Drug Regulatory Affairs Interview: Things to Remember

 Disclaimer: This article is more helpful for anyone who is fresher, wishing to start career or having about 0 to 2 years of experience in drug regulatory affairs. For writing this article, it was important to talk to people who regularly conduct interviews and ask them what are their expectations and what are they looking in candidate while conducting interviews. I was fortunate enough to receive inputs from experienced professionals who have been regularly conducting technical DRA (Drug Regulatory Affairs) interviews from many years. Furthermore, this article is not about preparation on general questions like- “tell me about yourself, where do you see yourself in next five years or why do you want to join our company etc.” There are many sites with best answers for preparation on general interview questions. This article attempts to focus more on expectations of interviewers from candidates and technical preparation for drug regulatory affairs interview for 0-2 years of experienced aspirants. Also it is to be noted that every interviewer has his/her own way of judging and selecting candidates as per suitability of vacancy. Hence this article should be considered as only a guide or reference while preparing for drug regulatory affairs interview.

Drug regulatory affairs interview questions may be grouped in following categories:

I)                   CMC (Chemistry, Manufacturing and Controls) based

II)                Life cycle management based

III)              Labelling

IV)             Publishing

V)                Miscellaneous

I) CMC (Chemistry, Manufacturing and controls) based questions:

CMC is major and important part of any dossier or drug master file. Below questions could be asked related to CMC part:

I.A) Filing process:

One of the very basic questions that may be asked by interviewer irrespective of market or the number of years of experience a candidate has, is filing process for the said market. For this it is expected to know complete process right from application of filing to final submission.

 I.B) Administrative requirements:

Knowledge of administrative requirements are also one of the important parameters. Even this requirement varies from country to country.  In many cases, administrative documents are screened before reviewing the dossier. If any of the documents are missing, then the agency may not start review until administrative requirements are fulfilled. Try to know how what all documents are required; how many copies are required in administrative section of dossier.

I.C) Differences in market: 

All countries follow ICH guidelines, however, still there are differences in requirement of dossier for each country. Knowing these differences can be of good advantage while working in regulatory field. E.g. Differences in DMF requirements in US and EU market. Differences between South Africa and Brazil market. etc. 

I.D) Variation guidelines:

Variation is also another name for the term “change”. So when any sort of changes occurs, it is expected to report the changes to respective regulatory authority of the country where the product is registered. There are guidelines mentioned by health agencies of respective countries on how to report changes. The changes may vary from minor to major. So even variation guidelines have been prepared accordingly. Hence if you are well versed with variation guidelines, you may save lot of time and even money of the organization by minimizing the changes and reporting accordingly. 

 II) Lifecycle management: 

II.A)      Knowledge about eCTD:

Major nations of the world are accepting electronic submissions through eCTD format. Other nations are in process of switching to eCTD. Soon we may see all regulatory submissions in eCTD format throughout the world. Hence if you are having knowledge about eCTD, then it will be an added advantage. Try searching websites to learn about various eCTD softwares available in market. 

II.B) Timelines :

All countries have their own timelines for approvals, sending queries from date of submission, audits trigger points, etc. Try to know these timelines required for as many countries as possible. This will keep you well aware of status for ongoing project. Some countries require that changes in submitted drug master file should be submitted on annual basis. 

III) Publishing: 

Publishing is basically filing or submitting compiled dossier or drug master file through electronic submission gateway to intended country. This is done with the help of publishing softwares. Get to know various publishing softwares available in market. There is separate vacancy only for publishing in some organizations.

IV) Labelling:

Labelling is basically part of finished formulation. Commonly expected questions could be differences between SMPC (Summary of Product Characteristics) and PIL (Patient information leaflet) and pack insert, components or contents of labelling materials, minimum requirements that should be present on a label etc. Like publishing, even for labelling there are separate vacancies in some organizations.

V) Miscellaneous:

Below points, though grouped as miscellaneous are very important for preparation of interview.

V.A) Purpose:

If you are complete fresher in field of drug regulatory affairs, then you should always expect this question of “WHY?”. With so many options available in pharmaceutical sector, there is high chance of being asked as why did you choose this career in particular. This question should be answered with complete sincerity since your answer could decide type of questions that would be asked further. 

