1. The document discusses procedures for handling complaints and product recalls in the pharmaceutical industry. It defines complaints, outlines standard operating procedures for complaint handling, investigation and corrective actions. 2. Recall procedures include classification of recalls based on health hazards, forming a recall team, developing a recall strategy, notifying customers, and terminating a recall once all affected products are removed from the market. 3. Key aspects of complaint handling covered are documentation of complaints, investigating complaints by analyzing customer and retained samples, determining if complaints are confirmed or non-confirmed, and providing feedback to customers.

1. COMPLAINTS AND RECALLS HANDLING. PRESENTED BY, HUSNA KANWAL QURESHI. M.Pharm, 1st yr, 2 nd sem. UNDER THE GUIDANCE OF Dr. T. MAMATHA M.Pharm, Ph.D. QUALITY ASSURANCE.

2. COMPLAINT HANDLING DEFINATION OF COMPLAINT: “ Complaint is defined as statement that is something wrong or not good enough, which shows customer dissatisfaction about the company and the product”. Example: Complaint about packaging materials, Concerning about the product etc .

3. NEED FOR COMPLAINT HANDLING SYSTEM It gives the company an opportunity to improve the quality of the product It is helpful to maintain cGMP It maintains committed relationship between the customer and company It is the regulatory obligation.

4. SOP on complaint handling OBJECTIVE: To lay out the procedure for investigation and reporting the market complaints. RESPONSIBILITY: The quality assurance manager along with manager of the complaint related department. PROCEDURE: Complaints shall be classified in following categories to facilitate investigation: Product quality complaints (non therapeutic). Packaging complaints (shortages and packaging error). Medical complaints (therapeutic problems).

6. Time period for investigation after receipt of complaints: Product quality complaints – within 5 days. Packaging and quality complaints – within 10 days. Medical complaint – within 3 days. Complaint records shall be maintained at least one year after expiration date of medicines. Complaint records shall be reviewed and a monthly summary shall be prepared for the management.

7. PRODUCT NAME COMPLAINT CATEGORY Batch no. Mfg.date expiry date Packaging/ product quality/ medical. Packaging details: Name / address of the complainant: Complaint reported through: Complainant sample enclosed: yes / no Quality of sample enclosed: Investigation report Total quantity involved PCR received by On: Investigation done by: Action taken Conclusion: Confirmed/not confirmed PCR no: PCR approved by: recommended corrective actions

8. Product complaint data sheet Product complaint data sheet should have the following details: Serial number assigned to the complaints. Exact nature of the complaints. Name of the complainants. Address of the complainants. Date of complaint received. If verbal, name of the person who received the complaint. Name of the product, strength and batch number of the product. Reference to analytical record number.

9. Quantity involved in the complaint. Size of sample obtained from the complainant. Evaluation of complaint by QC department. Materials and records used to perform evaluation. Other possible effected materials, products and results of their investigation. Name and signature of the investigator(s) and date. Action taken by the company. Copy of reply sent to complainant.

10. Steps in handling of complaints The proposed handling system is in compliance with the GMP Guidelines of EU, USA and Brazil and is presented in four steps: Receiving complaints. Technical investigation. Corrective actions/feedback to Customers. 4. Monthly reports/trend analysis.

11. Receiving complaints It is important to have open channels with with customers in order to receive their suggestions, doubts and complaints. Generally, these channels are toll-free numbers, e-mails, chat-rooms and P.O. boxes. The most flexible channels are toll-free numbers and chat-rooms. A person must be appointed in charge of receiving complaints and inputting them into appropriate investigation form that shall be addressed.

12. The investigation form must include: Information about the complainant: - Name - Address - phone no. - E mail Information about the drug product - Product name - Lot no - MFG & Exp date - Amount of the product with the problem. - Detailed description of the complaint.

13. customer Company's contact person QA complaint officer Make a complaint through toll free no., E-mails, P.O. Box Open the investigation, including information about the customer and about the complaint(product name, lot no., mfg & expiry date and complaint description.) Ask the customer to return the product for analysis.

14. Technical investigation Upon receipt of the investigation form, the QA unit is able to start the investigation. It is divided into two phases: Documentation based investigation. Laboratory analysis. Documentation based investigation : The primary documentation to be reviewed consists of: Complaint files: This is constituted to check how many other complaints of the same nature had occurred to a specific lot and how they were handled. Batch records must be verified in order to see if there were any non-conformance during the production.

