complaint and its handling

This content includes about the complaints in pharmaceutical industry and how they are handled .

1. M. Pharm Sem-I Presentations Title:Complaint and its handling SUBMITTED TO SAVITRIBAI PHULE, PUNE UNIVERSITY , PUNE FOR PARTIAL FULFILMENT OF REQUIREMENTS FOR THE AWARD OF MASTER OF PHARMACY IN THE SUBJECT Quality Management System IN THE FACULTY OF SCIENCE AND TECHNOLOGY Bhujbal Knowledge City, MET’s Institute of Pharmacy, Adgaon, Nashik, 422003. Maharashtra, India Academic Year-2021-2022 1 Presented By-Shaikh Saniya Zakir Guided By-Dr.Sapana Ahirrao

2. COMPLAINT AND ITS HANDLING What is complaint? Complaint is defined as a statement that something is wrong or not good enough.Generally In pharmaceutical industry,complaints are regarding the quality of product. A complaint shows customer dissatisfaction about a product, and consequently about a company. Complaints can be regarding- The bottle is leaking Cap is difficult to open One tablet in the blister is missing There is no effect, solution or tablet colour is different and so on 2

3. Objective: To immedietly recall the product Investigate and to take corrective measure against the product in question “Recall” -A firm’s removal or correction of a marketed product that FDA considers to be in violation of laws Types of complaints: Quality complaints Adverse reaction complaints Medical related complaints 3

4. Quality complaint: concerned with physical,chemical and biological properties or conditions such as labelling or packaging Adverse reaction complaints: due to allergic reactions,unwanted/fatal/near fatal reactions Medical related complaints: such as lack of efficacy or clinical response 4

5. Steps involved in handling of complaints Step 1:Receiving complaints Important to have open channels with customer to receive suggestions,doubts,complaints Toll free nos.,emails,chatrooms etc. Necessary to have a person in charge of receiving and inputting them into investigation Then address to QA unit for investigation 5

6. Step 2:Technical investigation Once receipt of investigation form,the QA unit starts investigation,divided into two phases: Documentation Based Checking wether the same complaint occurred in preceeding lot or if any noncompliance seen in the lot during its production Labortary Analysis Phase Informing QC labortary to analyze both samples (complaint &retained) If customer unable to send complaint sample,the retained sample will be used for analysis or investigation 6

7. There are three possible conclusions,as follows after QA unit is done with the investigation. 1)Confirmed complaint: When both complaint & retained samples showed out of specification(OOS)/only the complaint sample showed OOS results,but it is clearly a single unexplained failing product e.g when single tablet is missing in the blister strip but no deviation seen in retained sample during analysis(quality problem is identified in the product) 2)Non-confirmed complaint: When both complaint & retained samples showed result in compliance with specifications or only complaint sample showed OOS result considerd as single unexplained failing product e.g tablets show a change in colour due to exposure to various environmental factors(it is due mishandling of product and inappropriate storage conditions maintained,not a manufacturing deviation) 7

8. 3)Counterfeit/tamper suspicion: When the retained sample is within the specification but the complaint sample is OOS with no reason for that considerd as counterfeit/tamper suspicion e.g when packaging material is different from original,colour of product is different from original product The complaint officer needs to check if the complaint has any serious or unexpected adverse reaction, if any is to be reported to the concerned authorities Retention time of complaint files is regulated by the concernrd country authority; however 30 days is reasonable time to conclude investigation Complaint files should be retained for at least 1 year after the expiry date of the lot 8

9. Step 3:Corrective Action And Preventive Actions(CAPA) and feedback to customer The criteria for choosing appropriate action depends on nature of complaint If deviation is a single unexplained failing product or not,if a CAPA is opened,a multidisciplinary team consisting representatives of QA,QC,DRA and production management is established If a quality problem in a particular lot ,other lots also should be investigated 9

10. The company must evaluate if there is any probability with the use or exposure to the product may cause permenant injury,life threatening,temporary or any medical health problem As feedback to customer,company must write a response letter to the explainant about the investigation, actions taken,results obtained or implications(if quality problem is confirmed) The customer should be sent a free replacement product alongside 10

11. 4)Monthly reports and trend analysis Monthly reports should be elaborated in order to evaluate the amount and nature of the complaints recieved and to perform trend analysis of the company. The monthly reports must answer the following questions: How many complaints did the company received in the period? How many were confirmed? How many were non confirmed or counterfeit? Important to know “top 10” products which received majority of complaints(the detailed information). How much the complaint handling cost the company? The detailed reports should be maintained about the complaint. 11

