How to get a job in the field of Regulatory Affairs ?

This article is aimed at listing down the simple steps/facts, which I hope will help in solving the big riddle of getting a job in the field of regulatory affairs !

First of all, I would like to share my personal experiences in pursuit of job in the field of Regulatory Affairs. After my B.Pharmacy, I was pretty much sure that I wanted to get into RA., so I enrolled into the course offered by BII-Industry Program in RA, which was famous back then. I also enrolled into a short term industry oriented course for pharma graduates which included RA as one of the topics. I had also began researching regarding RA on the internet, but could get info in bits and pieces (This was the reason for me to start Regulatory One). 

After considerable time of enrolling into the above courses, I got a call for interview in my first company. I had few more freshers (beginners) for competition at the time of interview. I cleared the interview and got the job due to the fact that I had done suitable home work and my research study on DMF (Drug Master files), which was part of my course, was of great help. I am trying to state the fact that, if you want to get a job, you need to have special skills which are not there with your competitors!

The information which I learnt, while I worked on Regulatory One, helped  me to get my 2nd job.

Gaining Skills in Regulatory Affairs - 

• If  you have done M.pharmacy (not in RA)- My suggestion would  be-do a diploma/PG diploma course related to RA through part-time/distance. My personally preferred course and institute is PG Diploma in Pharmaceutical Regulatory Affairs from  Jamia Hamdard University since it is accredited by NAAC in 'A' category and they have contact classes in major cities. The feed back I received regarding the course was that, its good.

•  If  you are B. Pharmacy graduate and want to make a career in RA -I would recommend you to do M.Pharmacy in Pharmaceutical RA .

         The list of institutes offering M.Pharmacy in RA are given in the below link.

          http://www.regulatoryone.com/2011/10/institutes-offering-regulatory-affairs_03.html

•  Browse, through the websites of Regulatory Agencies like FDA, MHRA, CDSCO and try to gain as much knowledge as possible. In the below page of Regulatory One, Link to the updated news section in the websites of premier regulatory agencies of world is provided.       

         http://www.regulatoryone.com/p/updated-news.html

• In FDA's website there are links like CDER learn , Educational Resources and Webinars which contain lots of useful information. Similarly there are training modules in MHRA' s website.Of course, all the above listed useful links are absolutely free to access !

• Among all the ICH guidelines- M4 (and allied guidelines M4Q, M4S, M4S), Q1A , Q1E ,Q2, Q3A, Q3B, Q3C, Q6A are the most important references for RA professionals. Knowing them is very important. 

• Go through all the articles, which I have written in Regulatory One. I personally believe that, if a beginner goes to the interview after reading the articles that I have written, they could easily clear the interview.

• The below listed link is very useful at the time of interview, especially for beginners (freshers).            

         http://www.regulatoryone.com/p/regulatory-affairs-interview-questions.html

Writing Skills -

• For a Regulatory Affairs professional, having good writing skills is very important, since he/she is involved in compilation of dossiers, responding to queries from regulatory agencies. 

Resume -  

• Make sure that, you have a well formatted, unique resume which is different from others. If possible, get the resume reviewed by an expert. Ensure to highlight the course which you have done related to RA and specific skill with respect to RA.
• Upload your resume in job websites like Monster and Naukri. Ensure to fill up all your details and have a complete profile.

Networking -  Networking is an important tool for getting to know about any openings in the field of Regulatory Affairs. In the professional Networking sites like Linkedin, having your complete profile is very important. The following things are to be considered/taken note of, while setting up your profile-

• Have your detailed profile, with special emphasis on your educational qualification, skills related to regulatory affairs. 

• Ensure that the information is given in a properly structured manner, without any grammatical errors.

• Ensure that the photo which you have uploaded is a one in which you are in formal dress and definitely not the one, which you had taken during your vacation in a casual dress!

• Join groups related to Regulatory Affairs like Drug Regulatory Affairs, Global Regulatory Affairs, Regulatory Affairs Job Opportunities etc and take active part in discussions in a relevant way.

• Request people who are in senior positions in RA field to be part of your Networks. If they accept to be part of your network, send them an email,(in a properly structured manner, without any typo/grammatical errors) requesting them to let you know if there are any openings in their company. Respect their privacy, and do not ask them for their personal numbers. If they see your profile and they find you to be good enough, they may definitely let you know, if there are any openings.