15. Laboratory analysis phase It consists of requesting the Quality Control (QC) laboratory to analyze. Complaint samples. Retained samples. Complaint samples are the customer sample. Retained samples – the reserve samples representative of the lot manufactured (which were kept under appropriate conditions of temperature, humidity and light so that the drug product was not affected). The company elects a person in the QA unit to be in charge of technical investigation of each complaint, e.g. a Complaint Officer.

16. Documentation based Check complaint files for previous complaints of same nature. Check batch records.

17. There are three possible conclusions, as follows: Confirmed complaints. Non confirmed complaints. Counterfeit/ tamper suspicion. CONFIRMED COMPLAINTS: When both complaint and retained samples showed out-of-specification (OOS) results or when only the complaint sample showed OOS results. Example : a single unexplained failure may be when one tablet is missing in the intact blister strip in the complaint sample, but no deviation was found in the retained samples or during the in-process controls and final QC analysis recorded in the batch record.

18. NON-CONFIRMED COMPLAINTS: When both complaint and retained samples showed results in compliance with specifications or when only the complaint sample showed OOS results. OOS results in a complaint sample can be attributed to misuse or mishandling, when the drug product was not kept under appropriate conditions of temperature, humidity and light so that the identity, strength, quality and purity of the drug product could be affected. Example: Tablets of the complaint sample show a change in their appearance that is characteristic of a light, humidity or high temperature exposure.

19. COUNTERFEIT / TAMPER SUSPICION: When the retained sample is within the specification but the complaint sample is clearly OOS with no reason for that, such as a counterfeit or tampered drug product. Example: when packaging material is different from the original; an example of tampering is when the color of the drug product is completely different from the original or when any foreign substance was added to the product.

20. The Complaint Officer must also check if the complaint represents a serious and unexpected adverse drug experience. The Complaint Officer and the QA Manager must sign off the investigation form once the investigation is completed. 30 days is a reasonable time to conclude an investigation. Complaint files should be retained for at least 1 year after the expiry date of the lot.

21. CORRECTIVE ACTIONS AND FEEDBACK TO CUSTOMERS For all confirmed complaints, corrective actions must be implemented. These actions can range from a simple and quick training to some employees to a formal Corrective Action and Preventive Action (CAPA) handling. If a CAPA is opened, a multidisciplinary team consisting of representatives of QA, QC, Regulatory Affairs and Production Management must be established. Concerning non-confirmed complaints originating from misuse or inadequate handling of the drug product. The customer should receive a written response together with scientific information on the correct use and handling. Contd …

22. As feedback to the customer, the company must write a response letter to the complainant to explain the investigation approach taken, the results obtained and any implications, in case the quality problem was confirmed. The customer should be sent a free replacement product together with the response letter, since the customer returned the product (the ‘complaint sample’) to the company for analysis and a quality problem was found.

24. MONTHLY REPORTS AND TREND ANALYSIS Monthly reports should be elaborated in order to evaluate the amount and the nature of the complaints received and to perform a trend analysis of these complaints. The monthly reports must answer the following questions: How many complaints did the company receive in the period? How many were confirmed? How many were non-confirmed or were counterfeit/tamper suspicion? Graphic methods of displaying data are important adjuncts to data analysis and presentation. The report must be readily available mainly during GMP inspections.

25. Documentation final product complaint report Nature of the complaint-------------------------- Date------------------ Complaint:------------------------- Originator of the complaint & title ---------------------------- Distribution contact person & title ---------------------------- Method of notification---------------------------- Name------------------------------------------------------ Phone No.------------------------------ P.O#-------- Date shipped-------------Invoice#------- Product name:----------------- Control no:---------- EXP date:---------------- Quantity involved---------------------

26. Total quantity shipped---------------------------------------- Reason for complaint return request-------------------------- Complaint#------------ Product-------------------- Evaluation of complaints: 1.Physical characteristics------------------------- 2.Sign of deterioration ---------------------------- 3.Other observation-------------------------------- Quality control Findings: 1.Returned sample-------------------------- 2.Returned sample re assay--------------- 3. initial data-------------------------------------

27. 4.Quality control comments & suggestions ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Quality control-------------------,Date-------------------- Complaint#____________________________________ Product_______________________________________ Packaging/Labeling/Inserts evaluation_______________________________________________________________________________________________________________________________ Remarks___________________________________________________________________________________