V.B) ICH guidelines: 

Knowledge of ICH guidelines is very necessary for every drug regulatory affairs aspirant. These are very basic requirements and it is expected to know ICH guidelines very well. Though not all guidelines may be asked in interview, but one should not miss out on important guidelines as well. Q1A, Q1B, Q2A, Q2B, Q3A, Q5C, Q6A, Q6B, M7 are one of the important guidelines. This in any way doesn’t mean to mug up the guidelines. The whole purpose of ICH guidelines knowledge will be lost if guidelines are mugged up. It is very important to co-relate the guidelines with dossier or drug master file sections. 

V.C) Fees:

Knowledge about fees may probably be considered more important than technical knowledge itself. Almost all countries have their own DMF filing fees, dossier filing fees, facility fees, variation fees etc. This fee changes every year from country to country. Some regulatory agencies display fees on websites while some do not display fees. With knowledge of fees, if you are able to save the big amount by avoiding variations, timely filing etc. then you could be an important asset for hiring company. 

V.D) Formulas: 

ICH recommends various formulas for factors like having better control over impurities, calculation of daily dose requirement, calculating retest period, assigning expiry period, genotoxic impurities etc. As a regulatory professional it is expected to have knowledge about these formulas which can be very helpful while reviewing or preparation of specifications. 

V.E) Current updates: 

Being updated with most recent development or changes can be very advantageous not only for facing the interview but also in the long run of career. You may surprise the interviewers by showing level of curiosity in subject matter. Check all the recent developments even on the day of you interview, because changes happen on daily basis. This is not only applicable to DRA, but for all fields. Following is a real incident faced by an experienced RA professional few years ago in one of the drug regulatory affairs interview. After some technical questions, this person was asked about full form of ICH. As mentioned in first point, ICH is a very basic requirements and it is expected to know ICH guidelines very well. This person answered it correctly. But at the end of interview, he asked the interviewers as why such a basic question like full form of ICH was asked to him since he was not even a fresher. One of the interviewers replied that full from of ICH had been recently changed from International CONFERENCE of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use to International COUNCIL of Harmonisation of Technical Requirements for Pharmaceuticals for Human use. Most candidates still mentioned CONFERENCE instead of COUNCIL 

V.F) Brief knowledge on Quality Assurance (i.e. QA): 

A brief knowledge on quality assurance can be of great use while working in DRA. Complete information of QA is not expected but knowing basic terms like what is a change control, what is a CAPA, what is a change notification, what is an LIR etc. will help a lot. Knowing these terms will be beneficial in understanding the system of document flow. 

V.G) Know what NOT to do: 

This is a bit of tricky and difficult part especially for persons with no experience. Knowing what not to do comes from experience and learning from mistakes. All the guidelines, information on regulatory agency websites and other platforms will mostly display what is required and what needs to be done. Even in this article, above mentioned points are regarding what to do. But if you know about the things that should not be done, then there are great chances of avoiding major blunders. RTR guidelines (Refuse to Receive standards) mentioned in USFDA website is kind of guidelines that clearly mentions set of things that should not be done during submissions and if they are found during screening, then agency may refuse to receive the submission. 

Above points mainly focused on technical requirements that are expected in drug regulatory affairs interview. However, there are few non-technical things may be considered more important than having technical knowledge. Below are some of non-technical things that some interviewers consider more to be important than having good technical knowledge. Some interviewers even claimed that if a candidate is very strong in technical knowledge but not at all good in a few non-technical things then that candidate does not qualify for the post in spite of being technically sound. Let’s explore some very important non-technical things which need some serious attention. 

V.H) Communication skills:

Having good communication skills is one of the most important requirement in any career. Not only in career, but even in personal life communication skills matter a lot. In regulatory affairs field, one has to communicate daily with lots of people within the company, with stake holders, local and international customers, auditors, people in higher position in health agencies, owners and presidents of other companies etc. communication not only refers to verbal communication but also how you write emails. The words you use in your emails while communicating with different levels of persons speak a lot about the person you are. You need to have strong communication skills when it comes to dealing with such important persons of industry. One of the interviewer even said that if a person is having very good communication skills but technically, not up to expectations still that person qualifies for the job. Technical flaws could be overlooked as those things can be learnt in working environment but poor communication skills cannot be overlooked since a lot of work is mostly based on communication skills. Hence having good communication skills is very important while working in drug regulatory affairs. 

