Introduction to Regulatory Affairs & Explanation of terms related to Regulatory Affairs

Introduction 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, labelling , 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

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 drugs 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, and 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 ishttp:/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.