General Misconceptions- I guess, some of you might have got the free advice- "Start of your career by working in Quality Control /Quality Assurance. Then you will have a better chance of getting a job in RA". This logic is absolute false. Why will a company prefer a person with experience in QC/QA over a person with experience in RA ?

Guys, a person who is a fresher (beginner) can get a job in RA. The best example is, myself !

Hope, the above article will help you in getting a job in the field of Regulatory Affairs. 

Best of Luck! 

P.S-

• The above article is intended, mainly for the people from India, who are interested to make a career in the field of RA.

• I am not in a position where I could refer/recommend for a job. So, kindly do not email me your resumes.

Sample Quality Overall Summary

I am sure that, many of you may be interested to take a look at complete NDA/ANDA/Dossier/ASMF. Since, they contain confidential information, no company would like to share it in public domain. But guys! you could check out sample Quality Overall Summary (part of Module-2) of an ANDA submission. FDA has posted samples of Quality overall summary (QOS) in its website the links of which are provided below-

Sample Quality Overall Summary of ANDA submission for Ersatztine Tablets USP

Sample Quality Overall Summary of ANDA submission for MK Controlled release Capsules

Module 2- It is part of  NDA/ANDA/Dossier/DMF/ASMF, where the summaries of Modules-3,4,5 are presented. It could  be correlated to an abstract of research article or trailer of a movie! The module-2 (Common Technical Document Summaries) consist of the following sections-

2.1 Common Technical Document Table of Contents (Modules 2-5)

2.2 CTD Introduction

2.3 Quality Overall Summary

2.4 Nonclinical Overview

2.5 Clinical Overview

2.6 Nonclinical Written and Tabulated Summaries

• Pharmacology
• Pharmacokinetics
• Toxicology

2.7 Clinical Summary

• Biopharmaceutic Studies and Associated Analytical Methods
• Clinical Pharmacology Studies
• Clinical Efficacy
• Clinical Safety
• Literature References
• Synopses of Individual Studies

 As discussed by me earlier, you need to refer -M4 Guideline, M4Q Guideline, M4S Guideline, M4E Guideline to file a  NDA/ANDA/Dossier/DMF/ASMF in CTD format.

Reference-M4 Guideline

Keywords - Sample Quality Overall Summary, Module-2, M4 Guideline, FDA.

ORPHAN DRUGS

I. What are Orphan Drugs?

In the USA, Orphan Drugs are defined as “those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but it is not expected to recover the costs of developing and marketing a treatment drug”.

In the EU, Orphan Drugs are defined as “those that are intended for diagnosis, prevention or treatment of diseases that affect fewer than 5 in 10,000 people across the EU.”

In simple words “Orphan Drugs are those, which are intended for the treatment of rare diseases.”

The Companies which are involved in the research and development of Orphan Drugs are provided incentives by the Governments of various countries which are discussed below.

II. What is the need for designation of drugs used in the treatment of rare diseases as orphan drugs and providing incentives to pharmaceutical companies which are involved in developing orphan drugs?

For the development and commercialization of new medicines, lot of money and time is involved and moreover, the success rate of new medicines is less. Hence, we cannot expect a pharmaceutical company to work on medicines used for the treatment of rare diseases, since the market for rare diseases is very less.  Hence there is a need for providing incentives in order to encourage pharmaceutical companies which are involved in developing orphan drugs.

The following may be the general incentives provided by governments of various countries:

• Tax incentives.

• Enhanced patent protection and marketing rights.

• Clinical research financial subsidization.

• Creating a government-run enterprise to engage in research and development

III. Significant Legislations related to Orphan Drugs in USA and EU-

a) Orphan Drug Act of 1983-

• It is a law passed in the United States designed to facilitate the development and commercialization of drugs to treat rare diseases, called Orphan Drugs.

•  Orphan drug designation does not indicate that the therapeutic is either safe and effective or legal to manufacture and market in the United States.

Important features of Orphan Drug Act-

• The companies developing Orphan Drugs have marketing exclusivity for 7 years.

• The companies may get clinical trial tax incentives.