V.I) Team player 

Being a team player means how well you get along with the team and how your presence can benefit to the team. This is a type of quality that can be observed as the time passes by. Drug regulatory affairs is among those careers where you will realize that all days are not the same. Most of the days there are several new challenges. You might have to face a problem due to change in any guideline and you have to comply the requirements according to newly applicable guideline. it could also be request from regulatory agency which has to be sufficed within specified period of time etc. These are the kind of situations wherein quality of team player is developed in you. How well you support the team to get things done, how well you take a stand for your team during difficult situations are analyzed during such situations. 

V.J) Sincerity: 

A very basic but one of the very important quality that interviewers expect is sincerity. It is reflected not only in how you do your work but also how you present yourself and the way you have written your CV. One of the interviewers observed that just to make the CV look more attractive, some people even include about the things that they have only heard about, when asked in detail then there is no answer to what they have written. The interviewer further added that if you do not know the answer of any question that is being asked in interview, then accepting the fact that you don’t know its answer will be far more advantageous rather than giving any vague answers and trying to bluff. The interviewers are smarter than you and can spot in matter of seconds if you really know the answer or if you are trying to bluff it. 

So to conclude this article, these were some of the important points one needs to take care of before attending drug regulatory affairs interview. 

                                                       

Compilation of API drug master file with reference to ICH M4 Q (R1) guideline

Compilation of API drug master file with reference to ICH M4 Q (R1) guideline

This article is a summary of contents that should be part of API drug master file. Contents are referenced from ICH M4 Q (R1) guideline. Since this article is based on ICH guidelines, no changes have been made to content of guidelines and most of the data is included in as is form from the guideline. The information which is included in as is form is represented by “#” symbol at the end of respective title.

Module 2: Quality overall summary (QOS).

As the name suggests, this module should contain section wise summary of information which is presented in module 3.

Information that should be part of QOS:

• ü Sufficient information from each section to provide the quality reviewer with an overview of module 3.
• ü Should emphasize on critical key parameters of the product.
• ü  In case, any guideline is not followed in module 3, justification of the same should be included.

 Information that should NOT be part of QOS:

• Ø  Information, data or justification that was not already included in Module 3 or in other parts of the CTD.
• Ø  QOS normally should not exceed 40 pages of text, excluding tables and figures.

Below is a brief description summary of contents that should be included in quality over all summary (QOS).

Section number	Section name
2.3.S.1	General information
2.3.S.2	Manufacturer
2.3.S.3	Characterisation
2.3.S.4	Control of drug substance
2.3.S.5	Reference standards or materials
2.3.S.6	Container closure system
2.3.S.7	Stability

Section 2.3.S.1           General information

• Summarized (but not complete) Information included in section 3.2.S.1 should be presented.

Section 2.3.S.2           Manufacturer #

•  Information on the manufacturer;
•  A brief description of the manufacturing process (including, for example, reference to starting materials, critical steps, and reprocessing) and the controls that are intended to result in the routine and consistent production of material(s) of appropriate quality;
• A flow diagram, as provided in 3.2.S.2.2;
• A description of the source and Starting Material and raw materials of biological origin used in the manufacture of the drug substance, as described in 3.2.S.2.3;
• A discussion of the selection and justification of critical manufacturing steps, process controls, and acceptance criteria. Highlight critical process intermediates, as described in 3.2.S.2.4;
• A description of process validation and/or evaluation, as described in 3.2.S.2.5.
• A brief summary of major manufacturing changes made throughout development and conclusions from the assessment used to evaluate product consistency, as described in 3.2.S.2.6. The QOS should also cross-refer to the non-clinical and clinical studies that used batches affected by these manufacturing changes, as provided in the CTD-S and CTD-E modules of the dossier.

Section 2.3.S.3           Characterisation 

• A summary of the interpretation of evidence of structure and isomerism, as described in 3.2.S.3.1 and 3.2.S.3.2 should be included.

Section 2.3.S.4           Control of Drug Substance

• Brief summary of information included in section 3.2.S.4.1 specification should be included. This can be in tabular format.
• Similarly, summarized information on section 3.2.S.4.2 and 3.2.S.4.3 should be included.
• For batch analysis, tabulated summary of section 3.2.S.4.4 should be presented. E.g.:

Parameters	Specification	Batch 001	Batch 002	Batch 003
Description	Abc
Solubility	Xyz

Section 2.3.S.5           Reference Standards or Materials #

• Information from 3.2.S.5 (tabulated presentation, where appropriate) should be included.

Section 2.3.S.6           Container closure system #

• A brief description and discussion of the information, from 3.2.S.6 should be included.

