc.
Advice and strategize workable plans that would help the company to get its
product into the market and at the same time abiding by the regulatory
guidelines.
Hence, the general work profile of a Regulatory Affairs Consultant in a pharmaceutical
company includes filing DMFs and dossiers, being up to date with any amendments
that are released by regulatory authorities and maintain and submit all the documents
required for the approval of a drug to be marketed. To sum it up, it is the Regulatory
Consultants who act as a bridge between a pharmaceutical company and regulatory
authorities to get the product into the market.
THE ROLE OF THE REGULATORY PROFESSIONAL
A primary job responsibility for regulatory affairs specialists is evaluating current and
new products for compliance with applicable regulations. Other job duties may include
implementing internal organizational audits, handling the notarization of compliance
reports, and creating and communicating organizational regulatory work processes.
Regulatory affairs specialists will need to stay abreast of new applicable laws and
provide organizational management with updates on how the changes will affect the
business.
These specialists can create and maintain an electronic or hard copy filing system for
organizational records. Regulatory affairs specialists can also create and implement
compliance strategies for newly developed products. They could oversee the process
of replying to requests from customers or vendors. Regulatory affairs specialists
could also work with departments like engineering or product management to ensure
the creation and delivery of compliance-oriented customer services. These specialists
may evaluate marketing or promotional materials to guarantee all information meets
compliance standards.
Regulatory professionals are responsible for:
1. Keeping track of the ever-changing legislation in all the regions in which a
company wishes to distribute its products
2. Advising on legal and scientific restraints and requirements
3. Collecting, collating, and evaluating scientific data
4. Presenting registration documents to regulatory agencies and carrying out any
subsequent negotiations necessary to obtain or maintain marketing
authorization for the products concerned
5. Giving strategic and technical advice at the highest level in their companies,
making an important contribution both commercially and scientifically to the
success of the company as a whole
6. Helping the company avoid problems caused by badly kept records,
inappropriate scientific thinking, or poor presentation of data.
Additionally, the regulatory affairs department will often take part in the development
of product marketing concepts and is commonly required to approve packaging and
advertising before it is used commercially.
REQUIRED EDUCATION AND SKILLS
Individuals will need a bachelor's degree in product safety, chemistry, or a related field
to work as a regulatory affairs specialist. A strong knowledge of domestic and
international regulations will be beneficial. Interested individuals can seek
membership in industry organizations like the Regulatory Affairs Professionals
Society. The organization offers members certification, training, and networking
opportunities.
Excellent analytical abilities are one of the most important skills for regulatory affairs
specialists, as they must utilize their regulatory knowledge to ensure organizations
are in compliance. Regulatory affairs specialists should have strong communication
skills in order to collaborate with colleagues and interface with vendors, customers, or
sales representatives as needed. They should also have effective attention to detail in
order to successfully oversee regulatory initiatives.
IMPORTANT QUESTIONS
1.What is Regulatory Affairs?
Regulatory Affairs in a Pharmaceutical industry is a profession which acts as the
interface between the pharmaceutical industry and Drug Regulatory authorities across
the world. It is mainly involved in the registration of the drug products in respective
countries prior to their marketing.
2.What are the goals of Regulatory Affairs Professionals?
Protection of human health; Ensuring safety, efficacy and quality of drugs; and
Ensuring appropriateness and accuracy of product information
3.What are the Roles of Regulatory Affairs professionals?
i) Act as a liaison with regulatory agencies.
ii) Preparation of organized and scientifically valid NDA, ANDA, INDA ,MAA,DMF
submissions.
iii) Ensure adherence and compliance with all the applicable cGMP, ICH, GCP, GLP
guidelines, regulations and laws.
iv) Providing expertise and regulatory intelligence in translating regulatory
requirements into practical workable plans.
v) Advising the companies on regulatory aspects and climate that would affect their
proposed activities.
vi) Apart from the above main roles, there are various other roles which Regulatory
Affairs professionals play.
4.What is an Investigational New Drug (IND) application?
It is an application which is filed with FDA to get approval for legally testing an
experimental drug on human subjects in the USA
5.What is a New Drug Application?
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 FDA to market a new Pharmaceutical for sale in USA”.
6.What is an Abbreviated New Drug Application (ANDA)?
It is an application filed with FDA, for a U.S. generic drug approval for an existing
licensed medication or approved drug. In simple words, “It is an application for the
approval of Generic Drugs “
7.What is a Generic Drug Product?
A generic drug product is the one that is comparable to an innovator drug product in
dosage form, strength, route of administration, quality, performance characteristics
and intended use.
8.What is a DMF?
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:
i) It is submitted to FDA to provide confidential information.
ii) Its submission is not required by law or regulations.
iii) It is neither approved nor disapproved.
iv) It is filed with FDA to support NDA, IND, ANDA another DMF or amendments and
supplements to any of these.
v) It is provided for the 21 CFR (Code of Federal Regulations) 314. 420.
vi) It is not required when applicant references its own information
9.What are the types of DMF’s?