• The companies may have reduced taxes from the federal government.

b)  Rare Diseases Act-

This legislation amended the Public Health Service Act to establish the Office of Rare Diseases in USA. It also increased funding for the development of treatments for patients with rare diseases.

c) REGULATION (EC) No 141/2000 of European Union-

Features of REGULATION (EC) No 141/2000-

• This legislation lays down a Community procedure for the designation of medicinal products as orphan medicinal products.               

•  It provides incentives for the research, development and placing on the market of designated orphan medicinal products.          

•  It sets up a Committee for Orphan Medicinal Products (COMP) within the Agency

• Orphan drug status granted by the European Commission gives marketing exclusivity in the EU for 10 years after approval

In addition to the United States and the European Union, legislation has been implemented by Japan, Singapore, and Australia which  have all passed legislation that offers subsidies and other incentives to encourage the development of drugs that treat orphan diseases.

IV.Some of the Organizations/offices of Regulatory Agencies associated with Orphan Drugs:

a)      FDA Office of Orphan Product Development (OOPD)-

The OOPD has following roles-

• Evaluates scientific and clinical data submissions from sponsors to identify and designate products as promising for rare disease and to further advance scientific development of such promising medical products.

• It provides incentives for sponsors to develop products for rare diseases.

b)       National Organization for Rare Disorders (NORD)-

• It is a NGO based in USA, involved in providing information, advocacy, research, and patient services to help all patients and families affected by rare diseases.

• It was involved in lobbying along with other organizations for passing Orphan Drug Act in USA.

C ) Committee for Orphan Medicinal Products (COMP)-

• It is one of the scientific committee of EMA that is responsible for reviewing applications from people or companies seeking orphan medicinal product designation.

• It is also responsible for advising the European Commission on the establishment and development of a policy on orphan medicinal products in the EU, and assists the Commission in drawing up detailed guidelines and liaising internationally on matters relating to orphan medicinal products

d)  European Organization for Rare Diseases (EURORDIS)-

It is an NGO based in Europe, dedicated towards improving quality of life of all people living with rare diseases in Europe.

V.Significant results due to passage of legislations in support of Orphan Drugs-

• Many orphan drugs have been developed to treat rare diseases like Hodkins Lymphoma, congenital Factor XIII deficiency. glioma, multiple myeloma, cystic fibrosis,  phenylketonuria, snake venom poisoning, neoplastic meningitis etc.

• Before enactment of ODA in USA, only 38 drugs were approved to treat orphan diseases. From the passage of the ODA in 1983 until May 2010, the FDA approved 353 orphan drugs and granted orphan designations to 2,116 compounds, which is a significant achievement.

• Although the European Medicines Agency grants market access to its 27 member states, medicines only reach the market when each member state decides that its national health system will reimburse for the drug. For example, 35 orphan drugs reached the market in Belgium, 44 in the Netherlands, and 28 in Sweden in 2008. 35 such drugs reached the market in France and 23 in Italy in 2007.

Orphan Drugs Approved by the FDA in the year, 2011 (until November, 2011)-

S.No.	Name of Drug	Indication
1	Adcetris(brentuximab vedotin)	For treatment of Hodgkin’s lymphoma and ALCL (systemic anaplastic large celllymphoma).
2	Anascorp(Centruroides [Scorpion] Immune F(ab’)2 [Equine])	For treatment of clinical signs of scorpion envenomation.
3	Caprelsa (vandetanib)	To treat adult patients with metastatic (late-stage ) medullary thyroid cancer who are ineligible for surgery and who have disease that is growing or causing symptoms.
4	Corifact(Factor XIII Concentrate [Human])	For routine prophylactic treatment of congenital Factor XIII deficiency.
5	Firazyr(icatibant)	For treatment of acute attacks of a rare condition called hereditary angioedema (HAE) in people ages 18 years and older.
6	Xalkori (crizotinib) and companion genetic  test	To treat certain patients with late stage (locally advanced or metastatic), non-small cell lung cancers (NSCLC) who express the abnormal anaplastic lymphoma kinase (ALK) gene.
7	Yervoy (ipilimumab)	To treat patients with metastatic melanoma (late-stage skin cancer).
8	Zelboraf (vemuranfenib) with companion diagnostic	To treat patients with metastatic (late-stage) or unresected (cannot be removed by surgery) melanoma (skin cancer) in patients whose tumors express a gene mutation called BRAF V600E.
9	Nulojix (belatacept)	To prevent organ rejection in adult patients who have had a kidney transplant, in combination with other immunosuppressants.
10	Spherusol(Coccidioides immitis Spherule-Derived Skin Test Antigen)	For detection of delayed type hypersensitivity to C. immitis in individuals, 18-64 years of age, with a history of pulmonary coccidioidomycosis

Keywords- Orphan Drugs, rare diseases, Orphan Drug Act of 1983, Rare Diseases Act, Regulation (EC) No 141/2000, OOPD, NORD, COMP, EURORDIS.
.