Section 2.3.S.7           Stability #

This section should include a summary of the studies undertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions, the proposed storage conditions, retest date or shelf-life, where relevant, as described in 3.2.S.7.1.

The post-approval stability protocol, as described in 3.2.S.7.2, should be included.

A tabulated summary of the stability results from 3.2.S.7.3, with graphical representation

where appropriate, should be provided.

Module 3.2.S Drug Substance

Section number	Section name	Reference ICH Guidelines
3.2.S.1	General information
3.2.S.1.1	Nomenclature
3.2.S.1.2	Structure
3.2.S.1.3	General properties	Q6A and Q6B
3.2.S.2	Manufacturer
3.2.S.2.1	Manufacturer(s)
3.2.S.2.2	Description of manufacturing process and process controls
3.2.S.2.3	Control of materials	Q6A and Q6B
3.2.S.2.4	Control of critical steps and intermediates	Q6A and Q6B
3.2.S.2.5	Process validation and evaluation
3.2.S.2.6	Manufacturing process development	Q3A
3.2.S.3	Characterisation
3.2.S.3.1	Elucidation of structure and other characteristics	Q6A
3.2.S.3.2	Impurities	Q3A, Q3C, Q5C, Q6A, and Q6B
3.2.S.4	Control of drug substance
3.2.S.4.1	Specification	Q6A and Q6B
3.2.S.4.2	Analytical procedures	Q2A and Q6B
3.2.S.4.3	Validation of analytical procedures	Q2A, Q2B, and Q6B
3.2.S.4.4	Batch analysis	Q3A, Q3C, Q6A, and Q6B
3.2.S.4.5	Justification of specification	Q3A, Q3C, Q6A, and Q6B
3.2.S.5	Reference standards or materials	Q6A and Q6B
3.2.S.6	Container closure system
3.2.S.7	Stability
3.2.S.7.1	Stability summary and  conclusions	Q1A, Q1B, and Q5C
3.2.S.7.2	Post approval stability protocol and stability commitment	Q1A and Q5C
3.2.S.7.3	Stability data	Q1A, Q1B, Q2A, Q2B, and Q5C

3.1. TABLE OF CONTENTS OF MODULE 3

A Table of Contents for the filed application should be provided.

3.2. BODY OF DATA

3.2.S DRUG SUBSTANCE

3.2.S.1 General Information (name, manufacturer) #

3.2.S.1.1 Nomenclature

Information on the nomenclature of the drug substance should be provided.  For example:

• Recommended International Non-proprietary Name (INN);
• Compendial name if relevant;
• Chemical name(s);
• Company or laboratory code;
• Other non-proprietary name(s), e.g., national name, United States Adopted Name (USAN), Japanese Accepted Name (JAN); British Approved Name (BAN), and
• Chemical Abstracts Service (CAS) registry number.

3.2.S.1.3 General Properties

A list should be provided of physicochemical and other relevant properties of the drug substance, including biological activity for Biotech.

Reference ICH Guidelines:  Q6A and Q6B

Examples that should be included are description, solubility profile, pH values, melting point, boiling point, polymorphism, isomerism etc.

3.2.S.2 Manufacture #

3.2.S.2.1 Manufacturer(s)

The name, address, and responsibility of each manufacturer, including contractors, and each proposed production site or facility involved in manufacturing and testing should be provided.

3.2.S.2.2 Description of Manufacturing Process and Process Controls

The description of the drug substance manufacturing process represents the applicant’s commitment for the manufacture of the drug substance.  Information should be provided to adequately describe the manufacturing process and process controls.

A flow diagram of the synthetic process(es) should be provided that includes molecular formulae, weights, yield ranges, chemical structures of starting materials, intermediates, reagents and drug substance reflecting stereochemistry, and identifies operating conditions and solvents.

A sequential procedural narrative of the manufacturing process should be submitted.  The narrative should include, for example, quantities of raw materials, solvents, catalysts and reagents reflecting the representative batch scale for commercial manufacture, identification of critical steps, process controls, equipment and operating conditions (e.g., temperature, pressure, pH, time).

Alternate processes should be explained and described with the same level of detail as the primary process.  Reprocessing steps should be identified and justified.  Any data to support this justification should be either referenced or filed in 3.2.S.2.5.

3.2.S.2.3 Control of Materials #

Materials used in the manufacture of the drug substance (e.g., raw materials, starting materials, solvents, reagents, catalysts) should be listed identifying where each material is used in the process.  Information on the quality and control of these materials should be provided.