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)
10.What is a 505 (b)(2) application \?
505 (b)(2) application is a type of NDA for which one or more investigations relied on
by applicant for approval were not conducted by/for applicant and for which applicant
has not obtained a right of reference.
11.What kind of application can be submitted as a 505(b)(2) application?
New chemical entity (NCE)/new molecular entity (NME)Changes to previously
approved drugs
12. What are the examples of changes to approved drug products for which 505(b)(2)
application should be submitted?
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
Bio in-equivalence
13.What are the chemical classification codes for NDA?
New molecular entity (NME)
New ester, new salt, or another noncovalent derivative
New formulation
New combination
New manufacturer
New indication
Drug already marketed, but without an approved NDA
OTC (over the counter) switch
14.What are the differences between NDA and 505 (b)(2) application?
New Drug Application (NDA)
i) All investigations relied on by applicant for approval were conducted by/for applicant
and for which applicant has right of reference
ii) One or more investigation relied on by applicant for approval were not conducted
by/for applicant and for which applicant has not obtained a right of reference
505 (b)(2) Application
i) Generally, filed for newly invented pharmaceuticals.
ii) Generally, filed for new dosage form, new route of administration, new indication etc
for all already approved pharmaceutical.
Note - 505 (b)(2) application is a type of NDA.
15.What is a Marketing Authorization Application?
It is an application filed with the relevant authority in the Europe (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-
i) Applications for new active substances are described as 'full applications'.
ii) Applications for medicines containing existing active substances are described as
'abbreviated’ or ‘abridged applications’.
16.What is an ASMF?
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)”.
17.What are the types of active substances for which ASMFs are submitted?
i) New active substances
ii) Existing active substances not included in the European Pharmacopoeia (Ph. Eur.) or
the pharmacopoeia of an EU Member State
iii) Pharmacopeial active substances included in the Ph. Eur. or in the pharmacopoeia
of an EU Member State
18.What is the difference between DMF and ASMF (with respect to submission)?
i) ASMF is submitted as Applicant’s Part (Open Part) and Restricted Part (Closed Part)
ii) There isn’t any differentiation of DMF’s into parts
19.What is ICH?
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.
20.What is CTD?
The Common Technical Document (CTD) is a set of specification for application dossier,
for the registration of Medicines and designed to be used across Europe, Japan and the
United States. Quality, Safety and Efficacy information is assembled in a common
format through CTD. The CTD is maintained by the International Conference on
Harmonization of Technical Requirements for Registration of Pharmaceuticals for
Human Use (ICH).
CTD format for submission of drug registration applications/dossiers is widely
accepted by regulatory authorities of other countries too like Canada, Australia etc.
21.What are the ICH guidelines to be referred for preparation of registration
dossiers/applications of medicines (With respect to format and contents in each
module)?
M4 Guideline
M4Q Guideline
M4S Guideline
M4E Guideline
22.What are the modules in CTD?
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)
22.What is Orange Book?
It is the commonly used name for the book “Approved Drug Products Equivalence
Evaluations”, which is published by USFDA. It contains the list of drug products,
approved on the basis of safety and effectiveness by the Food and Drug Administration
(FDA) under the Federal Food, Drug, and Cosmetic Act.
23.What is Hatch-Waxman act?
It is the popular name for Drug Price Competition and Patent Term Restoration Act,
1984. It is considered as the landmark legislation which established the modern
system of generic drugs in USA. Hatch-Waxman amendment of the federal food, drug
and cosmetics act established the process by which, would be marketers of generic
drugs can file Abbreviated New Drug Application (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”.
24.What are the patent certifications under Hatch-Waxman act?
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)
(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.
25.What is meant by 180-day exclusivity?
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. The recent example
is- 180-day exclusivity was granted to Ranbaxy and Watson Laboratories for marketing
generic version of Lipitor (Atorvastatin calcium).
26.What are the procedures for Approval of Drug in EU?
Centralised Procedure (CP)
Decentralised Procedure (DCP)
Mutual Recognition Procedure (MRP)
National Procedure (NP)
27.What is the Full form of abbreviation, CEP?
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)
28.What is a CEP?
It is the certificate which is issued by Certification of Substances Division of European
Directorate for the Quality of Medicines (EDQM), when the manufacturer of a substance
provides proof that the quality of the substance is suitably controlled by the relevant
monographs of the European Pharmacopoeia.
29.What are regulatory standards?
Regulatory standards mean all laws, rules, regulation and Regulatory authority
advisory opinions or orders applicable to the manufacturing, marketing, sale,
reimbursement and/or pricing of any products.
30.What is the difference between CTD and ACTD?