References-
1.http://en.wikipedia.org/wiki/Orphan_drug
2.http://en.wikipedia.org/wiki/Orphan_Drug_Act

3.http://en.wikipedia.org/wiki/National_Organization_for_Rare_Disorders

http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/10/WC500004736.pdf

4.http://www.rarediseases.org/about/vision-mission

5.http://www.eurordis.org/content/brief-0

6.http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UCM278358.pdf
7.http://www.ema.europa.eu/ema/index.jspcurl=pages/about_us/general/general_content_000263.jsp&mid=WC0b01ac0580028e30&jsenabled=true
8.http://www.fda.gov/forindustry/developingproductsforrarediseasesconditions/default.htm
9.http://www.fda.gov/downloads/Drugs/NewsEvents/UCM182553.pdf

Effective Dossier Management

Importance of effective dossier management-

• The registration dossier for medicines is an important document which is submitted for review to regulatory agencies by pharma companies for approval to market their medicines.

•  Utmost care should be taken during its compilation and filing as it plays a direct role in earliest possible availability of medicines in the market which in turn translates into business for the company.

• Of course, regulatory affairs professionals need to ensure the safety, quality and efficacy of  the medicines for which they are filing registration dossier.

Note : The dossiers could be anything among DMF, ASMF, ANDA, NDA or MAA.

From my experience I could possibly think of 3 important aspects which play an important role in effective dossier management-

1. Planning aspects

2. Formatting and compilation aspects

3. Review aspects

1. Planning aspects-

• Deadline-It is important to know the deadline for filing the dossier and action plan should be prepared so as to meet the deadline.

• Understanding the registration requirements of respective agencies- Although most of the regulatory agencies accept the CTD format for registration dossier,  the requirements for approving  marketing applications may vary for individual agencies. For example- USFDA requires Batch Manufacturing Records to be provided, while it is not necessary for approval by European regulatory agencies. Hence it is necessary to completely read and understand the guidance document of each regulatory agency before going ahead with filing registration dossier with them. 

• Requirements Listing- Listing down all the requirements for preparing the registration dossier, for example in the preparation of section 3.2.S.1 of a DMF I need to have all the information on nomenclature, structure and general properties (like pH, Pka, solubility, partition coefficient, stereochemistry etc ) of drug substance. Similarly Listing down all the requirements for preparation of all the modules and their respective sections is an important aspect.

• Sending the requirements list to respective departments-Preparing an individual requirement list and sending them to each respective department. For example I need to have all the information regarding the general properties, synthetic scheme, manufacturing process development of drug from R & D department and finalised specification & test procedures, Batch manufacturing sheets from Quality assurance department.

2. Formatting and Compilation Aspects-

Format-

As per the ICH's M4 guideline the following are recommended-

• The display of information should be unambiguous and transparent, in order to facilitate the review of the basic data and to help a reviewer become quickly oriented to the application contents.

• Text and tables should be prepared using margins that allow the document to be printed on both A4 and 8.5 x 11” paper (For Europe and Japan regions A4 paper is recommended and 8.5 x 11” paper for USA).

• Times New Roman, 12-point font is recommended for narrative text.

• The left-hand margin should be sufficiently large that information is not obscured by the method of binding.

• Font sizes for text and tables should be of a style and size that are large enough to be easily legible, even after photocopying.

• Every page should be numbered, according to the granularity document (refer pages 6 to 14 of M4 guideline).

• Acronyms and abbreviations should be defined the first time they are used in each module.

• References should be cited in accordance with the current edition of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, International Committee of Medical Journal Editors (ICMJE).

• All pages of a document should include a unique header or footer that briefly identifies its subject matter.

