Basic Questions Of The Pharmaceutical Industry
1. What are user requirements?
Answer:
User Requirements Specification describes what users require from the System. User requirement specifications are written early in the validation process, typically before the system is created. It is written by the System Owner and End Users, with input from Quality Assurance. Requirements outlined in the URS are usually tested in the Performance Qualification. User Requirements Specifications are not intended to be a technical document; readers with only a general knowledge of the system should be able to understand the requirements outlined in the URS.
2. What is a validation plan?
Answer:
Validation Plans define the scope and goals of a validation project. Validation plans are written before a validation project and are specific to a single validation project. Validation Plans can include Deliverables (Documents) to be generated during the validation process Resources/Departments/Personnel to participate in the validation project, and a Time-Line for completing the validation project.
3. What is a Validation Summary Report?
Answer:
Validation Summary Reports provide an overview of the entire validation project. When regulatory auditors review validation projects, they typically begin by reviewing the summary report. The validation summary report should include: A description of the validation project and All test cases performed, including if those test cases passed without issue All deviations reported, including how those deviations were resolved.
4. What is a Change Request?
Answer:
Change Control is a general term that describes the process of managing how changes are introduced into a controlled system. In validation, this means how changes are made to the validated system. Change control is required to demonstrate to regulatory authorities that validated systems remain under control after system changes. Change Control systems are a favorite target of regulatory auditors because they vividly demonstrate an organization's capacity to control its systems.
5. What is the difference between calibration and Validation?
Answer:
Calibration is a demonstration that, a particular Instrument or device produces results within specified limits by comparisons with those produced by a reference or traceable standard over an appropriate range of measurements.
Validation is a documented program that provides a high degree of assurance that a specific process, method, or system consistently produces a result meeting pre-determined acceptance criteria.
In calibration, the performance of an instrument or device is compared against a reference standard. But in validation such reference standard is not used.
Calibration ensures that instruments or measuring devices produce accurate results.
Whereas validation demonstrates that a process, equipment, method, or system produces consistent results (in other words, it ensures that uniform batches are produced).
6. What are Regulatory Affairs?
Answer:
Regulatory Affairs in the Pharmaceutical industry is a profession that 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 before their marketing.
7. What are the goals of Regulatory Affairs Professionals?
Answer:
Protection of human health Ensuring safety, efficacy, and quality of drugs Ensuring appropriateness and accuracy of product information.
8. What are the Roles of Regulatory Affairs professionals?
Answer:
Act as a liaison with regulatory agencies Preparation of organized and scientifically valid NDA, ANDA, INDA, MAA, and DMF submissions Ensure adherence.
9. What is a New Drug Application?
Answer:
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 the USA.
10. What is an Abbreviated New Drug Application (ANDA)?
Answer:
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 “
11. What is a Generic Drug Product?
Answer:
A generic drug product is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics, and intended use.
12. What is the difference between GMP & cGMP?
Answer:
GMP: GMP is the part of Quality assurance that ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.
GMPs are aimed primarily at diminishing the risks inherent in any pharmaceutical production.
Such risks are essentially of two types:
1. Cross-contamination (in particular of unexpected contamination)
2. Mix-ups (confusion)
cGMP: Current Good Manufacturing Practices. This means any procedure/system adopted by the manufacturer that proves to be necessary and important for the identity, strength, and purity of a product.
13. What is the definition of Validation?
Answer:
Validation is the documented program that provides a high degree of assurance that a specific process, method, or system will consistently produce a result meeting predetermined acceptance criteria.
14. What is the definition of Qualification?
Answer:
Qualification is the action of proving and documenting that any equipment or ancillary systems are properly installed, work correctly, and lead to the expected results. Qualification is part of validation, but the individual qualification steps alone do not constitute process validation.
15. What are the types of validation?
Answer:
Process validation, Analytical method validation, cleaning validation, facility validation, Utility validation & software validation.
16. What is the definition of the procedure?
Answer:
A documented description of the operation to be performed, the precautions to be taken, and measures to be applied directly or indirectly related to the manufacture of an intermediate / API (Reference: ICH Q7A).
17. What are the types of different training programs?
Answer:
1. Induction training
2. Job oriented training
3. cGMP training
4. On-going training
18. What are the different types of cleanings?
Answer: There are three types of cleanings:
• Batch to Batch cleaning
• periodically cleaning
• Product change over cleaning
19. What is the expiry date & re-test date?
Answer:
Expiry date: The date placed on the container/labels of an API designated the time during which the API is expected to remain within established shelf life specifications if stored under defined conditions and after which it should not be used.