The ACTD consists of Parts I to IV which have subsections A to F whereas ICH-CTD has
5 Modules with subsections that are numbered. The administrative data of Part I is part
of ACTD whereas Module 1 of ICH-CTD is purely country specific.
31.What is dossier preparation?
Dossier is a collection of documents on the particular subjects. Any preparation of
pharmaceutical product for human use go through the process of reviewing and
assessing the dossier of pharmaceutical product which contains details information
about administrative, quality, non-clinical and clinical data.
Though there is no specifically recognized format, the teaching dossier
typically consists of two basic components: a teaching narrative statement or
philosophy, which is a short reflective narrative (two to three pages), and an appendix,
which consists of supporting documentation.
32.What is CMC in regulatory affairs?
Chemistry, Manufacturing, and Controls (CMC) Regulatory Affairs (RA) is a specific
area within RA that has the ultimate responsibility for providing CMC regulatory
leadership and strategy required to achieve regulatory approvals.
FULL FORMS OF SOME ABBREVIATIONS
1 NDA : New Drug Application
2 ANDA : Abbreviated New Drug application
3 IND : Investigational New Drug Application
4 DMF : Drug Master file
5 ASMF : Active Substance Master File
6 MAA : Marketing Authorization Application
7 CEP : Certificate of Suitability to the monographs of the European Pharmacopoeia
8 ICH : The International Conference on Harmonisation of technical requirements for
registration of Pharmaceuticals for human use.
9 CTD : Common technical document for the registration of pharmaceuticals for human
use.
10 AP : Applicant’s Part
11 RP : Restricted Part
12 OP : Open Part
13 CP : Closed Part
14 NME : New Molecular Entity
15 NCE : New Chemical Entity
16 SmPC : Summary of Product Characteristics
17 PL : Packaging Leaflet
18 RMS : Reference Member State
19 CMS : Concerned Member State
20 CHMP : The Committee for Medicinal Products for Human Use
21 CPMP : Committee for Proprietary Medicinal Products
22 CVMP : Committee for Medicinal Products for Veterinary Use
23 SUPAC : Scale-up and post approval changes
24 BACPAC : Bulk Active Chemicals Post Approval Changes
25 CGMP : Current good Manufacturing Practice
26 GCP : Good clinical Practice
27 GLP : Good Laboratory Practice
REGULATORY AGENCIES
S.NO Country /Region Regulatory Agency
1 United States of America - United States Food and Drug Administration (USFDA)
2 United Kingdom - Medicines and Healthcare Products Regulatory Agency (MHRA)
3 European Union - European Medicines Agency (EMA)
4 European Union - European Directorate for the Quality of Medicines (EDQM)
5 Australia - Therapeutic Goods Administration (TGA)
6 Canada - Therapeutic Products Directorate (TPD) in Health Product and food branch
(HPFB) of Health Canada (HC)
7 Japan - Pharmaceutical and Medical Devices Agency (PMDA)
8 France - Agence Francaise de Securite Sanitaire des Produits de Sante
(AFSSAPS)Translated into English as- French Agency for the Safety of Health Products
9 Germany - Bundesinstitut für Arzneimittel und Medizinprodukte, (BfArM)Tanslated
into English as- Federal Institute for Drugs and Medical Devices
10 Brazil - Agência Nacional de Vigilância Sanitária (ANVISA)Tanslated into English as-
The National Health Surveillance Agency
11 India - Drugs Controller General of India (DCGI) who heads Central Drugs Standard
Control Organization (CDSCO)
12 Switzerland - Swiss Agency for Therapeutic Products (SWISSMEDIC)
14 Singapore - Health Sciences Authority (HSA)
CONCLUSION
Building a career in regulatory affairs is all about gaining two skill sets: soft skills,
such as expertise in communication and “technical” or hard skills, such as in-depth
knowledge of drug development and related regulations and processes. It also helps to
have a good mentor, to be willing to take chances, to develop an area of specialization,
to be able to work outside of your comfort zone and, later, at the management levels,
learn how to spot talent and help it to develop.
IMPORTANT LINKS FOR REFERENCE
https://www.globalpharmatek.com/blog/what-is-regulatory-affairs
https://www.topra.org/TOPRA/TOPRA_Member/Careers/Starting_out.a
spx
https://gratisol.com/regulatory-affairs-interview-questions/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3555014/
As always, there are several key considerations you should explore in order to determine
if a career in regulatory affairs is right for you. Most importantly, you should evaluate
both your personal and professional goals to better understand how a career in
regulatory affairs can help you meet your goals.
Before Anything else, preparation is a key to success…
Gather a decent amount of information specific to the industry and the
company! Be prepared, and let your personality do the rest!
I wish you all the best in your future interviews! Feel free to reach out with
questions and comments. Follow @Pooja Bansal on LinkedIn and
#clinicareers for more such content.
https://www.linkedin.com/in/pooja-bansal-helpingjobseekers-clinicareers/
https://www.instagram.com/clini.careers/