28. Resultant action taken: 1.Method,Date of customer notification & authorized action_____________________________________________________________________________________ 2.Comments_____________________________________________________________________________________________________________________________ 3.Completion date for action taken _______________ 4.Quality assurance evaluation _______________________________________________________________________________________________________________________________

29. Customer complaint record book Report no. Date received Product name Received by Product lot no. Date investigation started Date investigation ended

30. RECALL HANDLING ‘‘ Recall’’ means a firm’s removal or correction of a marketed product that the Food and Drug Administration considers to be in violation of the laws it administers and against which the agency would initiate legal action, e.g., seizure. The main objectives of this recall plan are: Stop the distribution and sale of the affected product. Effectively notify Management, customers and regulatory authority. Efficiently remove the affected product from the marketplace, warehouse and/or distribution areas. Dispose and Conduct a root cause analysis and report the effectiveness and outcome of the recall. Implement a corrective action plan to prevent another recall .

31. SOP on recall RESPONSIBILITY: General manager / vice president: (QA/QC, Regulatory) General Manager: manufacturing. In case of adverse event a committee evaluates the crisis. It consists of following individuals: GM/V.P/QA/QC, Regulatory GM Manufacturing GM, Formulation and Development Medical advisor Vice president - Marketing Vice president – International Marketing Vice president – Technical Operations

32. PROCEDURE: Any employee becoming aware of such medicine should immediately notify to higher authorities. Immediately quarantine existing in-house of relevant medicine . Record the following information : The product name, strength, packs size, batch no., mfg and expiry date. The total number of units released for sale. Date on which distribution commenced. Total number of units distributed. Number of units still in stock. Nature of reported violation. In the light of above information higher officials evaluates the health hazard presented by the violation medicine and documents it on “ medicine recall control document”.

33. INDIAN PHARMACEUTICALS LIMITED Medicine recall control document Product information: Manufacturer --------------------------------------------------------------- 2. Product name--------------------------------------------------------------- Strength----------------------------------------------------------------------- Pack size-------------------------------------------------------------------- batch number --------------------------------------------------------------- total number of units originally released for sale: _________ Date of which distribution commenced: ______________ Total number of units distributed: _____________________ Number of units still in stock: At factory With stockiest (s) 10. The nature of the reported violation: __________________________________________________

34. Formulating a proposed recall strategy . It specifies the nature of communication to be used (phone, fax, telegram, letters, telemail, etc) as well as the level in the distribution chain to which recall is extended.(wholesalers, retailers, public, etc). Relevant records shall be submitted to regulatory authorities with proposed plan of action. INDIAN PHARMACEUTICALS LIMITED Medicine recall control document 3. RECALL STRATEGY 3.1. Nature of communication (phone, fax, telegraphs, letters, news papers, etc.) __________________________________________________ __________________________________________________ Depth of recall: (Wholesalers, retailers, general public) __________________________________________________

35. The GM, QA/QC Regulatory or GM manufacturing implements recall without delay. They also prepare an interim reconciliation report after 30 days and submit a copy to concerned authorities. After that prepares a final reconciliation report after 90 days and submits a copy for verification of the success of recall.

36. Signature of GM, QA/QC Regulatory G.M. manufacturing should be taken. Steps should betaken to prevent the re-occurrence. Prior to completion of recall the following points should be considered: Method of destruction of the product . A designed area to receive returned medicines. Inventory of medicine. Destruction authorization. The recall will be terminated when the GM, QA/QC Regulatory or GM manufacturing are assured that recall has been completed reasonably and a “medicine record status report” is completed.

37. INDIAN PHARMACEUTICALS LIMITED MEDICINE RECALL OR WITHDRAWAL, PROCEDURE STATUS REPORT Date: ________ product: ___________ Strength:____________ Pack size: ____________ B.no: _________Exp.date: ________ Nature of defect: ____________________________________ Reason for recall: _____________________________________ Indication of health risk or any other reason: ________________ Reported clinical problems: ______________________________ Method of communication to users: Method Action Date Target Group Number Phone Letter Telegram TV Radio, Press etc.