Re-test date: The date when a material should be re-examined to ensure that it is still suitable for use. The period during which the drug substance is expected to remain within its specifications and therefore, can be used in the manufacturing of the drug product, provided that the drug substance has been stored under the defined conditions.
20. What is contamination and cross-contamination?
Answer:
Contamination: The undesired introduction of impurities of a chemical or Microbiological nature, or foreign matter, into or onto a raw material, intermediate, or API during production, sampling, packaging or repackaging, storage, or transport.
Cross-contamination: Contamination of a material or a product with another material or product.
21. What is the Batch number and batch?
Answer:
Batch Number: A unique combination of numbers, letters, and/or symbols that identifies a batch (or lot) and from which the production and distribution history can be determined
Batch: A specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits. In the case of continuous production, a batch may correspond to a defined fraction of the production. Batch size may be defined either by a fixed quantity or the amount produced in a fixed time interval.
22. What is quarantine?
Answer:
The status of materials isolated physically or by other effective means pending a decision on their subsequent approval or rejection.
23. What is the definition of critical process parameters?
Answer:
A process parameter whose variability has an impact on a critical quality attribute and therefore should be monitored or controlled to ensure the process produces the desired quality.
24. What is the difference between theoretical and expected yield?
Answer:
Theoretical yield: The quantity that would be produced at any appropriate phase of production, based upon the quantity of material to be used, in the absence of any loss or error in actual production.
Expected yield: The quantity of material or the percentage of theoretical yield anticipated at any appropriate phase of production based on previous laboratory, pilot scale, or manufacturing data.
25. What is OOS?
Answer:
Out of Specification (OOS) results are those results, generated during testing that do not comply with the relevant specification or standards or with the defined acceptance criteria.
26. What is OOT and what is it?
Answer:
“OOT” stands for Out Of Trend. It means any test results obtained for a particular batch that is markedly different from the results of the batches in a series obtained using the same validated method.
27. What is CAPA?
Answer:
CAPA is Corrective Action & Preventive Action.
Corrective Action: Action taken to eliminate the causes of an existing non-conformity, defect, or other undesirable situation to prevent recurrence. [Actions taken after the occurrence of a defect or problem to stop the same from recurrence].
Preventive Action: Action taken to eliminate the causes of potential non-conformity, defect, or other undesirable situations to prevent occurrence. [Actions initiated before the occurrence of a defect or problem to prevent the same occurrence].
28. How will you close a market complaint?
Answer:
(a) If a satisfactory response is obtained from the complainant against our written reply
(b) If the material is recalled
(c) If no response is obtained from the complainant after 90 days (or specified in SOP) from the date of our written reply.
29. What is the difference between a controlled copy and an uncontrolled copy?
Answer:
Controlled copy: A controlled copy is a formal copy of the latest, correct issue of a document; an identified issue of a document to an individual or location of record. The controlled copy is officially tracked, updated & destroyed to ensure that it is current.
Uncontrolled copy: An informal copy of a document for which no attempt is made to update if after distribution; the document is marked “uncontrolled” and the user determines if the document is active before use.
30. What do you mean by reconciliation?
Answer:
A comparison, making due allowance for normal variation, between the amount of product or material theoretically & produced/used.
31. What do you mean by product recall?
Answer:
Product recall means the removal or withdrawal of marketed material due to violation of laws & regulations as per regulatory authorities or not conforming to the customers’ specifications.
32. What do you mean by residual solvent?
Answer:
These are the traces of the solvents left during the manufacturing of drug substances or drug products. Residual solvents are not completely removed by practical manufacturing techniques.
33. What will happen if cGMP is not followed?
Answer:
Non-compliance to cGMP may lead to:
- Poor quality of product/services
- Batch failure
- Market complaints and product recalls
- Company’s reputation affected
- Business will be affected
- Regulatory action
- Injuries or accidents
- Equipment failures
34. What are the safety systems in the plant?
Answer:
Some of the safety systems used in the plant are:
- Eye washer, safety showers
- Fire extinguishers
- Fire hydrants
- Face shields
- Goggles
- Helmets
- Nose masks
- Safety shoes
- Safety belts
- Hand gloves
- Training on safety rules and use of safety equipment.