12. Problem: A pharmaceutical company had produced an uncoated white tablet product with reliable and reproducible product attributes and process performance. No ongoing problems, process trends, or patient complaints were discovered during annual product quality reviews and process monitoring. Green to greenish-blue and occasionally brown spots were observed on the tablets during routine batch production. 12 Case Study:

13. Investigation part 1:Evaluation of the problem The examination of tablets with green spots revealed that the spots were only present on the tablet surface and not within the tablet core. The tablet press was then disassembled and examined. It was discovered that a brown low viscosity oil, rather than a thick grease, was used as lubricant on the upper punches. Because oil is mobile and can creep, the upper punches' dust cups were examined and found to be worn. Dust or grease cups are used to keep grease or lubricant from falling into the compressed media. 13

14. It was thus hypothesised that the spots were caused by a low viscosity upper punch lubricant (rather than a high viscosity grease) moving down the surface of the upper punches via gravity, passing through the worn dust cups, and then onto the tablet punch surfaces, resulting in the formation of spots on the tablet surfaces during tablet compression. Then formulation materials were also checked,but there was no problem seen with them. 14

15. Then lot numbers of each component was checked against the lot numbers used in the product batches that experienced spots.  Only one item was found to be different in the tablet lots that experienced spotting – a new lot of talc(glidant). Talc, also known as hydrated magnesium silicate, is a natural mineral that is mined.Being a natural ingredient, it is inherently predisposed to variation;  t alc contains a wide variety of impurities, one of which is chlorite (ores associated with talc).  For example, naturally occurring talc can be green, white, gray, brown, or colorless.  Green talc is usually due to the presence of the chlorite minerals,hence the green colour spots related to chlorite. 15

16. Investigation part 2:Identify and implement CAPA The analysis then focused on an interaction between the top punch lubricant in the tablet press, aggravated by worn punch dust cups, interacting with the chlorite impurities in some lots of talc, and resulting in the creation of coloured spots. Next is confirming this hypothesis, Samples of the final blend, containing the new lot of talc associated with green spots, were obtained.  An aliquot of the upper punch lubricating oil was added and mixed.  The blend turned the same greenish color as the tablet spots, thus confirming the interaction. I mpurity profile of the talc is checked(inherent variation). Test methods for chlorites in talc was reviewed.  However, as there are several kinds of chlorites in talc, and as powerful analytical methods would be required. Discussions were also held with the Production Department about switching the tablet press tooling lubricant from an oil to a grease, as greases are less mobile than oils. 16

17. After evaluation found that the oil used as the lubricant in Production resulted in the discoloration, while other oils did not.  Training was done with the tablet press operators regarding the problem. Summary of CAPA:   The following CAPAs and activities were carried out: A new lubricant for compressing machines that is compatible has been discovered. Dust cups for tablet punch were replaced with new ones. A new lubricating process for the compressing machine was implemented. Personnel were trained on the situation, what problems to check for, and why the corrective steps were taken. Documentation for the project was prepared, reviewed, and approved. 17

18. Conclusion: The spots were determined to be caused by interactions between trace impurities in talc (formulation ingredient) and the tablet press punch lubricant, as well as worn dust cups used in the tablet compressing process. The usage of new punch dust cups, as well as a new talc-compatible lubricant, was implemented.The root cause found is the issues in tablet press operation . To properly shut the CAPA, all investigations, assessments, and conclusions were documented. 18

19. References: 1. Potdar, M. A. (2009). CURRENT GOOD MANUFACTURING PRACTICE FOR PHARMACEUTICALS., 590-594 2. J. D. (2007). GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICALS (NaN ed., Vol. 169). Informa healthcare USA,Inc. ,169,188,193 3. GMP Complaint Handling System - GMP7.com 4. https://www.pharmatutor.org/articles/systematic-approach-complaint-handling-pharmaceutical-industries-updated-review 5. https://www.pharmaguideline.com/2011/08/sop-for-handling-of-market-complaints.html 6. https://onlinelibrary.wiley.com/doi/pdf/10.1002/qaj.398 7. https://www.ivtnetwork.com/article/compliance-case-study-17-spots-tablets-%E2%80%93-investigation 19