July 1, 2021: Pharmaceutical Interview Questions and Answers
1. What is the Good Manufacturing Practice (GMP) or Current Good Manufacturing Practice (CGMP)? Provide reference of GMP regulations of different countries.
Quality of pharmaceuticals is important for the patient safety and are very carefully regulates by respective country regulators.
GMP or CGMP refers to the Current Good Manufacturing Practice regulations enforced by the respective country regulations.
GMP provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the GMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations.
US FDA uses terminology CGMP. According to the U.S. FDA, “‘C’ in CGMP stands for “current,” requiring companies to use technologies and systems that are up-to-date in order to comply with the regulations. Systems and equipment that may have been “top-of-the-line” to prevent contamination, mix-ups, and errors 10 or 20 years ago may be less than adequate by today’s standards.”
GMP regulations governed by different countries and its reference guidance are detailed as follows. Following table provide reference for most common regulatory bodies. This will provide understanding on how GMP regulations are forced by different regulatory bodies.
|Country||Regulatory Body||Reference regulations under respective country’s law|
|United States||U.S. FDA||Code of Federal Regulations (CFR): |
21 CFR Part 210. Current Good Manufacturing Practice in Manufacturing Processing, packing, or Holding of Drugs.
21 CFR Part 211. Current Good Manufacturing Practice for Finished Pharmaceuticals.
21 CFR Part 212. Current Good Manufacturing Practice for Positron Emission Tomography Drugs.
21 CFR Part 600. Biological Products: General.
21 CFR Part 314. For FDA approval to market a new drug.
|European Union (EU) Countries||European Commission – Health and Food Safety||The entire body of EU medicines legislation (EudraLex) is compiled in “The rules governing medicinal products in the European Union”. Pharmaceutical sector is compiled in Volume 1 and Volume 5 of the publication “The rules governing medicinal products in the European Union”: |
Volume 1 – EU pharmaceutical legislation for medicinal products for human use
Volume 5 – EU pharmaceutical legislation for medicinal products for veterinary use
|Countries following WHO guidance||World Health Organization (WHO)||WHO good manufacturing practices for pharmaceutical products: main principles, Annex 2, WHO Technical Report Series 986, 2014|
|India||Ministry of health and family welfare||The drugs and cosmetics act, 1940 and The drugs and cosmetics rules, 1945 Schedule M: Good Manufacturing Practices and requirements of premises, plant and equipment for pharmaceutical products|
|Canada||Health Canada||Good Manufacturing Practices Guidelines by Health Products and Food Branch Inspectorate Good Manufacturing Practices (GMP) refer to Division 2, Part C of the Food and Drug Regulations. The guidelines apply to pharmaceutical, radiopharmaceutical, biological, and veterinary drugs and were developed by Health Canada in consultation with their stakeholders. Division 1A, Part C of the Food and Drug Regulations defines activities for which GMP compliance is to be demonstrated prior to the issuance of an establishment license. Guidance based on PIC/S|
|Japan||Pharmaceuticals and Medical Devices Agency (PMDA)||Pharmaceuticals and Medical Devices Agency (PMDA) was established and came into service on April 1, 2004, under the Law for the Pharmaceuticals and Medical Devices Agency, as a consolidation of the services of the Pharmaceuticals and Medical Devices Evaluation Center of the National Institute of Health Sciences (PMDEC), the Organization for Pharmaceutical Safety and Research (OPSR/KIKO), and part of the Japan Association for the Advancement of Medical Equipment (JAAME). GMP Ministerial Ordinance (Ministerial Ordinance on Standards for Manufacturing Control and Quality Control for Drugs and Quasi-drugs) No. 179, 2004|
|Australia||Therapeutic Goods Administration||AUSTRALIAN CODE OF GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS Therapeutic Goods Act 1989. This upholds the main objective of the Act, which is to ensure the safety, quality, efficacy and timely supply of therapeutic goods for Australian consumers. Guidance based on PIC/S|
|New Zealand||Medsafe||New Zealand Code of Good Manufacturing Practice for Manufacture and Distribution of Therapeutic Goods Part 1: Manufacture of Pharmaceutical Products (2009) Guidance based on PIC/S|
2. What is Standard Operating Procedure (SOP)?
SOPs are documented Standards Operating Procedure, authorized by Quality Unit or Quality Assurance department having sets of written instructions to be followed by employees on day to day basis to carryout operations in consistent manner to achieve pre-determined specification and a quality end-result.
Examples of Standard Operating Procedures are as follows:
– SOP for entry and exit in the manufacturing facility
– SOP for operation and cleaning of compression machine
– SOP for preparation of SOP
– SOP for pest control
– SOP for material receipt
– SOP for preventive maintenance program
– SOP for operation of High Performance Liquid Chromatography (HPLC) instrument
3. What is the typical content of Standard Operating Procedure (SOP)?
Objective or Purpose
List of Annexes
Format for recording Revision history
4. What is Master Formula Record, Master Formula, Manufacturing Formula, and Master Production and Control Record?
Master Formula Record, Master Formula, Manufacturing Formula, and Master Production and Control Record mean the same thing. This is an approved master document that describes the full manufacturing process of the drug product. [Reference: 1]
5. What is drug substance?
Drug substance is an active ingredient that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the human body, but does not include intermediates used in the synthesis of such ingredient. [Reference: 2]
1. WHO GMP Guidelines: Guide to Master Formulae, WHO/FWC/IVB/QSS/VQR, 2011
EU and PIC GMP guidelines: EudraLex Volume 4, Chapter 4: Documentation
PIC/S guidelines: Chapter 4: Documentation
Health Canada GMP guidelines: Good manufacturing practices guide for drug products (GUI-0001), Manufacturing control, C.02.011
U.S. FDA: CFR 21, Chapter I, Subchapter F: Biologics, Part 211 Current Good Manufacturing Practice for Finished Pharmaceuticals; Subpart F–Production and Process Controls, Sec. 211.100 Written procedures; deviations; and Subpart J–Records and Reports; Sec. 211.186 Master production and control records
U.S. FDA: CFR 21, Chapter I, Subchapter F: Biologics; Subchapter C: Drugs General; Part 211 Current Good Manufacturing Practice for Finished Pharmaceuticals; Subpart J– Records and Reports; Sec. 211.188 Batch production and control records.
India: The drugs and cosmetics act, 1940 and The drugs and cosmetics rules, 1945, Schedule M, 12. Documentation and records]
2. PART 314 — APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG, Subpart A – General Provisions Sec. 314.3 Definitions.
3. 21 CFR PART 210: CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL Sec. 210.1 Status of current good manufacturing practice regulations.
5. Wet Granulation:
End-Point Determination and Scale-Up, By Michael Levin, Ph. D., Metropolitan Computing Corporation East Hanover, New Jersey, USA
6. Saudi Pharmaceutical Journal
Volume 20, Issue 1, January 2012, Pages 9-19, Saudi Pharmaceutical Journal, Review article, Upgrading wet granulation monitoring from hand squeeze test to mixing torque rheometry Author links open overlay panel Walid F. Sakr Mohamed A. Ibrahim Fars K. Alanazi Adel A. Sakr