35. Write the different parts of 21 CFR and details of different subparts of 21 CFR 211.
Answer:
21 CFR Part 11: Electronic records, Electronic signatures, Electronic copies of electronic records.
21 CFR Part 58: GLP for Non-clinical Laboratory studies regulation.
21 CFR Part 210: cGMP in manufacturing, processing, packing/holding of drug.
21 CFR Part 211: cGMP regulations for finished pharmaceuticals.
21 CFR Part 820: GMP regulations for medical devices.
36. What is the difference between a drug substance and a drug product?
Answer:
Drug substance (API): 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 (Reference: ICH Q7A).
Drug product: The dosage form in the final immediate packaging intended for marketing (Reference: ICH Q7A).
37. What is the difference between intermediate and drug substances (API)?
Answer:
Intermediate: A material produced during steps of the processing of an API that undergoes further molecular change or purifications before it becomes an API (Reference: ICH Q7A).
API: Any substance or mixture of substances intended to be used in the manufacturing of a drug (medicinal) product and that when used in the production of a drug, becomes an API 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 & function of the body (Reference: ICH Q7A).
38. Which Guidelines are followed for the preparation of SMF?
Answer:
PIC/S and EU Guideline (Eudralex Volume-4).
Preparation: SMF is Prepared by Quality Assurance and Reviewed by Plant Head and Authorised by Head QA.
Contents of SMF:
1. General Information
2. Personnel
3. Premises and Equipment
4. Documentation
5. Production
6. Quality Control
7. Contract Manufacture and Analysis
8. Distribution, Complaints, and Product Recall.
9. Self-Inspection
Review Period; Any changes after approval of SMF shall be recorded in Annexure-II to keep track of changes taking place. All such changes shall be collated and amended in the next revision.
Site Master File shall be revised at the end of every calendar year or as and when required through the change control management system.
Storage Period; The Site Master File shall be stored by the QA department for 10 years.
39. What is the Definition of MARKET COMPLAINTS?
Answer:
A complaint is any expression of dissatisfaction with a product or service marketed.
Any written/ genuine verbal communication received directly from any customer, retailer, distributor, healthcare professional, regulatory agency, patient (Consumer), or field staff, regarding the safety, identity, strength, purity, efficacy, quality, shortages, or any other such complaints shall be considered as a Market Complaint.
Critical Complaint:
A complaint that strongly indicates the purity, identity, safety, or efficacy of a product may have been compromised and has the potential to cause a life-threatening or serious health situation.
Major Complaint:
A complaint that indicates the purity, identity, safety, or efficacy of a product may have been
compromised, but does not present as a life-threatening or serious health risk.
Minor Complaint:
A complaint that is neither critical nor serious
TIMELINES FOR INVESTIGATION:
The investigation shall be completed within 7 working days for critical complaints and 30 working days for Major/Minor (or as per Technical Agreement requirement or Regulatory Agency requirement where appropriate) and the same shall be sent to the marketing department immediately after the investigation.
40. What is the Definition of PRODUCT RECALL?
Answer:
Removal or correction of marketed products for reasons relating to deficiencies in quality, safety, or efficacy, including labeling considered to violate the laws.
Wholesale Level: All distribution levels between the manufacturer and retailer.
Class I Recall: Notification and acknowledgment of receipt of recall notification within 24hrs.
Class II Recalls: Notification and acknowledgment of receipt of recall notification within 48 hours.
Class III Recalls: Notification and acknowledgment of receipt of recall notification within 5 days.
Mock recall shall be done to evaluate the effectiveness of arrangements periodically to recall the products from EU / US / Australia / other export markets and domestic markets. A mock recall applies only to markets where the product is already marketed.
The frequency of Mock Recall shall be once in two years or as per MA Holder / Contract giver
requirement.
41. Which TYPES OF PASS BOX?
Answer:
1. Dynamic Pass Box
2. Static Pass Box
DYNAMIC PASS BOX
For Material transfer from unclassified area to classified area.
This Pass box has a HEPA filter and UV Light
Frequency of Validation is every six months
Test:
1. Air Velocity
2. Filter Integrity
3. Particle count
STATIC PASS BOX
For Material transfer from classified area to classified area.
42. What is the Batch production and control record (BPCR)?
Answer:
BPCR is prepared for each intermediate and API and includes the complete information relating to the completion of each significant step in the Batch production.