3.2.S.2.4 Controls of Critical Steps and Intermediates #

Critical Steps:  Tests and acceptance criteria (with justification including experimental data) performed at critical steps identified in 3.2.S.2.2 of the manufacturing process to ensure that the process is controlled should be provided.

Intermediates:  Information on the quality and control of intermediates isolated during the process should be provided. All in-process specifications, intermediate specifications and its certificate of analysis should be included in this section.

Reference ICH Guidelines:  Q6A and Q6B 

3.2.S.2.5 Process Validation and/or Evaluation #

Process validation and/or evaluation studies for aseptic processing and sterilisation should be included. A process validation report should be attached in this section of drug master file.

3.2.S.2.6 Manufacturing Process Development #

A description and discussion should be provided of the significant changes made to the manufacturing process and/or manufacturing site of the drug substance used in producing nonclinical, clinical, scale-up, pilot, and, if available, production scale batches. Reference should be made to the drug substance data provided in section 3.2.S.4.4.

Reference ICH Guideline: Q3A

3.2.S.3 Characterisation #

3.2.S.3.1 Elucidation of Structure and other Characteristics

Confirmation of structure based on e.g., synthetic route and spectral analyses should be provided. Information such as the potential for isomerism, the identification of stereochemistry, or the potential for forming polymorphs should also be included.

3.2.S.3.2 Impurities

This section is most important part of drug master file. This part can also be termed as “heart of drug master file” and can prove to be the toughest part for compilation of drug master file. All possible impurities should be identified, listed and described. A discussion should be included for control of impurities. Below is example for listing of impurities in tabular form:

Sr. No.	impurity name & structure	Type of impurity/ source of impurity
01.	Abc	Process related impurity
02.	Xyz	Degradation impurity

Reference ICH Guidelines:  Q3A, Q3C, Q5C, Q6A, and Q6B

3.2.S.4 Control of Drug Substance #

3.2.S.4.1 Specification

The specification for the drug substance should be provided.

Reference ICH Guidelines: Q6A and Q6B

3.2.S.4.2 Analytical Procedures #

The analytical procedures used for testing the drug substance should be provided.

Reference ICH Guidelines: Q2A and Q6B

3.2.S.4.3 Validation of Analytical Procedures #

Analytical validation information, including experimental data for the analytical procedures used for testing the drug substance, should be provided.

Reference ICH Guidelines: Q2A, Q2B, and Q6B

3.2.S.4.4 Batch Analyses #

Description of batches and results of batch analyses should be provided.

Reference ICH Guidelines: Q3A, Q3C, Q6A, and Q6B

3.2.S.4.5 Justification of Specification #

Justification for the drug substance specification should be provided.

Reference ICH Guidelines: Q3A, Q3C, Q6A and Q6B

3.2.S.5 Reference Standards or Materials #

Information on the reference standards or reference materials used for testing of the drug substance should be provided.

Reference ICH Guidelines: Q6A and Q6B

3.2.S.6 Container Closure System #

A description of the container closure system(s) should be provided, including the identity of materials of construction of each primary packaging component, and their specifications. The specifications should include description and identification (and critical dimensions with drawings, where appropriate). Non-compendial methods (with validation) should be included, where appropriate.

The suitability should be discussed with respect to, for example, choice of materials, protection from moisture and light, compatibility of the materials of construction with the drug substance, including sorption to container and leaching, and/or safety of materials of construction.

3.2.S.7 Stability #

3.2.S.7.1 Stability Summary and Conclusions

The types of studies conducted, protocols used, and the results of the studies should be summarized. The summary should include results, for example, from forced degradation studies and stress conditions, as well as conclusions with respect to storage conditions and retest date or shelf-life, as appropriate.

Reference ICH Guidelines:  Q1A, Q1B, and Q5C

3.2.S.7.2 Post-approval Stability Protocol and Stability Commitment

The post-approval stability protocol and stability commitment should be provided.

Reference ICH Guidelines:  Q1A and Q5C

3.2.S.7.3 Stability Data

Results of the stability studies (e.g., forced degradation studies and stress conditions) should be presented in an appropriate format such as tabular, graphical, or narrative. Information on the analytical procedures used to generate the data and validation of these procedures should be included.

Reference ICH Guidelines:  Q1A, Q1B, Q2A, Q2B, and Q5C