Note: For any person who is new/relatively new to the field of RA it is important to read and understand CTD guidelines of ICH (M4, M4Q,M4S, M4E) before starting to compile any dossier. (Refer the post CTD in my blog)

Compilation-

The following compilation aspects are important-

• The information should be specific, clear, precise and accurate.

• Typographical and grammatical errors should be avoided.

• The information should be arranged in a sequential order in computer. Each module could have a separate folder and in turn each section of a module could have a separate folder. This kind of orderly arrangement will help in easy access of information and help in taking printouts of finalized copy conveniently.

• The line spacing should be preferably single.

• All the documents received from other departments should be cross-checked so as to ensure that they are free from errors.

• Ensuring the specifications & test procedures are designed in accordance with ICH guidelines Q3A, Q3B, Q3C, Q6A and Q6B. Stability Protocols are designed as per ICH guidelines Q1A through Q1E . Similarly ensuring that various documents are designed as per ICH guidelines. This can be ensured during drafting stages of preparation of various documents.

• After the finalized soft copy is ready, printouts should be taken using a good quality printer and arranged sequentially in a module and section wise manner. 

• As per the note given in the website of  EMA-"All Microsoft Office documents submitted to the European Medicines Agency must be in a format compatible with MS Office 2003. Office 2007 and Office 2010 formats cannot currently be accepted".

3.Review Aspects

• .Every human being is prone to make mistakes; hence it is important to re check the information in the dossier before filing it with regulatory agencies. 

• It is also important that a dossier meant to be filed with a regulatory agency should be cross verified by a person other than the one who has complied the dossier.

• It is very useful to have a check list so as to ensure that all the required information is present in the dossier before submission to regulatory agency.

• The USFDA has a check list which is very useful while filing an ANDA- ANDA checklist

• The module 1 of CTD in most of the cases is completely different for various agencies hence care should be taken in compiling this section.

Avoiding Deficiencies-

You can learn without necessarily making mistakes. EDQM has compiled a list of top 10 deficiencies of CEP dossier which will go a long way in preventing you from making the same mistakes.

Key software skills for effective dossier management-

• Proficiency in MS office (Yes, I know that most of you are proficient! ).

• Proficiency in Adobe Acrobat tools. (Especially useful in preparing NeeS dossier and eCTD ).

• Proficiency in ISIS draw or Chem sketch softwares, which are useful in drawing chemical structures.

• Since we generally receive number of mails on a daily basis, we could sort the emails by using labels based on the sources. This will make your job easy while accessing mails.

• eCTD is mandatory for the centralised procedures in Europe and it could be made mandatory for the other procedures as well in the future. Hence it is important to undergo training in the use of eCTD software.(My fellow Indian countrymen, let me know if there are any institutes which are offering training in the use of eCTD software back here in India)

P.S- 

1. This article is mainly intended to provide guidance for the  preparation of  paper format of registration dossier, but not eCTD or NeeS format.

2. I have posted this article based on my experiences. There could be other key aspects which are to be considered in preparation of registration dossier for medicines.

Keywords- registration dossier, planning aspects, formatting and compilation aspects, review aspects,  M4, M4Q, ANDA check list.

References :

http://ich.org/

http://www.ema.europa.eu/

http://www.fda.gov/

Drug discovery and development process

Youtube Link to an interesting video on Drug Discovery and Developmental  Process released by Novartis.

Note : Click on the above link to watch the video.

Explanation of terms related to Regulatory Affairs

In this post I am going to define and explain the terms which I referred to in the previous post (Introduction to Regulatory affairs) .These terms are most frequently asked in interviews, so make note of them.


Investigation new drug application (INDA) - It is an application which is filed with FDA to get approval for legally testing an experimental drug on human subjects in the USA.


There are three IND types:


An Investigator INDA- 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 INDA- 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. 312.34.  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 must contain information in three broad areas:

• Animal Pharmacology and Toxicology Studies
• Manufacturing Information
• Clinical Protocols and Investigator Information

The link in FDA's website which gives complete information about INDA is http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/default.htm


New Drug Application (NDA) :


The FDA defines it as "The NDA application 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."


The goals of the NDA are to provide enough information to permit FDA reviewer to reach the following key decisions:

• Whether the drug is safe and effective in its proposed use(s), and whether the benefits of the drug outweigh the risks.

• Whether the drug's proposed labeling (package insert) is appropriate, and what it should contain.