38. GM, QA/QC Regulatory or GM manufacturing shall prepare a “ Standardized recall letter” and “press statement”. INDIAN PHARMACEUTICALS LIMITED STANDARD RECALL LETTER Dear customer: It has come to our notice (product name) _______________ having batch number ______________ or has shown ________ please refrain from prescribing or dispensing any of this batch number and return all your stock of this batch number to our office at: __________________________________________ All returned stock or this batch number will be replaced as free of charge. We apologies for any inconvenience caused to you and thank you for your co-operation. Yours faithfully, G.M. QA/QC Regulatory

39. After the authorization by GM, QA/QC Regulatory or GM manufacturing, the recalled material along with stock in hand shall be destroyed and that should be recorded . RECALL CLASSIFICATION: FDA classified the product recall depending on the health hazard caused by the product . Class I is a situation in which there is a reasonable probability that the use of, or exposure to, a violative product will cause serious adverse health consequences or death. Class II is a situation in which use of, or exposure to, a violative product may cause temporary or medically reversible adverse health consequences. Class III is a situation in which use of, or exposure to, a violative product is not likely to cause adverse health consequences.

40. RECALL POLICY: Recall is an effective method of removing or correcting consumer products that are in violation of laws administered by the FDA. Recall may be undertaken voluntarily and at any time by manufacturers and distributors, or at the request of FDA. Recall is generally more appropriate and affords better protection for consumers. Seizure, multiple seizure, or other court action is indicated when a firm refuses to undertake a recall requested by the Food and Drug Administration.

41. HEALTH HAZARD EVALUATION: An evaluation of the health hazard presented by a product being recalled or considered for recall will be conducted by an ad hoc committee of Food and Drug Administration. It involves the assessment of hazards to various segments of the population, degree of seriousness, likelihood of occurrence, consequences etc. RECALL TEAM: A recall coordinator is to be appointed and members of a recall team identified from the various functional areas. All members must ensure that all procedures are carried out effectively and efficiently. The team should receive appropriate training. The Recall Management Team list shall be updated at least four times a year.

42. NAME ALTERNATE PERSON BUSINESS PHONE AFTER HOURS PHONE RESPONSIBILITIES DURING RECALL Chief Executive Officer Production Manager Decision Making Media Communication Contacting Accounts CFIA,/ Health Departments Contact Obtaining Legal Counsel Quality Assurance Manager Production Manager Quality Assurance / Technical Advisory Complaint Investigation CFIA / Health Departments Contact

43. RECALL STRATEGY: A recall strategy that takes into account the following factors : (i) Results of health hazard evaluation. (ii) Ease in identifying the product. (iii) Degree to which the product's deficiency is obvious to the consumer or user. (iv) Degree to which the product remains unused in the market-place. (v) Continued availability of essential products.

44. Elements of a recall strategy: Depth of recall. Public warning . Effectiveness checks: Level A--100 percent of the total number of consignees to be contacted. Level B- greater that 10 percent and less than 100 percent of the total number of consignees. Level C--10 percent of the total number of consignees to be contacted. Level D--2 percent of the total number of consignees to be contacted. Level E--No effectiveness checks .

45. TERMINATION OF RECALL: A recall will be terminated when the FDA is confident that product has been removed from market in accordance with recall strategy. FDA’s written notice to the regulatee is the real termination.

46. PRODUCT RECALL CHART Contd ….

48. References 1.Us Food &drug administration.21 code of federal regulation-part 211.198. 2. Current good manufacturing practices of pharmaceuticals - Manohar . A . Potdar. 3. How to practice GMP By P.P. Sharma 4. Validation in pharmaceutical industry by P.P. Sharma. 5. Recall Manual (http://www.google.co.in/#sclient=psy&hl=en&source=hp&q=RECALL+MANUAL&pbx=1&oq=RECALL+MANUAL&aq=f&aqi=g2g-v2g-m1&aql=&gs_sm=e&gs_upl=30014l34331l0l35759l13l12l0l0l0l0l1466l12191l6-4.7l11l0&bav=on.2,or.r_gc.r_pw.&fp=259c071b4fb78fb5&biw=1358&bih=566)

49. References 6. Complaint Handling in Pharmaceutical Companies Glaucia Karime Braga*; Faculty of Pharmaceutical Sciences, University of Sao Paulo, Brazil. 7. WHO technical reports series, No. 908, 2011. 8. Good Manufacturing Practices for pharmaceuticals – A Plan for total Quality control from manufacture to consumer 5th edition - Sidney H. Willig. 9. www.interscience.com 10. www.google .com 11.www.photobucket.com