• Whether the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity.

In simple terms - "NDA is an application which is filed with the FDA by a pharma company for getting  approval for their newly discovered drug".

The link in FDA's website which gives complete information about NDA is -http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/NewDrugApplicationNDA/default.htm

Abbreviated New Drug Application (ANDA):  is an application for a U.S. generic drug approval for an existing licensed medication or approved drug.

A generic drug product is one that is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use.  All approved products, both innovator and generic, are listed in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).

The link in FDA's website which gives complete information about ANDA is http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/default.htm

Marketing authorisation application (MAA): is an application (to the relevant authority ; typically the UK's MHRA or the European Commission's Committee for Medicinal Products for Human Use (CHMP) to market a drug or medicine.

The U.S. Food and Drug Administration equivalent of Marketing authorisation application (MAA) is a New Drug Application (NDA).


The link in MHRA's website which gives complete information about MAA is http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Marketingauthorisations/index.htm

Active Pharmaceutical Ingredient (API) (or Drug Substance):

Any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in the production of a drug, becomes an active ingredient of the drug product.  Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body.

Active Substance Master File (ASMF)/Drug Master File (DMF) : is a document containing complete information on an Active Pharmaceutical Ingredient (API) or finished drug dosage form. It is known as European Drug Master File (EDMF) or Active Substance Master File (ASMF) and US-Drug Master file (US-DMF) in Europe and United States respectively.

The DMF contains factual and complete information on a drug product's chemistry, manufacture, stability, purity, impurity profile, packaging, and the cGMP status of any human drug product.

Current good Manufacturing Practice (cGMP) : are practices and the systems required to be adapted in pharmaceutical manufacturing, quality control, quality system covering the manufacture and testing of pharmaceuticals or drugs including active pharmaceutical ingredients, diagnostics, foods, pharmaceutical products, and medical devices. 

International Conference on Harmonisation 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.

Good Clinical Practice (GCP): is an international quality standard that is provided by International Conference on Harmonisation (ICH), that defines standards, which governments can transpose into regulations for clinical trials involving human subjects.

Good Laboratory Practice (GLP):  specifically refers to a quality system of management controls for research laboratories and organizations to try to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical (including pharmaceuticals) safety and efficacy tests.

Introduction to Regulatory Affairs

Here is my first post related to Regulatory Affairs!

What is Regulatory Affairs?

Regulatory Affairs is a profession within regulated industries namely-pharmaceuticals, medical devices, energy and banking. It has specific meaning within healthcare industries namely- pharmaceuticals, medical devices, biologics and functional foods.(In this blog I am going to deal about Regulatory Affairs related to pharmaceuticals meant for human use).

Regulatory Affairs in the pharma industry may be defined as "The interface between the pharmaceutical company and the regulatory agencies across the world."

In the above presentation, I am conveying the fact that -among all the departments of a pharma company Regulatory Affairs Department acts as the interface between  the pharmaceutical company and the regulatory agencies across the world.

Regulatory agency in the present context may be defined as "The competent government agency which is responsible for ensuring that medicines work and are acceptably safe."

Origin of Regulatory Affairs-

• Elixir Sufanilamide, prepared using DEG (a poison) as solvent resulted in the death of more than 100   people  in the USA in 1937. This incident led to the passing of the 1938 Federal Food, Drug and Cosmetic act in USA.

• Thalidomide use by pregnant women for treating morning sickness was linked to the cause of birth deformities in more than 10,000 children in late 1950s and early 1960s. This incident led to the Kefauver-Harris Amendment in USA-it is a 1962 amendment to the Federal Food, Drug and cosmetic act.

Similarly, other tragic incidents led to various acts/amendments.

Goals of Regulatory Affairs as profession-

• Protection of human health
• Ensuring safety,efficacy and quality of drugs
• Ensuring appropriateness and accuracy of product information

Roles of Regulatory Affairs professionals-

• Act as a liaison with regulatory agencies
• Preparation of organized and scientifically valid NDA, ANDA,INDA ,MAA,DMF submissions
• Ensure adherence and compliance with all the applicable cGMP, ICH, GCP, 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 main roles, there are various other roles which Regulatory Affairs professionals play.

Now,coming to the most important part of this post-

What work is done in Regulatory Affairs Department?

• A new drug/generic drug manufactured by a pharmaceutical company just cannot be released into the market for human use.

• Here the Regulatory Affairs Department comes into play. 

• Regulatory Affairs Department of a pharmaceutical company files all the information related to the development, manufacture, control, stability studies, packing, labeling , safety and efficacy studies of drugs with the Regulatory agencies in a prescribed format as ANDA/NDA/MAA/DMF etc.

•  The Regulatory agency reviews the information provided in accordance with regulations, guidelines and if they are satisfied with information provided, approval will be  granted for marketing of the drug by pharmaceutical companies for human use.

General work profile of a Regulatory Affairs professional in an API (Active Pharmaceutical Ingredient) manufacturing company-

•   Filing a DMF/ASMF with regulatory agencies in support of the NDA/ANDA/INDA/MAA filed by a Formulator (Drug Product manufacturer who uses API of that particular API manufacturing company).

•  Filing dossier of API with EDQM for obtaining CEP.

• Assessing and filing amendments/variations to the information (which may be related to manufacture, control, stability studies etc ) in DMF/ASMF/Dossier of particular API with the Regulatory agencies. Major amendments are to be reported prior to their implementation while minor amendments may be reported annually. The classification of amendments will be dealt in the later posts.

• Taking approval of customers of API before implementing any major changes regarding the information mentioned in DMF/ASMF/Dossier. The updated DMF/ASMF may be submitted to the customer simultaneously along with amendments/variations filed with the agency.

• Preparing and submitting Open part/Applicant’s part of DMF to the customers of API (Drug products manufacturer) which may be filed by customer with the Regulatory agency.

• Preparing and submitting the LoA (Letter of Access/Letter of Authorisation) to the API customers and Regulatory Agencies. LoA is the letter which authorizes the regulatory agency to review the DMF /ASMF of the API manufacturer against the NDA/ANDA/MAA of the API customers (Formulators).

• ·Preparing Technical Packages for existing/prospective customer for initial assessment of the API.   

• Filing Annual/Biannual/Quinquennial reports (Which contain list of changes to the   DMF/ASMF/Dossier) with the regulatory agencies.

• Maintenance of the complete history of each API (Filing history with agencies/customers, amendments, annual reports).

• Taking part in the drug development process by advising the R & D scientists regarding various guidelines,laws and regulations. 

Note: Apart from the above work profile there may be other responsibilities for Regulatory Affairs professionals too.

                    

 General work profile of a Regulatory Affairs professional in a Drug Product /Finished  

 product/Formulation manufacturing company -

•  Filing a NDA/ANDA/MAA of drug products with regulatory agencies for getting marketing approval.

• Assessing and filing supplements/amendments/variations to the information (which may be related to manufacture, control, stability studies etc ) in NDA/ANDA/MAA with the Regulatory agencies for prior approval or after their implementation. Major supplements/amendments are to be reported prior to their implementation while minor supplements/amendments may be reported annually. The classification of amendments will be dealt in the later posts.

• Filing Annual/Biannual reports (Which contain list of changes to the NDA/ANDA/MAA) with the regulatory agencies.

• Reporting any adverse effects which have occurred/may occur due to the use drug products.

• Maintenance of the complete history of each Drug products (Filing history with agencies/customers, amendments, annual reports)

• Taking part in design and revision of drug product labels, packing leaflets.

• Taking part in the Formulation development process by advising the R & D scientists regarding various guidelines,laws and regulations. 

Note: Apart from the above work profile there may be other responsibilities for Regulatory Affairs professionals too.

PS

You may be wondering what the abbreviations NDA,ANDA, CEP etc are all about..????


I am presenting the full forms of all the abbreviations below and will explain them in my next post.

NDA-    New Drug Application
ANDA- Abbreviated New Drug application
INDA  - Investigational New Drug Application
MAA  -  Marketing Authorisation Application
DMF   - Drug Master file
ASMF -Active Substance Master File
CEP-     Certificate of suitability to the monograph of European Pharmacopoeia
cGMP- Current good Manufacturing Practice
ICH,-    The International Conference on Harmonisation of technical requirements for registration of
              Pharmaceuticals for human use.
GCP-    Good clinical Practice
GLP-    Good Laboratory Practice

Reference:

http://www.wikipedia.org/